Specific Internal Organs Research Articles

Improving the pharmacokinetics, biodistribution and plasma stability of monobodies.

Cancer is a leading cause of death worldwide. Several targeted anticancer drugs entered clinical practice and improved survival of cancer patients with selected tumor types, but therapy resistance and metastatic disease remains a challenge. A major class of targeted anticancer drugs are therapeutic antibodies, but their use is limited to extracellular targets. Hence, alternative binding scaffolds have been investigated for intracellular use and better tumor tissue penetration. Among those, monobodies are small synthetic protein binders that were engineered to bind with high affinity and selectivity to central intracellular oncoproteins and inhibit their signaling. Despite their use as basic research tools, the potential of monobodies as protein therapeutics remains to be explored. In particular, the pharmacological properties of monobodies, including plasma stability, toxicity and pharmacokinetics have not been investigated. Here, we show that monobodies have high plasma stability, are well-tolerated in mice, but have a short half-life in vivo due to rapid renal clearance. Therefore, we engineered monobody fusions with an albumin-binding domain (ABD), which showed enhanced pharmacological properties without affecting their target binding: We found that ABD-monobody fusions display increased stability in mouse plasma. Most importantly, ABD-monobodies have a dramatically prolonged in vivo half-life and are not rapidly excreted by renal clearance, remaining in the blood significantly longer, while not accumulating in specific internal organs. Our results demonstrate the promise and versatility of monobodies to be developed into future therapeutics for cancer treatment. We anticipate that monobodies may be able to extend the spectrum of intracellular targets, resulting in a significant benefit to patient outcome.

Histological Alterations in the Internal Organs of Wistar Han Rats (Rattus norvegicus) Euthanized by Five Different Methods.

Selecting a method of euthanasia is an important step in designing research studies that use animals; euthanasia methods must be humane, cause minimal pain and suffering to the animal, and preserve the tissue architecture of the organs of interest. In this study, we evaluated the histomorphology of the internal organs (lung, spleen, heart, kidney, liver, brain, and adrenal gland) of rats submitted to five different methods of euthanasia, with the goal of determining which protocol caused the least alteration of histomorphology. Twenty adult Wistar Han rats (Rattus norvegicus) were divided into 5 groups of 4 rats each (2 females and 2 males) and were euthanized by CO₂ or isoflurane inhalation, sodium thiopental or xylazine plus ketamine overdose, or decapitation. All euthanasia was performed in accordance with published guidelines and local legal require- ments. Necropsy was performed immediately after euthanasia. Specific internal organs were removed and placed in formalin and submitted for routine histologic processing. Histomorphological examination of hematoxylin and eosin-stained tissues revealed circulatory alterations in multiple organs, predominantly congestion in multiple tissues, pulmonary hemorrhage, and hepatic degeneration. The euthanasia methods that induced the most severe alterations were exposure to CO₂ and anesthetic overdose with xylazine plus ketamine or sodium thiopental. Euthanasia by overexposure to isoflurane caused less damage, and the alterations were of minimal severity. Decapitation resulted in the lowest incidence of lesions in multiple organs but due its traumatic nature, it caused the highest incidence of pulmonary hemorrhage. In selecting a method of euthanasia, factors to consider are the species of animal, the purpose of the research, and the practical ability to perform the procedure to achieve maximal animal welfare without iatrogenic changes that could compromise the outcome and reproducibility of the study.

Where does language come from? The development of a naïve biological understanding of language

We examined 3- to 10-year-old U.S. children’s naïve biological beliefs about spoken language, probing developing beliefs about where language is located in the body. Experiment 1 (N = 128) introduced children to two aliens, each having eight parts: internal organs (brain and lungs), face parts (mouth and ears), limbs (arms and legs), and accessories (bag and hat). Participants were assigned to the Language condition (in which the aliens spoke two different languages) or the control Sports condition (in which the aliens played two different sports). We assessed children’s reasoning about which parts were necessary to speak a language (or play a sport) by asking children to (a) create a new alien with the ability to speak a language (or play a sport) and (b) remove parts of an alien while preserving its ability to speak a language (or play a sport). In the Language condition, with age, children attributed language-speaking abilities to internal organs and face parts. In Experiment 2 (N = 32), a simplified language task revealed that 3- and 4-year-old children demonstrated a weaker, albeit present, biological belief about language. In Experiment 3 (N = 96), children decided at what point an alien would lose its ability to speak the language as the experimenter added or removed parts. Children attributed language-speaking abilities to specific internal organs and face parts (brain and mouth). We demonstrate that children believe that language is contained to specific parts of the body and that this “metabiological” reasoning increases with age.

Minimally invasive autopsy for fetuses and children based on a combination of post-mortem MRI and endoscopic examination: a feasibility study.

Less invasive perinatal and paediatric autopsy methods, such as imaging alongside targeted endoscopy and organ biopsy, may address declining consent rates for traditional autopsy, but their acceptability and accuracy are not known. The aims of this study were to provide empirical data on the acceptability and likely uptake for different types of autopsy among key stakeholders (study 1); and to analyse existing autopsy data sources to provide estimates of the potential efficacy of less invasive autopsy (LIA) and its projected utility in clinical practice (study 2). Study 1: this was a mixed-methods study. Parents were involved in research design and interpretation of findings. Substudy 1: a cross-sectional survey of 859 parents who had experienced miscarriage, termination of pregnancy for fetal anomaly, stillbirth, infant or child death, and interviews with 20 responders. Substudy 2: interviews with 25 health professionals and four coroners. Substudy 3: interviews with 16 religious leaders and eight focus groups, with 76 members of the Muslim and Jewish community. Study 2: a retrospective analysis of national data in addition to detailed information from an existing in-house autopsy database of > 5000 clinical cases that had undergone standard autopsy to determine the proportion of cases by clinical indication group for which tissue sampling of specific internal organs significantly contributed to the diagnosis. Substudy 1: 91% of participants indicated that they would consent to some form of LIA, 54% would consent to standard autopsy, 74% to minimally invasive autopsy (MIA) and 77% to non-invasive autopsy (NIA). Substudy 2: participants viewed LIA as a positive development, but had concerns around the limitations of the technology and de-skilling the workforce. Cost implications, skills and training requirements were identified as implementation challenges. Substudy 3: religious leaders agreed that NIA was religiously permissible, but MIA was considered less acceptable. Community members indicated that they might consent to NIA if the body could be returned for burial within 24 hours. Study 2: in 5-10% of cases of sudden unexplained death in childhood and sudden unexplained death in infants, the final cause of death is determined by routine histological sampling of macroscopically normal organs, predominantly the heart and lungs, and in this group routine histological sampling therefore remains an important aspect of investigation. In contrast, routine histological examination of macroscopically normal organs rarely (< 0.5%) provides the cause of death in fetal cases, making LIA and NIA approaches potentially highly applicable. A key limitation of the empirical research is that it is hypothetical. Further research is required to determine actual uptake. Furthermore, because of the retrospective nature of the autopsy data set, findings regarding the likely contribution of organ sampling to final diagnosis are based on extrapolation of findings from historical autopsies, and prospective data collection is required to validate the conclusions. LIA is viable and acceptable (except for unexplained deaths), and likely to increase uptake. Further health economic, performance and implementation studies are required to determine the optimal service configuration required to offer this as routine clinical care. The National Institute for Health Research Health Technology Assessment programme.

Effects of Bacillus subtilis and zinc on the growth performance, internal organ development, and intestinal morphology of male broilers with or without subclinical coccidia challenge.

Effects of antibiotic (bacitracin), anticoccidial (narasin), and alternative (Bacillus subtilis and zinc) feed additives on growth performance, internal organ development, and intestinal morphology of commercial broilers with or without subclinical coccidia challenge were determined. A total of 1,344 1-day-old male Ross × Ross 708 broilers were randomly distributed into 12 treatments (6 diets × 2 challenge treatments, 8 replication pens/treatment) in 96 floor pens. The 6 dietary treatments were as follows: a control diet (corn and soybean-meal basal diet), a probiotic diet (basal diet + Bacillus subtilis), a zinc diet (basal diet + 100ppm zinc), a probiotic and zinc combined diet, an anticoccidial diet (basal diet + narasin), and a practical diet (basal diet + narasin + bacitracin). On day 21, each chick in the challenge treatment was gavaged with a 10× dose of a commercial vaccine containing live Eimeria oocytes, whereas each chick in the non-challenge treatment was gavaged with equivalent distilled water. The subclinical coccidia challenge increased the relative weights of pancreas and decreased the ileal crypt depth of broilers at 26 d of age, increased feed conversion ratios from day 15 to 28 and 29 to 40, and increased the relative weights of duodenum and bursa on day 54. As compared to other diets, anticoccidial and practical diets increased BW gain and decreased feed conversion ratio from day 15 to 28, and increased the day 40 carcass weights. As compared to control diets, probiotic diets decreased BW gain and increased the mortality from day 15 to 28; however, probiotic diets did not affect the overall growth performance from day 0 to 54 or carcass yield on day 54. Growth measurements during periods of day 29 to 40 and day 41 to 54 were not affected by any feed additive. From this study, a subclinical coccidia challenge enlarged specific internal organs and compromised the feed conversion ability of broilers. Dietary Bacillus subtilis did not affect overall growth rate or carcass yield of broilers under subclinical coccidia challenge.

Untargeted metabolomics-like screening approach for chemical characterization and differentiation of canopic jar and mummy samples from Ancient Egypt using GC-high resolution MS.

In Ancient Egypt it was common practice to embalm corpses and specific internal organs to ensure eternal life. The exact nature of the employed embalming fluids, particularly for organ preservation within the canopic jars, is debated. Therefore, the aim of the current study, was to chemically characterize and differentiate canopic jars (n = 28) and mummies (n = 6) using gas chromatography - high resolution mass spectrometry (GC-HR MS) with a new untargeted metabolomics-like screening approach; as part of a larger minimal-invasive transdisciplinary study on Ancient Egyptian human tissues. Post-analytical data processing included deconvolution, screening against the NIST 14 spectral database as well as a high resolution metabolomics library, and positive peak evaluation. In the majority of samples the presence of a coniferous resin was indicated by the detection of longiborneol in combination with abietadiene acid derivatives and guajacol. Beeswax, proposedly used for symbolic reasons and/or as a binding agent, was detected in 10 samples. Previously not mentioned in the literature, but identified in the current sample set, were medical-related substances like aniseed constituents, salicylic acid, chamazulene and jacobine. By applying an untargeted metabolomics-like approach to archaeological samples for the first time, extensive statistical analysis was made possible (using both identified and non-identified features; adding up to 4381 features), which showed significant differences in the overall chemical composition of canopic jar and mummy samples using principle component analysis (PCA) and partial least square-discriminant analysis (PLS-DA). This emphasizes the necessity for more extensive canopic jar studies in the future in order to interpret findings correctly.

Evaluation of Reflexology by "BIOCERAMIC Resonance" Operation producing Weak Force Field during Simultaneous Acupoint Stimulation of Urinary Bladder Point on Subject's Ear Resulting in Electric Current Change on Urinary Bladder reflex Point on Subject's Hands, and Related New Research Finding.

It was postulated in our previous publications that the meridian channels as conceived in Traditional Chinese Medicine (TCM) are various standing waves arising from harmonic rhythmic sound frequencies originating from the human heart beat. BIOCERAMIC is an artificial material able to produce a weak force field causing different biophysical and systemic health benefits, with the key characteristics of hydrogen bonds weakening and microcirculation enhancement. Since discovering that the effects of a BIOCERAMIC field can be transmitted via sound waves propagation, we then also developed a BIOCERAMIC Resonance device to produce weak force field throughout the body, and achieve resonance with the body's meridian channels to reinforce microcirculation. Since our previous research proved BIOCERAMIC can produces changes in ectodermal current levels, the present evaluation on reflexology is done by the application of Electric Current Detection (ECD) to the palmar surface of the hands matching correlative organs and glands loci to reflex points according to standard reflexology. The procedure will compare changes in the electrical current observed before and after a session of BIOCERAMIC Resonance treatment on the soles of the subjects' feet. We also conducted a procedure using corona discharge (Kirlian) photography of the hands to examine whether the coronal intensities could be affected by application of the BIOCERAMIC patch. Intensities are shown on the screen of a computer using special software that categorizes intensities into five zones. Under the continuous treatment of BIOCERAMIC Resonance on soles of the feet and simultaneous stimulation on the specific point on the surface of the ear representing the urinary bladder. The electrical current (Aji ampere) on the areas in the hands are decreased from the beginning of the experiment, but only the specific area on the surface of the ear representing the urinary bladder was exhibited increased of the electrical current (Aji ampere), with statistically significant difference (p<0.05). To the other study we evaluated the validity of reflexology and corona discharge (Kirlian) photography by applying BIOCERAMIC Resonance and small adhesive patches made from the BIOCERAMIC material. Significant differences were evident on four out of five different zones of the computerized images. Our findings suggest the existence of presupposed virtual channels or reflex points on the skin surface of the feet, hands, and ears that connect or somehow reflect back to specific internal organs, as mapped out on standard charts found in reflexology. Furthermore, the depicted corona intensities from five zones shown on a computer screen of corona discharge photography seem to indicate that the volunteer subjects are affected by the BIOCERAMIC patches. This study demonstrates the operation of the BIOCERAMIC Resonance device is able to produce weak force field through the body, which is objectively measurable and thereby scientifically integrating the concepts of reflexology, meridian channels and biofield therapy.

Assemblable Hand for Laparoscopic Surgery with Phased Array and Single-Element Ultrasound Probes

During laparoscopic surgery, large internal organs should often be manipulated while being internally visualized. For this purpose, we study an assemblable two-fingered hand implemented with an ultrasound probe. The fingers are separately introduced into the abdominal cavity through small incisions and are assembled into a hand sufficiently large to grasp or manipulate the large organ. Two types of ultrasound probes are employed; a phased array probe of a commercially available ultrasound diagnosis system, and a single-element probe. Using the latter probe, the hand is assembled through 12 mm trocars and is assessed in an in vivo experiment. Ultrasound echo sensing is found to retrieve diagnostic information regarding specific internal organs. It also visualizes the finger and its back during grasping, which can improve the safety of hand grasping and manipulation. Furthermore, ultrasound echo sensing can assist the measurement of the relative position and orientation of the two grasping fingers.

Subacute Toxicological Analysis of Excessive &amp;lt;i&amp;gt;Staphylococcus epidermidis&amp;lt;/i&amp;gt; Administration in Mice

We performed subacute toxicological analysis of mice that received repeated oral administration of excess Staphylococcus epidermidis every day for 4 weeks. No mouse died and no abnormalities of specific internal organs were induced by excessive S. epidermidis administration. Furthermore, acute toxicity analysis following oral and intraperitoneal administration of excess S. epidermidis showed no toxicity in the test mice.

An Integrated Multiscale Mechanistic Model for Cancer Drug Therapy

In this paper, we established a multiscale mechanistic model for studying drug delivery, biodistribution, and therapeutic effects of cancer drug therapy in order to identify optimal treatment strategies. Due to the specific characteristics of cancer, our proposed model focuses on drug effects on malignant solid tumor and specific internal organs as well as the intratumoral and regional extracellular microenvironments. At the organ level, we quantified drug delivery based on a multicompartmental model. This model will facilitate the analysis and prediction of organ toxicity and provide important pharmacokinetic information with regard to drug clearance rates. For the analysis of intratumoral microenvironment which is directly related to blood drug concentrations and tumor properties, we constructed a drug distribution model using diffusion-convection solute transport to study temporal/spatial variations of drug concentration. With this information, our model incorporates signaling pathways for the analysis of antitumor response with drug combinations at the extracellular level. Moreover, changes in tumor size, cellular proliferation, and apoptosis induced by different drug treatment conditions are studied. Therefore, the proposed multi-scale model could be used to understand drug clinical actions, study drug therapy-antitumor effects, and potentially identify optimal combination drug therapy. Numerical simulations demonstrate the proposed system's effectiveness.

Fetopathological Aspects of Holoprosencephaly

Holoprosencephaly (HPE) is a congenital central nervous system malformation estimated to occur in 1/250 conceptuses and 1/10,000 live births. While the severe forms, which are incompatible with life, are easier to detect in the prenatal period, the milder forms can remain unrecognised. As this can have serious consequences for the pregnancy and malformation carriers it is of crucial importance to find ways of timely detection of this pathological condition. The present study AIMED at finding an association of holoprosencephaly with facial dysmorphia and anomalies of visceral organs that would alert the physician to be very careful in making the prenatal diagnosis, which may require termination of pregnancy by medical indications. The study included 15 fetuses diagnosed with holoprosencephaly out of 2095 cases analysed post-mortem in the Fetopathology Clinic at the Centre for Maternity and Neonatology in the town of Tunisia over a period of 3 years (Oct. 2006 - Oct. 2009). The fetuses were analysed macro- and microscopically. All forms of holoprosencephaly include elements of facial dysmorphism with the facial phenotypes of cyclopia, cebocephaly and ethmocephaly. It can be associated with specific internal organs anomalies, the hydrocephaly being the most common anomaly of the central nervous system. Our study suggested that holoprosencephaly can be correlated with craniofacial anomalies affecting the midfacial and medium craniovisceral structures. The anatomical variations of HPE and the phenotypic facial correlations require a systematic and targeted study of central nervous system.

A Neurosegmental Perspective of the Classical Back Shu Points

Abstract In traditional acupuncture, acupoints in the paraspinal musculature along the Bladder channel can be used to stimulate specific internal organs. These are the so-called Back Shu points (BSP) or Transporting points. Some of these insertion sites, based on millennia of clinical observations, are functionally accurate. This review of the neuroanatomical literature, discussing the spinal segmental innervation of the thoracic and abdominal organs, found significant discrepancies in the anatomic levels reported to produce reflex neural stimulation of any given organ. Based on these findings, clinically important corrections to the optimal spinal segmental levels to stimulate organ function are suggested. A broad range of clinical applications is afforded to the practitioner by the stimulation of the posterior branch of the spinal nerves with acupuncture needles and electricity. This article discusses the classical BSP from a contemporary neuroanatomical perspective and proposes a new model of clinical ...

BIOACCUMULATION DYNAMICS OF HEAVY METALS IN &lt;sub&gt;Oreochromis nilotycus&lt;/sub&gt;: PREDICTED THROUGH A BIOACCUMULATION MODEL CONSTRUCTED BASED ON BIOTIC LIGAND MODEL (BLM)

In estuarine ecosystem, sediments are not only functioning as heavy metal scavenger, but also as one of potential sources for heavy metals to the ecosystem. Due the capability of aquatic organisms to accumulate heavy metals, there is possibility of heavy metals to exert their toxic effect towards the organisms and other organisms positioned in higher trophic level, such as fish, and further to human beings. To understand the different processes of heavy metal bioaccumulation in a dynamic manner, a bioaccumulation model is required. Since bioaccumulation starts with the uptake of chemical across a biological membrane, the bioaccumulation model was constructed based on Biotic Ligand Model (BLM). The input for the model was determined from laboratory scale simulated estuarine ecosystem of sediment-brackish water (seawater:Aquaâ 1:1) for determining the heavy metal fractions in sediments; simulated Oreochromis nilotycus - brackish water (fish-water) ecosystem for determining the rate constants; simulated fish-water-sediment ecosystem for evaluating the closeness between model-predicted and measured concentration, routes and distribution within specific internal organs. From these bioaccumulation studies, it was confirmed that the internalization of metals into the cells of gills and internal epithelias follows similar mechanisms, and governed mostly by the waterborne or hydrophilic heavy metals. The level of hydrophilic heavy metals are determined by desorption equilibrium coefficients, 1/KD, and influenced by salinity. Physiologically, the essential Cu and Zn body burden in O. nilotycus are tightly homeostasis regulated, shown as decreasing uptake efficiency factor, EW, at higher exposure concentrations, while non essential Cd and Hg were less or not regulated. From the distribution within specific internal organs, it was revealed that carcass was more relevant in describing the bioaccumulation condition than liver. It is clear that every heavy metal has its own bioaccumulation dynamics, depend to the metal studied and environmental conditions, however the obtained parameters are applicable to bioaccumulation of Cd and Hg in natural estuarine ecosystem of Segara Anakan, Central Java. Keywords: heavy metal, estuarine, bioaccumulation, model, dynamics

Mixed handedness prevails among children and adolescents with infantile asthma and diabetes

Non-right handedness has been associated with allergic diseases and asthma. Infantile diabetes, too, has been associated with non-right handedness but, to date, data are more consistent on a link between left handedness and asthma than on diabetes. We surmised that mixed handedness, as an indicator of neurodevelopmental disturbance of brain laterality, rather than left handedness is more prevalent among children with asthma and diabetes mellitus. A total of 100 families with a child or an adolescent diagnosed with infantile asthma (n = 50) or diabetes mellitus type 1 (n = 50) attending the Paediatric Clinic of the 'Brotzu' Hospital in Cagliari (Italy) in 2006 agreed to participate in the study. The Annett Hand Preference Questionnaire was used to test handedness. Compared with 99 same-age and -sex controls, cases were marginally less likely to be right handed (71% vs. 86%; OR = 0.82, 95% CI = 0.54-1.25), and statistically more likely to be mixed handed (20% vs. 6%; OR = 3.30, 95% CI = 1.27-8.56) than controls: chi(2) = 8.84, d.f. = 2, p = 0.01. Children with asthma or diabetes did not differ from controls by season of birth; however, mixed-handed (n = 12, 46%) and left-handed (n = 6, 35%) children were statistically more likely to be born in winter as against the other seasons than those who were right handed (n = 36, 23%). Severity was also marginally related to the chance of being classified as non-right handed. People with a genetic predisposition to immune disorders could be more likely to have been negatively affected by infection and inflammation during fetal life, thus developing a deviation in handedness during neurodevelopment, as well as suffering the consequence of disordered immunity during childhood, such as allergic reactions (asthma) and immune-mediated damage to specific internal organs (diabetes type 1).

Modulation of visceral function by selective stimulation of the left vagus nerve in dogs.

The superficial regions of the left vagus nerves of a dog were selectively stimulated with 39-electrode spiral cuffs having 13 circumferential groups of three electrodes (GTE) to modulate the function of the innervated internal organs and glands. Under general anaesthesia, the cuffs were chronically implanted around the nerve in the neck in two adult Beagle dogs and remained viable for 16 months. The regions were stimulated with biphasic, rectangular current pulses (2 mA, 200 micros, 20 Hz) delivered to the group of GTE lying close to the region innervating the specific internal organs or glands. The results showed that specific electrode configurations had actions on the heart (GTE 9), lungs (GTE 4) and pressure in the urinary bladder (GTE 1). It was also shown that GTE no. 10 significantly modified the endocrine function of the pancreas. The results of this study clearly demonstrate that internal organs and glands can be selectively stimulated via the selective stimulation of innervating superficial regions of the autonomous peripheral nerve.

Multivariate biological profiling of the subacute effects of halogenated aliphatic hydrocarbons

Abstract Ten halogenated aliphatic hydrocarbons have been investigated for subacute toxic effects in rats. The biological testing involved 248 measurements for each one of the compounds; the resulting data contain information regarding effects on clinical chemistry and hematology patterns, as well as data on changes in total body weight and weights of specific internal organs. Principal component analysis was used to analyze the multivariate response data. This multivariate biological profiling showed that, with the current experimental protocol, primarily four compounds could be identified as having biological profiles deviating from the others. These compounds were trichloromethane, 1,2‐dichloroethane, 1,1,2,2‐tetrachloroethane and 2‐chloropropane. By identifying compounds with deviating/unique biological profiles, the present work forms a basis for future quantitative structure‐activity relationships analysis of these data.

SIMPLE NON-INVASIVE EARLY DETECTION AND LOCALIZATION OF SPECIFIC CANCER TISSUES OF INTERNAL ORGANS AND DIFFERENTIATION OF CANCER TISSUE FROM SURROUNDING AREAS INFECTED BY CANCER RELATED VIRUSES, AS WELL AS EVALUATION OF THEIR MICRO-CIRCULATORY CONDITION &amp; DRUG UPTAKE USING THE BI-DIGITAL O-RING TEST

In 1984, the author first developed a simple, quick, non-invasive, economical method of detecting cancer in specific internal organs, using the Bi-Digital O-Ring Test (BDORT), with a microscope slide of specific cancer of a specific internal organ as a reference control substance. The detection rate for cancer screening was much greater than with any standard diagnostic tests. When imaging was performed using the BDORT, the area of positive response to the cancer positive slide was often much greater than the actual size of the cancer itself. This was due to the fact that most of the cancer tissue of the lungs or digestive system contained viruses such as HTLV-3 (often found in adenocarcinoma of the lung, stomach, head of pancreas, and colon) or HTLV-1 (often found in small-cell carcinoma of the lung and certain types of leukemia). The extent of the virus positive area was often far greater than that of the cancer tissue itself and was distributed in a much greater area surrounding the cancer. For this reason, the virus alone showed a response which could be mistaken for cancer tissue. The author succeeded in differentiating the exact location of cancer tissue itself from surrounding cancer related virus (with or without other microbes) positive area by using a pair of identical microscope slides with the same cancer tissue. One of the slides was exposed to ultra-violet rays (peak wavelength of 253.7 nm mercury vapor atomic resonance spectral line) for 40 seconds-4 minutes. After this exposure, the BDORT response to the virus (with or without other microbes) associated with the cancer tissue was completely eliminated, while the response to the cancer tissue was maintained. Using an ultraviolet exposed cancer slide, the imaging of the part of the body which responded to this virus-free cancer slide indicated the actual location of the cancer tissue, which was often confirmed by standard X-ray or other imaging methods when the thickness of the tumor was relatively large. These cancers detectable by standard laboratory tests had strikingly weakening response to the BDORT (-3.5 and -4), with ultra-violet exposed cancer slide as well as for antibody of Oncogen C-fos. The smallest size of cancer tissue detected by this method was less than 1mm in diameter in the very early stage of the cancer, which usually cannot be detected by current laboratory tests.(ABSTRACT TRUNCATED AT 400 WORDS)

Connections found between each meridian (heart, stomach, triple burner, etc.) & organ representation area of corresponding internal organs in each side of the cerebral cortex; release of common neurotransmitters and hormones unique to each meridian and corresponding acupuncture point & internal organ after acupuncture, electrical stimulation, mechanical stimulation (including shiatsu), soft laser stimulation or QI Gong.

Using the "Bi-Digital O-Ring Test Imaging Technique", the author has been able to accurately localize meridians and acupuncture points that correspond to specific internal organs and has found that most general patterns of meridians and the number of acupuncture points on each of the meridians of specific internal organs of the 12 main internal organs described in the literature of ancient Chinese medicine, are more or less correct, with the exception of some variations and inaccuracies. Each meridian of specific internal organs was found to be connected to the organ representation area in the cerebral cortex of specific internal organs. The acupuncture point has an area and occupies 3-dimensional space. It has a circular or slightly oval boundary with diameter in the range of 3 mm to 2.7 cm, although 6-12 mm are the most common diameters in human adults, with the exception of the area outside the corners of the nailbeds of the fingers and toes. Using the "Bi-Digital O-Ring Test Molecular Identification Method", the author also found that within the boundary of most acupuncture points and meridian lines (including Heart, Stomach, and Triple Burner) were high concentrations of neurotransmitters and hormones, including Acetylcholine, Methionine-Enkephalin, Beta-Endorphin, ACTH, Secretin, Cholecystokinin, Norepinephrine, Serotonin, and GABA. On all these meridian lines, in addition to the above neurotransmitters and hormones, Dopamine, Dynorphin 1-13, Prostaglandin E1 (PGE1) and VIP were found, but the latter do not usually exist within the boundary of the acupuncture point with the exception of the center midline of the acupuncture point where the meridian line is situated. Serotonin, Norepinephrine, and Cholecystokinin appeared in either one of the above 2 patterns, depending on the individual. Usually, no significant amounts of these neurotransmitters and hormones were found at the surrounding area outside of meridian and acupuncture points. However, the essential amino acid L-Tryptophan (which is a precursor of Serotonin), was usually found outside of the boundary of the acupuncture point and the meridian but not within the boundary of the acupuncture point and the meridian. Wherever Serotonin appeared, L-Tryptophan disappeared significantly and when the Serotonin disappeared, L-Tryptophan reappeared. In addition to the above common neurotransmitters and hormones, the Heart meridian had additional Atrial Natriuretic Peptide in both the meridian and its acupuncture points. Similarly, the Stomach meridian had additional Gastrin in both the meridian and its acupuncture points. Likewise,the Triple Burner meridian had additional Testosterone (in the male) and Estrogen (especially Estriol and Estradiol in the female.

Imaging of the stomach, and localization of the stomach meridian & its acupuncture points in a human cadaver by the use of the indirect "Bi-Digital O-Ring Test Imaging Technique".

Since 1984, using the "Bi-Digital O-Ring Test (Molecular Identification, Localization and) Imaging Technique" originally developed by Y. Omura, the imaging of the outline of normal and abnormal internal organs has been successfully applied for clinical diagnosis and evaluation of therapeutic effects, without the use of expensive imaging instrumentation. Not only has it become possible to non-invasively image each internal organ and localize specific malignant tumors of specific internal organs, as well as neurotransmitters, but it has also recently become possible to demonstrate the presence and exact locations of the meridians corresponding to specific internal organs and their acupuncture points along the meridians through the use of either the Direct or Indirect "Bi-Digital O-Ring Test (Molecular Identification, Localization and) Imaging Techniques" while holding a microscopic slide of the specific human internal organ tissue. However, very little information was available to demonstrate the presence of the meridians and their acupuncture points in a human cadaver. In this study, we were able to demonstrate by use of the Indirect "Bi-Digital O-Ring Test (Molecular Identification, Localization and) Imaging Technique" the presence of meridians corresponding to specific internal organs and acupuncture points on the meridians, all of which were nearly identical to those found in a living human. For example, the authors found that the stomach meridian at both ends of one of the most well-known acupuncture points, Stomach 36, is located within 1 mm of the surface of the skin, and the average diameter of the meridian is less than 1 mm. Stomach 36 in this particular cadaver had a round shape with a diameter of approximately 1.8 cm at the skin surface. The acupuncture point, St. 36, in this cadaver at the skin surface was round in shape and extended to the deepest underlying muscle layer of the tibialis anterior muscle, in three dimensions. In spite of the fact that the Indirect Bi-Digital O-Ring Test Imaging Technique showed a distinct pathway for the stomach meridian and the location of St. 36, there was no apparent difference to the naked eye between the meridian and the surrounding non-meridian tissue, nor between St. 36 and surrounding non-acupuncture point area. However, there seems to be a more dense connective tissue network between the skin layer and the fascia on the muscle tissue at the acupuncture point, as compared with the surrounding non-acupuncture point area.(ABSTRACT TRUNCATED AT 400 WORDS)