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Biomedical subjects

V Kumar

Publications and source records attributed to V Kumar.

At least 253 records · Page 14Linked to original sources

A characteristic cutaneous direct immunofluorescent pattern associated with Ro(SS-A) antibodies in subacute cutaneous lupus erythematosus.

BACKGROUND: Antibodies to Ro(SS-A) are present in most patients with subacute cutaneous lupus erythematosus (SCLE). Patients with SCLE also have cutaneous immune deposits. However, no correlation of Ro(SS-A) antibodies with immune deposits in skin biopsy specimens has been described. OBJECTIVE: The purpose of this study is to describe characteristic direct immunofluorescence (IF) findings in 32 patients and their association with serum antibodies and clinical diagnosis. METHODS: Serum from patients with characteristic cutaneous direct IF findings was examined for antinuclear antibodies by indirect IF and for antibodies to ribonucleoprotein, Sm, Ro(SS-A), and La(SS-B) by gel immunodiffusion. RESULTS: Twenty-two of 32 patients who exhibited discrete speckled IgG staining predominantly, but not exclusively, of the basal cell cytoplasm had SCLE. Ro(SS-A) antibodies were identified in 23 of 26 patients and Ro(SS-A) and/or La(SS-B) in 25 of 26 patients. CONCLUSION: Direct IF staining characterized by discrete speckled IgG deposits in the basal cell cytoplasm is associated with Ro(SS-A) antibodies and SCLE.

Acute Disease

Studies on an Ostertagia ostertagi strain suspected to be resistant to benzimidazoles.

Four calves were infected with a susceptible (laboratory) strain of Ostertagia ostertagi and four with a field strain suspected to be resistant to benzimidazoles. After 25 days two calves from each group were treated with 3.5 mg kg-1 fenbendazole. Egg output fell to zero in all treated calves. Treated calves did not harbour worms at slaughter 35 days after infection. Significant differences between the strains were shown for ED50 values for thiabendazole in the egg hatch assay, but not in the tubulin binding assay. It is concluded that benzimidazole resistance in the suspected strain cannot be confirmed.

Animals

Assessing Alzheimer severity with a global clinical scale.

Diagnosis of dementia needs to be complemented by precise determination of disease severity across the broad spectrum of disease progression. The Mini-Mental State Exam (MMS), the Activities-of-Daily-Living assessment (ADL) and the Clinical Dementia Rating scale (CDR) were modified for direct comparability and administered to 112 outpatients and 45 nursing home residents with a range of dementia severity from mild to profound. The scales showed the highest correlations for the probable Alzheimer's disease patient group (62) (Global Assessment of Dementia; GAD vs. ADL: r = 0.91; Extended Mini-Mental Assessment; EMA vs. GAD: r = 0.91; ADL vs. EMA: r = 0.86). For these patients, scores on the individual scales tended to be similar. Disparity among the three scores for individual cases was associated with the presence of comorbidities. The high correlations and correspondence among these scales demonstrate their reliability, validity, and utility in the assessment of dementia severity. The use of an average of these measures, with their increased precision, may give a more accurate indication of dementia severity over a broader range of impairment.

Activities of Daily Living

Saccharomyces cerevisiae cells secreting an Aspergillus niger beta-galactosidase grow on whey permeate.

We describe the construction of a lactose-utilizing Saccharomyces cerevisiae that expresses the cDNA for a secreted, thermostable beta-galactosidase (lacA) from Aspergillus niger. Yeast cells expressing the lacA gene from the yeast ADH1 promotor on a multicopy plasmid secrete up to 40% of the total beta-galactosidase activity into the growth medium. The secreted product is extensively N-glycosylated, and cells expressing the lacA gene grow on whey permeate (4% w/v lactose) with a doubling time of 1.6 hours. Such strains may offer a solution to the increasing problem of waste whey disposal.

Alcohol Dehydrogenase

Activation of B lymphocytes by NK cells.

The ability of NK cells to induce differentiation of B lymphocytes to IgM secretion in vitro has been investigated. Homogeneous preparations of NK cells obtained from IL-2 propagated splenocytes from SCID mice were found to have the ability to induce resting B lymphocytes to proliferate and secrete significant amounts of IgM. The induction is greatly enhanced by the presence of both IL-2 and IL-5 and does not require T lymphocytes or adherent cells in the responding population. Cell contact between the two populations is not necessary suggesting that the effect is mediated by soluble factor(s) which can be produced even by irradiated NK cells. Because the activity cannot be replaced by either r-tau-IFN or tumor necrosis factor-alpha or inhibited by antibodies to these lymphokines, a novel NK cell-derived factor(s) may be involved. The implications of this interaction between NK cells and B lymphocytes are discussed.

Animals

Alzheimer Disease Assessment Scale: a subtest analysis.

The Alzheimer Disease Assessment Scale (ADAS) was administered to 61 Alzheimer patients, 52 elderly controls, and 80 controls between age 7 and 54 years. The Alzheimer group was categorized into different severity levels of dementia based on MMSE scores: very mild (> or = 24), mild (> or = 20), moderate (10-19), and severe (0-9). All 11 ADAS Cognitive subtest scores for the mild, moderate, and severe dementia groups were statistically worse than the elderly control group. This was also the case for the very mild group, except for Naming, Commands, Constructional Praxis, and Ideational Praxis. In terms of magnitude of effect, memory and spontaneous language items were the earliest indicators on the ADAS, while praxis, commands, and naming items were only sensitive later in the course of the disorder. The best single indicators of progression throughout the severity continuum of dementia (i.e., from normal to severe) were the Orientation subtest, the ADAS Cognitive score, and the ADAS Total score. The ADAS Noncognitive subtests generally did not show the progression with increasing dementia that was evident on the ADAS Cognitive subtest. Differences in educational level had no statistically significant effects on any of the ADAS subtest scores, and age differences were few and small in magnitude. The differential rate of decline of the various ADAS subtests appears to reflect both the changing pattern of cognitive impairments as a function of severity of DAT and also to some extent the psychometric limitations of some of the subtests.

Aged

Differentiation of bullous pemphigoid from epidermolysis bullosa acquisita on frozen skin biopsies.

Patients with bullous pemphigoid and epidermolysis bullosa acquisita may have similar clinical, histologic, and routine immunohistologic features. These two diseases can be distinguished by routine diagnostic studies either on a patient's serum tested by indirect immunofluorescence on salt-split normal skin or by obtaining a fresh perilesional skin biopsy, inducing a split at the lamina lucida, and testing for the site of IgG deposition by direct immunofluorescence. Often the serum studies are negative, while direct immunofluorescent studies yield the characteristic linear IgG staining of the basement membrane zone. To eliminate the need for a repeat biopsy to make a laboratory differential diagnosis, we studied the efficacy of salt-splitting perilesional skin biopsies that had been previously submitted and frozen for routine direct immunofluorescent studies. The biopsies were thawed, salt-split, and processed for direct immunofluorescence. Three epidermolysis bullosa acquisita biopsies and seven bullous pemphigoid biopsies examined demonstrated IgG staining at sites consistent with their respective diagnoses. The IgG appeared in the dermal side of the split biopsies in epidermolysis bullosa acquisita and predominantly, or exclusively, in the epidermal side in bullous pemphigoid. Thus the direct immunofluorescent study of previously frozen and subsequently salt-split skin biopsies may be used for the differential diagnosis of bullous pemphigoid from epidermolysis bullosa acquisita. In most cases, it may eliminate the need for a repeat biopsy.

Basement Membrane

A distinct stratum corneum antigen in psoriasis and its reactions with stratum corneum autoantibodies.

Stratum corneum antibodies are ubiquitous and can be detected by various immunological methods. Of these, the ones detected by hemagglutination undergo changes in antibody titers and have been implicated in psoriasis. The purpose of our study was to examine if differences exist in the activities of the antigens isolated from psoriatic scales in comparison to normal callus. Stratum corneum antigens were prepared by trypsin-phenol-water extraction. The water phase, which contains the stratum corneum antigen, was used to sensitize the red blood cells in the hemagglutination assay. The antibody activity in human sera was determined before and after absorption with antigens isolated from callus, psoriatic scales, and cell envelopes. We found notable differences in the antigens obtained from callus and psoriatic scales. These include higher antibody titers to the antigens of the scales, the presence of unique antigenic determinants on psoriatic scales and the localization of the antigen on cell envelopes. These immunological differences were corroborated by the marked biochemical differences of certain amino acids, most notably glycine and proline, and these differences were unique to psoriatic scales as they were not shared with other hyperproliferative disorders.

Amino Acids

Murine natural killer cells and marrow graft rejection.

Rejection of bone marrow transplants in lethally irradiated mice differs from rejection of solid tissue grafts in several respects. The genetic laws that govern rejection of solid tissue grafts often fail with hemopoietic grafts. For example, F1 hybrids between two H-2 disparate strains of mice often reject parental bone marrow cells (BMC), and conversely, marrow cells of F1 hybrids (H-2 heterozygous) are usually not rejected by either parent or an unrelated allogeneic recipient. Thus, unlike the classical MHC antigens, the hemopoietic histocompatibility (Hh) antigens relevant in marrow graft rejection are inherited in a recessive pattern. The major Hh (Hh-1) locus maps within the mouse H-2 complex between the H-2S and H-2D regions, and it can therefore be dissociated from the class-I MHC genes. Nevertheless, it is possible that class-I MHC antigens play a role in the formation or expression of Hh-1 antigens. Three models that explain the possible relationship between class-I MHC and Hh-1 genes and the noncodominant pattern of inheritance of Hh antigens are presented. The effector cells responsible for resisting BMC grafts are different from those responsible for rejection of solid tissue grafts. Three cell types, natural killer cells (CD3-, NK1.1+), cytotoxic T cells (CD3+, CD8+), and T cells with natural killer cell markers (CD3+, NK1.1+) have been implicated in the rejection of BMC grafts. Involvement of these cell types is reviewed and the relative roles played by each are discussed. Evidence supporting the existence of Hh-1 specific subsets of NK cells is presented.

Animals

Quantitative studies of immunofluorescent staining. VII. Quantitative reference standard slide for standardization of fluorescence microscopes.

We evaluated a quantitative reference standard (QRS) slide with 10-microns beads with different concentrations of Coulter Electronics green dye No. 1. Microfluorospectrophotometric readings of the QRS slides provided quantitative comparisons between the sensitivity of the different fluorescence microscopes. The visual comparisons between beads with a range of intensities of fluorescence of Coulter Electronics green dye No. 1 indicated that the end points vary with different optical systems as do the end points in standard indirect immunofluorescent titrations. Fluorescent emission wavelength of QRS slide beads gave the same peak as fluorescein-labeled beads; both differed from the peak of orange beads of an 'Optical Standard' slide. Since shelf life studies show no changes in fluorescence intensity of beads over a period of 27 months or longer, QRS slide beads can afford a device for standardization of fluorescence microscopes used for immunofluorescent tests.

Animals

A preliminary study of correlation of immuno-histological and ultrastructural characteristics of neural granuloma in leprosy patients.

With an aim to better understand the pathogenesis of nerve damage in leprosy, peripheral nerve biopsies from six untreated leprosy cases (3 BT/TT and 3 BL/LL) were studied by electronmicroscopy and immuno-histology. In addition to routine histopathology for diagnosis, infiltrating cells of granuloma were characterized after preparation of single cell suspension. The lymphocytes in the lesion were characterized by E and EAC rosetting and macrophage phagocytic system (MPS) cells were studied using histochemical markers like esterase and peroxidase. The results indicate that the lymphocyte content was significantly greater in tuberculoid neural granuloma compared to lepromatous nerves and these formed rosettes with sheep erythrocytes (E) and expressed HLA-DR antigen suggesting that they are activated T cells. Infiltrating macrophages in both the tuberculoid and lepromatous neural granuloma were esterase positive, peroxidase negative and did not form rosettes with sheep erythrocytes or EAC. Ultrathin sections of tuberculoid granuloma showed lymphocytes clearly associated to epithelioid macrophages having well developed Golgi apparatus and rough endoplasmic reticulum. Correlation of these immunological and ultrastructural characters suggests that hypersensitivity mechanisms are possibly responsible for nerve damage in tuberculoid leprosy. Ultrastructural examination of lepromatous nerves, on the other hand, showed the predominance of macrophages with large nucleus, heavily bacillated Schwann cells, and a few lymphocytes. The correlation of immuno-histological and ultrastructural characters indicates that the mechanism(s) of nerve damage in lepromatous leprosy are basically different wherein hypersensitivity appears to play a very limited role.

Academies and Institutes

Alzheimer disease assessment scale: useful for both early detection and staging of dementia of the Alzheimer type.

The Alzheimer Disease Assessment Scale (ADAS) was administered to 61 patients with dementia of the Alzheimer type (DAT) and 52 elderly controls. The DAT group was subdivided into different severity levels of dementia based on scores from the Mini-Mental State Exam: very mild (greater than or equal to 24), mild (20 to 23), moderate (10 to 19), and severe (0 to 9). The mean scores on the ADAS Cognitive subscale for the four levels of dementia (very mild = 23.1 +/- 7.7, mild = 22.9 +/- 8.9, moderate = 38.6 +/- 9.8, severe = 54.8 +/- 7.6) were statistically different from one another (p less than 0.0001, except very mild vs. mild) and were significantly worse than the scores of the elderly control group (5.5 +/- 2.7, p less than 0.0001, ANOVA). Furthermore, the ADAS Cognitive subscale was highly effective in discriminating individual Alzheimer patients from elderly controls. The ADAS Cognitive score correctly classified 100% of the very mild group, 91% of the entire mild group, and 100% of the moderate and severe groups when a cutoff score of 2 SDs above the control group mean was used. Age and education had only minimal effects on the ADAS Cognitive score. The ADAS is a valuable screening test that only takes 30 min to administer and has utility in both early detection and staging of DAT.

Adolescent

Hematologic relapse of chronic myelogenous leukemia following allogeneic bone marrow transplantation: apparent graft-versus-leukemia effect following abrupt discontinuation of immunosuppression.

Two patients with hematologic relapse of chronic myelogenous leukemia (CML) following allogeneic BMT were treated by abrupt discontinuation of cyclosporine. Both patients rapidly attained complete hematologic and cytogenetic remission and remain free of disease with long follow-up. In the first patient, disappearance of CML was associated with the development of graft-versus-host disease (GVHD). In the second patient GVHD did not develop until after clearing of disease had been documented by cytogenetic analysis. Laboratory studies in the second patient disclosed the presence of lytic activity against both K562 and autologous CML cells that enhanced with IL2. Correlation with serial immunophenotyping data from this patient suggests that the effector for this graft-versus-leukemia (GVL) reaction could have been a T lymphocyte. Abrupt discontinuation of post-transplant immunosuppression with cyclosporine may represent a therapeutic approach to CML which has recurred following BMT. Moreover, investigation of this clinical phenomenon in subsequent cases may permit direct study of the cellular mechanisms involved in the GVL effect.

Adult

Serologic markers of gluten-sensitive enteropathy in bullous diseases.

BACKGROUND AND DESIGN: Dermatitis herpetiformis (DH) is characterized immunologically by the presence of IgA immune deposits in the skin and by the presence of various serum antibodies. Of these, antibodies to gliadin, reticulin, and endomysium have been found to be significant. There are, however, conflicting reports as to the exact specificity and sensitivity of these serologic markers in diagnosing DH. We examined the disease specificity of these three antibody markers in 14 patients with DH, in 98 patients with pemphigus and pemphigoid, and in 26 normal subjects. Reticulin and endomysium antibodies were detected by indirect immunofluorescence and gliadin antibodies by means of the enzyme-linked immunosorbent assay method. RESULTS: Among the various bullous diseases, endomysial and reticulin antibodies were found to be disease specific for DH. Endomysial antibodies occurred in twice the number of DH patients (72%) compared with the occurrence of reticulin antibodies (36%). Antigliadin antibodies were detected in two thirds of DH patients and were not disease specific since increased frequencies of these antibodies were also detected in patients with pemphigus and pemphigoid. CONCLUSION: These studies support the earlier findings of the high degree of specificity of endomysial antibodies for DH and, thus, help to differentiate DH from other bullous disorders.

Antibodies

[Immunodiagnosis of Taenia saginata cysticercosis].

Many different serological tests have been investigated in order to replace the current "knife and eye" method at the slaughterhouse, which detects only a small fraction of the cattle infected with cysticercosis. Among the assays for the detection of antibodies against the cysticerci of Taenia saginata, the ELISA is certainly the most sensitive, although it is unable to detect lightly infected animals. Consequently it only allows a group diagnosis in naturally infected cattle. The use of purified antigens of T. saginata, T. crassiceps and T. hydatigena did not improve significantly the reliability of these antibody detection tests. Recently monoclonal antibodies have been developed against surface or excretory- and secretory antigens of T. saginata metacestodes, allowing the detection of circulating antigens in the serum of infected cattle. Furthermore these monoclonal antibodies can distinguish animals carrying living, infectious cysticerci from those harbouring only dead cysticerci. Research is currently going on in order to improve the sensitivity of this antigen detection test, so that it can replace the current unreliable meat inspection methods in the slaughterhouse.

Animals

Termination of photorefractoriness in the brahminy myna, Sturnus pagodarum: role of photoperiods and gonadal hormones.

In brahminy myna a photosensitive species, long days caused full gonadal development followed by rapid regression, whereas short days inhibited these responses. Experiments were performed to investigate the effects of duration of photoperiod and gonadal hormones on the recovery of photosensitivity to long photoperiods in male birds. Groups of photorefractory birds were subjected to 8-, 9- or 11-hr daily photoperiods for 45 (6.5 weeks) or 63 (9 weeks) days and then transferred to 15 h daily photoperiods for 60 days to check for the regaining of photoresponsivity. A control group was held under 15L:9D throughout the period of study. Another experiment included three groups of photorefractory males, which were maintained on 9L:15D for 9 weeks and administered with, birth-1day-1 alternately for first 30 days olive oil or different doses (10 or 100 micrograms) of testosterone propionate (TP)/bird/day alternately for first 30 days, and then transferred to 15L:9D for another 30 days to test the recovery of photosensitivity. The results indicated that (i) a period of exposure to short daylengths is required to dissipate photorefractoriness, (ii) termination of photorefractoriness is dependent on the length and duration of photoperiods and (iii) TP inhibits the recovery of photosensitivity in a dose dependent manner.

Animals

Susceptibility of south Indian strains of Mycobacterium tuberculosis to tuberactinomycin.

A total of 114 strains of Mycobacterium tuberculosis isolated from sputum samples of 114 patients of pulmonary tuberculosis in south India, were coded and tested for their in vitro susceptibility to tuberactinomycin (Tum) incorporated in Lowenstein-Jensen (LJ) medium. Of these strains, 95 (83.3%) and 15 (13.2%) were susceptible to Tum at 25 and 50 mg/l respectively. Only 4 (3.5%) strains were inhibited at 100 mg/l or more. Of the 37 drug sensitive strains, 2 (5.4%) were not susceptible to Tum at 25 mg/l compared to 17 (22.1%) of 77 strains-resistant to one or more of antituberculosis drugs (P less than 0.02). The drug susceptibility pattern of the strains revealed that there was no significant association of resistance between Tum and streptomycin or rifampicin or ethambutol or ethionamide or isoniazid. However, 15 (53.6%) of 28 kanamycin (K) resistant strains were not susceptible to Tum at 25 mg/l. This cross resistance between Tum and K was further studied in 24 and 15 K sensitive and resistant strains respectively, by correlating their proportion resistance at 16 mg/l and it was found to have a significant positive correlation (r = 0.55; P less than 0.01).

Drug Resistance, Microbial