Pleomorphic Nature Research Articles

Genetic diversity in Hirsutella thompsonii isolates based on random amplified polymorphic DNA analysis

Hirsutella thompsonii Fisher is a host-specific fungal pathogen of the diverse group of arthropods known as the Acari. It particularly affects eriophyid mites, and the identification of its isolates is a difficult task due to its pleomorphic nature. Seven isolates of H. thompsonii var. thompsonii and H. thompsonii var. synnematosa collected from various agro-climatic regions of India were subjected to PCR analysis using random decamer primers to differentiate between them. Random amplified polymorphic DNA analysis revealed that all of the isolates from the citrus rust mite, Phyllocoptruta oleivora Ashmead (Acari: Eriophyidae), clustered together, with the exception of one, HtCRMB. The only isolate of H. thompsonii from Aceria guerreronis keifer (Acari: Eriophydae), HtPDBC, clustered separately.

76. Development of Multigene Lentiviral Vectors Containing the Encephalomyocarditis Virus IRES and Foot-and-Mouth Disease Virus 2A Cleavage Factor

Recombinant measles viruses have shown potent oncolytic effects against tumors in animal models. In order to test the potential of recombinant measles viruses as virotherapy agents in humans, a large quantity of high-titer purified virus is needed. The characteristics of measles virus particles add to the difficulty of scalable purification for clinical administration: large pleomorphic size (100–300 nm), enveloped, inefficient budding from the infected cell, and cytotoxicity to the producer cell. The size and pleomorphic nature of the measles virus particles prevents a final sterile filtration step, requiring aseptic processing conditions to be maintained throughout the entire production process. In support of a Phase I clinical trial using a measles virus expressing a soluble form of carcinoembryonic antigen (MV-CEA) for treatment of ovarian cancer, a process was developed to manufacture a high-titer, large-scale, clinical-grade product using current Good Manufacturing Practices.

Detection of secreted cysticercal antigen: a useful tool in the diagnosis of inflammatory neurocysticercosis

Neurocysticercosis is a common parasitic disease of the human central nervous system. It is particularlyprevalent in developing countries, where it has a serious public health and economic impact. A major diagnostic problem with neurocysticercosis is its pleomorphic nature. Conventional diagnosis of neurocysticercosis still requires brain-computed tomography and/or magnetic resonance imaging, which are definitive but often prohibitively expensive and inaccessible in endemic areas. Herein, the monoclonal antibody HP 10 antigen-trapping enzyme-linked immunosorbent assay, which has been used successfully to detect viable Taenia solium cysticercosis, was evaluated using cerebrospinal fluid (CSF) from Mexican neurocysticercosis patients with various defined pathologies. Sensitivity was higher in cases of inflammatory compared with non-inflammatory disease (94.1% vs. 33.3%) and in cases of multiple- compared with single-cyst cysticercosis (85% vs. 33.3%). Positivity was a strong indicator of active, inflammatory, multiple-cyst neurocysticercosis detecting 100% (15/15) of such cases. The overall specificity, as determined using CSF samples from patients with other neurological symptoms, was 97.7% (42/43). Since the assay only detects viable infection, it is of known value in the follow-up of treated patients to determine whether treatment has been successful. Thus, antigen detection may be of particular value in the assessment of symptomatic patients, who may potentially benefit from rapid treatment.

Identification of Novel Interactions in HIV-1 Capsid Protein Assembly by High-resolution Mass Spectrometry

The pleomorphic nature of the immature and mature HIV-1 virions has made it difficult to characterize intersubunit interactions using traditional approaches. While the structures of isolated domains are known, the challenge is to identify intersubunit interactions and thereby pack these domains into supramolecular structures. Using high-resolution mass spectrometry, we have measured the amide hydrogen exchange protection factors for the soluble capsid protein (CA) and CA assembled in vitro. Comparison of the protection factors as well as chemical crosslinking experiments has led to a map of the subunit/subunit interfaces in the assembled tubes. This analysis provides direct biochemical evidence for the homotypic N domain and C domain interactions proposed from cryo-electron microscopy image reconstruction of CA tubes. Most significantly, we have identified a previously unrecognized intersubunit N domain–C domain interaction. The detection of this interaction reconciles previously discrepant biophysical and genetic data.

High-risk features of lupus nephritis: importance of race and clinical and histological factors in 166 patients

The pleomorphic nature of lupus nephritis has confounded efforts to refine estimates of prognosis. Consideration of interactions among prognostic factors may help to identify high-risk patients. By univariate and multivariate survival analysis, race and attributes of severe active lupus nephritis were evaluated as potentially important prognostic factors in 166 patients upon entry into prospective therapeutic trials of lupus kidney disease. Black patients were significantly more likely than others to develop renal insufficiency. Cellular crescents emerged as the most predictive active pathological feature and interstitial fibrosis was the strongest chronic histological prognostic factor. Combinations of these morphological attributes identified particularly high-risk individuals. Patients with 50% or more cellular crescents and those with less extensive cellular crescents plus moderate to severe interstitial fibrosis were at markedly increased risk for doubling serum creatinine compared to those who lacked these histologic features (P < 0.0001). Azotaemia, anaemia, hypocomplementaemia, hypertension, tubular atrophy and glomerular sclerosis were also associated with an increased probability of renal function deterioration. Serum creatinine, haematocrit, race, and kidney pathology data emerged as independent predictors of renal insufficiency. Black patients in this study were more likely than the others to have high-risk histological features, including extensive cellular crescents (> or = 50%) and moderate to severe interstitial fibrosis, prior to randomization. Combinations of high-risk demographic, clinical and histological attributes identify patients at increased risk for progressive renal function deterioration. Several factors, including the severity of kidney biopsy findings, probably contribute to the poor prognosis of Black patients in this study population.

Some contributions of electron microscopy to the study of the rickettsiae

Electron microscopy has provided valuable insights into the study of rickettsiae as intracellular parasites from several important perspectives. This tool has allowed researchers to delineate the fine structural features of these organisms and to show that they truly resemble free-living bacteria. Furthermore, it has been shown that there are subtle, but distinct differences in the outer envelope structure of some members of the genus Rickettsia that may explain reported differences in tinctorial properties and in their sensitivity to certain antibiotics. With Coxiella burnetii, electron microscopy has helped significantly in the characterization of the pleomorphic nature of the organism including formation of terminal bodies that resemble endospores of gram-positive bacteria. Electron microsxopy has also helped to define the relationship of the rickettsiae to their host cells. For example, ultrastructural analysis can reveal whether organisms exist free within the cytoplasm or nucleus (members of the genus Rickettsia), or whether they are bound by a phagosomal or phagolysosomal membrane (Ehrlichia and Coxiella). Finally, although all rickettsiae eventually destroy their host cell, it has been shown through transmission electron microscopy that this destruction might be mediated by different mechanisms that are specific for different rickettsial species.

Dental abnormalities as a component of the Laurence-Moon-Bardet-Biedl syndrome

Previous reports have described the diversity of the phenotypic expression of the Laurence-Moon and Bardet-Biedl syndrome. This report describes two brothers whose features include the previously unreported defect of oligodontia in addition to retinitis pigmentosa, hypogenitalism, strabismus, short stature, and developmental delay. The reports over the last century have emphasized the varied expression from family to family and even differences among members of the same family. This report broadens the already pleomorphic nature of this syndrome.

Molecular evidence that SJL reticulum cell sarcomas are derived from pre-B cell. Clonal rearrangement of heavy chain but not of light chain immunoglobulin genes.

In order to investigate the clonal origin of SJL reticulum cell sarcoma (RCS), two-color cell membrane-staining and molecular biologic analyses were performed. Flow cytometric analysis revealed that the SJL RCS consists of about 50 to 60% Thy-1-positive and 20 to 30% B220-positive cells and that the majority of the Thy-1-positive cells are L3T4-positive, whereas a few are Lyt-2-positive. In spite of this pleomorphic nature of SJL RCS shown by cell membrane analysis, when the immunoglobulin heavy chain J segment (JH) was used to probe the DNA obtained from the tumor, we observed clonal rearrangements of the gene. Results of the cell-sorting experiment combined with Southern hybridization using the JH gene probe confirmed that those clonally expanding cells are Ia and B220 antigen-positive. Furthermore, all tumors derived from a given mouse showed the same rearrangement pattern. However, no clonal rearrangement was observed when the DNA was probed with the T cell receptor beta-chain gene or with immunoglobulin kappa- or lambda-light chain genes. From these data, we conclude that SJL RCS is a tumor of B cells and that the neoplastic event takes place at an immature B cell stage.

An overview of bacterial skin disease in the dog

Pyodermas are a common cause of skin disease in the dog. Despite their frequency of occurrence, many pyodermas are misdiagnosed or improperly managed. Misdiagnosis is often associated with the pleomorphic nature of canine pyodermas and resultant difficulty in recognition. Therapeutic failures or partial successes in the management of other pruritic dermatoses may be due to the failure to diagnose a secondary pyoderma. Veterinary surgeons may be satisfied with the presumptive diagnosis of another disease such as atopy, seborrhea, flea allergy, or food allergy and overlook the presence of a secondary pyoderma. When pyodermas occur in conjunction with other diseases in which self-trauma is a component, lesions of pyoderma may be obscured. Common pitfalls in the management of pyodermas may be avoided if the veterinary surgeon is cognisant of the various possible predisposing factors, utilises a logical classification scheme, and builds a therapeutic plan based on this information.

Hudson memorial lecture: Wilson's disease: genetics and biochemistry--their relevance to therapy.

AbstractWilson's disease is an inherited metabolic disorder affecting children, adolescents and young adults. Before puberty the initial signs and symptoms are almost always related to liver damage, with or without haemolysis. After puberty neurological signs become increasingly prominent, always involving the motor centres, sometimes personality, never the sensory nervous system. The most characteristic physical sign is the Kayser Fleischer corneal pigment ring resulting from deposition of copper in Descemet's membrane.The primary genetic defect is not known but the disease appears to result from a failure, by the hepatocytes, to excrete copper via the bile. As a result this metal accumulates first in the liver then, when this organ is saturated, in the brain, the corneae, and to a lesser extent the kidneys. Once present in excess in the tissues copper poisons various enzyme systems leading to cellular damage and death. At present there is no satisfactory explanation for the pleomorphic nature of the disease much less of the often gross assymetry of the lesions in the brain.Treatment entails the establishment of a negative copper balance until the abnormal body stores of the metal have been removed. Thereafter the patient must be kept in balance for life. There are two main drugs available for this purpose, penicillamine and triethylene tetramine (Trientine). Both will achieve biochemical and clinical reversal of the disease. Penicillamine can give rise to a wide range of toxic reactions, mostly on an immunological basis; it is therefore essential to monitor the blood count and renal function regularly. Less is known at present of the potential of Trientine to induce unwanted side effects.Wilson's disease is characterized by recessive inheritance. It can be diagnosed in the presymptomatic stage by finding typical abnormalities of copper metabolism. All families should be screened and, where appropriate, prophylactic treatment started, thus aborting the clinical evolution of the disease.

Haemophilus influenzae Meningitis

Fifteen cases of Haemophilus influenzae (HI) meningitis in adults occurring of Cleveland during the last 11 years are presented. The majority of patients had factors predisposing to infection such as otitis, pneumonia, diabetes or alcoholism. In addition, 7 of the 15 patients developed meningitis at various intervals following head trauma and neurosurgery, and 3 patients required dural repairs for CSF rhinorrhea. The diagnosis of meningitis may be difficult to establish resulting in delay in appropriate therapy in some cases. Nuchal rigidity was absent frequently; CSF lymphocytosis can be seen initially. The CSF Gram stain may be negative or the pleomorphic nature of the organism on Gram-stain may make distinction from other gram-negative organisms difficult. The majority of patients had meningitis due to non-Type B HI in contrast to previous reports of this illness in children and adults. One of our patients had beta-lactamase producing HI isolated from CSF. We believe that chloramphenicol should be included in the initial empiric therapy for adults with meningitis and gram-negative coccobacillary rods on Gram-stain or negative CSF Gram-stains.

Scanning electron microscopy of epiplexus macrophages (Kolmer cells) in the dog.

Young dogs (6-14 weeks) were perfused with buffered aldehydes by standard techniques. The inferior medullary velum and tela choroidea were removed intact from the fourth ventricle, post-osmicated, dehydrated, critical point dried, coated with palladium-gold and examined in a Cambridge Stereoscan S4 scanning electron microscope. Selected samples after thorough scanning were routinely prepared for transmission electron microscopy (TEM). This study depicts numerous epiplexus (Kolmer cell) macrophages that exhibit extreme polymorphism. Because of the pleomorphic nature of these cells and their processes, classification based on external morphology is not practical. TEM shows their internal structure to be that of a macrophage. Bleb-like structures and bulbous projections appear to emerge from certain ependymal cell surfaces which seem to be completely or partially devoid of cilia.

CORRELATION OF ADRENOCORTICAL HISTOPATHOLOGY WITH ARTERIOSCLEROSIS IN BREEDER RATS.

ABSTRACT Spontaneous arteriosclerosis develops in repeatedly bred male and female rats. Virgin rats of an age comparable to breeder rats do not develop arteriosclerosis. The arteriosclerosis becomes increasingly severe with each successive breeding. In a parallel manner, the thymus gland involutes and the adrenal glands become hypertrophied and hyperplastic with each breeding. During the early stages of the development of arteriosclerosis, the adrenal cortex shows storage of lipids. With continued breeding, the zona glomerulosa increases in width and becomes depleted of lipid. In some cases, growth of the adrenal medulla causes compression of the cortex against the capsule of the gland and the pleomorphic nature of the medullary cells resembles a phaeochromocytoma. In some female breeders with severe arteriosclerosis the adrenal cortex shows severe haemorrhage and thromboses causing marked reduction of the cortex. The histophysiological changes observed in the adrenal cortex of breeder rats are believed to be analogous to conditions seen in humans with hyperadrenocorticism or Cushing's disease. It is suggested that there may be a close correlation between the abnormal adrenal function engendered by repeated breeding and the development of the arteriosclerosis.

Embryonic potency of embryoid bodies derived from a transplantable testicular teratoma of the mouse

Testicular teratomas occur relatively frequently in inbred strain 129 mice. Occasionally they grow progressively and survive serial transplantation indefinitely. One such tumor has been maintained for approximately six years, and it still retains its highly pleomorphic nature. When established as an ascitic tumor, this teratoma is capable of producing thousands of free-floating formations that resemble 5- and 6-day mouse embryos. The aim of this investigation was to test the histogenetic capacities of these embryoid bodies. Single embryoid bodies were transplanted into the anterior chamber of the eyes of mature strain 129 mice. Growths resulting from these intraocular grafts were examined histologically and some were retransplanted subcutaneously to form solid tumor sublines. Both the intraocular and subcutaneous grafts contained many types of tissues, including a variety of epithelia; neural tissue; cartilage with peripheral ossification; smooth, cardiac, and voluntary muscle; trophoblastic giant cells; layers of ectoderm and endoderm; and undifferentiated embryonal cells. It is concluded that the embryoid bodies derived from the testicular teratomas of strain 129 mice have similarities in embryonic potency as well as in morphology to normal mouse embryos.

Peritoneal mesothelioma

Although some authorities still question the actual existence of the mesotheliomas, neoplasms arising from the lining cells of the serous cavities, as distinct pathologic entities, most workers seem to believe that they are established neoplastic entities, their origin from mesothelium seemingly established by tissue culture studies. The present concepts of mesotheliomas emphasize their pleomorphic nature. While formerly pleural, pericardial and peritoneal mesotheliomas, and solitary fibrous and diffuse, superficial mesotheliomas were considered as separate entities, the tendency now is more to consider them merely as pleomorphic forms of the same pathologic process. Thus the mesotheliomas may be fibroblastic, epithelial, completely undifferentiated or mixed in type, and may involve any serosal surface. A case is presented herein which meets most of the criteria for the mesotheliomas and which shows definite pleomorphic characteristics and malignant, invasive tendencies but no metastases.