Dietary practices and beliefs in adolescent girls.
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Adolescent↗
Biomedical subjects
V K Sharma
Publications and source records attributed to V K Sharma.
Molecular executors of cell death--differential intrarenal expression of Fas ligand, Fas, granzyme B, and perforin during acute and/or chronic rejection of human renal allografts.
Two distinct cytolytic pathways have been characterized: one in which the interaction between the Fas antigen and its ligand results in apoptosis, and another in which the pore forming protein perforin and the serine protease granzyme B contribute to DNA fragmentation and cell death. We investigated intrarenal expression of these molecular executors of cell death in light of the potential participation of cytolytically active cellular elements in the antiallograft repertory. Reverse transcriptase-polymerase chain reaction was used to identify intrarenal expression of Fas antigen, Fas ligand, granzyme B and perforin in eighty human renal allograft biopsies; mRNA display was correlated with the Banff histological diagnosis of renal allografts. Our studies demonstrate that: (1) intrarenal expression of Fas ligand mRNA and of granzyme B mRNA are correlates of acute but not chronic rejection; (2) Fas ligand mRNA is not detectable in allografts in the absence of rejection; (3) intrarenal coexpression of members of each lytic pathway (Fas ligand and Fas, granzyme B, and perforin) and that of both pathways (e.g., Fas ligand and granzyme B) are correlates of acute rejection; and (4) a direct correlation exists between the histological severity of acute rejection and intrarenal coexpression of mRNA encoding Fas ligand, Fas, granzyme B, and perforin. Our studies identify, for the first time, the differential expression of the two major lytic pathways in acute and chronic allograft rejection and suggest that specific therapy directed at the cytotoxic attack molecules might be efficacious in the prevention and/or treatment of acute rejection.
Acute Disease↗
CD2 antigen targeting reduces intragraft expression of mRNA-encoding granzyme B and IL-10 and induces tolerance.
We explored the hypothesis that CD2 antigen-specific therapy would reduce intragraft gene expression and facilitate the emergence of transplantation tolerance. This postulate was tested in a murine pancreatic islet cell allograft model in which a novel mAb directed at the CD2 antigen, RM2-2 anti-CD2 mAb (RM2-2 mAb), was used to regulate CD2 antigen-dependent antiallograft response. Peritransplant administration (day -1, 0, and day + 1 with respect to transplantation) of RM2-2 mAb resulted in significantly longer survival of DBA/2 pancreatic islet cell allografts in the B6AFl recipient compared with untreated recipients. RM2-2 mAb therapy facilitated the induction of antigen-specific tolerance: whereas retransplantation with the original donor strain (DBA/2) islet cell allograft was successful, retransplantation with a third-party donor (SJL) islet cell allograft was not. In vivo administration of RM2-2 mAb therapy resulted in a decrease in the percentage of T cells that coexpressed the CD2 antigen (demonstrated by two-color flow cytometry) and in a decrease in intragraft expression of cytotoxic cell specific granzyme B mRNA and IL-10 mRNA (detected by RT-PCR). Our data, in addition to demonstrating for the first time the efficacy of RM2-2 anti-CD2 mAb, suggest that CD2 antigen is a suitable target for the induction of transplantation tolerance.
Animals↗
Urinary excretion of renal brush border membrane enzymes in leprosy patients--effect of multidrug therapy.
Renal function at the brush border membrane level has been studied using characteristic enzymes, such as alkaline phosphatase, leucine-aminopeptidase and gamma-glutamyl transpeptidase. Urinary enzyme studies were performed using leprosy patients, classified on the basis of bacteriological index (BI>3; n=20, BI<3; n=12, BI-ve; n=10) and compared with control subjects (n=10). The role of enzymuria in monitoring WHO-recommended multidrug therapy (MDT) has been evaluated in these patients. A significant increase in the enzyme activities (p<0.01), as well as significant (p<0.01) proteinurea in 24-hour urine samples of both the smear positive groups (BI>3, BI<3) prior to therapy compared to control subjects, indicates proximal tubular functional impairment at brush border membrane level. In the smear negative (BI-ve) group, no significant difference was observed in enzyme activities as compared with the control group. In a follow-up study (BI>3;n=13, BI<3; n=4) the activities of all the enzymes decreased significantly in all the groups when compared to a corresponding untreated group. The follow-up study was not carried out on the smear negative group. The surprising finding was the differential behaviour of r-glutamyl transpeptidase, whose activity increased significantly (p<0.01) even after therapy in BI>3 group when compared with untreated patients. However in a detailed work-up including hepatic and renal function tests, the serum biochemistry was found to be normal both before and after therapy. Urinary excretion of brush border enzymes seems to be related to bacterial load, and their potential in studying the effect of MDT remains unclear.
Alkaline Phosphatase↗
Intragraft TGF-beta 1 mRNA: a correlate of interstitial fibrosis and chronic allograft nephropathy.
Chronic allograft nephropathy is a relentlessly progressive process and a major cause of long-term graft dysfunction and ultimate failure. Interstitial fibrosis, tubular atrophy, and glomerular and vascular lesions characterize this mechanistically unresolved disorder. Given the prominent role of TGF-beta 1 in tissue repair and in fibrosis, we have explored the hypothesis that fibrosis and chronic allograft nephropathy would be distinguished by intragraft TGF-beta 1 mRNA expression. This postulate was tested by mRNA phenotyping of RNA isolated from 127 human renal allograft biopsies. Reverse transcription assisted polymerase chain reaction was used to amplify and identify ingraft gene expression. Our investigation demonstrated a significant correlation between intragraft TGF-beta 1 mRNA display and renal allograft interstitial fibrosis and chronic allograft nephropathy. In contrast, intragraft expression of mRNA encoding immunoregulatory cytokines, IL-2, IFN-gamma, IL-4, IL-10, or cytotoxic attack molecules, granzyme B and perforin was not a correlate of interstitial fibrosis or chronic allograft nephropathy. Our studies identify, for the first time, a significant association between intragraft TGF-beta 1 mRNA expression and renal allograft interstitial fibrosis, and advance a candidate molecular mechanism for chronic allograft nephropathy.
Base Sequence↗
Drug related involvement of specific sites in fixed eruptions: a statistical evaluation.
Different drugs produce fixed eruptions over different parts of the body. However, the significance of preferential site involvement in fixed eruptions due to specific drugs has not been statistically evaluated. One hundred and twenty five patients of fixed drug eruption (FDE) were studied to examine this question. Different sites affected by individual drugs were classified as lips alone, genitalia alone, lips and genitalia together, trunk alone, trunk and limbs together, and generalized. Statistical analysis was carried out for 7 common drugs causing FDE in 5 or more patients. Cotrimoxazole, a combination of sulfamethoxazole and trimethoprim, was the most common offender for FDE (32.8%), followed by analgin (12%), tetracycline (8%), pyrazolones (8%), metronidazole (6.4%), ciprofloxacin (5.6%), and phenytoin sodium (4%). Major sites involved by FDE were trunk and limbs (24%), lips alone (20.8%), genitalia alone (20%), generalised (14.4%), lips and genitalia together (11.2%), and trunk alone (8.8%). Seventy-two (57.6%) patients had multiple lesions; 33 (42.4%) had single lesions. Involvement of mucocutaneous junctions of lips and genitalia by FDE was frequently caused by cotrimoxazole and tetracycline; trunk and limbs, by analgin and pyrazolones. Generalised eruptions were commonly caused by cotrimoxazole and phenytoin. The present statistical analysis confirms the clinical impression that genitalia alone are frequently involved in FDE due to tetracyclines (p < 0.001). FDE over trunk and limbs was significantly associated with analgin (p < 0.001), and generalised eruptions, with phenytoin sodium (p < 0.001). The association of FDE over lips with cotrimoxazole was statistically not significant.
Adolescent↗
Profile of alopecia areata in Northern India.
BACKGROUND: Epidemiologic studies of alopecia areata (AA) are available from USA, Japan and European countries, but there is a paucity of literature on AA from Asian countries, especially from the Indian subcontinent. METHODS: In a prospective, hospital-based study lasting for a decade (1983-1992), the epidemiology of AA was studied, including associated diseases and risk factors for development of severe AA. Simultaneously a similar study was carried out in age- and sex-matched controls. RESULTS: Eight hundred and eight patients (532 men, 276 women) and 572 age- and sex-matched controls (370 men, 202 women) were studied. The incidence of AA was 0.7% of new dermatology outpatients. The majority of patients (712, 88%) were below 40 years of age, including 196 children < 16 years of age (24%). Almost half (46%) of the women patients had onset of AA in childhood, compared to only 19% in men (P < 0.001). Alopecia was total, universal, or extensive in 154 patients (19%). An onset in the first two decades was more often associated with severe alopecia (P < 0.001), especially in men (P < 0.01). Alopecia areata was recorded in family members of 70 patients (9%), being more frequent in the severe forms of AA (16%). Evidence of atopy was recorded in a total of 146 instances (18%). The frequency of atopy was the same in circumscribed alopecia (18.1%) and severe alopecia (18.2%). Nail changes were found in 162 patients (20%) and were more frequent in 76 (47%) with the severe form of AA (P < 0.001). On 39 occasions (5%), autoimmune-related diseases were detected: vitiligo in 15 (1.8%), thyroid disorders in 8 (1%), lichen planus in 6 (0.7%), collagen vascular diseases in 5 (0.6%), diabetes mellitus in 4 patients (0.4%), and pemphigus foliaceus in 1 (0.1%) patient. Patients with family members having vitiligo (recorded in 5.9% of patients), were more frequently affected with severe alopecia (P < 0.001). CONCLUSIONS: Alopecia areata in North Indians showed a preponderance in men (M:F = 2:1) and the majority of persons with disease (88%) were below 40 years of age. Onset in childhood was more frequent in girls or women, but the incidence of severe alopecia was higher in boys or men with onset at an earlier age. Diseases associated with autoimmunity were seen in only 5% of patients. Atopy was found to be associated in 18% of patients, but its reported association with younger age of onset and severe alopecia was not confirmed. Presence of vitiligo in family members and onset before 20 years of age, especially in boys or men, were found to be risk factors for severe alopecia.
Adolescent↗
Pulsed administration of corticosteroids in the treatment of alopecia areata.
BACKGROUND: Widespread alopecia areata (AA) is difficult to treat and modalities such as topical and systemic steroids, topical sensitizers (e.g., squaric acid dibutylester and diphencyprone), psoralen-ultraviolet A (PUVA) therapy, minoxidil, and immunomodulators have been tried. METHODS: Patients with widespread alopecia (> 40% scalp involvement), including alopecia totalis (AT) and universalis (AU), were treated with 300 mg oral prednisolone pulses at 4-week intervals, for a minimum of 4 doses or until cosmetically acceptable hair growth was obtained. Response to therapy was monitored by serial photographs and patients were examined monthly for side effects of steroids. A 1000 mg oral prednisolone pulse was administered to five patients with alopecia totalis/universalis and to three failures of the 300 mg-pulse treatment. RESULTS: Thirty-two patients (24 men, 8 women) with a mean age of 29 years were recruited. They had alopecia for a mean period of 2.8 years. Twenty-seven patients (21 alopecia areata, 5 alopecia universalis, 1 alopecia totalis) received 300 mg pulse therapy and eight patients received 1000 mg prednisolone pulses. Fourteen (58.3%) patients (13 AA, 1 AT) out of 24 evaluated treated with 300 mg pulse therapy showed complete or cosmetically acceptable hair growth. Response was evident on average after 2.4 months and was cosmetically acceptable at 4 months. Three (AA, AT, AU-one each) out of seven patients assessed for the 1000-mg pulse had cosmetically acceptable hair growth at 6-9 month. CONCLUSIONS: An oral monthly pulse of prednisolone 300 mg is effective, safe, and can be administered on an outpatient basis. It is recommended as one of the modalities for the treatment of widespread alopecia areata.
Administration, Oral↗
Contact dermatitis in agricultural workers: rôle of common crops, fodder and weeds.
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Adult↗
Identification and characterization of the origin of conjugative transfer (oriT) and a gene (nes) encoding a single-stranded endonuclease on the staphylococcal plasmid pGO1.
The genes mediating the conjugative transfer of the 52-kb staphylococcal plasmid pGO1 are within a 14.4-kb gene cluster designated trs. However, a clone containing trs alone cannot transfer independently and no candidate oriT has been found within or contiguous to trs. In this study, we identified a 1,987-bp open reading frame (ORF) 24 kb 3' and 13 kb 5' to trs that was essential for conjugative transfer: transposon insertions into the ORF abolished transfer and a plasmid containing the ORF could complement these transposon-inactivated pGO1 mutants for transfer. Analysis of the nucleotide sequence of this ORF revealed significant homology between the amino terminus of its predicted protein and those of several single-stranded endonucleases. In addition, a 12-bp DNA sequence located 100 bp 5' to the ORF's translational start site was identical to the oriT sequences of the conjugative or mobilizable plasmids RSF1010, pTF1, R1162, pSC101, and pIP501. The ability of the ORF, designated nes (for nicking enzyme of staphylococci), to generate a single-stranded nick at the oriT was demonstrated in Escherichia coli by alkaline gel and DNA sequence analysis of open circular plasmid DNA. Plasmids that could be converted to the open circular form by the presence of oriT and nes could also be mobilized at high frequency into Staphylococcus aureus recipients with a second plasmid containing only trs. We propose that the 14.4 kb of trs and the approximately 2.2 kb of the oriT-nes region, coupled with an origin of replication, make up the minimal staphylococcal conjugative replicon.
Amino Acid Sequence↗
Role of mecA transcriptional regulation in the phenotypic expression of methicillin resistance in Staphylococcus aureus.
The gene required for methicillin resistance in staphylococci, mecA, encodes the low-affinity penicillin-binding protein 2a (PBP2a). Transcriptional regulation of mecA is accomplished in some isolates by mecR1 and mecI, cotranscribed chromosomal genes that encode a putative signal transducer and a transcriptional repressor, respectively. Two Staphylococcus aureus strains that have identical mecR1-mecI nucleotide sequences, BMS1 and N315P, both exhibit low-level, heterotypic expression of methicillin resistance and contain no beta-lactamase coregulatory sequences. mecR1-mecI was amplified from BMS1 by PCR and was shown to be functional on a high-copy-number plasmid when introduced into an S. aureus strain with a deleted mecR1-mecI locus. Cloned mecR1-mecI repressed phenotypic expression of methicillin resistance, mecA transcription and PBP2a production and mediated PBP2a induction in response to certain beta-lactam antibiotics. However, mecR1-mecI had different regulatory activities in its native chromosomal location in N315P compared with those in BMS1. Uninduced mecA transcription was markedly repressed in N315P, and mecI inactivation increased mecA transcription and PBP2a production 5- and 40-fold, respectively. Furthermore, the N315P phenotype changed from low-level, heterotypic resistance with intact mecI to high-level, homotypic resistance in strains with disrupted mecI. In contrast, uninduced BMS1 produced abundant mecA transcript and PBP2a, while the disruption of mecI had no effect on phenotype and little effect on mecA transcription or PBP2a production. Thus, mecI-mediated repression of mecA appears to be dysfunctional in BMS1 because of the presence or absence of additional regulatory cofactors. Furthermore, heterotypic resistance expression in this strain is independent of mecA transcriptional regulation.
Bacterial Proteins↗
Molecular and functional identification of m1 muscarinic acetylcholine receptors in rat ventricular myocytes.
The expression of muscarinic acetylcholine receptor (mAChR) subtypes in freshly isolated adult rat ventricular myocytes was investigated by reverse transcription of cellular mRNA followed by amplification of cDNA using the polymerase chain reaction (PCR). After reverse-transcriptase PCR, bands were obtained corresponding to the expected sizes for the m1 and m2 but not for the m3 to m5 mAChRs. The identity of the m1 and m2 bands was confirmed by single-cell PCR, restriction digest mapping, and Southern blot analysis. The presence of m1 and m2, but not m3, mAChR protein in these cells was shown by indirect immunofluorescence studies using subtype-specific antibodies. It was further investigated whether the identified m1 mAChR was responsible for the stimulatory effects on Ca2+ transients by high concentrations of carbachol ( > 10 mumol/L) known to occur in these cells. In pertussis toxin-treated ventricular myocytes electrically stimulated at 1 Hz, carbachol (300 mumol/L) increased the basal Ca2+ level from 96 +/- 7 to 118 +/- 8 nmol/L and the peak Ca2+ transient level from 519 +/- 32 to 640 +/- 36 nmol/L (mean +/- SEM P < .05 for both, n = 8). These effects of carbachol on Ca2+ transients were antagonized by 10 nmol/L pirenzepine, an m1 mAChR-selective antagonist. In contrast, the m2 mAChR-selective antagonist methoctramine (up to 100 nmol/L) did not inhibit the response. These results are the first to use single-cell PCR to probe cardiomyocyte-specific gene expression and indicate that m1 mAChRs are expressed on adult rat ventricular myocytes in addition to m2 mAChRs. The results further suggest that m1 mAChRs mediate the stimulatory responses on Ca2+ transients to high concentrations of cholinergic agonists seen in these cells.
Animals↗
Cardiac status in typhoid fever.
Fifty adult patients with culture-proved typhoid fever were subjected to daily clinical, electrocardiographic (ECG), and electrolyte assessment to evaluate and correlate their cardiac status. Transaminases and creatine kinase (CCK-MB) were estimated on alternate days and echocardiographic assessment was done once during hospitalization. The patients were distributed into groups: I (21) who did not have any ECG or enzymes changes, IIa (17) who had both ECG as well as enzymes changes, IIb (5) who had ECG changes only, and IIc (7) who had elevated enzymes only. Various types of ECG abnormalities were observed in 22 patients. Transaminases were significantly raised (P < 0.001) in group IIa and IIc patients (24). However, CK-MB was significantly raised (P < 0.001) only in the 5 patients of group IIa. There was no relationship among the elevated enzyme levels, severity of disease, and ECG changes. Further, ECG changes were observed during the convalescence stage also, but transaminases were found to be elevated only during the acute stage. It is concluded that definite injury to the heart occurs during typhoid fever. However, it is difficult to ascertain the exact time and extent of the injury. Further, CK-MB was not found to be superior to transaminases for assessment.
Adult↗
Light-induced phase response curves of the circadian activity rhythm in individual field mice, Mus booduga.
The circadian rhythm of locomotor activity of the field mouse Mus booduga was studied and single animal phase response curves (PRCs) (n = 8) were constructed for 15-min daylight pulses of 1000 lux intensity. The light pulses, presented at different phases of the circadian cycle, evoked advancing and delaying phase shifts (delta phi s) depending on the circadian time (CT) of light pulse application. delta phi s By light pulses applied at the same phase are strongly correlated with the animals' circadian period (tau). The results indicate a significant correlation between (i) tau and the area under the advance zone of the PRC (A) (r = +0.72, p < 0.05), (ii) tau and the area under the delay zone of the PRC (D) (r = -0.98, p < 0.00001), (iii) tau and the difference between the area under delay and advance zone of PRC (D-A) (r = -0.97, p < 0.0001), and (iv) between tau and delta phi s (at various phases of the circadian cycle) and further suggest that the waveform and time course of PRC depend on the animals' endogenous period (tau).
Animals↗
Fixed drug eruption due to ciprofloxacin.
We describe seven patients with fixed drug eruption (FDE) due to ciprofloxacin, five confirmed by rechallenge. These cases make up 8.75% of all cases of FDE seen by us during 1992-93. Isolated, and striking involvement of the lips was seen in two patients. To our knowledge, only a single case of FDE to ciprofloxacin previously has been reported. Our experience suggests that, with widespread use, ciprofloxacin could become one of the common drugs causing FDE.
Adult↗
Immunoregulatory and fibrogenic activities of cyclosporine: a unifying hypothesis based on transforming growth factor-beta expression.
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Animals↗
A flowcytometric study of CD4+ & CD19+ cell lymphopenia in patients with alopecia areata.
Twenty five patients with alopecia areata and 20 healthy controls were studied by flowcytometry employing direct two colour immunofluorescence in erythrocyte lysed whole blood. A significant reduction was observed in helper/inducer (CD4+) lymphocytes (29.4 +/- 7.4 vs 39.45 +/- 8.0, P < 0.01) and B (CD 19+) lymphocytes (11.04 +/- 6.57 vs 15.0 +/- 5.05, P < 0.01) in comparison with healthy controls. Decrease in T-lymphocytes (CD3+) and suppressor/cytotoxic (CD8+) was not significant and activated (HLADR+) lymphocytes and natural killer cells (CD16+ and CD56+) were within normal limits. Our findings suggest a significant T helper (CD4+) and B (CD19+) cell lymphopenia in alopecia areata.
Adolescent↗
Evaluation of risk factors for fatal neonatal sepsis.
OBJECTIVE: To evaluate risk factors for fatal neonatal sepsis. DESIGN: Prospective study. SETTING: Referral neonatal unit of a teaching hospital. SUBJECTS: 171 neonates admitted with sepsis. METHODS: Clinical examination and investigations on the day of admission were recorded and the neonates followed up to determine the final outcome. RESULTS: The overall fatality was 48.5%. In the univariate analysis, the factors significantly associated with death were weight, gestational age, age at onset of sepsis, hypothermia, requirement of IPPV, presence of refractory septic shock, neutropenia, metabolic acidosis and raised prothrombin time. However, in the multivariate analysis, only neutropenia, metabolic acidosis, increased prothrombin time and refractory septic shock retained their significance. The adjusted odd's ratio (95% confidence interval) were 0.095 (0.04 = 0.22), 1.14 (1.04-1.25), 1.04 (1.002-1.08) and 11.82 (5.47-69.40), respectively. CONCLUSION: Even in a setting with high fatality rates, high risk of mortality in neonatal sepsis can be identified and targeted for intensive intervention.
Analysis of Variance↗