Biomedical subjects
B Singh
Publications and source records attributed to B Singh.
Upper aerodigestive tract squamous cell carcinoma. The human immunodeficiency virus connection.
OBJECTIVE: To evaluate the incidence, distribution, and course of squamous cell carcinoma (SCC) of the upper aerodigestive tract in patients infected with the human immunodeficiency virus (HIV) and compare it to SCC in non-HIV-infected patients. DESIGN: Case-control study of all patients with SCC during a 9.5-year period from January 1985 through June 1994. SETTING: Two academic tertiary care centers in a metropolitan location. PARTICIPANTS: Five hundred thirty-nine patients (18 to 95 years old) with SCC of the upper aerodigestive tract. RESULTS: Infection with HIV was present in 4.5% of the patients with SCC of the upper aerodigestive tract. Patients infected with HIV were significantly younger than noninfected patients (P < or = < .001), accounting for 21.3% of those patients younger than 45 years (P < .001). No significant difference in tumor location was present between HIV-infected and noninfected patients; however, HIV-infected patients had larger tumors (P = .004) and a more advanced tumor stage (TNM classification) at presentation (P = .05). Tumor-related survival was significantly poorer in patients with HIV infection (P = .01), with 57% at 1 year and 32% at 2 years, compared with 74% and 59%, for non-HIV-infected patients. The detrimental effect of HIV infection on survival remained significant after adjusting for the confounding effects of age, tumor stage, and location of the tumor. All study patients with HIV infection had cancer risk factors such as tobacco and/or alcohol abuse. CONCLUSIONS: Infection with HIV possibly accelerates the development of SCC in patients with significant risk factors, presumably by impairing normal immune surveillance mechanisms. The decreased survival rates among these patients suggests that the SCC may be more aggressive or that other cofactors assume greater importance. A history of tobacco and/or alcohol abuse in patients with HIV infection warrants aggressive screening and early detection, to allow for early detection, which may help increase survival.
Responses of pulmonary intravascular macrophages to 915-MHz microwave radiation: ultrastructural and cytochemical study.
BACKGROUND: Microwave (MW) radiation is being increasingly used as a source of heat supplementation during early postnatal development of pigs. Although MW radiation does not cause deleterious physiological effects, no specific information exists regarding its impact on immune cells such as macrophages. Pulmonary intravascular macrophages (PIMs) are emerging as important inflammatory cells due to their endocytic and secretory potential. An in vivo study was conducted to evaluate the effects of infrared, and low and high power MW radiation on the PIMs of pigs. METHODS: Pigs were exposed to infrared (IR), low MW (LMW; 6.1mW cm-2), and high MW (HMW; 11.4mW cm-2) radiation at 915 MHz (n = 2 for each treatment) for 24 hr. The controls (n = 2) were exposed to natural light for the same period of time. Lung tissues were processed for ultrastructural examination and acid phosphatase (AcPase) cytochemistry. In addition, rough endoplasmic reticulum (RER) as a fraction of cytosol of the PIMs was counted. RESULTS: Ultrastructural and numerical data suggested enhanced secretory activity in the PIMs of LMW-treated pigs as indicated by the increased RER:cytoplasm ratio, prominent Golgi complex profiles, and accumulation of secretory vesicles in conjunction with microtubules as compared with the control, IR, and HMW-exposed pigs. High MW treatment induced some damage to pulmonary interstitium as deduced from the presence of extracellular AcPase precipitates and disrupted collagen matrix. Intracellular globules were noticed in the PIMs of IR and LMW-treated pigs but not in the control and HMW-radiated animals. CONCLUSIONS: Elaboration of structural signs of secretory activity in the PIMs by LMW radiation in the absence of pulmonary pathological changes indicates its potential for cell activation in addition to the already established role of LMW in heat supplementation. This activation could be due to either increased core body temperature or initiation of intracellular signaling by the LMW radiation. This study also shows that the HMW radiation is capable of inducing pathology in the form of changes in the pulmonary interstitial matrix and may not be a good source of supplementary heat.
Embolization of a Wiktor stent within a stent: successful nonsurgical management.
A case of embolization of an unexpanded Wiktor stent while attempting to traverse an expanded Wiktor stent is reported. The embolized stent was subjected to longitudinal axial traction, using a balloon catheter to cause stretching and partial unraveling. This partially unraveled stent was deployed across the dissection to scaffold it. The patient had no postprocedure complications.
A novel 70-kDa Triton X-114-soluble antigen of Plasmodium falciparum that contains interspecies-conserved epitopes.
In order to identify novel conserved integral membrane and other membrane-associated proteins of Plasmodium falciparum, lambda gt11-P. falciparum DNA library phages were immunoscreened with convalescent-phase mouse sera and rabbit antiserum against Triton X-114-soluble proteins of P. falciparum. One recombinant phage clone, L857, reacted with both of the antibody probes. Insert DNA (857 bp long) in L857 was 69% dA+dT rich and hybridized to a fragment of 1800 bp from mung bean nuclease-digested P. falciparum genomic DNA. The cloned parasite DNA did not show notable sequence homology with any known protein gene. The L857-encoded polypeptide, p34 (M(r) 34 kDa) was expressed in bacteria, fused to glutathione S-transferase (GST). The fusion peptide, GST-p34 (M(r) 62 kDa), was recognized by immune serum against Triton X-114-soluble antigens of P. falciparum and was reactive with anti-P. falciparum, anti-Plasmodium yoelii, and anti-GST sera. Rabbit antiserum raised against the fusion peptide recognized a 70-kDa protein from lysates of P. falciparum cells and a putative homologous 100-kDa protein from lysates of P. yoelii. The rabbit serum anti-fusion peptide antibodies bound to acetone-fixed P. falciparum-infected erythrocytes and, in immunofluorescent antibody tests, produced a punctate pattern of fluorescence suggesting that the 70-kDa native protein is associated with an apical organelle of the parasite.
Testing order restricted hypotheses with proportional hazards.
Inferences for survival curves based on right censored continuous or grouped data are studied. Testing homogeneity with an ordered restricted alternative and testing the order restriction as the null hypothesis are considered. Under a proportional hazards model, the ordering on the survival curves corresponds to an ordering on the regression coefficients. Approximate likelihood methods are obtained by applying order restricted procedures to the estimates of the regression coefficients. Ordered analogues to the log rank test which are based on the score statistics are considered also. Chi-bar-squared distributions, which have been studied extensively, are shown to provide reasonable approximations to the null distributions of these tests statistics. Using Monte Carlo techniques, the powers of these two types of tests are compared with those that are available in the literature.
Comparative study of the efficacy of metoprolol and verapamil in patients with syncope and positive head-up tilt test response.
Head-up tilt testing is a reliable diagnostic tool for patients with recurrent unexplained syncope. It has also been used to assess the drug efficacy for the treatment of patients with syncope. The objective of this study was to assess the efficacy of verapamil compared with metoprolol in a randomized crossover design for patients with syncope and a positive tilt test response. Twenty-eight patients with a positive head-up tilt test were randomized to receive either metoprolol or verapamil; the test was repeated after 7 days of therapy. Of the 15 patients initially given metoprolol, 2 (13.3%) did not respond; both were crossed over to verapamil, to which they remained unresponsive. Of the 13 patients who initially received verapamil, 8 (61%) did not respond; after crossing over to metoprolol therapy, 1 remained unresponsive. Overall, 20 of 23 patients receiving metoprolol had negative results on repeat tilt testing, whereas only 5 of 15 patients receiving verapamil had negative results (p < 0.001). In conclusion, the results of this study suggest that verapamil is considerably less efficacious than metoprolol in managing neurocardiogenic syncope.
CD28/B7 regulation of Th1 and Th2 subsets in the development of autoimmune diabetes.
CD28 ligation delivers a costimulatory signal important in T cell activation. This study demonstrates that the disruption of the CD28/B7 pathway early in the nonobese diabetic mouse strain, using CD28-/- and CTLA41g transgenic mice, promoted the development and progression of spontaneous autoimmune diabetes. Functional analyses of T cells isolated from CD28-deficient mice demonstrated that the GAD-specific T cells produced enhanced Th1-type cytokines (IL-2 and IFN gamma) and diminished Th2-type cytokine, IL-4. Moreover, there was a significant decrease in serum levels of anti-GAD antibodies of the IgG1 isotype consistent with a profound suppression of Th2-type responses in these animals. Thus, the early differentiation of naive diabetogenic T cells into the Th2 subset is dependent upon CD28 signaling and extends our understanding of the importance of Th1/Th2 balance in the regulation of this spontaneous autoimmune disease.
VLA-beta 1 integrin subunit-specific monoclonal antibodies MB1.1 and MB1.2: binding to epitopes not dependent on thymocyte development or regulated by phorbol ester and divalent cations.
We report here the isolation of two new monoclonal antibodies (MB1.1 and MB1.2) against mouse VLA-beta 1 integrin subunit. Characterization by flow cytometry demonstrated binding of MB1.1 and MB1.2 to freshly isolated thymocytes, primary bone marrow mast cell lines, as well as cell lines of distinct lineage each expressing different combination of VLA integrins. The specificity of MB1.1 and MB1.2 was determined by (1) their binding to antigen with M(r) about 120 kDa, and (2) the ability of antiserum against the carboxyl terminal of VLA-beta 1 subunit to deplete antigens for MB1.1 and MB1.2 in sequential immunoprecipitation experiments. The epitopes for MB1.1 and MB1.2 were in close proximity to each other since preincubation of cells with one MAb inhibited the binding of the other. However, MB1.1 and MB1.2 differed in their affinity for the beta 1 subunit. In addition, neither MAbs had any effect on cell adhesion to matrix proteins indicating that the epitopes involved are distant from VLA integrin ligand-binding sites. MB1.1 and MB1.2 appear to differ from the two MAbs so far reported against mouse VLA-beta 1 subunit, KMI6 and 9EG7. Thus, the epitopes for MB1.1 and MB1.2 were readily detectable on unfractionated thymocytes whereas KMI6 has been reported to bind only a fraction of CD4-8- and CD4-8+ thymocytes. Phorbol ester and Mn2+, which have been shown to regulate the binding of 9EG7, had no effect on MB1.1 and MB1.2 binding to VLA-beta 1 integrin subunit.
Peptide analogs with different affinites for MHC alter the cytokine profile of T helper cells.
The interaction of the TCR with the immunogenic peptide bound to MHC class II molecules leads to the activation of the CD4(+) T helper cells. T helper cells have been divided into two subsets, Th1 and Th2, on the basis of the cytokines secreted by them. Th1 cells which secrete IL-2, IFN-gamma and tumor necrosis factor-beta induce delayed-type hypersensitivity, while Th2 cells secreting IL-4, IL-5, IL-6 and IL-10 induce humoral immune response. However, the mechanism of selective activation of Th1 and Th2 cells in response to different antigens is not fully understood. In this study we examined the selective activation of Th1 and Th2 cells in response to strongly immunogenic synthetic peptides EYK(EYA)3, abbreviated as K3; EYK(EYA)4, abbreviated as K4; and EYKEYAAYA(EYA)2, abbreviated as K1A2. These peptides are recognized by H-2(d) T cells in the context of I-Ad, and are strongly cross-reactive in both T cell response and antibody response. The peptide K1A2 has very high affinity for I-Ad while K3 has a much lower affinity. K4 has affinity intermediate between K1A2 and K3. The peptide K1A2 induced Th1 and K3 induced Th2 cells in BALB/c mice as suggested by their cytokine profiles. K4 induced both Th1- and Th2-type cytokines. This was also confirmed by the analysis of both IgG1 and IgG2a responses in vivo. There was a shift toward a Th1-type cytokine profile when K3-primed T cells were challenged with K1A2 in vitro but K1A2-primed cells did not show any shift when challenged with K3. Immunization with higher doses of K3 shifted the response towards Th1 type, while immunization with lower doses of K1A2 did not shift the response toward Th2. We conclude that cells primed with high-affinity peptide are committed to differentiate into Th1 irrespective of the priming dose and affinity of challenge antigen. On the other hand, the differentiation of cells primed with low-affinity peptide depends upon the dose of immunization and binding affinity of the challenge antigen for MHC.
Difficult intubation: a case of "gone with the wind".
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Laryngeal tuberculosis in HIV-infected patients: a difficult diagnosis.
Unrecognized laryngeal tuberculosis (TB) poses a significant hazard to otolaryngologists. However, the changing manifestations of TB in patients with human immunodeficiency virus (HIV) infection can make its diagnosis difficult. In our population of 146 patients with TB involving the head and neck, HIV infection was present in 70 cases (48%). The prevalence of laryngeal TB in this population was 5.5% (8 patients). Concomitant HIV infection was present in 2 (25%) of 8 patients with laryngeal TB. A delay in the diagnosis of laryngeal TB occurred in 100% of patients with HIV infection, compared with 17% of non-HIV-infected patients (P = .055). The cause of the delayed diagnosis was multifactorial, mainly the presence of multiple confounding variables and the carcinoma-like appearance of the laryngeal TB lesions in HIV-infected patients. To reduce risk for transmission of TB to health care providers, a high level of suspicion must be present for all patients with laryngeal lesions, especially those with HIV infection.
Measurements of anomalous elastic scattering of 59.54-keV photons.
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Autoantibodies to human heat shock protein (hsp)60 may be induced by Escherichia coli groEL.
The 65-kD hsp from Mycobacterium tuberculosis has been reported to induce an autopathogenic subset of T cells in at least two animal models of autoimmune disease. Reports of increased expression of human hsp60 in the inflamed synovial tissue of rheumatoid arthritis (RA) patients, increased proliferation of RA synovial fluid T cells to mycobacterial hsp65, and increased levels of anti-mycobacterial hsp65 antibody in synovial fluid, have suggested that the highly homologous human (hu) hsp60 may be recognized as an autoantigen iin RA patients. In the present study, we have examined by ELISA the serum IgG antibody levels to mycobacterial hsp65 and hu hsp60, as well as to the Escherichia coli hsp60, groEL, in patients with RA, systemic lupus erythematosus (SLE), Reiter's syndrome, active tuberculosis, and normal controls. In all these groups, the levels of anti-groEL and anti-hu hsp60 were significantly higher than the anti-mycobacterial hsp65. Anti-hu hsp60 was positively correlated with anti-groEL, but not with anti-mycobacterial hsp65. Anti-hu hsp60 was competitively inhibited by either soluble groEL or hu hsp60, but little or none by mycobacterial hsp65. Reiter's sera were found to have somewhat higher levels of anti-groEL and anti-hu hsp60 than did normal controls. We conclude that IgG anti-hu hsp60 autoantibodies arise primarily as a consequence of the humoral immune response to E. coli groEL through the recognition of cross-reactive epitopes.
Specificity of cANCA for Wegener's granulomatosis.
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Isolation of a tannin-protein complex-degrading fungus from faeces of hill cattle.
Faecal samples of 52 hill cattle fed largely on oak leaves were screened for tannin-protein complex-degrading micro-organisms under different culture conditions using tannin-treated brain heart infusion agar medium. None of the animals were found to harbour tannin-protein complex-degrading enterobacteria. However, a fungus identified as Aspergillus niger van Tieghem having tannin-protein complex-degrading activity, was consistently isolated from the faeces of such animals. Optimum growth and sporulation was noticed under aerobic conditions at 30 degrees C on Czapek Yeast Agar medium.
Reversibility of "tachycardia induced cardiomyopathy" following the cure of idiopathic left ventricular tachycardia using radiofrequency energy.
We report a case of incessant ventricular tachycardia with right bundle branch block and left axis deviation morphology resulting in severe LV dysfunction and congestive heart failure. Radiofrequency ablation of the appropriate site in the region of posteroapical part of the LV septum resulted in the cure of the arrhythmia. On a 3-month follow-up, the LV size and function returned to normal.
Inhibition of v-Mos kinase activity by protein kinase A.
We investigated the effect of cyclic AMP-dependent protein kinase (PKA ) on v-Mos kinase activity. Increase in PKA activity in vivo brought about either by forskolin treatment or by overexpression of PKA catalytic subunit resulted in a significant inhibition of v-Mos kinase activity. The purified PKA catalytic subunit was able to phosphorylate recombinant p37v-mos in vitro, suggesting that the mechanism of in vivo inhibition of v-Mos kinase involves direct phosphorylation by PKA. Combined tryptic phosphopeptide two-dimensional mapping analysis and in vitro mutagenesis studies indicated that Ser-56 is the major in vivo phosphorylation site on v-Mos. In vivo phosphorylation at Ser-56 correlated with slower migration of the v-Mos protein during sodium dodecyl sulfate-polyacrylamide gel electrophoresis. However, even though Ser-56 was phosphorylated by PKA, this phosphorylation was not involved in the inhibition of v-Mos kinase. The alanine-for-serine substitution at residue 56 did not affect the ability of v-Mos to autophosphorylate in vitro or, more importantly, to activate MEK1 in transformed NIH 3T3 cells. We identified Ser-263 phosphorylation, the Ala-263 mutant of v-Mos was not inhibited by forskolin treatment. From our results, we propose that the known inhibitory role of PKA in the initiation of oocyte maturation in mice could be explained at least in part by its inhibition of Mos kinase.