Specificity of antineutrophil cytoplasmic antibody: comment on the article by Choi et al.
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Biomedical subjects
Publications and source records attributed to V Kumar.
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Immune regulatory interactions have been largely attributed to antagonistic T helper cell subsets whose cytokines are mutually inhibitory (Th1 vs. Th2). Here we emphasize two additional levels of regulation: the first involves the recognition of portions of antigen receptors of effector T cells, resulting in the induction of both CD4 and CD8 regulatory populations, capable of diminishing the responses by the pathogenic effector itself. The second includes a collection of cell populations found constitutively in all individuals whose specificity for antigen, if any, is being currently investigated. These two additional types of interaction involve cells belonging to a functional regulatory subset and include contributions from both innate and adaptive mechanisms of immune regulation. The answers to many quandaries in autoimmune disease may be sought by seeking to engage these lesser-understood regulatory populations.
Conventional building materials and by-products from coal power plants which are being used or have the potential for use in buildings in India were analysed for natural radioactivity due to the presence of 226Ra, 232Th and 40K using gamma-ray spectroscopy. The materials examined in this work showed the radioactivity levels below the limit estimated from radium equivalent activity the criterion formula for gamma-activity suggested for acceptable radiation doses attributable to building materials in OECD countries.
Hyphae of Phyllactinia corylea produce two kinds of special branches on the host surface: adhesion bodies which serve as fungal attachment and stomatopodia which enter the leaf through stomata. Conidial germination on host and non-host surfaces was examined with a scanning electron microscope to explain the stimuli responsible for development of the special branches, and the involvement of host recognition in the process. Conidia germinated within 4 h on host and non-host surfaces, but on non-host surfaces the emergence of the germ tube was not always directed towards the substratum. Adhesion bodies were formed from the tips of germ tubes at the first contact point on host and non-host surfaces. Development of stomatopodia was more specific and they were formed precisely over stomata on the host surface. Stomatopodia-like structures were occasionally formed over finely ridged leaf veins on the host surface and over some fine scratches on synthetic surfaces. The experiments showed that while conidial germination and development of adhesion bodies are in response to contact stimuli, the development of stomatopodia is a response to precise topographical signals, and the directional emergence and attached growth of germ tubes involve host recognition.
Natural killer (NK) cells spontaneously detect and kill cancerous and virally infected cells through receptors that transduce either activating or inhibiting signals. The majority of well studied NK receptors are involved in inhibitory signaling. However, we have previously described an activating receptor, 2B4, expressed on all murine NK cells and a subset of T cells that mediate non-major histocompatibility complex (MHC) restricted killing. Anti-2B4 monoclonal antibodies directed against IL-2-activated NK cells enhanced their destruction of tumor cells. Recently, we determined binding of 2B4 to CD48 with a much higher affinity than CD2 to CD48. Here we describe the molecular characterization of a cDNA clone homologous to mouse 2B4, isolated from a human NK cell library. The cDNA clone contained an open reading frame encoding a polypeptide chain of 365 amino acid residues. The predicted protein sequence showed 70% similarity to murine 2B4. Additionally, it has 48, 45, and 43% similarity to human CD84, CDw150 (SLAM), and CD48, respectively. RNA blot analysis indicates the presence of 3 kb and 5 kb transcripts in T- and NK-cell lines. A single transcript of 3 kb is identified in poly(A)+ RNA from human spleen, peripheral blood leukocytes, and lymph node, whereas, the level of expression in bone marrow and fetal liver was indeterminate. Preliminary functional data suggests that NK-cell interaction with target cells via 2B4 modulates human NK-cell cytolytic activity.
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A new group of potent antibacterial compounds, non-iron metalloporphyrins (MPs), is described. MPs possess a strong antibacterial activity against Gram-positive bacteria, Gram-negative bacteria and mycobacteria. Anaerobically grown bacteria and microorganisms that do not respire and/or express haem uptake systems were resistant to MPs. Antibacterial activity of MPs was not affected by known antibiotic resistance mechanisms operating in bacteria. The most potent MP against Y. enterocolitica, methicillin-resistant S. aureus and M. smegmatis was gallium protoporphyrin IX (Ga-PPIX). When tested alone, Ga ions and metal-free porphyrins had approximately 100-fold higher minimum inhibitory concentration (MIC) values for these organisms. Ga-PPIX was not degraded by MP-sensitive bacteria, indicating that the whole molecule is responsible for antibacterial activity. MPs are antibacterial 'Trojan horses', as they exploit haem transport systems of Gram-negative bacteria as portals of entry into the cell. Bacterial mutants in superoxide dismutases, catalases and stationary-phase sigma factors were hypersensitive to Ga-PPIX. The extreme sensitivity of sod mutants to MPs and the requirement for active respiration for MP activity suggests that these compounds stimulate the production of reactive oxygen radicals in bacteria. Ga-PPIX was not toxic to primary human fibroblasts, several established cell lines and experimental animals at concentrations > 100-fold higher than the MIC for sensitive bacteria.
OBJECTIVE: To evaluate the magnitude and range of complications encountered during no-scalpel vasectomy (NSV) and to identify any limiting factor or contraindication to NSV. SUBJECTS AND METHODS: A total of 4255 men visiting a family welfare clinic of a city hospital in Delhi, India, or outpatients of the surgery department, opted for NSV; 4253 procedures were performed from September 1989 to December 1997, with two not performed because of technical difficulties. The success and complication rates were recorded. RESULTS: The complication rates with NSV were surprisingly low; seven complications were encountered, comprising two small haematomas (0.047%), three painful nodules (0.07%), three wound infections (0.07%) and two vasal fistulae, a complication not previously described. A meticulous procedure should avoid this last complication. The mean duration of NSV was 9.5 min. CONCLUSION: NSV is a refined and rapid technique of vasectomy with an extremely low complication rate. Being a minimally invasive procedure, it allays the fear of incision commonly encountered in men choosing vasectomy.
Both dietary dehydroepiandrosterone (DHEA) and food restriction can prevent or modulate the initiation or progression of a number of diseases in rodents and prolong life span. We sought to determine if these interventions have common mechanisms of action in regulating lymphocyte functions and cell numbers. We observed that male C57BL/6 mice receiving DHEA in the diet (0.45%, w/w) ate approximately 50% as much food as mice on the DHEA-free diet, and this was reflected in decreased body weights throughout a 10-week period. Mice either fed the DHEA-containing diet or pair-fed to the DHEA-treated mice had decreased spleen and thymus weights and lymphocyte cell numbers compared to mice having free access to the control diet. Mice were fed these diets for 2 weeks before and 2 weeks after exposure to sublethal irradiation (500 cGy). In mice fed DHEA or pair-fed, there was a decrease in spleen cell numbers, and B cells were the most severely affected. The frequency of apoptosis in peripheral blood cells increased from <5% in nonirradiated controls to >50% within 4 days after starting DHEA or pair-feeding. Shortly after irradiation, >87% of blood lymphocytes were hypodiploid (apoptotic) in all groups. By 9 days only 27% of lymphocytes in mice on the control diet were hypodiploid compared to 62% in DHEA and 74% in pair-fed mice. In addition, both DHEA and pair-fed mice had significant reductions in T-cell function (contact hypersensitivity to dinitrofluorobenzene), B cell function (antibody response to trinitrophenolated-lipopolysaccharide), and NK cell function (lung clearance of radiolabeled YAC-1 tumor cells) 2 weeks after irradiation. In a complementary study, peripheral blood lymphocytes from naïve mice were treated overnight with various concentrations of either DHEA or hydrocortisone 21-acetate. Only glucocorticoid-treated cells underwent apoptosis. Thus, DHEA induces apoptosis in vivo but not in vitro. We conclude that dietary DHEA induces apoptosis and decreased lymphocyte production and function in C57BL/6 mice largely by reducing food intake.
During an outbreak of dengue fever in 1996, 66 children between 45 days and 12 years of age with dengue fever and 25 healthy controls were studied for antioxidants and other biochemical abnormalities. As per World Health Organization (WHO) criteria, 14 children were classified as having classical dengue (DEN), 42 with dengue haemorrhagic fever (DHF), and 10 (including three who died) as having dengue shock syndrome (DSS). Superoxide dismutase (SOD), glutathione peroxidase (GPX), and albumin (ALB), the three main antioxidants studied, were found to be abnormal in 96, 94, and 40 per cent of the cases respectively. The levels for aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine phosphokinase (CPK), total protein (TP), total cholesterol (CHO), and triglycerides (TGL) were abnormal in 79, 50, 30, 93, and 67 per cent of the cases respectively. Among the different groups of dengue the abnormalities were more marked in children with DSS than in those with DEN and DHF, especially with respect to ALB, TP, TGL, AST, ALT, and CPK (p < 0.005). This preliminary report of dengue confirms the assumption of free radical generation and alteration in antioxidant status during acute illness. However, to understand their complex interaction in disease progression and therapeutic utility, further studies are required.
One hundred cases of pyodermas in children were investigated clinically and bacteriologically. Nasal and throat swabs from all cases were subjected to bacteriological examination. Most of the children (42%) were in the 1-4 year age group. The majority (58%) belonged to lower socio-economic groups with poor standards of hygiene. A history of over-crowding was obtained from 87% of cases, 82% were undernourished. Most of the children (68%) reported during the hot and humid months of June, July, August, and September. Primary pyodermas were observed in 72% of the children, and secondary pyodermas in 28%. Impetigo was the commonest primary pyoderma (48.61%); among secondary pyodermas, infected scabies was noted predominantly (42.86%). The face and legs were more commonly involved. Bacteriological cultures from pyoderma lesions revealed a single microorganism in the majority of the patients (84%). Staphylococcus aureus was isolated in pure culture from 48% and pure beta-hemolytic streptococci from 36%. A combination of both was obtained from 16%. No other organism was isolated from any case. A similar pattern was also observed in cultures from the nose and throat. Only 46 out of the 64 strains (84.3%) of Staphylococcus aureus isolated from pyoderma were typable. The majority (39.1%) showed a mixed pattern of phages; the second commonest was the non-allocated phage type (30.4%). Nasal flora had more of the non-allocated phage type (50%); two out of the three strains (66.6%) isolated from the throat showed a mixed pattern. All the strains of beta hemolytic streptococci, isolated either from lesions of pyoderma, nose, or throat belonged to group A. Staphylococcus aureus and showed a high sensitivity to netilmycin (100%), ofloxacin (98.4%), amoxycillin/clavulanic acid (96.9%), ciprofloxacin (89.1%) and gentamycin (84.4%) but a high resistance to penicillin (85.9%). A greater correlation was noted between nasal flora and organisms causing pyodermas. A change in the pattern of organisms causing pyodermas in children and their antibiotic sensitivities in this part of the globe has been observed in this study. The role of endogenous nasal and throat flora in the causation of pyodermas has also been highlighted.
Detecting antibiotic resistance in Mycobacterium tuberculosis is becoming increasingly important with the global recognition of drug-resistant strains and their adverse impact on clinical outcomes. Current methods of susceptibility testing are either time-consuming or costly; rapid, reliable, simple, and inexpensive methods would be highly desirable, especially in the developing world where most tuberculosis is found. The luciferase reporter phage is a unique reagent well-suited for this purpose: upon infection with viable mycobacteria, it produces quantifiable light which is not observed in mycobacterial cells treated with active antimicrobials. In this report, we describe a modification of our original assay, which allows detection of the emitted light with a Polaroid film box designated the Bronx Box. The technique has been applied to 25 M. tuberculosis reference and clinical strains, and criteria are presented which allow rapid and simple discrimination among strains susceptible or resistant to isoniazid and rifampin, the major antituberculosis agents.
Thyroid hormone status influences the Zn2+ and metallothionein levels in intestine, liver, and kidney. To evaluate the impact of thyroid hormones on Zn2+ metabolism, Zn2+ uptake studies were carried out in intestinal and renal brush-border membrane vesicles (BBMV). Steady-state Zn2+ transport in intestinal and renal cortical BBMV was increased in hyperthyroid (Hyper-T) rats and decreased in the hypothyroid (Hypo-T) rats relative to euthyroid (Eu-T) rats. In both the intestinal and renal BBMV, Hyper-T rats showed a significant increase in maximal velocity compared with Eu-T and Hypo-T rats. Apparent Michaelis constant was unaltered in intestinal and renal BBMV prepared from the three groups. Fluorescence anisotropy of diphenyl hexatriene was decreased significantly in intestinal and renal brush-border membrane (BBM) isolated from Hyper-T rats compared with Hypo-T and Eu-T rats. A significant reduction in the microviscosity and transition temperature for Zn2+ uptake in intestinal and renal BBM from Hyper-T rats is in accordance with the increased fluidity of these BBMs. These findings suggest that the increased rate of Zn2+ transport in response to thyroid hormone status could be associated with either an increase in the number of Zn2+ transporters or an increase in the active transporters due to alteration in the membrane fluidity. Thus the thyroid hormone-mediated change in membrane fluidity might play an important role in modulating Zn2+ transport activity of intestinal and renal BBM.
A total of 446 lymph node biopsy specimens showing histological evidence of tuberculosis were classified into four groups based on the organization of the granuloma, the type and numbers of participating cells and the nature of necrosis. These were, hyperplastic (22.4%)--a well-formed epithelioid cell granuloma with very little necrosis, reactive (54.3%)--a well-formed granuloma consisting of epithelioid cells, macrophages, lymphocytes and plasma cells with fine, eosinophilic caseation necrosis, hyporeactive (17.7%)--a poorly organized granuloma with macrophages, immature epithelioid cells, lymphocytes and plasma cells and coarse, predominantly basophilic caseation necrosis and nonreactive (3.6%)--unorganized granuloma with macrophages, lymphocytes, plasma cells and polymorphs with non caseating necrosis. Though the number of bacilli in the sections differed in each group, there were no differences in culture positivity, Mantoux reaction or the clinical features. It is likely that the spectrum of histological responses seen in tuberculous lymphadenitis is the end result of different pathogenic mechanisms underlying the disease.
Chronic ulcerative diseases of the oral mucosa are commonly seen in clinical practice. On clinical and histological appearance, the lesions may be hard to differentiate from each other. The establishment of definite diagnosis is essential because the patient may require different management and have widely varying prognosis. Immunofluorescence studies aid greatly in the process of determining the diagnosis of a number of chronic ulcerative diseases. This article reviews these chronic ulcerative diseases, describing their clinical, microscopic, and immunofluorescence characteristics. Methods of diagnosis and management of the diseases also are discussed.
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Most species use daily light in one way or the other in regulation of their short and/or long term activities. Light is perceived by pigment(s) present in the retinal (RP) and/or extra-retinal photoreceptors (ERPs). ERPs may be located at various sites in the body but in non-mammalian vertebrates they are found predominantly in the pineal body and hypothalamic region of the brain, Light radiations directly penetrate brain tissues to reach and stimulate the hypothalamic (deep-brain) photoreceptors. How does light information finally reach to the clock is not fully understood in many vertebrate groups? In mammals, however, the light information from the retina to the clock (the hypothalamic suprachiasmatic nuclei, SCN) is relayed through the retino-hypothalamic tract (RHT) which originates from the retinal ganglion cells, and through the geniculo-hypothalamic tract (GHT) which originates from the photically responsive cells of a portion of the lateral geniculate nucleus (LGN), called the intergeniculate leaflet (IGL). A response to light (the photoperiodic response) is the result of the interpretation of light information by the photoperiodic system. Apart from the duration, the animals use the gradual shifts in the intensity and wavelength of daily light to regulate their photoperiodic clock system. The wavelengths to which photoreceptors are maximally sensitive or the wavelengths which have greater access to the photoreceptors can induce a maximal response. There can also be differential effects of wavelength and intensity of light on circadian process(es) involved in the entrainment and induction of the photoperiodic clock. This may have some adaptive implications. Entrainment to daily light-dark (LD) cycle may be achieved at dawn or dusk, depending whether the animal is day- or night-active, when there is relatively low intensity of light. By contrast, photoperiodic induction in many species occurs during long days of spring and summer when plenty of daylight at higher intensity is available later in the day.