Immunology Pathology Research Articles

New Degree in Clinical Laboratory Science

I recently read that the American Society for Clinical Laboratory Science (ASCLS) is considering the establishment of a doctoral degree in clinical laboratory science (DCLS) (http://laboratorymanageradvanceweb.com/common/editorial/editorial.aspx?CC=96819). As described in the article, the new holder of the DCLS would be “appropriately trained to advise on the proper selection performance and interpretation of laboratory tests.” He/she would be knowledgeable in the discussion predictive values, the clinical significance of test results developing algorithms, and sorting out clinical issues as they relate to laboratory testing. Isn't this exactly what doctoral-level scientists in various areas of the laboratory, e.g., microbiology, chemistry, immunology, and molecular pathology, currently do? While it is true that the thrust of the academic Ph.D. degree is research and teaching, it is the postdoctoral training and certification in the various areas of clinical laboratory science that defines the role that the individual plays in the clinical laboratory, not the degree.

Effect of Ilex extracts and isolated compounds on peroxidase secretion of rat submandibulary glands

Free radicals are involved in diverse disorders such as tumoral, central nervous system alterations, immunological and inflammatory pathologies. Peroxidase is an oral enzyme involved in the defense of the oral cavity. Ilex species such as Ilex paraguariensis St. Hil. and the commercial product made with it “Yerba Mate” are used traditionally as antirheumatics and for the treatment of gastrointestinal diseases among others and also as a beverage with nutritional and stimulant properties. The presence of polyphenolic derivatives and flavonoids in the aqueous extract has been determined by HPLC analysis. In this study, the activity of aqueous extracts of I. paraguariensis and “Yerba Mate” on peroxidase secretion in female rat submandibular glands was investigated. The contribution to this pharmacological activity by some major hydrocynnamic acid derivatives present in the crude extracts, such as chlorogenic acid and caffeic acid and the most abundant methylxanthine, caffeine, was also evaluated. Spectrophotometrical determination of peroxidase activity showed that both extracts produced a significant increase in both secreted peroxidase and total peroxidase activity, though “Yerba Mate” showed a higher activity (EC 50 “Yerba Mate”: 148 ± 10 μg/ml; EC 50 I. paraguariensis: 841 ± 20 μg/ml). The HPLC/DAD analysis of the crude extracts was performed and chlorogenic acid, caffeic acid and caffeine were identified and quantified. The results (expressed as W/W percentage of dried material) were as follows: I. paraguariensis: chlorogenic acid: 2.80 ± 0.30, caffeic acid: 0.023 ± 0.004, caffeine: 1.06 ± 0.06; “Yerba Mate”: chlorogenic acid: 1.98 ± 0.37; caffeic acid: 0.020 ± 0.003, caffeine: 0.70 ± 0.06. Caffeine and chlorogenic acid were proved to play an important role in the induction of peroxidase secretion induced by the extracts.

Bacterial Disease in HIV-Infected Patients

Bacterial Disease in HIV-Infected Patients

Probiotics: do they have a role in oral medicine and dentistry?

This review describes current knowledge on probiotic bacteriotherapy from the oral health perspective. Recent experimental studies and results from randomized controlled trials have shown that certain gut bacteria, in particular species of Lactobacillus and Bifidobacterium, may exert beneficial effects in the oral cavity by inhibiting cariogenic streptococci and Candida sp. Probiotics have been successfully used to control gastro-intestinal diseases. They also appear to alleviate symptoms of allergy and diseases with immunological pathology. The mechanisms of probiotic action appear to link with colonization resistance and immune modulation. Lactic acid bacteria can produce different antimicrobial components such as organic acids, hydrogen peroxide, carbon peroxide, diacetyl, low molecular weight antimicrobial substances, bacteriocins, and adhesion inhibitors, which also affect oral microflora. However, data is still sparse on the probiotic action in the oral cavity. More information is needed on the colonization of probiotics in the mouth and their possible effect on and within oral biofilms. There is every reason to believe that the putative probiotic mechanisms of action are the same in the mouth as they are in other parts of the gastrointestinal tract. Because of the increasing global problem with antimicrobial drug resistance, the concept of probiotic therapy is interesting and pertinent, and merits further research in the fields of oral medicine and dentistry.

What is antibody-mediated pure red cell aplasia (PRCA)?

Antibody (Ab)-mediated pure red cell aplasia (PRCA) is an immunological pathology associated with the production of neutralizing Abs that inhibit the erythropoietic activity of endogenous erythropoietin (EPO) and recombinant erythropoiesis-stimulating agents (ESAs). Although this disorder occurs very rarely, the number of reported cases has increased dramatically in recent years, predominantly in patients with chronic kidney disease (CKD)-associated anaemia receiving subcutaneous (s.c.) injections of one particular formulation of recombinant epoetin-alpha. This disorder is differentiated from classic forms of PRCA that are caused by chemical toxaemia (i.e. erythroblastopenia induced by chemical compounds), lymphoproliferative neoplasms, thymoma, human parvovirus B19 and certain autoimmune disorders. Patients with Ab-mediated PRCA develop resistance to EPO and severe anaemia that follows a period of successful erythropoietic response, and exhibit characteristic decreases in blood haemoglobin (Hb) level and in the number of circulating reticulocytes. However, it is not yet possible to predict which patients will develop PRCA or when in the course of their treatments PRCA may develop. Laboratory confirmation of Ab-mediated PRCA requires bone marrow examination demonstrating few or no erythroid precursors and the presence of serum anti-EPO Abs using a validated assay. These neutralizing anti-EPO Abs recognize the protein core of the EPO molecule; carbohydrate groups on EPO can affect the binding of Abs but are themselves not immunological determinants. Animal models are being developed to increase further our understanding of the immunological mechanisms underlying the onset and progression of Ab-mediated PRCA.

Effects of Extended-Wear Soft Contact Lenses on the Ocular Surface and Central Corneal Thickness

Purpose: New contact lens materials with high oxygen permeability are said to be convenient for the extended-wear (EW) schedule. We evaluated the short-term effect of EW soft contact lens usage on ocular surface and central corneal thickness. Patients and Methods: Fifty-two eyes of 26 patients were included in the study. Sixteen of the patients used the high oxygen-permeable lenses for a 30-day extended-wear schedule (group I). Ten patients used the lenses on a daily wear basis (DW, group II). All patients were evaluated for visual acuity and central corneal thickness by corneal and conjunctival biomicroscopy, Schirmer and tear break-up time (BUT) tests. Impression cytology was performed in the superior/temporal, inferior/nasal quadrants of the conjunctiva, 1 mm from the limbus, with cellulose acetate filter paper. The specimens were graded under light microscopy according to Nelson’s classification. Results: Three patients in the EW group were excluded from the study as they discontinued lens usage due to slight discomfort and hyperemia. Biomicroscopic findings and tear function tests indicated no increased pathological results. Central corneal thickness decreased from 554 ± 9.55 to 546 ± 9.30 µm (mean ± SEM) in the EW group (p = 0.002), whereas no significant change occurred in the DW group. Cytological evaluation of the EW group showed an 88% increase in metaplasia (p = 0.007), especially close to the limbal areas and in the superior quadrants; this ratio was 30% in the DW group. Snake-like chromatin changes were found to be increased, from 4 to 6 patients, in the EW group while it remained the same in the DW group (p > 0.05). Individual comparisons of the initial and final pathological conditions of the ocular surfaces in the two groups showed that there was an increase in pathology in the EW group while there was no significant difference in the DW group. Conclusions: On a 30-day extended-wear basis with high oxygen-permeable lenses, the possible development and increase of conjunctival cytologic changes secondary to mechanical trauma is one of the main remaining problems. Conjunctival and related immunologic pathologies should not be overlooked when prescribing an extended-wear lens schedule.

Variability in diagnostic criteria for chronic fatigue syndrome may result in substantial differences in patterns of symptoms and disability.

Chronic fatigue syndrome (CFS) is an illness that involves severe, prolonged exhaustion as well as neurologic, immunologic, and endocrine system pathology. Because the pathogenesis of CFS has yet to be determined, case definitions have relied on clinical observation in classifying signs and symptoms for diagnosis. The current investigation examined differences between CFS as defined by Fukuda and colleagues and a set of criteria that has been stipulated for myalgic encephalomyelitis (ME). Dependent measures included psychiatric comorbidity, symptom frequency, symptom severity, and functional impairment. The ME and Fukuda et al. (1994) CFS criteria were compared with a group having chronic fatigue due to psychiatric reasons. Significant differences occurred primarily with neurologic, neuropsychiatric, fatigue/weakness, and rheumatological symptoms. These findings suggest that it might be inappropriate to synthesize results from studies of this illness that use different definitions to select study populations.

The role of pteridines in physiology and pathology.

Disorders or persistent noxious stimulation of the neuroimmunological circuitry can lead to neoplastic, neurological, immunological, psychiatric, or multiorgan pathology. The cause/effect relationship has encouraged a search for neuroimmunological markers possessing functional or pathological correlates. Among the molecules studied, those associated with the biopterin biosynthetic pathway (including neopterin) have proven to be useful and informative. This review addresses the relevance of the latter mediators to our understanding of the pathophysiology of neoplastic, neurological, psychiatric, and immunological disease processes.

Transplants of the future?

Book1 December 2001free access Transplants of the future? Robin Weiss Robin Weiss Search for more papers by this author Robin Weiss Robin Weiss Search for more papers by this author Author Information Robin Weiss EMBO Reports (2001)2:1067-1067https://doi.org/10.1093/embo-reports/kve262 PDFDownload PDF of article text and main figures. ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinked InMendeleyWechatReddit Figures & Info Xeno: The Promise of Transplanting Animal Organs into Humans by David K C Cooper and Robert P Lanza Oxford University Press, New York, NY 274 pages, US$ 30.00 ISBN 019 512 8338 The prospect of xenotransplantation brings into profile a number of fascinating facets of modern medicine: hi-tech surgery and immunology, genetically modified donor animals, the threat of unleashing new zoonoses (animal-to-human infections) and a number of legal, health economics and ethical issues. All these points and more are brought together in this popular scientific book. Xeno is written for the proverbial ‘intelligent layperson’, and molecular biologists can surely be included in that definition. David Cooper and Robert Lanza, physicians from Harvard Medical School and Advanced Cell Technology, respectively, know their field intimately and give a readable and exciting account of the developments and prospects for xenotransplantation. They are enthusiasts, but they do not skip lightly over the uncertainties or dangers. They have a gift for describing the life of a transplant surgeon, from scrubbing up for theatre to explaining the complexities of immune rejection. My only reservation is that the figures and photographs could have been displayed more imaginatively. Xeno explains the reasons why pigs are the animals of choice as donors (in the UK, we are admonished for using the word ‘donor’ because the pigs have not given their informed consent!). The various types of immune rejection across discordant species barriers are beautifully elucidated, including a chapter on tolerance named the ‘Immunological holy grail’. While the authors are right up to date, they also have a sense of history about the pioneers of transplantation and immunological rejection. I had previously thought there were only three major immunological barriers, but I learned in chapter 6, ‘A spoonful of sugar’, that there are four: hyperacute rejection, delayed antibody-mediated rejection, acute cellular rejection and chronic rejection. The first two are unique to xenografts (and ABO blood group mismatched human transplantation), while the latter two are in common with human-to-human allografts. If xenotransplantation becomes a reality, it is likely to begin with cellular therapies rather than whole organs, which are the main emphasis of Xeno. Pig islet cells could help millions of people with insulin-dependent diabetes mellitus; extracorporeal pig hepatocyte perfusion could tide a patient over until her or his own liver recovers or a human donor becomes available. Cellular therapies also hold promise for degenerative neurological diseases such as Parkinson's disease and stroke. But the authors of Xeno make little reference to alternative therapies, such as human stem cells or mechanical devices to aid the heart. It remains an open question, not least because of infection hazards, whether xenotransplantation will become as routine as the authors suggest. For those who prefer a more academic book, Xenotransplantation edited by Jeff Platt (ASM Press, Washington DC, 2001) provides a learned, multi-author volume. At the other end of the spectrum, Organ Farm by Jenny Bryan and John Clare (Carlton Books, 2001) is based on a series of superb British television programmes on xenotransplantation. It has more personal anecdotes and numerous daring colour photographs of xenotransplantation in action—a more handsome volume than Xeno at less cost. But I would recommend Xeno to the readers of EMBO reports. Biography The author is at the Department of Immunology and Molecular Pathology, University College London, London, UK. E-mail: [email protected] Next ArticleNext Article Volume 2Issue 121 December 2001In this issue RelatedDetailsLoading ...

Clostridium difficile cytotoxin B in adults with diarrhea: a comparison of patients treated or not treated with antibiotics prior to infection

Departments of Medicine and Immunology Microbiology, Pathology and Infectious Diseases, Karolinska Institute, Huddinge University Hospital, Huddinge, Sweden ObjectiveTo study the detection rate of Clostridium difficile cytotoxin B in stool specimens from adults with diarrhea as related to previous antimicrobial treatment. MethodsStool specimens from 802 adult patients with diarrhea and 203 healthy controls were tested for C. dificile cytotoxin B using a cell cytotoxicity assay. Antibiotic susceptibility testing of C. difficile was performed with the E test. ResultsOf 173 patients treated with antimicrobial medication within 5 weeks of onset of diarrhea, 60 (35%) were positive for C. difficile cytotoxin B (group A) compared to only 41 (7%) of 629 untreated patients (group B) and two of the 203 (1%) healthy controls. Compared to patients in group A, patients in group B possessed characteristics not usually connected with C. difficile disease. They were generally younger (median age 40 years vs. 73 years), had been hospitalized less frequently (10% vs. 67%), had more often travelled abroad within the previous 2 weeks (46% vs. 1%), and more often had multiple enteropathogens (41% vs. 3%). Minimal inhibitory concentrations for vancomycin, metronidazole and fucidic acid to C. difficile isolates ranged from 0.5 to 4 mg/L, from 0.125 to 256 mg/L and 0.25 to 4 mg/L, respectively. ConclusionsThe detection rate of C. difficile cytotoxin B in patients with diarrhea, not associated with antibiotic treatment, is comparable to that in healthy control subjects. It probably merely reflects a carrier state without clinical significance.

Proceedings of the Tenth International Conference on Trichinellosis. August 20-24, 2000, Fontainebleau, France.

The Tenth International Conference on trichinellosis, organized by the International Commission on Trichinellosis, gathered together 147 scientists from 34 countries. The 173 presentations ranged over most aspects of this parasitic zoonosis: history, epidemiology, speciation, biology, immunology, biochemistry, human and animal pathology, new diagnostic methods and control.

A Comparison of the 1988 and 1994 Diagnostic Criteria for Chronic Fatigue Syndrome

Chronic Fatigue Syndrome (CFS) is an illness that involves severe, prolonged fatigue as well as neurological, immunological, and endocrinological system pathology. Because the pathogenesis of CFS has yet to be determined, case definitions have relied on clinical observation in classifying signs and symptoms for diagnosis. In an attempt to address various criticisms and inconsistencies in diagnostic criteria, there have been several revisions of the CFS case definition. The current investigation examined the differences between 1988 and 1994 definitions as well as participants who had a psychiatric explanation for their fatigue. Dependent measures included psychiatric comorbidity, symptom frequency, and functional impairment. The 1988 criteria, compared to the 1994 criteria, appeared to select a group of participants with more symptomatology and functional impairment, but these groups did not significantly differ in psychiatric comorbidity. Implications of these findings are discussed.

Molecular and Immunologic Pathology for the Endoscopist: Special Techniques

Special techniques for the endoscopic biopsy include both immunologic (IHC) and molecular approaches (ISH, PCR). Both approaches have been adapted to foster additional diagnostic power with little or no additional work by the endoscopist. The techniques take advantage of tissue-specific antigens, unique markers in infectious diseases, and unique nucleic acid sequences present in some malignancies. From these advantages, benign conditions may be more easily distinguished from malignant ones, the causes of some infectious diseases can be confirmed, and clinically relevant classification of malignancies can be made. Some special techniques have added difficulties, such as fastidious requirements for some IHC or Southern blotting. At UCLA, approaches with the least technical challenges are those in practice for endoscopic biopsy. Lastly, the information gleaned from special techniques requires endoscopic and histopathologic context for accurate interpretation.

IgG index in acute idiopathic peripheral facial palsy.

Etiologic hypotheses in acute idiopathic peripheral facial palsy (AIPFP) mostly point to an immunologic dysfunction, probably virus-induced. Though various immunologic abnormalities are reported, the problem is still unsolved. We investigated intrathecal immunoglobulin synthesis in AIPFP as a clue for central nervous system (CNS) immunopathology. We studied IgG index in 24 patients with AIPFP, 10 with other neurological diseases (OND) and 17 with multiple sclerosis (MS). CSF and serum IgG were measured by radial immunodiffusion technique. IgG index is calculated according to Tibbling's formula. IgG indexes were abnormal in 6 patients with AIPFP, 3 with OND and 10 with MS patients. There was no statistical difference between AIPFP and OND groups, while marked difference existed between AIPFP and MS groups. Though IgG indexes were high in 25% of AIPFP patients, statistical analyses did not show any significance of this finding. Lack of a positive result might reflect non-existence of an extensive immunologic pathology within CNS, excluding a very limited one.

Diagnosis of bronchopulmonary infections by quantification of microflora.

The quantification of bacteria and fungi in sputum or bronchoaspirate is of clinical value for the diagnosis of respiratory tract infections. We have developed an easy method to count the micro-organisms in patients with respiratory tract infections. This consists of the quantification of micro-organisms by subsequent streakings of a calibrated loop on agar. The correlation between microbiological quantitative data and the clinical status of patients with lower respiratory tract infections is discussed. The data seem to indicate that certain bacteria present in sputum or bronchoaspirate above a certain concentration may be responsible for lower respiratory tract infections. In patients with immunological disorders or chronic pathologies even lower concentrations of micro-organisms in bronchial secretions probably are enough to cause infections. The advantage of this counting method of the microbic species from the respiratory tract consists of their quantification: thus we can attribute an etiological role to a high concentration of the germs, while micro-organisms at low concentrations are probably contaminants. By this method isolated colonies are obtained after 12-18 hours. The bacterial quantification, by respiratory samples examination of the same patient in the following days, allows us to evaluate the efficacy of antibacterial therapy, producing a reduction of bacterial concentration.

Molecular genetics, immunology and experimental pathology of melanoma

Molecular genetics, immunology and experimental pathology of melanoma

Devenir du purpura thrombopénique immunologique: à propos de 100 observations

The authors describe the clinical and biological characteristics and the evolution of 100 patients with immunologic thrombocytopenic purpura (ITP). In 24 cases, ITP reveals or preceeds immunologic or hematologic pathologies.

Molecular Interactions among Herpesviruses and Human Immunodeficiency Viruses

The average interval between human immunodeficiency virus (HIV) infection of an adult through sexual intercourse or blood transfusion and development of clinical AIDS is 10 and 8 years, respectively [1, 2]. The slow but relentless progression of immunologic dysfunction and clinical pathology characteristic of HIV infection is not due to HIV being an intrinsically slowly growing agent, however, but rather to the nature of viral gene regulation and virus-cell and infected cell-host interactions. Retroviruses such as HIV are complex and unusual parasites. They have evolved unique associations with their cellular hosts, including regulatory events that enable them to establish a persistent infection from which replicationcompetent virus may be induced (rescued) through a variety of pathways. Such chronic infection does not represent true molecular latency, with absent expression of viral RNA transcripts and protein. Latency is here defined more generally as the establishment of a virus in its host for prolonged periods in the absence of symptomatology, followed by lytic or other cytopathic episodes. It involves two essential elements: trans-acting viral gene products and their ds-responsive targets, and immune responses ineffectual in recognizing or clearing virions and virus-infected cells [3]. With respect to AIDS, early in the course of HIV infection absolute numbers of CD4+ T lymphocytes may be within normal limits while many measures of cellular immunity are markedly perturbed [4]. This was initially puzzling as, by the limits of in situ hybridization, ^ in 10,000 circulating or tissue-associated T and B lymphocytes and monocytes was reported to contain HIV nucleic acid [5]. Recent data indicate, however, that much greater numbers of cells may be chronically infected in vivo, persisting as stationary cell intermediates from which HIV may be rescued by a variety of seemingly disparate stimuli. The frequency of infected peripheral CD4+ T lymphocytes in AIDS patients is at least 196

The testosterone hypothesis: Assessment since Geschwind and Behan, 1982

The Geschwind hypothesis proposes a causal interaction among non-right-handedness, immune disorders, and learning disabilities, including dyslexia, via the intrauterine action of the male hormone testosterone. Some epidemiologic studies have supported at least a statistical association among the three traits; others have not. The associations between learning disorders and immune disease and between learning disorders and non-righthandedness appear to be better supported than that between immune disorders and non-right-handedness. However, none of data thus far accumulated are conclusive because it is not clear that the samples studied have been truly representative.The neuropathologic evidence, both in autopsy studies in human dyslexics and in animal models of developmental cortical abnormalities, are consistent with but not diagnostic of immunological pathology. Mechanisms are discussed by which an abnormal immune system could thus injure the developing brain, with an emphasis placed on abnormal maternal-fetal interactions, including maternal autoimmune disease and maternal-fetal incompatibility. A genetic origin is also possible in which the maternal role is less significant.

Progress in Hematology

As the scientific literature expands and the rate of accumulation of new information accelerates, the need for critical synthesis of the literature is more and more strongly felt. An analogy can be made to a forest in which the rapid growth of weeds overrides the rather imperceptible growth of trees, making the forest impassable. Periodically, an overview is needed to evaluate critically and place in perspective the lasting areas of contribution. For more than two decades,<i>Progress in Hematology</i>has served this useful purpose in a field that includes hematology in its broadest sense, covering related areas of immunology, oncology, and clinical pathology. A volume is published every two to three years. This most recent volume contains ten chapters, treating many if not all of the exciting areas of "Progress in Hematology." Among them are chapters on lymphocyte subpopulations and the significance of their markers, eosinophils, chromosome banding techniques, factor