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Biomedical subjects

B Singh

Publications and source records attributed to B Singh.

At least 127 records · Page 7Linked to original sources

Hürthle cell carcinoma: a critical histopathologic appraisal.

PURPOSE: Controversy exists over the ability of morphology to predict the biologic behavior of Hürthle cell carcinoma. The aim of this study was to conduct a critical histopathologic review of Hürthle cell carcinoma and to correlate morphologic parameters with clinical outcome. PATIENTS AND METHODS: Patients with histologically confirmed Hürthle cell carcinoma treated between 1940 and 2000 form the basis of this study. Adenomas were excluded. Tumors of unknown malignant behavior ([UMB] n = 17) had solid growth pattern, incomplete capsular invasion (Ci), or both but no vascular invasion (Vi). Minimally invasive carcinomas ([MIC] n = 23) had one focus of intra- or extracapsular Vi, one focus of complete Ci, or both. Widely invasive carcinomas ([WIC] n = 33) demonstrated more than one focus of Vi, more than one focus of Ci, or both. The primary end points were relapse-free survival (RFS) and disease-specific survival (DSS). Rates of recurrence/death were estimated by Kaplan-Meier method. The univariate influence of prognostic factors on end points was analyzed by log-rank test, and multivariate analysis was performed by Cox regression. RESULTS: Median follow-up was 8 years. No patients with UMB or MIC relapsed or died of disease. Of WIC, 73% relapsed and 55% died of disease. Age, size, and extent of resection did not influence outcome. Adverse predictors of RFS and DSS among WIC were extrathyroidal extension, nodal metastasis, positive margin, and solid growth pattern (P <.05). Both Ci and Vi were associated with worse DSS (P <.05). On multivariate analysis, extrathyroidal extension and nodal metastases were independent predictors of outcome (P <.05). CONCLUSION: Patients with Hürthle cell carcinoma have a prognosis that is predicted by well-defined histomorphologic characteristics. Unlike differentiated thyroid cancer, nodal metastases predict a worse outcome in widely invasive Hürthle cell carcinoma, as does extrathyroidal extension.

Carcinoma↗

Phagocytosis of breast cancer cells mediated by anti-MUC-1 monoclonal antibody, DF3, and its bispecific antibody.

Human epithelial mucin, MUC-1, is commonly expressed in adenocarcinoma including 80% of breast cancers. erbB-2 is overexpressed in approximately 30% of breast cancers. Expression of MUC-1 and erbB-2 may be partially overlapping but discoordinate. Therefore, combined use of antibodies directed against these two antigens might increase the number of patients who benefit from immunotherapy. Monoclonal antibody (MAb) DF3 recognizes the MUC-1 tandem repeat. We investigated phagocytosis and cytolysis of cultured human breast cancer cells by monocyte-derived macrophages mediated by MAb DF3 and its bispecific antibody (BsAb) DF3xH22 with the second epitope directed against the Fc component of phagocytic cells. Purified monocytes from healthy donors were cultured with granulocyte macrophage colony-stimulating factor with or without IFN-gamma. antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent cellular cytotoxicity (ADCC) assays were performed with these macrophages and MUC-1-expressing target cells (ZR75-1) in the presence of MAb DF3 and BsAb DF3xH22. ADCP was measured by two-color fluorescence flow cytometry using PKH2 (green fluorescent dye) and R-phytoerythrin (RPE) (red)-conjugated MAb against human CD14 and CD11b and was confirmed by confocal microscopy. ADCC was measured by (51)Cr release assay. Immunohistochemical staining studies of MUC-1 and erbB-2 were performed on 67 primary breast cancer tissues. Expression of MUC-1 and erbB-2 was partially overlapping but discoordinate in 67 consecutive breast cancers. Both MAb DF3 and BsAb DF3xH22 mediated ADCP. However, ADCP mediated by MAb DF3 was greater than that mediated by BsAb DF3xH22. ADCC as detected by (51)Cr release was not seen with either antibody. The addition of IFN-gamma to monocyte-derived macrophage cultures inhibited ADCP compared to granulocyte macrophage colony-stimulating factor alone. Given the partially overlapping but discoordinate expression of MUC-1 and erbB-2 in breast cancer, therapy directed toward both antigens should be considered. MAb DF3 and the BsAb DF3xH22, can effectively mediate phagocytosis of MUC-1-expressing target cells. Further investigations are needed to determine whether this antibody-induced phagocytosis results in long-term specific T-cell activation against MUC-1.

Adenocarcinoma↗

Capacitation and acrosome reaction in buffalo bull spermatozoa assessed by chlortetracycline and Pisum sativum agglutinin fluorescence assay.

Studies on buffalo sperm capacitation have been limited because of the non-availability of a direct assay system. We describe two methods for detecting the acrosomal status of buffalo spermatozoa, namely chlortetracycline (CTC) fluorescence assay and Pisum sativum agglutinin (FITC-PSA) stain. We also test them under various treatment regimens and simultaneously standardize and calibrate them with transmission electron microscopy. An initial comparison of three physiological media, such as Krebs-Ringer bicarbonate buffer, Tyrode solution and Brackett & Oliphant medium (having different calcium concentrations and osmolality) used for studying the capacitation of buffalo spermatozoa and assessed by CTC, FITC-PSA, Giemsa stain and TEM, revealed Brackett & Oliphant medium to be marginally better than the other two media. When stained with chlortetracycline, three distinct fluorescent patterns were visible in buffalo spermatozoa under capacitating conditions. These were 'F' with fluorescence in the post acrosomal region characteristic of uncapacitated acrosome-intact cells; 'B' with fluorescence on the anterior portion of the sperm head and a dark band in the post-acrosomal region, characteristic of capacitated, acrosome intact cells and 'AR' with a fluorescent band on the posterior portion of the head, characteristic of acrosome-reacted cells. The FITC-PSA intensely labels the acrosomal region of acrosome intact buffalo sperm. Acrosome reacted sperms had diminished acrosomal labelling by both the probes used. Buffalo spermatozoa was not capacitated when calcium was either omitted from the medium or chelated with EGTA. In the presence of Ca2+ ionophore, A23187, 68% at 4 h and 85% at 8 h completed the acrosome reaction. Time course studies revealed a 4 h incubation period at 1.71 mM Ca2+ concentration to be necessary before transformation of 'F' to 'B' cells could take place. Spontaneous acrosome reaction induced at 6 and 8 h incubation of buffalo spermatozoa in KRB medium resulted in conversion of 'B' cells to 'AR' cells while 'F' cells remained unchanged. A simultaneous evaluation of acrosome intact and acrosome-reacted cells using FITC-PSA, Giemsa and TEM gave results similar to examination by CTC stain. Both the assays are rapid, reproducible, reliable and they detect an increase or decrease in physiological acrosome reactions. They thus can be used to study effects of calcium and prove to be good monitoring systems to identify buffalo sperm capacitation and acrosome reaction in individual buffalo bulls for fertility studies.

Acrosome Reaction↗

Transplanted MHC class I-deficient nonobese diabetic mouse islets are protected from autoimmune injury in diabetic nonobese recipients.

The injury of transplanted islets may occur by both autoimmune and alloimmune processes directed against MHC targets. To examine the role of MHC class I in islet graft injury, we transplanted syngeneic and allogeneic beta2-microglobulin-deficient islets into diabetic nonobese diabetic (NOD) mice. Loss of graft function was observed within 14 days using allogeneic C57BL/6 and BALB/c MHC class I deficient as well as wild-type MHC class I-bearing NOD donor islets. However, islets isolated from MHC class I-deficient NOD mice (NOD-B2 m-/-) survived indefinitely when transplanted under the kidney capsule of diabetic NOD recipients. Transplanted NOD-B2 m-/- islets were surrounded by a nondestructive periinsular infiltrate that expressed interleukin-4 in addition to interferon-gamma. These studies demonstrate the primary role of MHC class I molecules in causing autoimmune destruction or recurrent diabetes in transplanted islets.

Animals↗

Tolerance induction by acylated peptides: suppression of EAE in the mouse with palmitoylated PLP peptides.

Treatment of SJL mice either before or after challenge with palmitoylated PLP139-151 (PAL139-151) completely suppressed or considerably reduced both acute and relapsing stages of EAE induced with PLP139-151. In the presence of Pertussis toxin, treatment with PAL139-151 was less effective, but treatment with a mixture of PAL139-151 and PAL178-191, the palmitoylated PLP epitope to which T cell recognition spreads, resulted in almost complete protection. Proliferation of lymphocytes from treated mice were sharply reduced, and adoptive transfer of lymph node lymphocytes from treated mice to naive recipients resulted in the reduction of the acute phase of EAE and in delayed relapses following challenge. The results suggest that treatment with PAL139-151 leads to both anergy and the generation of regulatory cells.

Adoptive Transfer↗

Regulation of Staphylococcus aureus pathogenesis via target of RNAIII-activating Protein (TRAP).

Staphylococcus aureus can cause disease through the production of toxins. Toxin production is autoinduced by the protein RNAIII-activating protein (RAP) and by the autoinducing peptide (AIP), and is inhibited by RNAIII-inhibiting peptide (RIP) and by inhibitory AIPs. RAP has been shown to be a useful vaccine target site, and RIP and inhibitory AIPs as therapeutic molecules to prevent and suppress S. aureus infections. Development of therapeutic strategies based on these molecules has been hindered by a lack of knowledge of the molecular mechanisms by which they activate or inhibit virulence. Here, we show that RAP specifically induces the phosphorylation of a novel 21-kDa protein, whereas RIP inhibits its phosphorylation. This protein was termed target of RAP (TRAP). The synthesis of the virulence regulatory molecule, RNAIII, is not activated by RAP in the trap mutant strain, suggesting that RAP activates RNAIII synthesis via TRAP. Phosphoamino acid analysis shows that TRAP is histidine-phosphorylated, suggesting that TRAP may be a sensor of RAP. AIPs up-regulate the synthesis of RNAIII also in trap mutant strains, suggesting that TRAP and AIPs activate RNAIII synthesis via distinct signal transduction pathways. Furthermore, TRAP phosphorylation is down-regulated in the presence of AIP, suggesting that a network of signal transduction pathways regulate S. aureus pathogenesis.

Adaptor Proteins, Signal Transducing↗

Long-term weight loss and changes in blood pressure: results of the Trials of Hypertension Prevention, phase II.

BACKGROUND: Weight loss appears to be an effective method for primary prevention of hypertension. However, the long-term effects of weight loss on blood pressure have not been extensively studied. OBJECTIVE: To present detailed results from the weight loss arm of Trials of Hypertension Prevention (TOHP) II. DESIGN: Multicenter, randomized dinical trial testing the efficacy of lifestyle interventions for reducing blood pressure over 3 to 4 years. Participants in TOHP II were randomly assigned to one of four groups. This report focuses only on participants assigned to the weight loss (n = 595) and usual care control (n = 596) groups. PATIENTS: Men and women 30 to 54 years of age who had nonmedicated diastolic blood pressure of 83 to 89 mm Hg and systolic blood pressure less than 140 mm Hg and were 110% to 165% of their ideal body weight at baseline. INTERVENTION: The weight loss intervention included a 3-year program of group meetings and individual counseling focused on dietary change, physical activity, and social support MEASUREMENTS: Weight and blood pressure data were collected every 6 months by staff who were blinded to treatment assignment RESULTS: Mean weight change from baseline in the intervention group was -4.4 kg at 6 months, -2.0 kg at 18 months, and -0.2 kg at 36 months. Mean weight change in the control group at the same time points was 0.1, 0.7, and 1.8 kg. Blood pressure was significantly lower in the intervention group than in the control group at 6, 18, and 36 months. The risk ratio for hypertension in the intervention group was 0.58 (95% CI, 0.36 to 0.94) at 6 months, 0.78 (CI, 0.62 to 1.00) at 18 months, and 0.81 (CI, 0.70 to 0.95) at 36 months. In subgroup analyses, intervention participants who lost at least 4.5 kg at 6 months and maintained this weight reduction for the next 30 months had the greatest reduction in blood pressure and a relative risk for hypertension of 0.35 (CI, 0.20 to 0.59). CONCLUSIONS: Clinically significant long-term reductions in blood pressure and reduced risk for hypertension can be achieved with even modest weight loss.

Adult↗

Right aortic arch with isolated left brachiocephalic artery.

Right aortic arch with complete isolation of the left brachiocephalic artery is an extremely uncommon anomaly of the aortic arch. This case reports the hitherto unreported association of the right aortic arch with isolated left brachiocephalic artery presenting with a subclavian steal syndrome detected in a 36-year-old female patient being investigated for increasing attacks of episodic dizziness, vertigo, and left upper limb claudication spanning 1 year. A review of the literature relevant to this condition is presented. It is likely that with advances in imaging techniques and a wider clinical usage of these investigative modalities there will be further recognition of these uncommon conditions.

Adult↗

Intravascular low-power laser irradiation after coronary stenting: long-term follow-up.

BACKGROUND AND OBJECTIVE: A high restenosis rate remains a limiting factor for percutaneous transluminal coronary angioplasty and stenting. The objective of this study was to evaluate the effect of intravascular red laser therapy (IRLT) on restenosis after stenting procedures in de novo lesions. STUDY DESIGN/MATERIALS AND METHODS: A total of 68 consecutive patients were treated with IRLT in conjunction with coronary stenting procedures. Mean lesion length was 16.5 +/- 2.4 mm. Reference vessel diameter (RVD) and pre-minimal lumen diameter (MLD) were 2.90 +/- 0.15 mm and 1.12 +/- 0.26 mm, respectively. RESULTS: After treatment, MLD was 2.76 +/- 0.32 mm with no procedural complications or in-hospital adverse events. Angiographic follow-up (n = 61) revealed restenosis in nine patients (14.7%) with rate by artery size of > 3 mm (n = 21) 0%; 2.5--3.0 mm (n = 28) 14.2%; and < 2.5 mm (n = 12) 41.6%. CONCLUSION: Intravascular red light therapy is safe, feasible, and reduces expected restenosis rate after coronary stenting.

Aged↗

Estimation of triterpenoids from Heliotropium marifolium Koen. ex Retz. in vivo and in vitro. I. Antimicrobial screening.

The hexane extract of Heliotropium marifolium yielded a mixture of triterpenoids: beta-sitosterol, stigmasterol, beta-amyrin, friedelan-3beta-ol (epifriedelenol), cycloartenone, beta-amyrin acetate, friedelin and epifriedenyl acetate. Isolated triterpenoid and reference antibiotics (gentamycin/mycostatin) were tested against selected pathogenic bacteria and fungi, e.g. Escherichia coli, Staphylococcus aureus, Aspergillus niger and Penicillium chrysogenum. The inhibition zone (IZ) and the activity index (AI) of isolated compounds were recorded and it was found that epifriedenyl acetate (IZ = 17; AI = 1.06) was the most active. The present study deals with the quantification and assessment of their growth inhibitory potency. It has been reported that cycloartenone was the major triterpenoid in both in vivo (0.54%) and in vitro (0.11%) cell cultures.

Bacteria↗

Hepatoprotective activity of indigtone--a bioactive fraction from Indigofera tinctoria Linn.

A bioactive fraction, indigtone (FA), obtained by fractionation of a petroleum ether extract of the aerial parts of Indigofera tinctoria, showed significant dose related hepatoprotective activity against CCl(4) induced liver injury in rats and mice. Hexobarbitone induced 'sleeptime', zoxazolamine induced 'paralysis time', levels of transaminases, bilirubin and total protein in serum were employed as indices of liver injury. Pre and post treatment with FA significantly reversed the majority of the parameters altered by the hepatotoxin. This indicated the preventive and restorative effect of FA in the process of CCl(4) induced liver damage. The fraction possessed a high therapeutic ratio, as no mortality was observed up to a dose of 2 g/kg p.o. in mice.

Animals↗

Adaptogenic activity of a novel, withanolide-free aqueous fraction from the roots of Withania somnifera Dun.

The practitioners of the traditional Indian system of medicine regard Withania somnifera Dun. as the 'Indian ginseng'. A new withanolide-free aqueous fraction was isolated from the roots of this plant and was evaluated for putative antistress activity against a battery of tests such as hypoxia time, antifatigue effect, swimming performance time, swimming induced gastric ulceration and hypothermia, immobilization induced gastric ulceration, autoanalgesia and biochemical changes in the adrenal glands. This bioactive fraction exhibited significant antistress activity in a dose-related manner in all the parameters studied. The extract of Withania somnifera root (a commercial preparation available locally) was used to compare the results. A preliminary acute toxicity study in mice showed a good margin of safety.

Animals↗

Individual and combined effects of berberine and santonin on spore germination of some fungi.

Berberine and santonin were isolated from rhizomes of Berberis aristata and unexpanded flower buds of Artemisia maritima, respectively. Efficacy of these two chemicals individually as well as of their mixtures, was tested against spore germination of some saprophytic and obligate fungi. While berberine individually was effective against most of the fungi, Helminthosporium spp. were least affected even at the highest dose (1500 ppm). Santonin was equally effective against several fungi. Mixture of both alkaloids found to be more effective than individual ones. Keeping the dose of berberine constant and santonin at two different concentrations (viz. 250 and 500 ppm) the spore germination of Helminthosporium oryzae was stimulated. Increasing concentration of santonin inhibited the spore germination of all other fungi tested, Colletotrichum capsici being affected only by 20 and 5% (at berberine concentration of 250 and 500 ppm, respectively). On the other hand, santonin being constant and berberine at different concentrations, the mixture was effective against all the fungi.

Artemisia↗

Additional renal arteries: incidence and morphometry.

Advances in surgical and uro-radiological techniques dictate a reappraisal and definition of renal arterial variations. This retrospective study aimed at establishing the incidence of additional renal arteries. Two subsets were analysed viz.: a) Clinical series--130 renal angiograms performed on renal transplant donors, 32 cadaver kidneys used in renal transplantation b) Cadaveric series--74 en-bloc morphologically normal kidney pairs. The sex and race distribution was: males 140, females 96; African 84, Indian 91, White 43 and "Coloured" 18, respectively. Incidence of first and second additional arteries were respectively, 23.2% (R: 18.6%; L: 27.6%) and 4.5% (R: 4.7%; L: 4.4%). Additional arteries occurred more frequently on the left (L: 32.0%; R: 23.3%). The incidence bilaterally was 10.2% (first additional arteries, only). The sex and race incidence (first and second additional) was: males, 28.0%, 5.1%; females, 16.4%, 3.8% and African 31.1%, 5.4%; Indian 13.5%, 4.5%; White 30.9%, 4.4% and "Coloured" 18.5%, 0%; respectively. Significant differences in the incidence of first additional arteries were noted between sex and race. The morphometry of additional renal arteries were lengths (cm) of first and second additional renal arteries: 4.5 and 3.8 (right), 4.9 and 3.7 (left); diameters: 0.4 and 0.3 (right), 0.3 and 0.3 (left). Detailed morphometry of sex and race were also recorded. No statistically significant differences were noted. Our results of the incidence of additional renal arteries of 27.7% compared favourably to that reported in the literature (weighted mean 28.1%). The study is unique in recording detailed morphometry of these vessels. Careful techniques in the identification of this anatomical variation is important since it impacts on renal transplantation surgery, vascular operations for renal artery stenosis, reno-vascular hypertension, Takayasu's disease, renal trauma and uro-radiological procedures.

Adolescent↗

Regulation of sodium influx in the NaCl-resistant (NaCl(r)) mutant strain of the cyanobacterium Anabaena variabilis.

A NaCl(r) mutant of the diazotrophic cyanobacterium Anabaena variabilis has been isolated by NTG mutagenesis and selection for NaCl resistance. The NaCl(r) strain has been characterized with respect to its mechanism of NaCl tolerance and regulation of Na(+) influx. NaCl(r) strain exhibits low Na(+) influx, accumulated high level of glycine betaine as a compatible solute, and persistent synthesis of SSPs at a higher rate than its wild-type counterpart. DCMU, an inhibitor of PS-II, inhibited Na(+) influx, suggesting that Na(+) influx is an energy-dependent process and that the energy is derived from photophosphorylation. This contention is further supported by the inhibition of Na(+) influx under dark conditions. The inhibition of Na(+) influx by KCN, DNP, NaN(3) also supports the involvement of oxidative phosphorylation in the regulation of active Na(+) influx. Thus, it appears that the synthesis of SSPs, accumulation of compatible solutes, and exhibition of low Na(+) influx in the NaCl(r) strain made this organism NaCl tolerant.

Anabaena↗

Isolation and partial characterization of Het- Fix- mutant strain of the diazotrophic cyanobacterium Anabaena variabilis showing chromatic adaptation.

We propose a model to describe the changes taking place in biochemical processes/events to explain the development of heterocyst and nitrogenase in a diazotrophic cyanobacterium Anabaena variabilis. For this purpose, a mutant strain of A. variabilis lacking heterocyst differentiation and incapable of growth with dinitrogen as the sole source of nitrogen has been isolated after nitrosoguanidine (NTG) mutagenesis and selection by penicillin enrichment. The mutant strain (Het- Fix-) thus isolated has morphological variation and was incapable of reducing acetylene under anaerobic conditions, indicating its mutational loss of the process of nitrogen fixation. The Het- Fix- mutant strain had reduced glutamine synthetase (transferase) activity compared with its wild-type counterpart, suggesting a link between nif gene expression and the expression of gln A, the structural gene of GS. The Het- Fix- mutant strain compared with its wild-type strain also had an extremely high level of phycobiliprotein and a low level of carotenoids. Furthermore, the coiling of vegetative filaments in the Het- Fix- mutant strain, which reduced the surface area to be exposed to light, was a direct indication of the chromatic adaptation, because the mutant strain was found to be photosensitive, showing bleaching of the cells under high light intensity.

Anabaena↗