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Biomedical subjects

J Scott

Publications and source records attributed to J Scott.

At least 415 records · Page 23Linked to original sources
PubMed1989

Characterization of the inositol 1,4,5-trisphosphate-induced calcium release from permeabilized endocrine cells and its inhibition by decavanadate and p-hydroxymercuribenzoate.

The inositol 1,4,5-trisphosphate (IP3)-sensitive Ca2+ compartment of endocrine cells was studied with alpha-toxin- and digitonin-permeabilized rat insulinoma (RINA2) and rat pheochromocytoma (PC12) cells. The Ca2+ uptake was ATP-dependent, and submicromolar concentrations of IP3 specifically released the stored Ca2+. Half-maximal Ca2+ release was observed with 0.25-0.5 mumol of IP3/l, and the amount of Ca2+ released due to IP3 could be enhanced by additional loading of the Ca2+ compartment. Consecutive additions of the same concentration of IP3 for 1-2 h always released the same amount of Ca2+ without desensitization, providing an ideal basis to further characterize the IP3-induced Ca2+ release. Here we describe for the first time a reversible inhibitory effect of decavanadate on the IP3-induced Ca2+ release. Among the vanadium species tested (decavanadate, oligovanadate and monovanadate), only decavanadate was inhibitory, with a half-maximal effect at 5 mumol/l in both cell types. The effect of decavanadate could be overcome by increasing the amount of sequestered Ca2+ or added IP3. Decavanadate did not affect the ATP-driven Ca2+ uptake but oligovanadate was inhibitory on Ca2+ uptake. p-Hydroxymercuribenzoate (pHMB) at concentrations between 10 and 30 mumol/l also inhibited the Ca2+ release due to IP3. Thiol compounds such as dithiothreitol (DTT; 1 mmol/l) added before pHMB removed all its inhibitory effect on the IP3-induced Ca2+ release, whereas the inhibition caused by decavanadate was unaffected by DTT. Thus, the decavanadate-dependent inhibition functions by a distinctly different mechanism than pHMB and could serve as a specific tool to analyse various aspects of the IP3-induced Ca2+ release within endocrine cells.

Adenosine Triphosphate↗
PubMed1989

Sequence requirements for apolipoprotein B RNA editing in transfected rat hepatoma cells.

Apolipoprotein (apo) B mRNA undergoes a novel tissue-specific editing reaction, which replaces a genomically templated cytidine with uridine. This substitution converts codon 2153 from glutamine (CAA) in apo B100 mRNA to a stop codon (UAA) in apoB48 mRNA (Powell, L. M., Wallis, S. C., Pease, R. J., Edwards, Y. H., Knott, T. J., and Scott, J. (1987) Cell 50, 831-840). To examine sequences in the human apoB mRNA required for the editing reaction, a series of deletion mutants around the cytidine conversion site was prepared and transfected into a rat hepatoma cell line (McArdle 7777). This cell makes both apoB100 and apoB48. Editing was detected by a primer extension assay on cDNA that had been amplified by the polymerase chain reaction. RNAs of between 2385 and 26 nucleotides spanning the conversion site underwent similar levels of conversion. Editing was confirmed by cloning and sequencing of cDNA corresponding to the transfected RNAs. Conversion did not occur in transfected human hepatoblastoma (HepG2) or epithelial carcinoma (HeLa) cell lines, which do not make apoB48. These results verify that apoB48 is generated by a genuine tissue-specific RNA editing reaction and show that 26 nucleotides of apoB mRNA are sufficient for editing.

Animals↗
PubMed1989

An in vitro system for the editing of apolipoprotein B mRNA.

A novel form of RNA editing generates two forms of apolipoprotein B (apo-B) mRNA by converting C at nucleotide 6666 to U or a U-like base. We have established an in vitro system for the editing of apo-B mRNA using synthetic RNAs and S100 extracts from rat hepatoma cells. Editing was detected by a sensitive primer extension assay and confirmed by DNA sequencing. The in vitro editing activity is specific and sensitive to proteinase K. Apo-B100 RNAs were synthesized in vitro from deletion mutants spanning nucleotide 6666. Synthetic RNAs containing 2383, 483, and 55 nucleotides of apo-B mRNA sequence were edited in vitro with similar efficiency, but an RNA containing 26 nucleotides was not edited.

Animals↗
PubMed1989

Streptozotocin-induced diabetes is not a model for methylmalonic acidaemia.

The streptozotocin-treated diabetic rat was not found to be a suitable animal model for methylmalonic acidaemia as previously described. Urinary methylmalonic acid (MMA) was measured in adult Wistar rats prior to and following injection of streptozotocin (40 mg/kg). Plasma and tissue MMA levels were measured following the induction of diabetes and compared with data from control rats. MMA levels were determined by a gas chromatographic-mass spectrometric method (McMurray et al., 1986). Diabetes was confirmed by the 10 x increase in 24 h urine volume; glycosuria; glycaemia; and weight loss. Urinary MMA excreted did not change during the 11 week diabetic period and there was no difference between the pre- and post-diabetic phases (p less than 0.05). Plasma and tissue MMA concentrations were not elevated in this diabetic animal model. Also in contrast to earlier reports, the vitamin B12 levels of the diabetic rats were not elevated compared to controls (p less than 0.05).

Animals↗
PubMed1989

Early graft function following heart and lung transplantation.

Fifty-one patients underwent heart-lung transplantation between April 1984 and October 1988. The first five donor organs were removed in an adjacent operating theatre. Organs were subsequently removed from distant centres. The method of preservation consisted of cold cardioplegic arrest of the heart using St. Thomas' solution, followed by a simple, cold pulmonary artery flush of a lung perfusate developed at Papworth Hospital. Administration of the solution was preceded by an infusion of prostacyclin into the pulmonary artery during preliminary dissection of the donor organs. The total ischaemic time ranged from 48 to 51 min (mean 49.6 min) for the near procurement group and from 70 to 249 min (mean 154.2 min) for the distant procurement group. There were no primary organ failures. Function of the lungs was assessed by gas exchange, pulmonary function tests, time to extubation, and survival data. Serial radiological studies were used to monitor graft performance in the postoperative period. We report here on our clinical experience of early graft function following heart and lung transplantation.

Adolescent↗
PubMed1989

A quantitative study of the effects of chronic hypoxia on the histological structure of the rat major salivary glands.

Ten young adult female Wistar rats were placed in a decompression chamber at a simulated altitude of 5500 m for 28 days, after which they were killed and their salivary glands and thoracic organs were compared with those of eight matched control rats that had been maintained at sea-level atmospheric pressure. The prolonged hypoxic conditions were severe enough to induce structural changes in the heart and lungs of experimental rats, and their parotid and submandibular, but not sublingual, glands showed severe hyperaemic responses. However, no parenchymal changes occurred in any of the major salivary glands. The mean proportional volume of vascular tissue was increased by 57% in the parotid and 30% in the submandibular glands, and the mean intralobular capillary densities were also increased, by 29 and 18% respectively, in these two glands. The effectiveness of these vascular responses in protecting the salivary parenchymal elements against hypoxic degeneration probably reflects the high reserve potential normally present in salivary blood flow.

Animals↗
PubMed1989

Plasma lipoprotein lipids in relation to the MspI polymorphism of the apolipoprotein AII gene in Caucasian men. Lack of association with plasma triglyceride concentration.

Digestion of the human apolipoprotein (apo) A-II gene with the endonuclease MspI produces fragments of 3.0 or 3.7 kb, reflecting the presence or absence of a polymorphic site within an Alu sequence 3' to the gene. Patients with hypertriglyceridemia have been shown to have an increased prevalence of the 3.0 kb allele. To explore this observation further, plasma lipoprotein lipids were studied in a random sample of fasted middle-aged Caucasian men, of which 59 were 3.0 kb homozygotes, 24 were heterozygotes, and 2 were 3.7 kb homozygotes. After adjusting for the effects of age, height, weight, alcohol intake and cigarette consumption by covariance analysis, no statistically significant associations were present between genotype and the concentrations of triglyceride in whole plasma or the d less than 1.019 g/ml fraction of plasma (i.e., VLDL + IDL). Nor were the cholesterol concentrations in VLDL + IDL, low density lipoprotein (LDL, d = 1.019-1.063 g/ml), high density lipoprotein (HDL), HDL2 or HDL3 related to genotype. In an independent comparison of eight 3.0 kb homozygotes and eight 3.7 kb homozygotes (all Caucasians) drawn from a different community, genotype was unrelated to the triglyceride or cholesterol concentrations in VLDL (d less than 1.006 g/ml), IDL + LDL (d = 1.006-1.063 g/ml) or HDL, after adjustment for the effects of covariates. These results suggest that the MspI polymorphism of the apo A-II gene is not associated with genetic variation that significantly affects triglyceride transport in the majority of men.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoprotein A-II↗
PubMed1989

Chloride handling by submandibular cells from young and old rats with and without duct ligation.

To examine the relation between structure and function in aging salivary glands, we have studied the duct-ligated submandibular gland of rats. Following 5-8 days ligation, glands from young (7-8 months) and old (21-23 months) rats exhibited approximately 90% loss in proportional volume of acinar cells. Most remaining epithelium was highly abnormal. No significant differences were detected in the ability of cells prepared from young and old animals, either control or ligated, to flux 36Cl-. Both basal uptake and muscarinic-cholinergic stimulated release were comparable.

Aging↗
PubMed1989

Aggressive calcifying odontogenic cyst--a possible variant of ameloblastoma.

A case of an aggressive calcifying odontogenic cyst of the maxilla is presented. It recurred twice after surgical excision over the course of a year and was subsequently treated by maxillectomy followed by radiotherapy. The current histological criteria for the diagnosis of calcifying odontogenic cyst were satisfied but it is argued that they are drawn too widely. Since the majority of calcifying odontogenic cysts are benign in behaviour the presence of cytological indicators of local destruction and invasiveness alongside the usual features of calcifying odontogenic cysts (presence of dentinoid, epithelial ghost-cell degeneration) should be the over-riding prognostic considerations and should thus be reflected in the diagnostic title. Such tumours are best regarded as variants of ameloblastoma rather than as unusually aggressive forms of calcifying odontogenic cyst and an appropriate name would be 'dentinogenic ghost-cell ameloblastoma'.

Adult↗
PubMed1989

Metabolic changes in Asian Muslim pregnant mothers observing the Ramadan fast in Britain.

1. Metabolic changes associated with Ramadan fasting were studied in eleven Asian pregnant mothers. This was compared with a group of control mothers undergoing a normal physiological fast. 2. At the end of the Ramadan fast day there was a significant fall in glucose, insulin, lactate and carnitine, and a rise in triglyceride, non-esterified fatty acid and 3-hydroxybutyrate. When compared with the control group, none of the Ramadan mothers had a completely normal set of biochemical values at the end of the fast day. 3. Pregnancy outcome in the two groups was comparable. 4. We are wary of the metabolic departures from normal observed in the Ramadan fasting mothers. If asked we advise mothers to take up the dispensation from fasting during pregnancy which is allowed.

Adult↗
PubMed1989

Heat-related illnesses. When are they a true emergency?

During the hot, humid months of summer, heat-related illnesses are common. Many of these are minor and self-limited, but heatstroke is a true emergency because the body's cooling mechanisms have been overwhelmed. The condition must be recognized rapidly and treated immediately with fluid replacement and cooling. The most effective and accessible technique for cooling involves the use of cool mist and fans directed across the patient's body to promote rapid evaporation. With aggressive management, the effects of heatstroke are almost uniformly reversible. With proper precautions, its occurrence is universally preventable.

Emergencies↗
PubMed1989

The effects of chronic ethanol administration on stimulated parotid secretion in the rat.

Young adult male rats were maintained on a regimen of twice daily intragastric administration of 4 ml of 35% (v/v) ethanol in water (daily dose approximately 7.0 g/kg) or 4 ml of calorifically equivalent sucrose solution over approximately 100 days. A second control group received no intragastric solutions. Under Valium-Hypnorm anaesthesia, parotid saliva was collected by intra-oral duct cannulation following stimulation by pilocarpine (10 mg/kg, subcutaneously) or by isoprenaline (30 mg/kg s.c.). In the ethanol-dosed rats the initial parotid salivary flow rate was raised in comparison to control animals by 39% after pilocarpine stimulation and by 37% after isoprenaline stimulation. The protein concentration was significantly reduced in saliva from ethanol-dosed rats compared to control groups but the amylase activity per ml of saliva was not significantly different from control groups. After pilocarpine stimulation, the [K+] was significantly higher in ethanol-dosed rats than in controls, but the [Na+] was effectively lower (allowing for flow rate differences). The blood-ethanol level was zero at the time of collection of saliva, suggesting that the salivary differences are due to functional adaptation induced in acinar and ductal epithelia by prolonged repeated exposure to high doses of ethanol.

Alcoholism↗
PubMed1989

Incidental and purposeful random donor blood transfusion. Sensitization and transplantation.

We conducted a prospective study to gauge the frequency and degree of sensitization by transfusion and/or pregnancy in 797 candidates for first renal transplants. Sensitization was proportional to the number of blood transfusions. Multiple transfusions or a history of pregnancy without transfusions had similar effects on sensitization. The combination of transfusion and prior pregnancy resulted in sensitization of 1/3 of the candidates. Patients who were not sensitized and were accepted for 1-haplotype living-related donor grafts or first-cadaver donor grafts were transfused to receive a total of 5 units of packed red blood cells. Parous patients had an undue rate of antibody formation and alternate means of selecting and managing parous women are described. Nonparous candidates had a low rate of sensitization (8%) that did not prove an impediment to obtaining a transplant. Only 2% of prospective LRD graft recipients developed antibody against their intended donor. Transplant patients were generally managed with azathioprine and prednisone. One-haplotype LRD graft survival of protocol patients was 93.7% one year posttransplant, and 82.1% at 5 years. One-year CD graft survival was 77%. There was no reduction in graft survival when the interval between transfusion and transplantation exceeded one year. Random donor transfusion is effective in improving renal graft survival. Some recent multiinstitutional reports indicate a reduction or absence of the transfusion effect with current immunosuppression. Discarding blood transfusion as a preparation for transplantation may be ill-advised pending a prospective study.

Blood Transfusion↗
PubMed1989

Source of methyl groups in brain and nerve tissue in the rat.

Previous studies that demonstrated that mouse brain accumulated significantly more radioactivity from subcutaneously administered 5-methyltetrahydrofolate labelled in the methyl group compared to the label in the folate moiety are open to two interpretations. The methyl group could have been transferred to another compound (probably methionine) prior to its transport into the brain. Alternatively, if plasma 5-methyltetrahydrofolate per se is significantly involved in the provision of methyl groups to brain and nerve tissue it would be expected that the folate moiety would be returned to the plasma to complete the cycle and thus would appear not to have been taken up. In this article, using competition experiments that exploit the differences in the mechanism of transport of methionine and 5-methyltetrahydrofolate into brain and nerve, evidence is presented that in the rat the methyl group of 5-methyltetrahydrofolate is transported after its conversion to methionine.

Animals↗