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Biomedical subjects

D Singh

Publications and source records attributed to D Singh.

At least 109 records · Page 6Linked to original sources

Characterization of rat liver malonyl-CoA decarboxylase and the study of its role in regulating fatty acid metabolism.

In the liver, malonyl-CoA is central to many cellular processes, including both fatty acid biosynthesis and oxidation. Malonyl-CoA decarboxylase (MCD) is involved in the control of cellular malonyl-CoA levels, and functions to decarboxylate malonyl-CoA to acetyl-CoA. MCD may play an essential role in regulating energy utilization in the liver by regulating malonyl-CoA levels in response to various nutritional or pathological states. The purpose of the present study was to investigate the role of liver MCD in the regulation of fatty acid oxidation in situations where lipid metabolism is altered. A single MCD enzyme of molecular mass 50.7 kDa was purified from rat liver using a sequential column chromatography procedure and the cDNA was subsequently cloned and sequenced. The liver MCD cDNA was identical to rat pancreatic beta-cell MCD cDNA, and contained two potential translational start sites, producing proteins of 50.7 kDa and 54.7 kDa. Western blot analysis using polyclonal antibodies generated against rat liver MCD showed that the 50.7 kDa isoform of MCD is most abundant in heart and liver, and of relatively low abundance in skeletal muscle (despite elevated MCD transcript levels in skeletal muscle). Tissue distribution experiments demonstrated that the pancreas is the only rat tissue so far identified that contains both the 50.7 kDa and 54. 7 kDa isoforms of MCD. In addition, transfection of the full-length rat liver MCD cDNA into COS cells produced two isoforms of MCD. This indicated either that both initiating methionines are functionally active, generating two proteins, or that the 54.7 kDa isoform is the only MCD protein translated and removal of the putative mitochondrial targeting pre-sequence generates a protein of approx. 50.7 kDa in size. To address this, we transiently transfected a mutated MCD expression plasmid (second ATG to GCG) into COS-7 cells and performed Western blot analysis using our anti-MCD antibody. Western blot analysis revealed that two isoforms of MCD were still present, demonstrating that the second ATG may not be responsible for translation of the 50.7 kDa isoform of MCD. These data also suggest that the smaller isoform of MCD may originate from intracellular processing. To ascertain the functional role of the 50. 7 kDa isoform of rat liver MCD, we measured liver MCD activity and expression in rats subjected to conditions which are known to alter fatty acid metabolism. The activity of MCD was significantly elevated under conditions in which hepatic fatty acid oxidation is known to increase, such as streptozotocin-induced diabetes or following a 48 h fast. A 2-fold increase in expression was observed in the streptozotocin-diabetic rats compared with control rats. In addition, MCD activity was shown to be enhanced by alkaline phosphatase treatment, suggesting phosphorylation-related control of the enzyme. Taken together, our data demonstrate that rat liver expresses a 50.7 kDa form of MCD which does not originate from the second methionine of the cDNA sequence. This MCD is regulated by at least two mechanisms (only one of which is phosphorylation), and its activity and expression are increased under conditions where fatty acid oxidation increases.

Alkaline Phosphatase↗

Long-term (three years) effect of estrogen replacement therapy on major adverse cardiac events in postmenopausal women after intracoronary stenting.

This study examined whether estrogen replacement therapy (ERT) in postmenopausal women impacts intermediate and long-term outcome after successful coronary stenting. Our findings offer evidence that ERT significantly reduces target lesion revascularization after intracoronary stenting in postmenopausal patients who are on ERT before the intervention.

Angioplasty, Balloon, Coronary↗

The 2nd:4th digit ratio, sexual dimorphism, population differences, and reproductive success. evidence for sexually antagonistic genes?

The ratio between the length of the 2nd and 4th digit (2D:4D) is sexually dimorphic, with mean male 2D:4D lower than mean female 2D:4D. It recently was suggested that 2D:4D is negatively correlated with prenatal testosterone and positively correlated with prenatal estrogen. It is argued that high prenatal testosterone and low estrogen (indicated by low 2D:4D) favors the male fetus and low prenatal testosterone and high estrogen (indicated by high 2D:4D) favors the female fetus. The patterns of expression of 2D:4D are interpreted in terms of sexually antagonistic genes.We report data on the following. (a) reproductive success and 2D:4D from England, Germany, Spain, Hungary (ethnic Hungarians and Gypsy subjects), Poland, and Jamaica (women only). Significant negative associations were found between 2D:4D in men and reproductive success in the English and Spanish samples and significant positive relationships between 2D:4D in women and reproductive success in the English, German, and Hungarian samples. The English sample also showed that married women had higher 2D:4D ratios than unmarried women, suggesting male choice for a correlate of high ratio in women, and that a female 2D:4D ratio greater than male 2D:4D predicted high reproductive success within couples. Comparison of 2D:4D ratios of 62 father:child pairs gave a significant positive relationship. This suggested that genes inherited from the father had some influence on the formation of the 2D:4D ratio. Waist:hip ratio in a sample of English and Jamaican women was negatively related to 2D:4D. (b) Sex and population differences in mean 2D:4D in samples from England, Germany, Spain, Hungary (including ethnic Hungarians and Gypsy subjects), Poland, Jamaica, Finland, and South Africa (a Zulu sample). Significant sex and population differences in mean 2D:4D were apparent.

Journal Article↗

Both PCE-1/RX and OTX/CRX interactions are necessary for photoreceptor-specific gene expression.

RX, a homeodomain-containing protein essential for proper eye development (Mathers, P. H. Grinberg, A., Mahon, K. A., and Jamrich, M. (1997) Nature 387, 603-607), binds to the photoreceptor conserved element-1 (PCE-1/Ret 1) in the photoreceptor cell-specific arrestin promoter and stimulates gene expression. RX is found in many retinal cell types including photoreceptor cells. Another homeodomain-containing protein, CRX, which binds to the OTX element to stimulate promoter activity, is found exclusively in photoreceptor cells (Chen, S., Wang, Q. L., Nie, Z., Sun, H., Lennon, G., Copeland, N. G., Gillbert, D. J. Jenkins, N. A., and Zack, D. J. (1997) Neuron 19, 1017-1030; Furukawa, T., Morrow, E. M., and Cepko, C. L. (1997) Cell 91, 531-541). Binding assay and cell culture studies indicate that both PCE-1 and OTX elements and at least two different regulatory factors RX and CRX are necessary for high level, photoreceptor cell-restricted gene expression. Thus, photoreceptor specificity can be achieved by multiple promoter elements interacting with a combination of both photoreceptor-specific regulatory factors and factors present in closely related cell lineages.

Amino Acid Sequence↗

Increased expression of preprotachykinin-I and neurokinin receptors in human breast cancer cells: implications for bone marrow metastasis.

Neuropeptides are implicated in many tumors, breast cancer (BC) included. Preprotachykinin-I (PPT-I) encodes multiple neuropeptides with pleiotropic functions such as neurotransmission, immune/hematopoietic modulation, angiogenesis, and mitogenesis. PPT-I is constitutively expressed in some tumors. In this study, we investigated a role for PPT-I and its receptors, neurokinin-1 (NK-1) and NK-2, in BC by using quantitative reverse transcription-PCR, ELISA, and in situ hybridization. Compared with normal mammary epithelial cells (n = 2) and benign breast biopsies (n = 21), BC cell lines (n = 7) and malignant breast biopsies (n = 25) showed increased expression of PPT-I and NK-1. NK-2 levels were high in normal and malignant cells. Specific NK-1 and NK-2 antagonists inhibited BC cell proliferation, suggesting autocrine and/or intercrine stimulation of BC cells by PPT-I peptides. NK-2 showed no effect on the proliferation of normal cells but mediated the proliferation of BC cells. Cytosolic extracts from malignant BC cells enhanced PPT-I translation whereas extracts from normal mammary epithelial cells caused no change. These enhancing effects may be protein-specific because a similar increase was observed for IL-6 translation and no effect was observed for IL-1alpha and stem cell factor. The data suggest that PPT-I peptides and their receptors may be important in BC development. Considering that PPT-I peptides are hematopoietic modulators, these results could be extended to understand early integration of BC cells in the bone marrow, a preferred site of metastasis. Molecular signaling transduced by PPT-I peptides and the mechanism that enhances translation of PPT-I mRNA could lead to innovative strategies for BC treatments and metastasis.

Benzamides↗

Advances in microbial amylases.

This review makes a comprehensive survey of microbial amylases, i.e. alpha-amylase, beta-amylase and glucoamylase. Amylases are among the most important enzymes and are of great significance in present-day biotechnology. Although they can be derived from several sources, such as plants, animals and micro-organisms, the enzymes from microbial sources generally meet industrial demands. Microbial amylases could be potentially useful in the pharmaceutical and fine-chemical industries if enzymes with suitable properties could be prepared. With the advent of new frontiers in biotechnology, the spectrum of amylase application has widened in many other fields, such as clinical, medicinal and analytical chemistries, as well as their widespread application in starch saccharification and in the textile, food, brewing and distilling industries. In this review, after a brief description of the sources of amylases, we discuss the molecular biology of amylases, describing structures, cloning, sequences, and protoplast fusion and mutagenesis. This is followed by sections on their production and finally the properties of various amylases.

Amylases↗

Growing skull fracture of ethmoid: a report of two cases.

We describe a rare sequel of ethmoid fracture--a growing skull fracture associated with cerebrospinal fluid rhinorrhoea following trauma sustained in adult life. The natural history of its development, diagnosis, and the results of surgery are discussed. The literature is reviewed with regard to aetiology, incidence, imaging characteristics and management of this rare post-traumatic complication.

Adult↗

Screening sandflies for natural infection with Leishmania donovani, using a non-radioactive probe based on the total DNA of the parasite.

Digoxigenin-labelled total, Leishmania donovani DNA was used as a probe to detect the parasite in Indian Phlebotomus argentipes. The probe was quite sensitive, detecting as little as 0.3 pg parasite DNA, equivalent to approximately 100 parasites. Positive signals could be detected in 12 (32%) of the 38 small (two- to 30-fly) pools of the wild-caught P. argentipes investigated and in a pool of 10 laboratory-bred P. argentipes fed on a patient with post-kala-azar dermal leishmaniasis. None of the wild-caught P. papatasi, P. sergenti or Sergentomyia sp. or of the newly emerged, laboratory-bred P. argentipes investigated were positive by this probe. The results indicate that such a probe may be very useful in screening sandflies for L. donovani, and so detecting the main vectors and transmission pathways of this parasite, in India and elsewhere.

Animals↗

Reproductive, neuroendocrine, and immune consequences of acute exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin in the Siberian hamster.

The present study tested the hypothesis that acute treatment with 2, 3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) impairs fertility, disrupts the nocturnal melatonin rhythm, and suppresses lymphocyte function. Adult Siberian hamsters administered 2 or 100 microg TCDD/kg body weight/0.2 ml sesame oil had a delayed latency to first litter and an increased adult mortality compared to hamsters given 0.1 microg/kg or vehicle. Within 75 days of TCDD treatment, full reproductive capabilities were achieved. Moreover, the nocturnal melatonin rhythm was not disrupted in adults administered TCDD or in their progeny. Lymphocyte activity varied with respect to time of day and treatment. Lymphocyte proliferation was enhanced at night irrespective of TCDD treatment; during the day, 2 wk after the 2-microg/kg treatment, blastogenesis was reduced compared to that in the 0.1-microg/kg group or in vehicle-treated controls. In contrast, TCDD did not affect the mixed lymphocyte reaction in response to allogeneic antigen when assessed at 2 and 20 wk post-treatment. Thus, findings indicate that TCDD produced acute effects on fertility, mortality, and systemic lymphocyte proliferation, but long-lasting effects on specific aspects of reproductive, neuroendocrine, and immune cell functions were not observed.

Animals↗

Hypophyseal tuberculoma: direct radiosurgery is contraindicated for a lesion with a thickened pituitary stalk: case report.

OBJECTIVE AND IMPORTANCE: Hypophyseal tuberculomas are extremely rare lesions. The recognition of hypophyseal tuberculomas in the differential diagnosis of pituitary tumors is important, even with no evidence of systemic tuberculosis. CLINICAL PRESENTATION: A 27-year-old female patient presented with continuous, dull, generalized headaches and amenorrhea, with no history of visual diminution, galactorrhea, or endocrinological abnormalities and no evidence of systemic tuberculosis. The patient exhibited a normal water balance, without polyuria or polydipsia. A gynecological examination, including an endometrial biopsy for amenorrhea, did not reveal any abnormalities. Perimetric and endocrinological examination results were normal. Contrast magnetic resonance imaging revealed a dense enhancing intrasellar mass, with thickening of the pituitary stalk. INTERVENTION: Sublabial rhinoseptal transsphenoidal decompression of the lesion was performed. The histopathological features were consistent with a diagnosis of tuberculoma, and acid-fast bacilli were demonstrated in the surgically removed tissue with Ziehl-Neelsen staining. As soon as the histopathological features were known, the patient underwent a lumbar puncture for cerebrospinal fluid analysis, which indicated normal findings. An intradermal tuberculin test yielded negative results. The patient was treated with medical therapy for 18 months, and complete resolution of the lesion was observed in follow-up examinations. CONCLUSION: Hypophyseal tuberculomas are often mistaken for pituitary adenomas. The finding of a thickened pituitary stalk in contrast magnetic resonance imaging scans may be useful for the differentiation of these lesions from pituitary adenomas. Direct radiosurgery is not an appropriate primary treatment method for pituitary adenomas and is principally restricted to elderly, medically unfit patients with microadenomas and patients with residual or recurrent tumors after microsurgery. It is contraindicated for patients who exhibit a thickened pituitary stalk in contrast magnetic resonance imaging scans.

Adult↗

Generalized thermoelastic waves in homogeneous isotropic plates

The propagation of thermoelastic waves in homogeneous isotropic plate subjected to stress-free and rigid insulated and isothermal conditions is investigated in the context of conventional coupled thermoelasticity (CT), Lord-Shulman (LS), Green-Lindsay (GL), and Green-Nagdhi (GN) theories of thermoelasticity. Secular equations for the plate in closed form and isolated mathematical conditions for symmetric and skew-symmetric wave mode propagation in completely separate terms are derived. It is shown that the motion for SH modes gets decoupled from the rest of the motion and remains unaffected due to thermo-mechanical coupling and thermal relaxation effects. The phase velocities for SH modes have also been obtained. The results for coupled and uncoupled theories of thermoelasticity have been obtained as particular cases from the derived secular equations. At short wavelength limits the secular equations for symmetric and skew-symmetric waves in a stress-free insulated and isothermal plate reduce to Rayleigh surface waves frequency equations. Finally, the numerical solution is carried out for aluminum-epoxy composite material and the dispersion curves for symmetric and skew-symmetric wave modes are presented to illustrate and compare the theoretical results.

Journal Article↗

Enlarging single CT lesions can also spontaneously resolve.

Computed tomography in two patients, aged 9 and 14 years, with history of focal seizures, revealed single, small, enhancing CT lesions. These patients were treated with albendazole and anticonvulsants. Follow-up CT scans revealed an increase in the size of the solitary lesions. They were managed conservatively and further follow-up CT scans revealed complete resolution of the lesions. The report suggests that some enlarging CT lesions may also spontaneously resolve. The most likely cause of the enlarging lesions was albendazole therapy.

Adolescent↗

Thalamic epidermoid cyst. A case report.

A case of thalamic epidermoid cyst is reported. Its clinical presentation, radiological, operative findings and histological findings are discussed. Intraparenchymal epidermoids are uncommon and to our knowledge only one case of thalamic epidermoid has been reported earlier. The literature is reviewed in regard to incidence, location and etiology of Intracerebral epidermoid tumor cysts.

Adult↗

Effect of actinomycin D and cycloheximide on ischemic preconditioning-induced delayed cardioprotective effect in rats.

The present study was designed to investigate the effect of actinomycin D, a transcription inhibitor, and cycloheximide, a translation inhibitor, on the delayed cardioprotective effect of ischemic preconditioning. Left thoracotomy was performed in anaesthetized rats at 4th/5th intercostal space and polypropylene suture (5-0) was employed to occlude left common coronary artery. Ischemic preconditioning was produced by four episodes of 5 min of coronary artery occlusion followed by 5 min of reperfusion and thoracic cavity was sutured. Left thoracotomy was performed again after 24 hr of ischemic preconditioning and left coronary artery was occluded for 30 min followed by reperfusion for 120 min. Area at risk and infarct size was estimated by patent blue and TTC staining respectively. Total left ventricular RNA was isolated and estimated quantitatively. Ischemic preconditioning, 24 hr after its induction, produced significant decrease in myocardial infarct size occurred as a result of sustained ischemia and reperfusion but produced no marked effect on ventricular RNA content. Actinomycin D and cycloheximide only, in high dose, markedly attenuated ischemic preconditioning induced decrease in myocardial infarct size. However, no such effect was noted with low dose of cycloheximide. The results suggest that delayed cardioprotective effect of ischemic preconditioning may be mediated through denovo synthesis of protein(s) which is regulated both at transcriptional and translational level.

Animals↗

Is refractive surgery justified?

Refractive surgery may be defined as any kind of eye surgery in which attempt is made to produce a level of spectacle error that is accepted to the patient. Cataract surgery with lens implantation is the most often done refractive surgery on the eye. The following kinds of refractive surgery are being practised: With normal crystalline lens, phacic intra-ocular lens, surgery with cornea, using excimer laser, other newer techniques. Radial keratotomy is one procedure of refractive surgery with cornea. In this operation, radial cuts are made on the cornea starting near the edge of the pupil and reaching up to the limbus. Number of cuts vary from 4 to 24 depending upon the seventy of myopia. Its advantage is its cost effectiveness and can be performed in a remote area. There are two ways of excimer laser: photorefractive keratectomy (PRK) and laser assisted in-situ keratomileusis (LASIK). The processes are elaborated in the article. Before any refractive surgery is performed, it is imperative that the whole of the eye receives full and detailed attention. The patient needs to be explained of the procedure. Utmost care should be taken to observe sterilisation of the instruments and the environment.

Humans↗