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Biomedical subjects

C Wang

Publications and source records attributed to C Wang.

At least 1,297 records · Page 72Linked to original sources

Purification and autophosphorylation of insulin receptors from rat skeletal muscle.

Insulin receptors of rat skeletal muscle were purified by first extracting a plasma membrane-enriched pellet obtained from a muscle homogenate with Triton X-100, followed by WGA-Sepharose and insulin-Sepharose affinity chromatography. Routinely, 4-5 micrograms of purified receptor were obtained from 15 g of tissue. The purified receptors are composed of two major polypeptides with molecular weights of 130,000 and 95,000, respectively. The binding of [125I]insulin by the purified receptors was analyzed by a Scatchard plot. There are at least two binding components. The high-affinity component, with an apparent association constant (Ka) of 2.0 X 10(9) M-1, comprises 10% of the total insulin binding sites; while the low-affinity component, with a Ka value of 1.4 X 10(8) M-1, represents 90% of the binding sites. Assuming the insulin receptor to have a molecular weight of 300,000, the receptor binds 1.7 mol of insulin per mol at saturation. Insulin is capable of stimulating the autophosphorylation of the beta-subunit of the muscle insulin receptor (Mr 95,000) by 5-10-fold. The stoichiometry of this phosphorylation reaction was determined as 0.8 phosphate per insulin binding site after a 10 min incubation with 100 nM insulin. In a previous report, I showed that the insulin stimulation of glucose transport in diaphragms from neonatal rats was small, even although the diaphragms had normal levels of insulin receptors and glucose transporters (Wang, C. (1985). Proc. Natl. Acad. Sci. USA 82, 3621-3625). To determine whether or not receptor autophosphorylation might be related to this insensitivity to insulin, the level of receptor phosphorylation was quantitated in diaphragms from rats at different stages of development. Autophosphorylation remains unchanged from birth to 21 days of age, suggesting that the lower insulin-stimulated glucose uptake by diaphragms at early stages of postnatal development as compared to that by diaphragms of older rats, is not due to a difference in receptor kinase.

Age Factors↗

Bovine interstitial retinol-binding protein (IRBP)--isolation and sequence analysis of cDNA clones, characterization and in vitro translation of mRNA.

Three clones for b-IRBP were isolated by anti b-IRBP screening of two bovine retina libraries in the expression vector lambda gt11. The cDNA inserts were then used as hybridization probes to screen and isolate three more clones in a bovine retina library in the non-expression vector lambda gt10. The six overlapping clones generated a b-IRBP cDNA sequence of 3400 nucleotides. An open reading frame encoded the complete amino acid sequences of 8 of the 35 b-IRBP tryptic peptides purified in the present study. One tentative glycosylation site was identified. The coding region was followed by TAG translation terminating codon and an untranslated stretch of about 1700 nucleotides that ended in a sequence containing a presumptive AATAAA polyadenylation signal that was 18 nucleotides upstream from a 10 nucleotide oligo(A) tract. The coding region for b-IRBP would be expected to be 3300 bp long, but Northern blot hybridization experiments performed with bovine retina polyadenylated RNA and probes containing part of the coding region established that the mRNA for b-IRBP consisted of a major species of about 6300 bp, and a minor species of 5200 bp. In vitro translation of bovine retina polyadenylated RNA in a rabbit reticulocyte lysate system yielded an immunoreactive protein that was comparable in size with nonglycosylated, mature IRBP, showing that it is not synthesized from a large precursor, and supporting our finding that the mRNA contains an extensive non-coding region.

Amino Acid Sequence↗

CSF dopamine levels correlate with extraversion in depressed patients.

Cerebrospinal fluid (CSF) dopamine levels were studied in 16 male patients who also were tested for self-reported extraversion using the Eysenck Personality Inventory. Log CSF dopamine was significantly correlated with extraversion as predicted by recent theoretical work integrating mesolimbic dopamine function and active responding to external incentives as psychobiological traits. CSF dopamine levels were uncorrelated with the total score on the Hamilton Rating Scale for Depression, self-reported neuroticism, and age. The results are discussed in relation to other biological models of extraversion such as the construct of sensation-seeking behavior.

Bipolar Disorder↗

LHRH stimulates plasminogen activator and inhibits steroid production by granulosa cells of adult rat Graafian follicles.

We studied the effects of LHRH and its analogs on plasminogen activator production and progesterone and estradiol secretion by granulosa cells isolated from adult rat Graafian follicles. LHRH and its agonist ([des- -Gly10,D-Trp6,Pro9-NHEt]LHRH) stimulated small but significant increases in plasminogen activator production. This stimulatory action of LHRH was blocked by the addition of the specific antagonist ([D- pGlu1,D-Phe2,D-Trp3,6]LHRH). In contrast, LHRH treatment had no significant effect on basal steroid production by granulosa cells of Graafian follicles cultured for 2-6 days. However, LHRH decreased the FSH-stimulated steroidogenesis. This inhibitory effect of LHRH on steroidogenesis was abolished by concomitant addition of the LHRH antagonist. The results show that LHRH has a stimulatory effect on plasminogen activator production and a suppressive action on steroidogenesis in granulosa cells isolated from Graafian follicles of adult rats.

Animals↗

Seminal plasma transferrin and seminiferous tubular dysfunction.

Seminal plasma transferrin levels were assayed in 158 random semen samples collected from normospermic, oligospermic, and azoospermic men, and their relationships with seminal characteristics, sperm fertilizing capacity as assessed by the zona-free hamster ova penetration assay, and serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were evaluated. The concentrations of seminal plasma transferrin in azoospermic, oligospermic and postvasectomy samples were significantly lower than those in normospermic samples. Seminal plasma transferrin concentrations were similar in azoospermia due to obstruction of the reproductive tract or damage to the germinal epithelium. No significant difference in seminal plasma transferrin concentrations was observed in the groups of subjects with normal and elevated FSH or normal and elevated LH. A positive correlation was observed between seminal plasma transferrin concentration and sperm density and between total semen transferrin content and the total number of sperm in the ejaculate. There were no significant correlations between seminal plasma transferrin concentration and sperm motility, percent normal sperm, sperm fertilizing capacity, and serum FSH or LH concentration. The results indicate that seminal plasma transferrin is not a useful marker for Sertoli cell or seminiferous tubular dysfunction. In addition, it is doubtful that measurement of seminal plasma transferrin will yield additional information regarding the fertility potential of semen samples.

Follicle Stimulating Hormone↗

Imipenem/cilastatin: a multicentre international study of its clinical efficacy, safety and potential as empirical therapy.

Five hundred and sixty-nine patients were treated with imipenem/cilastatin in this multicentre, international noncomparative study of hospitalized patients with moderate to severe infections; 97.5% of 815 pathogens isolated were susceptible to imipenem, which reconfirms imipenem's broad in-vitro spectrum. Clinical efficacy could be assessed in 389 patients, the majority (72%) of whom received a daily dose of 1.5 g or less. Infections in the various body sites with the exception of the central nervous system were treated. A favourable clinical outcome was seen in 93% of the infections. Fifty-five of the 389 patients had been unsuccessfully treated with one or more antibiotics before being switched to imipenem/cilastatin. In these patients the daily dose was evenly distributed between 1.5 g/day (47%) or 2.0 g/day (40%); the rest of the patients received greater than 2 g/day. Intra-abdominal and respiratory tract infections were the most common, the majority (56%) of which were rated severe. Overall clinical efficacy (cured or improved) in these 55 patients was 82%. With the demonstrated clinical efficacy, particularly in the treatment of proven infections which have failed on other regimens, imipenem/cilastatin could have a distinct advantage as an initial choice for empirical therapy.

Adult↗

The safety profile of imipenem/cilastatin: worldwide clinical experience based on 3470 patients.

The relative safety of imipenem/cilastatin for 3470 patients was reviewed to see if the safety profile was similar to that seen for the first 1723 patients treated. The most common clinical adverse experiences were local ones related to the site of intravenous infusion. Gastrointestinal adverse experiences included nausea, vomiting, or diarrhoea. The frequency of pseudomembranous colitis was low (0 X 1%). The most common central nervous system abnormality was seizure. The most common background factor was central nervous system abnormality including prior history of seizure. Dermatological adverse experiences included rash, pruritus and urticaria. Bleeding and decreased renal function were uncommon. The most common laboratory changes included transient increased liver function values, eosinophilia, positive Coombs' test (not associated with haemolysis) and increased platelets. The current clinical and laboratory safety data are similar to those obtained in the early part of the clinical trials.

Bacterial Infections↗

Hypothalamic hypopituitarism following cranial irradiation for nasopharyngeal carcinoma.

Eight patients, one male and seven females, with no pre-existing hypothalamic-pituitary disease, who developed symptoms of hypopituitarism following cranial irradiation for nasopharyngeal carcinoma were studied 5 years or more after radiotherapy. All were GH deficient. Four of the patients with no GH response during insulin tolerance tests (ITT) showed increased GH in response to synthetic human growth hormone releasing factor (GRF-44). Four patients had impaired cortisol responses to ITT, and gradual but diminished cortisol responses to ovine corticotrophin releasing factor (CRF-41). There was no significant difference between mean peak increments in response to ITT and those in response to CRF-41. TSH responses to TRH were delayed in five and absent in two patients; four of these had low free T4 index. Prolactin was raised in all seven women and increased further in response to TRH. Two patients had impaired gonadotrophin responses to LHRH. None of the patients had clinical or biochemical evidence of diabetes insipidus. These data suggest that post-irradiation hypopituitarism in these patients results from radiation damage to the hypothalamus leading to varying degrees of deficiency of the hypothalamic releasing or inhibitory factors.

Adult↗

Salivary androgens in hirsutism: are they of use in routine evaluation?

In the biochemical evaluation of hirsutism, 50% or less of patients have an elevated total serum testosterone. Recent work has suggested that measuring salivary testosterone or a derived serum 'free testosterone index' may be of use in the evaluation of hyperandrogenism. We have measured serum total, derived serum free indices and salivary concentrations of testosterone and 5 alpha-dihydrotestosterone in an unselected group of hirsute patients in order to assess their value in the routine evaluation of hirsutism. The assays were performed using a novel oxidation procedure to overcome the need for chromatographic separation. The 'free testosterone index' gave the best discrimination. Salivary androgen concentrations were comparatively poor and cannot be recommended for routine use.

Adult↗

Hypothalamic defects in two adult patients with septo-optic dysplasia.

Two adult patients with unilateral hypoplastic optic nerves, absent septa pellucida and hypopituitarism are described. Patient 1, aged 20, presented with diabetes insipidus due to partial vasopressin deficiency. Patients 2, aged 29, presented with focal epilepsy. Both had short stature. They showed absent growth hormone (GH) response to insulin-hypoglycaemia or glucagon, but responded to 100 micrograms growth hormone releasing factor (GRF-44) with a rise in circulating GH, suggesting a hypothalamic defect in GH release though a co-existing pituitary defect cannot be excluded. Other hypothalamic-pituitary functions were normal. These two patients probably represent the milder form of the clinical spectrum of septo-optic dysplasia which, with the extensive use of CT brain scans, will be increasingly encountered by physicians attending adult patients.

Adult↗

World-wide clinical experience with norfloxacin: efficacy and safety.

This review covers 2346 norfloxacin treated patients in clinical trials world wide. These studies show that 400 mg of norfloxacin b.i.d. was effective and compared favorably with other standard oral agents in the treatment of urinary tract infections, including complicated and recurrent infections in men. This regimen given b.i.d. or t.i.d. was also effective in the treatment of acute gastroenteritis due to common gastrointestinal pathogens such as enterotoxigenic Escherichia coli, Salmonella spp., Shigella spp., Campylobacter spp. as well as less common organisms. A single 800 mg dose was effective in the treatment of gonorrhoea including patients with extra genito-urinary involvement and penicillinase producing strains of Neisseria gonorrhoeae. Preliminary data from ongoing trials have also shown that norfloxacin is effective in the prophylaxis of traveller's diarrhoea and infections in the granulocytopenic patient. These various regimens of norfloxacin were well tolerated with a low incidence (less than 3%) of drug related adverse experiences. The most common adverse experiences were nausea, headache, dizziness, rash, elevation of liver enzymes and eosinophilia.

Acute Disease↗

Fifty cases of primary hyperaldosteronism in Hong Kong Chinese with a high frequency of periodic paralysis. Evaluation of techniques for tumour localisation.

Fifty consecutive Chinese patients with primary hyperaldosteronism were studied. All were considered to have an adrenal cortical adenoma, this being proven by surgery in 46 cases. In contrast to other reports, periodic paralysis was a presenting feature in 42 per cent of patients. Other notable symptoms were palpitations (30 per cent) and syncope (12 per cent). Vascular complications were present in 20 per cent of cases. Mean serum potassium level at presentation was 2.1 +/- 0.1 (mean +/- SEM) and sodium 145.0 +/- 0.1 mmol/l. Serum potassium was significantly lower and plasma aldosterone higher in patients with periodic paralysis. Adrenal venography in order to localise the tumour was unreliable and was misleading in two cases. Adrenal venous sampling for steroid analysis was much more helpful, despite the difficulty of obtaining right adrenal venous blood. The side of the adenoma could be predicted in 97 per cent of cases from measurements of left adrenal venous and vena caval aldosterone levels. The use of high resolution CT gave 100 per cent accuracy in all 18 patients who underwent surgery, the smallest detected tumour being 0.8 cm in diameter. Surgery corrected hypokalaemia in all cases, and 37 of the 46 patients required no further antihypertensive treatment.

Adenoma↗

Synaptic delay in the lateral geniculate nucleus of the cat.

Unitary, presynaptic spike potentials were observed in single cell recordings from the dorsal lateral geniculate nucleus of the cat. In 11 cells, spontaneous S potentials (extracellularly recorded excitatory postsynaptic potentials) were preceded at a fixed interval by a small wave (the 'T' potential). In another 14 cells, a T potential, although not detected in single traces, was revealed by averaging 20-100 samples synchronized to the peak of the S potential. Provided the field response was not too large a T potential could also be detected in the response to a stimulus to the optic nerve. The T potential would appear to be the spike potential of the afferent optic axon which is excitatory to the geniculate cell because it precedes the S potential at a very exact interval and also follows the corresponding retinal ganglion cell spike at a very exact interval and because the interval between T potential and S potential is reversibly decreased by cooling with a temperature coefficient characteristic of synapses. T potentials ranged in amplitude from 8 to 134 microV and were all predominantly positive-going suggesting a failure of the nerve impulse to invade fully the terminals of the optic nerve. The time from the positive peak of the T potential to the start of the S potentials was taken as a good measure of the synaptic delay. The T-S interval averaged 0.29 ms (+/- 0.045 ms S.D.).

Action Potentials↗

Review of adverse experiences and tolerability in the first 2,516 patients treated with imipenem/cilastatin.

The clinical and laboratory data relating to the adverse experiences and tolerability of imipenem/cilastatin in the first 2,516 patients treated with the antibiotic are reviewed, with special reference to the last 793. Clinical adverse experiences were predominantly related to the gastrointestinal system (nausea and vomiting), local injection site, and allergy (rash). A low frequency of drug-related seizures was also reported. The most frequent adverse laboratory experiences were transient elevations of liver function test values. In general, the safety profile was similar to that of other beta-lactam antibiotics.

Adolescent↗