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Biomedical subjects

B Singh

Publications and source records attributed to B Singh.

At least 19 recordsLinked to original sources

COX-2 involvement in breast cancer metastasis to bone.

Cyclooxygenase-2 (COX-2) is expressed in 40% of human invasive breast cancers. Bone is the predominant site of metastasis in case of breast cancer. We investigated the role of COX-2 in a suitable mouse model of breast cancer metastasis to bone using the whole-body luciferase imaging of cancer cells. We provide several lines of evidence that COX-2 produced in breast cancer cells is important for bone metastasis in this model including (1) COX-2 transfection enhanced the bone metastasis of MDA-435S cells and (2) breast cancer cells isolated and cultured from the bone metastases produced significantly more prostaglandin E(2) (an important mediator of COX-2) than the parental injected cell populations of breast cancer cells. Next, we found that a COX-2 inhibitor, MF-tricyclic, inhibited bone metastasis caused by a bone-seeking clone both in prevention regimen (in which case mice started receiving MF-tricyclic 1 week before the injection of cancer cells) and in treatment regimen (in which case mice received MF-tricyclic after the development of bone metastasis). These studies indicate that COX-2 produced in breast cancer cells may be vital to the development of osteolytic bone metastases in patients with breast cancer, and that COX-2 inhibitors may be useful in halting this process.

Animals↗

Isolation and characterization of embryonic stem cell-like cells from in vitro-produced buffalo (Bubalus bubalis) embryos.

This study was carried out to isolate and characterize buffalo embryonic stem (ES) cell-like cells from in vitro-produced embryos. Inner cell mass (ICM) cells were isolated either mechanically or by enzymatic digestion from 120 blastocysts whereas 28 morulae were used for the isolation of blastomeres mechanically. The ICM cells/ blastomeres were cultured on mitomycin-C-treated feeder layer. Primary cell colony formation was higher (P < 0.05) for hatched blastocysts (73.1%, 30/41) than that for early/expanded blastocysts (25.3%, 20/79). However, no primary cell colonies were formed when blastomeres obtained from morulae were cultured. Primary colonies were formed in 14.1% (12/85) of intact blastocyst culture, which was significantly lower (P < 0.05) than that of 41.6% for ICM culture. These colonies were separated by enzymatic or mechanical disaggregation. Using mechanical disaggregation method, the cells remained undifferentiated and two buffalo ES cell-like cell lines (bES1, bES2) continued to grow in culture up to eight passages. However, disassociation through enzymatic method resulted in differentiation. Undifferentiated cells exhibited stem cell morphological features, normal chromosomal morphology, and expressed specific markers such as alkaline phosphatase (AP) and Oct-4. Cells formed embryoid bodies (EBs) in suspension culture; extended culture of EBs resulted in formation of cystic EBs. Following prolonged in vitro culture, these cells differentiated into several types of cells including neuron-like and epithelium-like cells. Furthermore, the vitrified-thawed ES cell-like cells also exhibited typical stem cell characteristics. In conclusion, buffalo ES cell-like cells could be isolated from in vitro-produced blastocysts and maintained in vitro for prolonged periods of time.

Animals↗

Histopathological mimicry in mucosal prolapse.

Mucosal prolapse solitary rectal ulcer syndrome is a condition which has frequently confused both pathologists and surgeons alike. Despite its recognition in the nineteenth century, it continues to be a diagnostic challenge. The significance of correctly diagnosing this condition is that it avoids the morbidity and mortality associated with major surgery or the side-effects of long-term medical treatment. This review considers the histological features of mucosal prolapse and how it may mimic other pathological conditions.

Diagnosis, Differential↗

Duplicate gallbladder: an unusual case report.

Duplication of the gallbladder, a rare congenital anomaly, is important in clinical practice as it may cause some clinical, surgical and diagnostic problems. In this report we present a case of duplicated gallbladder diagnosed serendipitously in a 63-year-old male patient who had previously undergone successful laparoscopic cholecystectomy (confirmed histologically) approximately a year before for gallstones. The patient was re-admitted with obstructive jaundice. An abdominal computed tomography scan and magnetic resonance cholangiogram both revealed the presence of a gallbladder, which was thereafter removed at surgery undertaken to palliate the jaundice.

Cholecystectomy↗

Altered balance of glutamatergic/GABAergic synaptic input and associated changes in dendrite morphology after BDNF expression in BDNF-deficient hippocampal neurons.

Cultured neurons from bdnf-/- mice display reduced densities of synaptic terminals, although in vivo these deficits are small or absent. Here we aimed at clarifying the local responses to postsynaptic brain-derived neurotrophic factor (BDNF). To this end, solitary enhanced green fluorescent protein (EGFP)-labeled hippocampal neurons from bdnf-/- mice were compared with bdnf-/- neurons after transfection with BDNF, bdnf-/- neurons after transient exposure to exogenous BDNF, and bdnf+/+ neurons in wild-type cultures. Synapse development was evaluated on the basis of presynaptic immunofluorescence and whole-cell patch-clamp recording of miniature postsynaptic currents. It was found that neurons expressing BDNF::EGFP for at least 16 h attracted a larger number of synaptic terminals than BDNF-deficient control neurons. Transfected BDNF formed clusters in the vicinity of glutamatergic terminals and produced a stronger upregulation of synaptic terminal numbers than high levels of ambient BDNF. Glutamatergic and GABAergic synapses reacted differently to postsynaptic BDNF: glutamatergic input increased, whereas GABAergic input decreased. BDNF::EGFP-expressing neurons also differed from BDNF-deficient neurons in their dendrite morphology: they exhibited weaker dendrite elongation and stronger dendrite initiation. The upregulation of glutamatergic synaptic input and the BDNF-induced downregulation of GABAergic synaptic terminal numbers by postsynaptic BDNF depended on tyrosine receptor kinase B activity, as deduced from the blocking effects of K252a. The suppression of dendrite elongation was also prevented by block of tyrosine receptor kinase B but required, in addition, glutamate receptor activity. Dendritic length decreased with the number of glutamatergic contacts. These results illuminate the role of BDNF as a retrograde synaptic regulator of synapse development and the dependence of dendrite elongation on glutamatergic input.

Animals↗

Herbicidal inhibitors of amino acid biosynthesis and herbicide-tolerant crops.

Acetohydroxyacid synthase (AHAS) inhibitors interfere with branched-chain amino acid biosynthesis by inhibiting AHAS. Glyphosate affects aromatic amino acid biosynthesis by inhibiting 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS). Glufosinate inhibits glutamine synthetase and blocks biosynthesis of glutamine. AHAS gene variants that confer tolerance to AHAS inhibitors have been discovered in plants through selection or mutagenesis. Imidazolinone-tolerant crops have been commercialized based on these AHAS gene variants. A modified maize EPSPS gene and CP4-EPSPS gene from Agrobacterium sp. have been used to transform plants for target-based tolerance to glyphosate. A gox gene isolated from Ochrobactrum anthropi has also been employed to encode glyphosate oxidoreductase to detoxify glyphosate in plants. Glyphosate-tolerant crops with EPSPS transgene alone or both EPSPS and gox transgenes have been commercialized. Similarly, bar and pat genes isolated from Streptomyces hygroscopicus and S. viridochromogenes, respectively, have been inserted into plants to encode phosphinothricin N-acetyltransferase to detoxify glufosinate. Glufosinate-tolerant crops have been commercialized using one of these two transgenes.

Adaptation, Physiological↗

Cervico-thoracic ganglion: its clinical implications.

Lesions of the cervicothoracic ganglion (CTG) result in interruption of sympathetic fibers to the head, neck, upper limb, and thoracic viscera. The accurate understanding of the anatomy of the CTG is relevant to sympathectomy procedures that may be prescribed in cases where conventional intervention has failed. This study documents the incidence and distribution of the CTG to avoid potential complications such as Horner's syndrome and cardiac arrhythmias. This study utilized 48 cadavers, in which a total of 89 sympathetic chains were dissected. The inferior cervical ganglion (ICG) and the first thoracic ganglion was fused in 75 cases (84.3%) to form the CTG. It was present bilaterally in 48 of these specimens (65.3%). Three different shapes of CTG were differentiated, viz. spindle, dumbbell, and an inverted "L" shape. The dumbbell and inverted "L" shapes demonstrated a definite "waist" (i.e., a macroscopically visible union of the ICG and T1 components of the CTG). Rami from the CTG was distributed to the brachial plexus, the subclavian and vertebral arteries, the brachiocephalic trunk, and the cardiac plexus. This study demonstrates a high incidence of a double cardiac sympathetic nerve arising from CTG. It is therefore imperative that in the technique of sympathectomy, for intractable anginal pain, the surgeon excises both these rami but does not destroy the ganglion itself. The ever-improving technology in endoscopic surgery has made investigations into the nuances of the anatomy of the sympathetic chain essential.

Adult↗

Isolation, structure elucidation and in vivo hepatoprotective potential of trans-tetracos-15-enoic acid from Indigofera tinctoria Linn.

The bioassay guided fractionation of the dried aerial part of Indigofera tinctoria Linn. led to the identification of an active fraction labelled as indigotin. On further chemical analysis, a compound isolated from indigotin was identified and characterized as trans-tetracos-15-enoic acid (TCA). The chemical structure of this compound was established on the basis of physical properties and spectral data, including NMR. It afforded significant hepatoprotection against carbon tetrachloride and paracetamol induced hepatotoxicity in experimental models. Silymarin, a well known plant based hepatoprotective agent, and N-acetylcysteine, which has proven efficacy as a replenisher of sulfhydryls, were used for relative efficacy. TCA was found to reverse the altered hepatic parameters in experimental liver damage. In the safety evaluation study the oral LD50 was found to be more than 2000 mg/kg, with no signs of abnormalities or any mortality for the 15 day period of observation after administration of a single dose of drug in mice. The studies revealed significant and concentration dependent hepatoprotective potential of TCA as it reversed the majority of the altered hepatic parameters in experimental liver damage in rats and mice and may be useful in the management of liver disorders.

Acetaminophen↗

A marked enhancement in phytase production by a thermophilic mould Sporotrichum thermophile using statistical designs in a cost-effective cane molasses medium.

AIMS: Statistical optimization of phytase production by a thermophilic mould Sporotrichum thermophile in a cost-effective cane molasses medium. METHODS AND RESULTS: Sporotrichum thermophile secreted phytase in cane molasses medium at 45 degrees C and 250 rev min(-1) after 5 days. The important factors identified by Plackett-Burman design (magnesium sulfate, Tween 80, ammonium sulfate and incubation period) were further optimized by response surface methodology (RSM). An overall 107% improvement in phytase production was achieved due to optimization. Supplementation of the medium with inorganic phosphate repressed the enzyme synthesis. When inorganic phosphate was reduced from the cane molasses medium by treatment with calcium chloride, the enzyme production increased. The phytase activity was not affected by the enzyme treatment with trypsin and pepsin. CONCLUSIONS: A twofold increase in phytase production was achieved due to optimization using statistical designs in a cost-effective cane molasses medium. SIGNIFICANCE AND IMPACT OF THE STUDY: Phytase production was doubled due to optimization. The enzyme, being resistant to trypsin and pepsin, thermostable and acid stable, can find application in animal feed industry for improving nutritional status of the feed and combating environmental phosphorus pollution.

6-Phytase↗

Noradrenaline and albumin in paracentesis-induced circulatory dysfunction in cirrhosis: a randomized pilot study.

OBJECTIVE: Therapeutic paracentesis in patients with cirrhosis is associated with a circulatory dysfunction. Intravenous albumin has been used to prevent the circulatory dysfunction; however, the use of albumin is controversial and costly. Splanchnic vasodilation is mainly responsible for circulatory dysfunction in these patients. There are no reports of use of noradrenaline, a vasoconstrictor, on the prevention of paracentesis-induced circulatory dysfunction in patients with cirrhosis. Therefore, we studied the preventive effect of noradrenaline on paracentesis-induced circulatory dysfunction in patients with cirrhosis after therapeutic paracentesis and compared it with that of intravenous albumin in a randomized pilot study. METHODS: Forty patients with cirrhosis and tense ascites underwent therapeutic paracentesis with albumin or noradrenaline in a randomized controlled trial at a tertiary centre. Effective arterial blood volume was assessed by measuring plasma renin activity at baseline and at 6 days after treatment. RESULTS: Effective arterial blood volume as indicated by plasma renin activity before and 6 days after paracentesis did not differ in the two groups (20.62 +/- 10.27-22.02 +/- 10.15 ng mL(-1) h(-1); P = 0.11 in the albumin group and 19.66 +/- 8.91-20.78 +/- 9.41 ng mL(-1) h(-1); P = 0.37 in the noradrenaline group). Plasma aldosterone concentration before and 6 days after paracentesis were also similar in both groups (1196.5 +/- 434.2-1217.0 +/- 405.7 pg mL(-1); P = 0.7 in the albumin group and 1206.0 +/- 522.5-1273.5 +/- 444.8 pg mL(-1); P = 0.22 in the noradrenaline group). The cost of noradrenaline treatment was significantly lower when compared with that of albumin (P < 0.001). CONCLUSIONS: Noradrenaline is as effective as albumin in preventing paracentesis-induced circulatory dysfunction in patients with cirrhosis after therapeutic paracentesis, but at a fraction of the cost.

Adult↗

Unusual case of well-differentiated papillary thyroid carcinoma lacking thyroglobulin expression while still concentrating radioiodine.

We present an unusual case of a well-differentiated papillary thyroid carcinoma with bilateral lung metastases. Despite undetectable serum thyroglobulin (Tg) on thyroid stimulating hormone (TSH) stimulation and no immunohistochemical evidence of Tg expression in the primary tumour, the patient showed significant uptake of radioiodine in both lungs. After five cycles of high dose radioiodine therapy, the patient went into complete remission and therefore had an excellent response to radioiodine treatment. This case is a rare exception to the rule of Tg production as a prerequisite for differentiated thyroid cancers to concentrate radioiodine.

Aged↗