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Biomedical subjects

K Singh

Publications and source records attributed to K Singh.

At least 19 recordsLinked to original sources

Differential processing of osteopontin transcripts in rat kidney- and osteoblast-derived cell lines.

Using immunoprecipitation and tryptic peptide microsequencing we confirmed the identity of normal rat kidney (NRK) cell-secreted 69-kDa major phosphoprotein as osteopontin (OP). We then immunoselected a 1.4-kilobase pair (kb) OP cDNA from a lambda gt11 library prepared from Kirsten sarcoma virus-transformed NRK (KNRK) cellular mRNA, using rabbit anti-69-kDa OP serum. Sequence analysis of this cDNA revealed the presence of a 52-nucleotide-long insert in the 5'-noncoding region, which was absent in OP cDNA cloned from the cDNA library of ROS 17/2.8 rat osteosarcoma cells. The insert sequence is flanked by putative intron splice junctions and is located 15-nucleotide upstream of the translational initiation site. An insert-specific 30-mer oligonucleotide probe hybridized to a single 1.5-kb RNA species from both NRK and KNRK cells, but not from ROS 17/2.8 cells. However, Southern analysis showed the presence of this insert sequence in the genomic DNA of both NRK and ROS 17/2.8 cells. Furthermore, PCR amplification of the insert-containing region using genomic DNAs from both NRK and ROS 17/2.8 cells gave products of identical size and sequence. Since OP is a single copy gene, these data provide strong evidence for differential cell type-specific processing of OP transcripts. In addition, we demonstrate that, in contrast to most transformed cells, levels of OP expression are significantly reduced in KNRK cells as compared to NRK cells.

Amino Acid Sequence

A role for IGF-1 in the rescue of CNS neurons following hypoxic-ischemic injury.

Three days after unilateral hypoxic-ischemic injury in infant rats insulin-like growth factor 1 (IGF-1) production by astrocytes was enhanced in the injured region. This was associated with increased expression of mRNA for IGF binding protein-3 but not for binding protein-1. In adult rats a single lateral cerebroventricular injection of IGF-1 two hours following a similar injury markedly reduced neuronal loss. It is suggested that endogenous IGF-1 is neurotrophic and that centrally administered IGF-1 may have therapeutic potential for brain injury.

Animals

Effect of Norplant implants on liver, lipid and carbohydrate metabolism.

In this study involving 100 women, the metabolic changes seen with Norplant use were evaluated. Besides a significant increase in serum bilirubin, there were no other changes in liver function to suggest possible hepatocellular dysfunction at the end of five years. Even the raised mean levels of bilirubin remained within the normal clinical range for the local population. As regards lipid metabolism, total triglycerides, cholesterol and LDL-cholesterol were decreased through the five years of Norplant use. The HDL-cholesterol showed a significant increase in the first year; it then decreased over the years to its preinsertion level at the end of five years. As a result, the HDL-cholesterol/Total cholesterol - HDL-cholesterol showed a significant increase in the first year and then decreased to almost its preinsertion value at the end of five years. The findings appear to indicate Norplant use not to be contributory to cardiovascular risk. The use of Norplant was not associated with any significant effect on carbohydrate metabolism.

Bilirubin

Effect of long-term use of Norplant implants on haemostatic function.

This study describes the effects of Norplant on haemostatic function after 5 years of use in 97 women. There was a decrease in vitamin-K dependent Factors II, V, VII and reduction in fibrinolytic activity at 2 and 4 years of use. Increased platelet numbers and accelerated platelet aggregation were found throughout the 5 years of Norplant use, whilst raised alpha 2-Macroglobulin (a2-M) and antithrombin III (ATIII) antigen level were observed for up to 4 years of use. Prolonged Norplant use does not appear to activate the coagulation system and does not enhance a state of hypercoagulation.

Antigens

Acceptability of Norplant implants for fertility regulation in Singapore.

The continuation rate at the end of this five-year clinical study was 60% with no accidental pregnancy occurring throughout the five years. The post-removal conception rate in women desiring pregnancy was 92% at the end of two years. The majority of acceptors described the overall experience with the implants as favourable. In fact, 75% of the women planning to use contraception after removal of the implants were going to use implants again.

Adult

Acceptability of Norplant-2 rods as a method of family planning.

The Norplant-2 rod system consists of two silastic rods in which levonogestrel has been incorporated with the polymer. The continuation rate at the end of five year was 62%. No accidental pregnancies occurred throughout the five years of use. The post-removal conception rate in women desiring pregnancy was 70.8% at the end of two years. The majority of acceptors were happy with the rods and 86.8% expressed the desire to have another set of implants inserted following removal of the first set. The study shows the Norplant-2 rod system to be a well accepted method of family planning.

Adult

Effect of Norplant-2 rods on liver, lipid and carbohydrate metabolism.

The effect of Norplant-2 rods on liver, lipid and carbohydrate metabolism was evaluated in 100 women using Norplant-2 rods. Besides a significant increase in serum bilirubin, there was no other obvious evidence to suggest any possible hepatocellular dysfunction with the use of Norplant-2 rods. As regards lipid metabolism, decreases in total triglycerides, cholesterol and LDL-cholesterol and HDL-cholesterol were initially seen. These parameters returned to their preinsertion mean at the end of five years. As a result, the value of the HDL-cholesterol/total cholesterol - HDL-cholesterol and LDL-cholesterol/HDL-cholesterol ratios remained around their preinsertion value at the end of five years. All this appears to indicate that the use of Norplant-2 rods is not directly contributory to cardiovascular risk. The use of Norplant-2 rods was not associated with any significant effect on carbohydrate metabolism.

Asia, Southeastern

Hypoxia-ischemia induces transforming growth factor beta 1 mRNA in the infant rat brain.

Transforming growth factor beta 1 (TGF beta 1) mRNA expression was examined after hypoxia-ischemia in rat brains using in situ hybridization. Twenty-one-day-old Wistar rats had unilateral ligation of the right carotid artery followed by either 15 or 90 min inhalational hypoxia. Fifteen min of hypoxia resulted in moderate damage with selective neuronal loss in cortical layer 3 and in the hippocampus of the ligated hemisphere. Seventy-two hours after hypoxia TGF beta 1 expression was markedly increased above control levels in those sites. Levels were normal after 120 h. Ninety min of hypoxia led to an infarction of the lateral cerebral cortex and hippocampus of the ligated hemisphere. One hour after hypoxia TGF beta 1 mRNA was expressed in the hippocampus of the damaged side. Seventy-two and 120 h after hypoxia, expressing cells were found throughout the cerebral cortex, piriform cortex, striatum, thalamus and hippocampus of the infarcted side. These data show that TGF beta 1 mRNA expression is induced after a hypoxic-ischemic insult in the brain. TGF beta 1 may be involved in post-asphyxial repair mechanisms.

Animals

Expression of insulin-like growth factor-binding protein 2 (IGF-BP 2) following transient hypoxia-ischemia in the infant rat brain.

Hypoxia-ischemia induced by unilateral carotid ligation followed by either 15 (moderate) or 90 (severe) min exposure to 8% oxygen was associated with induction of IGF-BP 2 mRNA expression. A specific rat IGF-BP 2 cDNA probe was used to determine the IGF-BP 2 mRNA distribution in brain sections using in situ hybridization. Untreated control rats and the non-ligated hemisphere in experimental rats expressed IGF-BP 2 mRNA in the choroid plexus, meninges and more weakly in the thalamus, hippocampus and cortical layer 5. Increased expression in experimental rats was limited to regions known to have neuronal damage. Three days after the moderate insult the signal was increased in the CA1/2 region of the hippocampus and thalamus of the ligated side. Three days after the severe insult IGF-BP 2 expression was found surrounding the infarcted regions while by 5 days after severe insult the whole infarcted volume showed induction. The results suggest a role for the IGFs in the post-asphyxial response. IGF-BP 2 may alter the bio-availability of IGF 1 or 2 or modulate their actions in the area of infarction, and thus promote cerebral repair and recovery.

Animals

Influence of the chemical composition on gamma ray attenuation by fatty acids.

The dependence of gamma ray attenuation on the chemical composition of fatty acids is investigated in the energy range from 10(-3) to 10(5) MeV. The mass attenuation coefficients (muF) and effective atomic numbers (Zeff) have been calculated for 27 different fatty acids. They show appreciable variation with the chemical composition of fatty acids in the region of gamma ray energies from 10(-3) to 10(5) MeV.

Fatty Acids

Optimal number of biopsy specimens in the diagnosis of carcinoma of the oesophagus.

The study evaluated 48 patients with carcinoma of the oesophagus to assess the optimal number of biopsy specimens required to obtain the highest yield. Eight specimens were obtained from each patient and two specimens were placed serially in each of four vials. The first vial provided a positive diagnosis in 95.8% of cases. The addition of two more specimens (second vial) increased the yield to 97.9% and the fifth and sixth specimens increased the positive yield to 100%. There was no statistically significant difference in the yield according to the site and the type of growth.

Adult

Bone marrow necrosis at transformation of chronic granulocytic leukaemia treated with interferon.

A patient with chronic myeloid leukaemia was treated with interferon without using conventional cytotoxic agents. Bone marrow necrosis developed at the onset of blast transformation. It is suggested that cytotoxic drugs should be given before treatment with interferon for chronic myeloid leukaemia. Cytotoxic drugs may also be needed to prevent rapid bone marrow growth once interferon has been withdrawn.

Antineoplastic Agents

Ovine placental lactogen is a potent somatogen in the growth hormone (GH)-deficient rat: comparison of somatogenic activity with bovine GH.

The somatogenic effects of recombinant ovine placental lactogen (oPL) were investigated in the GH-deficient dwarf rat and compared to those of identical doses of recombinant bovine GH (bGH) in three independent studies. Both oPL and bGH treatments resulted in an increase (P less than 0.05) in body weight gain compared to that in saline controls, with oPL treatment being more potent than bGH (P less than 0.05). In promoting linear growth, oPL was more potent (P less than 0.05) than bGH in some instances. The nitrogen content of dry carcass matter was increased with oPL treatment compared to saline (P less than 0.05), with a nonsignificant increase in bGH-treated animals. Carcass fat was similarly reduced by both oPL and bGH treatment (P less than 0.05) compared to saline. Serum insulin-like growth factor-I (IGF-I) concentrations were increased significantly (P less than 0.05) by both oPL and bGH treatments, with a significantly greater effect of oPL suggested in one study. No increase in hepatic IGF-I mRNA was evident with either treatment, suggesting that the increase in serum IGF-I is due to posttranscriptional mechanisms. The expression of IGF-binding protein-3 hepatic mRNA was increased (P less than 0.05) with bGH treatment compared to that after saline treatment, but was unaffected by oPL treatment, indicating regulation by GH at the transcriptional level. The binding of [125I]bGH to hepatic membrane preparations demonstrated no difference in specific binding compared to that in saline controls. However, [125I]oPL specific binding was greater in oPL-treated animals (P less than 0.05). Animals treated with bGH had reduced (P less than 0.05) hepatic GH receptor mRNA compared to saline controls, but oPL treatment had no effect. Thus, oPL is a potent anabolic and lipolytic agent in the dwarf rat, exerting greater somatogenic effects on some parameters than bGH. Our data suggest differences in receptor binding and effects on GH receptor and IGF-binding protein-3 expression with these two treatments, raising the possibility of actions through different pathways or differential effects at the GH receptor level.

Analysis of Variance

Combination therapy of parkinsonism with deprenyl.

In view of the encouraging results in various trials with deprenyl as an added drug therapy for Parkinson's disease, a pilot study to study deprenyl's efficacy in the Indian population was undertaken. Eleven patients were recruited in this open trial and were objectively assessed by Unified Rating Scale for Parkinsonism of Columbia University, Modified Hoehn and Yahr Staging and Schwab and England activities of daily living. Side effects, mood changes, changes in dyskinesia percentage, early morning dystonia and off period percentage were also noted. This study suggests improvement in the above parameters with minimal side effects.

Adult

Concentration of plasma and milk vitamin E and plasma beta-carotene of mastitic and healthy cows.

Variation of vitamin E in blood plasma and milk and beta-carotene in blood plasma of 38 healthy and 38 mastitic cows was studied. Cows were assigned to one of the two treatment groups: control and vitamin E supplemented. Vitamin E supplementation was started when cows were dried-off at the end of lactation and continued until 3 months post partum at the rate of 1000 IU per cow daily and then reduced to 500 IU for the remaining lactation. A cow was considered mastitic when somatic cell count of milk was greater than 500 x 10(3) cells/ml. Milk samples with somatic cell counts below 100 x 10(3) cells/ml were from healthy cows. Data on vitamin E concentration of plasma and milk and beta-carotene in plasma were analyzed by a least squares procedure. The model included the effects of treatment, mastitis status, stage of lactation, and all first order interactions. Mean vitamin E levels in plasma and milk of supplemented cows were significantly higher than of the non-supplemented cows. Plasma and milk levels of vitamin E as well as beta-carotene in plasma were significantly lower in mastitic than healthy cows. When data were analyzed with loge, of somatic cell count in milk as an independent regression variable, results were similar. There was a negative correlation of mastitis status with vitamin E levels in plasma (-0.48), milk (-0.24), and beta-carotene in plasma (-0.38).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals