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Biomedical subjects

D Wright

Publications and source records attributed to D Wright.

At least 217 records · Page 12Linked to original sources

Cutaneous cryptococcosis without evidence of systemic involvement.

As many as 15% of cases of systemic infection with Cryptococcus neoformans have cutaneous involvement. The existence of primary cutaneous disease is controversial. We report a patient with cutaneous cryptococcosis without evidence of visceral involvement at the time of diagnosis. She has been followed up for 5 years and remains free of systemic involvement. Cutaneous cryptococcosis does not always signify systemic disease.

Biopsy↗

Evidence for an intracellular precursor for human B-cell growth factor.

Human B-cell growth factor has been described as a trypsin-sensitive protein of Mr 12,000-14,000. Evidence is provided herein that this relatively low molecular weight product may be released from a larger precursor molecule of Mr 60,000-80,000. The precursor protein is confined to the cytosol of freshly isolated T lymphocytes, and only the Mr 12,000-14,000 moiety is released upon lectin stimulation. The precursor protein was subjected to limited tryptic digestion, which demonstrated that the biologically active fraction of the moiety resided in a relatively low molecular weight fragment. The T lymphocyte routinely possessed an intracytoplasmic pool of the precursor protein, the amount of which cyclically varied depending upon its depletion by the secretion process of a lower molecular weight product. Analysis of the mRNA size coding for the majority of B-cell growth factor activity, determined by translation in Xenopus laevis oocytes, suggested that the B-cell growth factor-specific mRNA resided in the greater than or equal to 15S range. This value is consistent with the size of the larger precursor. Therefore, it is proposed that a precursor-product relationship exists for the processing of human B-cell growth factor, analogous to that which has been described for several other cytokines.

Animals↗

Amphotropic retrovirus vector system for human cell gene transfer.

Retroviral vectors have been constructed for gene transfer in mammalian and avian cells, however most retroviral vector systems are complicated by the spread of a replication-competent helper virus. This problem has been circumvented by segregating the viral genome into cis- and trans-acting components. By establishing helper cell lines that produce the trans-acting viral gene products, one can propagate the cis-acting component in them and harvest defective viral particles that contain only the cis-acting component. The cis-acting component can provide a useful vehicle for the highly efficient transfer of genes into target cells. The defective vector systems described to date, however, are restricted in host range to murine, avian, rat, and dog cells. We describe a helper-free vector system based entirely on an amphotropic murine virus with a wide mammalian host range, including the ability to carry out efficient gene transfer into human cells. We also describe a double mutation constructed in the trans-acting genome which reduces the frequency of replication-competent recombinant viruses to undetectable levels.

Animals↗

Effects of specific active immunization on tumor recurrence following primary tumor resection in WF rats with 1,2-dimethylhydrazine-induced bowel cancer.

Primary gastrointestinal tumors were induced in male WF rats by 16 weekly sc injections of 1,2-dimethylhydrazine [(DMH) CAS: 540-73-8; 20 mg/kg/wk]. Twenty-four to 28 weeks after the start of DMH injections, all rats were surgically explored and gastrointestinal tumors were resected. Rats with no remaining microscopic disease after operation were immunized with one of four tumor isografts. The first isograft, DMH-W163, is a poorly differentiated mucinous adenocarcinoma explanted from a colon cancer in a DMH-treated animal. It has been shown to possess antigens that cross-react with other DMH-induced bowel adenocarcinoma isografts. The second isograft, DMH-W49, is a carcinosarcoma explanted from a DMH-treated primary colon cancer. It has intermediate antigenic cross-reactivity with other colon adenocarcinoma isografts in the WF model. The third isograft, DMH-W15, is a sarcoma explanted from a DMH-induced colon cancer that does not possess antigens cross-reactive with other DMH-induced colon adenocarcinomas. The fourth isograft, SPK, is a spontaneous (non-DMH-induced) renal cell carcinoma that is immunogenic but should not contain tissue-type-specific antigens cross-reacting with the bowel cancers. Immunized rats received three sc weekly injections of 1 X 10(3) irradiated cells. Concomitant control rats received no immunization after resection of the primary tumor. Within 24 weeks of primary tumor resection, 12 of 16 (75%) rats not immunized had tumor recurrence. Only 8 of 24 (34%) rats immunized with DMH-W163 had tumor recurrence (P less than .025 compared to controls). Fifty percent of animals (10/20) immunized with the carcinosarcoma DMH-W49 had a recurrence. Animals immunized with the non-cross-reacting DMH-W15 sarcoma isograft had a recurrence rate similar to that of controls (16/20, 75%). The rats immunized with SPK were not protected from recurrence. Twelve of 19 (63%) had a recurrence at or near the suture line within 24 weeks following primary tumor resection. These results confirm that adjuvant immunotherapy can decrease the rate of recurrence following primary tumor resection in this model. In addition, immunogens that possessed tissue-type-specific antigens were more effective in preventing tumor recurrence than those that did not.

1,2-Dimethylhydrazine↗

Xanthine oxidase deficiency and 'Dalmatian' hypouricaemia: incidence and effect of exercise.

In order to study the effects of raising the hypoxanthine concentration in plasma on its metabolism and renal handling, the effects of intense exercise have been investigated in a patient with xanthine oxidase deficiency. Despite the 90-fold increased concentration of hypoxanthine in plasma above resting levels in normal individuals, the intracellular concentration of the initial product of hypoxanthine in cells, IMP, was unaffected. Evolution may have stabilized intracellular nucleotide concentrations against the large fluctuations in plasma hypoxanthine which occur during exercise. The renal handling of hypoxanthine is consistent with 'filtration'. In contrast, xanthine clearances may exceed those for creatinine and urinary concentrations do not correlate with those for creatinine; 'secretion' may be involved. Xanthine excretion may reflect guanine breakdown. A retrospective survey of urate concentrations in blood from 47 420 patients followed by further selected investigations detected 2 women with persistent marked hypouricaemia and high urinary urate clearances, 'Dalmatian' hypouricaemia. High pressure liquid chromatographic analysis of plasma extracts can distinguish xanthine oxidase deficiency from other causes of hypouricaemia.

Erythrocytes↗

Cardiobacterium hominis: an elusive cause of endocarditis.

Cardiobacterium hominis is a fastidious bacterium of the normal mouth flora. It has rarely been recognised in the past as a human pathogen and has been difficult to recover from the bloodstream. Mistaken diagnoses and delays in therapy have been common. We report a 29-year-old man with C. hominis endocarditis who was initially treated for a presumed collagen-vascular disorder with anti-flammatory drugs. The organism was eventually recovered in brain-heart infusion medium after prolonged incubation, and cure was accomplished with parenteral penicillin. Special blood culturing methods should be used if endocarditis caused by a fastidious organism is clinically suspected.

Adult↗

Pattern of change of bronchomotor tone following reversal of neuromuscular blockade. Comparison between atropine and glycopyrrolate.

Specific airways conductance (s.Gaw) was measured using the forced airflow oscillation method, to study the effect of two regimens, commonly used for the reversal of neuromuscular blockade, on bronchomotor tone. Patients who had received neuromuscular blockers and had undergone elective surgery were randomly allocated to receive neostigmine 50 microgram kg-1 given concurrently with either atropine 20 microgram kg-1 (10 patients) or glycopyrrolate 10 microgram kg-1 (10 patients). Before administration, five baseline measurements of s.Gaw were obtained and measurements were then made at intervals of 1 min for the next 10 min. At 3 min there was a significant difference in s.Gaw between the two groups, higher values being found in the atropine group. At 10 min, no significant difference was seen between the groups, although both showed a significant decrease in s.Gaw compared with baseline values (P less than 0.05).

Atropine↗

Effect of exercise training and sucrose feeding on insulin-stimulated glucose uptake in rats with streptozotocin-induced insulin-deficient diabetes.

The effect of exercise training and a sucrose-rich diet on insulin-stimulated glucose disposal was studied in rats with streptozotocin-induced insulin deficiency. Rats were injected with streptozotocin (40 mg/kg), and 3 days later divided into three groups with equal degrees of hyperglycemia. One group of rats was allowed to run spontaneously on exercise wheels, another group remained sedentary but ate a sucrose-rich diet (66% sucrose), and the third also remained sedentary but consumed conventional rat chow. Three weeks later, we determined the effect of these various programs on postabsorptive plasma glucose and insulin levels, as well as on the ability of exogenous insulin to stimulate disposal of a glucose load during a period in which endogenous insulin was suppressed by epinephrine and propanolol. Basal plasma insulin levels were the same in all three groups, but plasma glucose levels were significantly lower (P less than 0.001) in exercise-trained rats, and significantly higher (P less than 0.05) in sucrose-fed rats, than in chow-fed diabetic rats. The inference that exercise training markedly enhanced insulin action in rats with insulin deficiency was borne out by direct estimation of insulin-stimulated glucose disposal. In contrast, sucrose-fed diabetic rats seemed to be more insulin-resistant than chow-fed diabetic rats. These results provide direct evidence that spontaneous exercise can dramatically attenuate the severity of diabetes in insulin-deficient rats by enhancing insulin action. DIABETES 32:165-168, February 1983.

Animals↗

Effect of age and diet on insulin secretion and insulin action in the rat.

The effects of aging on various aspects of insulin secretion and action were studied in male Sprague-Dawley rats, maintained from 1 1/2 to 12 mo of age on conventional rat chow, sucrose-rich, or calorie-restricted diets. In chow-fed rats, islet volume increased as the animals grew from 1 1/2 to 12 mo of age, but glucose-stimulated insulin secretion (per volume islet) declined over the same interval. In addition, in vivo insulin-stimulated glucose utilization fell in these rats. However, the plasma insulin response to an oral glucose challenge was sufficient to prevent frank decompensation of glucose tolerance (presumably due to an increase in total pancreatic endocrine cell mass). All these changes, with the exception of the decline in glucose-stimulated insulin secretion per volume islet, were accentuated by feeding sucrose. Thus, 12-mo-old sucrose-fed rats had larger islets and higher plasma insulin levels in response to an oral glucose challenge, and the rats were more insulin-resistant than chow-fed rats. However, glucose-stimulated insulin release per volume islet was similar in 12-mo-old chow-fed and sucrose-fed rats. In contrast, calorie restriction led to an amelioration in all but one of the age-related changes, i.e., islets from calorie-restricted rats were comparable in size to those of 2-mo-old rats, the animals had lower plasma insulin levels in response to an oral glucose load, and they were less insulin resistant than the other two groups of 12-mo-old rats. On the other hand, glucose-stimulated insulin secretion per volume islet was similar to that of the other 12-mo-old rats. These results suggest that aging leads to marked changes in both insulin secretion and insulin action. The decline in glucose-stimulated insulin secretion per unit endocrine pancreas appears to be an inevitable consequence of the aging process. In contrast, the age-related changes in islet size, insulin response to a glucose load, and in vivo insulin-stimulated glucose uptake are extremely responsive to variations in amount and kind of calories. DIABETES 32:175-180, February 1983.

Aging↗

Does insulin removal rate from plasma decline with age?

The effect of age on the rate of insulin removal from plasma was studied in both rat and man. The experimental approach was based on measurement of the steady-state plasma insulin concentration achieved during a period in which endogenous insulin secretion was suppressed and exogenous insulin infused. Rats, 1 1/2 and 12 mo of age, were infused with 2.5, 5.0, and 10.0 mU/kg of insulin during a 180-min period in which endogenous insulin secretion was suppressed by epinephrine and propranolol. Steady-state plasma insulin concentrations were approximately twice as high in the older rats at every insulin infusion rate. Similar results were seen in man; significant correlations were observed between height of steady-state plasma insulin concentration and advancing age during infusion of exogenous insulin and suppression of endogenous insulin with either exogenous insulin (r = 0.66, P less than 0.001) or epinephrine and propranolol (r = 0.47, P less than 0.01). Since infusion rates of exogenous insulin were identical in all studies, these results suggest that there is an age-related decrease in insulin catabolism.

Adult↗

Premedication with intramuscular midazolam: a prospective randomized double-blind controlled study.

One hundred A.S.A. physical status I and II surgical patients were randomized to receive midazolam, 0.07 mg/kg (group M, 31 patients), hydroxyzine, 1.0 mg/kg (group H, 34 patients), or midazolam diluent as a placebo (group P, 35 patients). Drugs were administered in the vastus lateralis muscle 60 to 90 minutes before anesthesia induction. Anesthesia was induced with thiopental, 3.0 mg/kg, followed by 1.0-mg/kg increments if required. An entry criterion was that patients score greater than or equal to 50% on a subjective Anxiety Visual Analog Test (AVAT). Anxiety was also objectively rated on a six-point scale by a trained observer. Patients and observer were unaware of type of premedication used. Midazolam and hydroxyzine produced significantly (p less than 0.05) greater reduction of anxiety than placebo on both the AVAT and objective anxiety evaluations. Peak onset appeared between 30 and 60 minutes after drug administration. Hemodynamic changes were similar in all groups, and no untoward reactions were encountered before anesthesia. The injection site 24 and 48 hours after administration showed evidence of mild tissue irritation in 68% of patients in group H, 26% of patients in group M, and none of the patients in group P. Midazolam is an efficacious, safe premedicant in relatively healthy patients. It has a prompt onset of action with only minimal tissue irritation.

Anxiety↗