Search PubMed⌕ Search

Biomedical subjects

B Singh

Publications and source records attributed to B Singh.

At least 307 records · Page 17Linked to original sources
PubMed1998

Traumatic thoracobiliary fistula: report of a case successfully managed conservatively, with an overview of current diagnostic and therapeutic options.

Thoracobiliary fistula is a rare complication of hepatic trauma that may present a diagnostic and therapeutic challenge. We report a case of a thoracobiliary fistula complicating thoracoabdominal trauma. Although numerous imaging modalities are able to detect the condition, optimal imaging is achieved with endoscopic retrograde cholangiography, which provides anatomic delineation and has the therapeutic potential of a sphincterotomy. Conservative therapy consists of a safe temporizing measure during the workup and may, on occasion, be the only therapy that is necessary provided that controlled drainage of the fistula is achieved. The current recommendation would be the exhaustion of nonoperative therapeutic modalities before resorting to surgical intervention.

Abdominal Injuries↗
PubMed1998

Presentation, course, and outcome of head and neck skin cancer in African Americans: a case-control study.

BACKGROUND: Several reports have shown that the presentation, course, and outcome of skin cancer is altered in African Americans. Subset data from these studies suggest that the course of head and neck skin cancer may be different from that occurring in other sites. However, very few studies have specifically investigated skin cancer involving the head and neck region in African-American patients. METHODS: Retrospective case-control study including 215 patients with skin cancer (squamous cell carcinoma [SCC], basal cell carcinoma [BCC], malignant melanoma, and adnexal tumors) presenting to a tertiary care institution over a 9.5-year period. Cases were defined as African Americans with skin cancer, and the control group included white and Latin-American patients with skin cancer. RESULTS: Skin cancer occurred in the head and neck region in 135 cases (62%). However, head and neck involvement was less common in African-American patients (44%) than the control group (76%; P < .001). The anatomic distribution of head and neck skin lesions was similar between the groups, with nasal and scalp skin most often involved. In the head and neck region, the ratio of BCC to SCC (4:1) was similar among all groups. In contrast, in non-sun-exposed regions, the ratio was 1:8.5 for African-American patients compared with 1:1 for the control group (P < .001). The overall distribution of malignant melanoma was not influenced by sun exposure in either groups. The study groups were similar in gender distribution, primary treatment modality, rates of positive margins, and development of second skin cancers. Although African Americans presented with more advanced lesions (P < .001), their disease-free interval was similar to the control group. Only the margin status was a significant predictor of disease-free survival by multivariate analysis, with a relative risk of 1.68 (95% CI: 1.58-18.24) CONCLUSIONS: Head and neck skin cancer is similar with regard to presentation and distribution in patients of all skin types. Moreover, in contrast to previous reports, the course of head and neck skin cancer may be less aggressive in African Americans, if appropriate treatment is provided. This report suggests that differences in skin cancer in African Americans reported in the literature reflect cancer occurring in non-sun-exposed regions.

Black or African American↗
PubMed1998

Sinus tachycardia with atrioventricular block: an unusual presentation during neurocardiogenic (vasovagal) syncope.

INTRODUCTION: Neurocardiogenic (vasovagal) syncope is characterized by hypotension and bradycardia. The presence of sinus tachycardia along with AV block during syncope in patients with neurocardiogenic syncope has not been described previously. METHODS AND RESULTS: Two female patients (18 and 16 years old) with recurrent syncope and documented sinus tachycardia at the time of syncope are described. Patient 1 had recurrent episodes of syncope. During one of these episodes, which occurred while she was being monitored, sinus tachycardia along with high-grade AV block was seen at the time of syncope and hypotension. Patient 2 had a history of recurrent syncope and seizure. During one of these episodes, she was documented to have ventricular asystole lasting for about 39 seconds. The sinus rate was 480 msec at the beginning, before slowing down to 960 msec prior to restoration of sinus rhythm with 1:1 AV conduction. The same scenario was repeated during head-up tilt testing. Both patients were treated successfully with oral disopyramide and, during a follow-up of 28 months and 9 months, have remained symptom-free. CONCLUSION: Sinus acceleration along with high-grade AV block during syncope and hypotension can occur in some patients with neurocardiogenic syncope. The exact mechanism of this phenomenon is unclear.

Adolescent↗
PubMed1998

Epitope dominance: evidence for reciprocal determinant spreading to glutamic acid decarboxylase in non-obese diabetic mice.

Autoimmune T-cell responses to peptide determinants of several autoantigens have recently been characterized. These data suggest that, in some autoimmune models, such as experimental autoimmune encephalomyelitis, T-cell responses may diversify from a nested set of peptides to include many other peptide regions. A similar immune phenomenon pertaining to autoimmune diabetes (IDDM) is observed in NOD mice. We have explored a similar pattern of T-cell responses related to age and disease status in NOD mice termed epitope dominance, which describes immune responses toward a pronounced subset of determinants of the autoantigen glutamic acid decarboxylase (GAD). Our studies have identified a total of five GAD epitopes between the 65 and 67 kDa isoforms. The magnitude of T-cell responses to these various determinants was dependent on the stage of disease as well as on whether mice were protected from disease. The T-cell responses of these epitopes in NOD mice correlated with the predicted binding of these peptides to the NOD class II molecule I-Ag7. We therefore propose a model which implicates antigen presenting cells as critical entities in the propagation of dominant responses to the presentation of autoantigens to T cells, particularly in the Th 1 environment of the NOD mouse. This hypothesis presents a new framework for the discussion and interpretation of the kinetics of T-cell responses to different peptide epitopes in autoimmune diseases such as IDDM.

Amino Acid Sequence↗
PubMed1998

Characterization of protective epitopes in a highly conserved Plasmodium falciparum antigenic protein containing repeats of acidic and basic residues.

The delineation of putatively protective and immunogenic epitopes in vaccine candidate proteins constitutes a major research effort towards the development of an effective malaria vaccine. By virtue of its role in the formation of the immune clusters of merozoites, its location on the surface of merozoites, and its highly conserved nature both at the nucleotide sequence level and the amino acid sequence level, the antigen which contains repeats of acidic and basic residues (ABRA) of the human malaria parasite Plasmodium falciparum represents such an antigen. Based upon the predicted amino acid sequence of ABRA, we synthesized eight peptides, with six of these (AB-1 to AB-6) ranging from 12 to 18 residues covering the most hydrophilic regions of the protein, and two more peptides (AB-7 and AB-8) representing its repetitive sequences. We found that all eight constructs bound an appreciable amount of antibody in sera from a large proportion of P. falciparum malaria patients; two of these peptides (AB-1 and AB-3) also elicited a strong proliferation response in peripheral blood mononuclear cells from all 11 human subjects recovering from malaria. When used as carrier-free immunogens, six peptides induced a strong, boostable, immunoglobulin G-type antibody response in rabbits, indicating the presence of both B-cell determinants and T-helper-cell epitopes in these six constructs. These antibodies specifically cross-reacted with the parasite protein(s) in an immunoblot and in an immunofluorescence assay. In another immunoblot, rabbit antipeptide sera also recognized recombinant fragments of ABRA expressed in bacteria. More significantly, rabbit antibodies against two constructs (AB-1 and AB-5) inhibited the merozoite reinvasion of human erythrocytes in vitro up to approximately 90%. These results favor further studies so as to determine possible inclusion of these two constructs in a multicomponent subunit vaccine against asexual blood stages of P. falciparum.

Amino Acid Sequence↗
PubMed1998

Induction of protective immune responses by immunization with linear multiepitope peptides based on conserved sequences from Plasmodium falciparum antigens.

A cysteine-containing peptide motif, EWSPCSVTCG, is found highly conserved in the circumsporozoite protein (CSP) and the thrombospondin-related anonymous protein (TRAP) of all the Plasmodium species analyzed so far and has been shown to be crucially involved in the sporozoite invasion of hepatocytes. We have recently shown that peptide sequences containing this motif, and also the antibodies raised against the motif, inhibit the merozoite invasion of erythrocytes. However, during natural infection, and upon immunization with recombinant CSP, this motif represents a cryptic epitope. Here we present the results of immunization studies with two linear multiepitopic constructs, a 60-residue (P60) and a 32-residue (P32) peptide, containing the conserved motif sequence. Both the peptides per se generated high levels of specific antibodies in BALB/c mice. P32 was found to be genetically restricted to H-2(d) and H-2(b) haplotypes of mice, whereas P60 was found to be immunogenic in five different strains of mice. The antibody response was predominantly targeted to the otherwise cryptic, conserved motif sequence in P60. Anti-P60 antibodies specifically stained the asexual blood stages of Plasmodium falciparum and Plasmodium yoelii in an immunofluorescence assay, recognized a 60- to 65-kDa parasite protein in an immunoblot assay, and blocked P. falciparum merozoite invasion of erythrocytes in a dose-dependent manner. Immunization with P60 also induced significant levels of the cytokines interleukin-2 (IL-2), IL-4, and gamma interferon in BALB/c mice. Moreover, >60% of mice immunized with P60 survived a heterologous challenge infection with a lethal strain of P. yoelii. These results indicate that appropriate medium-sized synthetic peptides might prove useful in generating specific immune responses to an otherwise cryptic but critical and putatively protective epitope in an antigen and could form part of a multicomponent malaria vaccine.

Amino Acid Sequence↗
PubMed1998

Branchial cleft cyst carcinoma: myth or reality?

Skepticism has surrounded the existence of branchial cleft carcinoma since the entity was first described in 1882. However, a landmark work of 1950 established four criteria for the diagnosis of branchial cleft carcinoma, the most important criterion being histologic proof of carcinoma arising from a normal cyst epithelium. Of the 43 cases found in an extensive review of the literature, only 7 cases have satisfied all four of the criteria. To this we add 2 patients who had recurrent infections of a cervical cyst as children and later developed carcinoma within these structures. Additionally, we propose a minor modification to the 1950 criteria and a paradigm for diagnosis and management of these lesions.

Adult↗
PubMed1998

Elevated level of cyclin D1 in mos-transformed cells.

Mos is a germ cell-specific serine/threonine protein kinase that plays an important role during meiotic divisions of oocytes. Upon expression in somatic cells, Mos causes cell cycle perturbations leading to neoplastic transformation. Mos activates the MAP kinase pathway in both oocytes and transformed somatic cells. To determine the mechanism of cell cycle perturbation in mos-transformed cells, we examined the status of some key regulators of G1 phase. We provide evidence that Mos causes an elevation in the level of cyclin D1 in NIH/3T3 cells. As expected from the increased cyclin D1 level, mos transformation of NIH/3T3 cells caused an increase in the protein kinase activities of cyclin D1-Cdk4 and cyclin E-Cdk2 and induced hyperphosphorylation of the retinoblastoma protein. Of importance, the level of cyclin D1 was also elevated in eye lens of the c-mos-transgenic mice compared to normal mice. Our results indicate that the mechanism of cellular transformation by Mos involves an elevation in the level of cyclin D1 in somatic cells.

3T3 Cells↗
PubMed1998

Intravascular Red Light Therapy after Coronary Stenting Ñ Angiographic and Clinical Follow-up Study in Humans.

In animal models of coronary restenosis, intravascular red light therapy (IRLT) using a diode laser source has been shown to reduce neointimal hyperplasia following balloon-induced injury and coronary stenting. We studied the safety and efficacy of catheter-based IRLT for preventing restenosis after coronary stenting in 22 patients with angina pectoris. IRLT was performed using a diode laser (650 nm) at an energy level of 10 megawatts delivered through a rapid exchange balloon system containing the fiberoptics. The procedure was successful in all patients, with no procedural or in-hospital complications. Two patients with recurrence of symptoms had angiography at 3 and 4.1 months respectively. Angiographic follow-up was also done after 6 months in the 20 remaining asymptomatic patients. The mean minimal lumen diameter (MLD) for the whole group at 6 months follow-up was 2.57 +/- 0.62 mm. The calculated late lumen loss was 0.49 +/- 1.12 mm with a late loss index of 0.21 +/- 0.54. Four patients (2 symptomatic and 2 asymptomatic) in the series developed angiographic restenosis. Clinical events at follow-up of 10.9 +/- 3.5 months were repeat angioplasty in 2 patients for symptomatic restenosis with a 91% event free survival. These preliminary results demonstrate that IRLT after coronary artery stenting is safe and feasible; it is associated with low rates of angiographic indices of restenosis.

Journal Article↗
PubMed1998

Sporadic breast cancers exhibit loss of heterozygosity on chromosome segment 10q23 close to the Cowden disease locus.

Cowden disease, a dominantly inherited syndrome characterized by a variety of proliferative lesions and predisposition to breast and thyroid cancer, has recently been linked to the polymorphic marker D10S215 on chromosome segment 10q23. Loss of heterozygosity in prostate cancer is linked to the same marker, whereas loss of heterozygosity in glioblastoma, endometrial cancer, and other malignancies also localizes to this region. Most recently, a putative tumor suppressor gene (PTEN/MMAC1) has been identified in the region between D10S215 and an adjacent, more telomeric marker (D10S541) and was found to be altered in breast cancers, prostate cancers, and glioblastomas. We examined 22 invasive breast cancers for loss of heterozygosity in the 10q23 region and found loss in 41% (9/22). There were two distinct regions of loss, including one near the D10S541 marker, with an approximately equal frequency of deletion in each. The observed pattern of deletion is consistent with the presence of a tumor suppressor gene between D10S215 and D10S541. Most of the poorly differentiated carcinomas in the case collection showed loss of heterozygosity in the region near D10S215, suggesting that this loss correlates with a poor prognosis.

Adenocarcinoma, Mucinous↗
PubMed1998

Resympathectomy for sympathetic regeneration.

Explanations for recurrent sympathetic activity after an apparently successful sympathectomy are varied and often tenuous. Among the theories given for recurrent sympathetic activity are the development of alternate neuroanatomic pathways, the possibility of an incomplete operation (failure to appreciate an alternative anatomic pathway at the time of surgery, i.e., nerve of Kuntz), and sympathetic regeneration. The latter, although long suspected, has never been conclusively demonstrated in humans. In this report, a case of recurrent sympathetic activity with conclusive evidence of sympathetic regeneration is described.

Adult↗
PubMed1998

Antitumour and radioprotective action of Podophyllum hexandrum.

A significant antitumour effect of P. hexandrum, a herb thriving at Himalayas (2500-4000 m), was observed in strain 'A' mice carrying solid tumours developed by transplanting Ehrlich ascites tumour (EAT). Subtoxic well tolerated sequential doses of aqueous extract of P. hexandrum (a daily dose of 34.5 mg/kg b.w. for 15 days) enhanced tumour doubling time (TDT) from 1.94 +/- 0.26 days to 19.1 +/- 2.5 days. However, no synergism was revealed between radiation and P. hexandrum, though both independently manifested antitumour effects. In normal mice, pre-irradiation administration of extract of P. hexandrum protected mice in a dose dependent manner (optimal dose being 34.5 mg/kg body.wt. rendering 72% survival for 30 days) against whole body lethal irradiation of 10 Gy. Radioprotective properties of P. hexandrum were found to be comparable to synthetic radioprotectors like diltiazem etc.

Animals↗
PubMed1998

Gadolinium chloride removes pulmonary intravascular macrophages and curtails the degree of ovine lentivirus-induced lymphoid interstitial pneumonia.

Ovine lentivirus (OvLV), a retrovirus, causes lymphoid interstitial pneumonia (LIP) in sheep. Pulmonary alveolar macrophages are believed to play a central role in lung inflammation caused by this virus. The pulmonary intravascular macrophage (PIM), a recently identified inflammatory cell, is under active investigation for its role in lung pathology. Gadolinium chloride (GC), a rare earth lanthanide, has been used in in vivo studies to abrogate macrophage function to understand their role in tissue pathology. We treated mock- and OvLV-infected lambs with GC once a week for 34 weeks to investigate the implications of PIMs in the pathogenesis of LIP using light and electron microscopy. Repeated treatments with GC did not cause any apparent physiological abnormalities in the lambs. Light microscopy on tissue sections showed that GC reduced the number of PIMs in OvLV-infected and mock-infected lambs. Ultrastructural examination of lung tissues from GC-treated lambs revealed electron-dense deposits of GC-like material in endosomes and cytoplasm of PIMs. The majority of the PIMs in GC-treated lambs appeared damaged. Semi-quantitative histological evaluation showed amelioration of the extent of LIP in GC-treated OvLV-infected lambs compared to placebo-treated OvLV-infected lambs. This study stresses the effectiveness of GC in eliminating PIMs and suggests their involvement in the pathogenesis of OvLV-induced LIP. The results also strengthen the usefulness of GC as a tool to study in vivo function of cells such as PIMs that are difficult to isolate for in vitro studies.

Animals↗