Biomedical subjects
Publications and source records attributed to S Rogers.
The results of treatment of cystic and antibiotic-resistant acne vulgaris in 96 consecutive patients with the oral retinoid isotretinoin (13-cis-retinoic acid; Roacentane) are reported retrospectively. The results show that the drug, while toxic in the short term, is highly effective in clearing acne.
The neuroendocrine responsivity to an acute serotonergic challenge with low-dose i.v. clomipramine was studied in seven drug-free depressed patients and seven age-matched healthy control subjects. The depressed patients had higher baseline prolactin concentrations than the healthy subjects, and their prolactin response to clomipramine, assessed as either the percent of baseline or the log-transformed concentration, was significantly different (delayed and blunted peak response) compared to healthy controls. The growth hormone response was exaggerated in the depressed patients, and there were also trends toward blunting in their cortisol and adrenocorticotropic hormone responses. These results are consistent with previous findings of altered neuroendocrine responses to a variety of putative serotonin agonists in depressed patients.
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The role of interleukin-1 (IL-1) as a regulator of the autonomous growth of the blast cells of acute myeloid leukaemia (AML) has been studied on samples isolated from 15 patients. In nine out of 10 patients with evidence of partial autonomous blast cell growth. IL-1 further stimulated cell growth in both suspension culture and in a clongenic assay. IL-1 also stimulated cell growth in two out of three cases with no evidence of autonomous growth whereas no additional stimulation was observed in two cases with totally autonomous growth. In blast cells stimulated by IL-1, synthesis of granulocyte-macrophage colony stimulating factor (GM-CSF) was increased and the proliferative response to IL-1 was inhibited by an antibody to GM-CSF. In all samples with evidence of autonomous growth, blast cell conditioned medium (BCCM) contained IL-1 activity (range 0.7-74.2 units ml) and a polyclonal antibody to IL-1 markedly inhibited autonomous growth in four samples. BCCM from three of these four samples contained GM-CSF, the synthesis of which was suppressed when BCCM was prepared in the presence of anti-IL-1. Our data suggests that endogenous IL-1 is an important factor in the regulation of the production of GM-CSF and hence of autonomous growth of AML blasts, but that other mechanisms regulating GM-CSF production may exist.
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Neuronal and muscle nicotinic acetylcholine receptor subunit combinations expressed in Xenopus oocytes were tested for sensitivity to various neurotoxins. Extensive blockade of the alpha 3 beta 2 neuronal subunit combination was achieved by 10 nM neuronal bungarotoxin. Partial blockade of the alpha 4 beta 2 neuronal and alpha 1 beta 1 gamma delta muscle subunit combinations was caused by 1,000 nM neuronal bungarotoxin. The alpha 2 beta 2 neuronal subunit combination was insensitive to 1,000 nM neuronal bungarotoxin. Nearly complete blockade of all neuronal subunit combinations resulted from incubation with 2 nM neosurugatoxin, whereas 200 nM neosurugatoxin was required for partial blockade of the alpha 1 beta 1 gamma delta muscle subunit combination. The alpha 2 beta 2 and alpha 3 beta 2 neuronal subunit combinations were partially blocked by 10,000 nM lophotoxin analog-1, whereas complete blockade of the alpha 4 beta 2 neuronal and alpha 1 beta 1 gamma delta muscle subunit combinations resulted from incubation with this concentration of lophotoxin analog-1. The alpha 1 beta 1 gamma delta muscle subunit combination was blocked by the alpha-conotoxins G1A and M1 at concentrations of 100 nM. All of the neuronal subunit combinations were insensitive to 10,000 nM of both alpha-conotoxins. Thus, neosurugatoxin and the alpha-conotoxins distinguish between muscle and neuronal subunit combinations, whereas neuronal bungarotoxin and lophotoxin analog-1 distinguish between different neuronal subunit combinations on the basis of differing alpha subunits.
Carbon in the form of 8-micron fibers induces growth of connective tissue. The purpose of this study was to measure and histologically characterize tissue ingrowth occurring in carbon fibers implanted for up to 12 months in abdominal-wall defects in rats, compared with polypropylene mesh. Carbon fibers induced significantly more tissue ingrowth than polypropylene mesh at 6 to 12 months postoperatively. The predominant tissues associated with carbon fibers and polypropylene mesh were dense connective tissue and fat, respectively. Fragmentation of the implants did not occur, and implant debris was not found in the regional lymph nodes. Carbon fibers are potentially useful for reinforcing abdominal-wall defects.
Because reduced high density lipoproteins may contribute to atherothrombotic brain infarction, we performed molecular biologic and metabolic studies to characterize high density lipoprotein metabolism with respect to its role in reverse cholesterol transport, to clone the high density lipoprotein receptor, and to determine gene polymorphism for apolipoprotein A-I, the major protein of high density lipoprotein, because altered structure may impair reverse cholesterol transport. For high density lipoprotein metabolism measurements, high density lipoprotein 3 was isolated, purified, and labeled with iodine-125. The radiolabeled high density lipoprotein 3 was reinjected, and daily blood samples were taken for 10 days. Synthesis rates and fractional catabolic rates were determined from the specific activities and daily decrements. Preliminary data indicate that stroke-prone individuals' fractional catabolic rates for high density lipoprotein 3 are twice those of normal individuals. Also, the conversion of high density lipoprotein 3 to high density lipoprotein 2 is reduced in these individuals, suggesting that high density lipoprotein may be abnormally processed in individuals prone to atherothrombic brain infarctions. We surveyed more than 100 patients with carotid stenosis using a 2.2-kb probe for the apolipoprotein A-I gene. A subset of these patients displays polymorphism with restriction enzymes SacI or PstI. These preliminary findings suggest that gene polymorphism for apolipoprotein A-I may provide a molecular clue of atherothrombic brain infarction.
Standardised data on blood pressure, 24 h urinary electrolyte excretion, body mass index (BMI) and alcohol intake were collected as part of the INTERSALT study in 598 men and women aged 20-59 years, selected randomly from three population groups in the United Kingdom. For the three centres combined, mean systolic blood pressure was 121.4 mm Hg and diastolic pressure 72.1 mm Hg, urinary sodium excretion 152.1 mmol/24 h, urinary potassium excretion 61.0 mmol/24 h, urinary sodium/potassium ratio 2.64 and BMI 25.2 kg/m2. Prevalence of heavy alcohol drinking in men (greater than or equal to 300 ml/week) was 27.5 per cent. Applying overall INTERSALT regression coefficients to the United Kingdom data suggested that modest changes in average sodium and potassium intakes, together with reductions in the prevalence of obesity and (in men) of heavy alcohol drinking could lead to important reductions in average population blood pressures and the prevalence of hypertension. The potential of this multifactorial approach to blood pressure control was illustrated by stratifying individuals within each of the United Kingdom centres by sodium and potassium excretion, BMI and alcohol intake. The 20 (out of 299) men considered at 'lower risk' for high blood pressure with respect to the above variables had systolic pressure lower by 11 mm Hg (P less than 0.01); for the 27 (out of 299) 'lower risk' women, systolic pressure was lower by 5 mm Hg (P = 0.06). These non-pharmacological approaches towards more favourable blood pressure levels could be accompanied by reductions in mortality from stroke and coronary heart disease.
The colony forming ability of single cells or very short filaments of 7 strains of cyanobacteria was tested on media solidified by agar or by agar substitutes (Gel Gro or Gel Rite). In addition, the effect of various methods for preparation of agar media on colony forming ability was measured. High efficiency colony formation for most of the strains required that the agar be autoclaved separately from the salts in the medium. The addition of thiosulfate, but not buffer, significantly increased the plating efficiency of most strains.
A randomised controlled trial with a factorial design was done to examine the effects of dietary intervention in the secondary prevention of myocardial infarction (MI). 2033 men who had recovered from MI were allocated to receive or not to receive advice on each of three dietary factors: a reduction in fat intake and an increase in the ratio of polyunsaturated to saturated fat, an increase in fatty fish intake, and an increase in cereal fibre intake. The advice on fat was not associated with any difference in mortality, perhaps because it produced only a small reduction (3-4%) in serum cholesterol. The subjects advised to eat fatty fish had a 29% reduction in 2 year all-cause mortality compared with those not so advised. This effect, which was significant, was not altered by adjusting for ten potential confounding factors. Subjects given fibre advice had a slightly higher mortality than other subjects (not significant). The 2 year incidence of reinfarction plus death from ischaemic heart disease was not significantly affected by any of the dietary regimens. A modest intake of fatty fish (two or three portions per week) may reduce mortality in men who have recovered from MI.
We recently reported (Rogers, S. W., and Rechsteiner, M. (1988) J. Biol. Chem. 263, 19833-19842) the metabolic stabilities of 35 structurally characterized proteins following their injection into HeLa cells. In this study 22 proteins from that set were radioiodinated, and their susceptibilities to proteolysis were measured in reticulocyte lysate. Degradation rates varied from less than 1% per h to almost 25% per h. ATP stimulated the degradation of 21 of the proteins with nucleotide enhancement typically in the range 2- to 3-fold. When structural features of the 22 proteins were compared with their degradation rates in lysate, no correlation was found with respect to charge, size, thermal stability, or N-terminal acylation. Furthermore, relative rates of proteolysis in lysate correlated only marginally with the metabolic stabilities of the 22 proteins as measured 24-48 h after injection into HeLa cells. Degradation rates for the 22 proteins in lysate did, however, show a strong correlation with their rates of turnover immediately after injection into the human cells. Since the enhanced proteolysis observed for many proteins soon after injection is thought to reflect disruption of HeLa cytoskeletal assemblies, this correlation provides further evidence that diffusibility or location can affect intracellular protein stability.
Patients with seasonal affective disorder (SAD) frequently report carbohydrate craving and note that carbohydrate ingestion energizes them. Bright artificial light has been shown to reverse the symptoms of SAD, including carbohydrate craving. In this study, 16 depressed SAD patients and 16 matched controls were fed two different isocaloric meals, one rich in protein and one rich in carbohydrates, in a crossover design. Although their biochemical response in terms of plasma large neutral amino acid concentrations was identical, SAD patients reported activation following carbohydrate ingestion, whereas normal controls reported sedation. Marked ordering effects on psychological parameters were noted, suggesting that order should be taken into account as a methodological consideration in meal studies.
This series of experiments investigated the relationship between various treatments consisting of estradiol benzoate (EB) and progesterone (P) on sexual receptivity and on concentrations of nuclear estrogen receptors (NER) and cytosolic progestin receptors (CPR) in the hypothalamus-preoptic area in female hamsters. The injection of 1 microgram EB at 0 and 24 hr resulted in higher levels of receptivity (after 0.25 or 0.5 mg P), NER and CPR compared to those obtained after a single injection of 2 micrograms EB. Animals treated with 5 micrograms EB at 0 and 24 hr displayed greater levels of receptivity (after 0.5 mg P) and had higher NER concentrations than animals given a single injection of 10 micrograms EB. Groups treated with either 1 microgram EB at 0 hr or 0.5 microgram EB at 0 and 24 hr did not differ and showed low levels of receptivity, NER and CPR, NER and CPR were also measured on each day of the estrous cycle. NER levels rose between Days 1 and 2, again between Days 2 and 3, and remained elevated on Day 4. CPR levels increased between Days 2 and 3, and there was no difference between Days 3 and 4. Taken together, these data suggest that receptivity in hamsters after estrogen exposure is correlated with the accumulation and maintenance of relatively high NER levels and on the induction of CPR. This can be accomplished by a single large injection of EB or by smaller split doses.
A randomized controlled trial has been set up to examine the effect of diet on the secondary prevention of myocardial infarction, involving 2033 men. The trial has a factorial design, subjects being randomized independently to receive advice or no advice regarding three dietary factors: 1. a reduction in total fat and an increase in polyunsaturated fat intake; 2. an increase in fatty fish intake; 3. an increase in cereal fibre intake. Nearly half the men under 70 years of age who survived myocardial infarction during the recruitment period entered the trial, the commonest reason for exclusion being that the subject was already eating (or intended to eat) a diet which included one or more of the regimens being investigated. Detailed dietary questionnaires were completed by each subject after 6 months in the trial. The results suggest that compliance with the advice is reasonably good. The differences between the diets of the groups given and not given advice on fish and fibre were substantial; the difference attributable to advice on fat has been somewhat less than anticipated, partly because of failure to comply with advice and partly because of spontaneous changes in the diets of control subjects.
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