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Biomedical subjects

N White

Publications and source records attributed to N White.

At least 127 records · Page 7Linked to original sources
PubMed1981

Diabetes responsive to intravenous but not subcutaneous insulin: effectiveness of aprotinin.

Patients with diabetes that is insensitive to subcutaneous insulin but sensitive to intravenous insulin have recently been described. We have studied this phenomenon is five female diabetics (14 to 31 years of age) who required excessive amounts of insulin (2.5 to 30.0 units per kilogram of body weight per day) to avoid recurrent ketoacidosis. Known causes of insulin resistance were excluded. All patients had normal responses to conventional doses of intravenous insulin (0.35 to 0.9 unit per kilogram per day). Four patients required continuous intravenous infusion of insulin for one to six months. When a mixture of aprotinin (a protease inhibitor) and regular porcine insulin was given subcutaneously, conventional doses (0.7 to 1.4 units per kilogram per day) produced euglycemia; plasma levels of free insulin rose, and ketonuria disappeared. Four patients had episodes of spontaneous, severe hypoglycemia before and during aprotinin therapy, necessitating continuous infusion of glucose for two to 14 days. Although no insulin was administered, hyperinsulinemia (50 to 2000 muU of free insulin per milliliter [359 to 14,350 pmol per liter]) was present. These findings suggest excessive degradation or sequestration of insulin at the site of injection.

Adolescent↗
PubMed1981

Lithium induces dose-related increases and decreases in activity levels in the rat.

The effect of intraperitoneal lithium chloride on the activity levels of rats was measured by counting photocell interruptions in an open field. Treatment with 0.15 mEq/kg increased activity and 1.5 mEq/kg decreased activity. In a second experiment behavioral observations were added to the photocell counts of open field activity, and the increase observed with 0.15 mEq/kg LiCl in Experiment 1 was compared with the increase in open field activity produced by 0.4 g/kg ethanol. The two drugs produced similar increases in cell counts and walking, and similar decreases in sitting and sniffing. Lithium produced significantly more rearing and behavior directed at the cage than did ethanol. Following Johnson's hypothesis of lithium action, these findings are discussed within the context of lithium-induced changes in responsiveness to the environment. We suggest that, at 0.15 mEq/kg, lithium chloride might increase reactivity to the environment.

Animals↗
PubMed1981

Pimozide attenuates conditioned taste preferences induced by self-stimulation in rats.

Conditioned taste preferences (CTPs) were observed in rats who drank flavored water followed by a session of self-stimulation. Control groups that did not self-stimulate did not exhibit CTPs. Other taste/SS pairings conducted under the influence of the dopamine receptor antagonist pimozide (0.1 or 0.3 mg/kg, IP) resulted in dose-dependent reduction in the size of the CTPs. No evidence of any aversive effects (conditioned taste aversions) of the pimozide treatment were observed in the no-stimulation control groups. These data suggest that, in addition to its effects on responding, low doses of pimozide reduce the rewarding properties of self-stimulation.

Animals↗
PubMed1981

Lithium increases selective attention in rats.

Both 0.15 and 1.50 mEq/kg lithium chloride were found to increase inspective exploration (i.e. behaviors directed at the close examination if discrete stimuli in a new environment) in rats. In addition, 1.50 mEq/kg LiCl decreased general activity, irrespective of the characteristics of the experimental situation. The dose-independent increase in inspective exploration was interpreted as increased selective attention to salient stimuli which provide information about the environment. This hypothesis predicts that both doses of lithium should decrease distractibility by irrelevant stimuli. This prediction was confirmed in a second experiment, in which the ability of a tone to suppress drinking by thirsty rat was reduced by both doses of lithium. A two-factor model of lithium's action in rats is proposed. Lithium produces a dose-independent improvement of selective attention to stimuli which provide detailed information about the environment. In addition, lithium exerts dose-related effects on activity levels: a mild increase in activity with dose in the 0.15-0.20 mEq/kg range and a decrease in activity with doses of 0.50 mEq/kg and higher.

Animals↗
PubMed1981

The natural history of retinopathy in insulin-dependent juvenile-onset diabetes.

We determined the cross-sectional natural history of retinopathy by prospective study of 461 insulin-dependent juvenile-onset diabetics. In so doing, we compared the sensitivity of ophthalmoscopy, photography, and fluorescein angiography in detecting retinopathy. Photography was far more reliable than ophthalmoscopy in detecting early retinopathy and equivalent to angiography. Retinopathy was not present at diagnosis of diabetes. After a lag period, the prevalence of retinopathy rose in sigmoidal fashion, reaching 50% at just over seven years duration, and asymptotically approaching 90% at 17--50 years. Proliferative retinopathy was first seen at 13 years duration, and its prevalence rose to 26% at 26--50 years. From the natural history we computed the dimensions of a proposed clinical trial to test the effect of tight metabolic control in prevention of retinopathy.

Diabetes Mellitus, Type 1↗
PubMed1981

The effect of weight loss on sex steroid secretion and binding in massively obese women.

We have previously reported increased testosterone and androstenedione concentrations and decreased sex hormone binding globulin (SHBG) concentrations in the plasma of massively obese women. We now report that these plasma hormone concentrations return to normal in twelve of the same women after substantial weight reduction and these changes are associated with more normal menstrual cycles. We conclude that body weight and fat are important determinants of sex steroid secretion and binding and thus influence menstrual function.

17-Ketosteroids↗
PubMed1981

2-hydroxyoestradiol inhibits prolactin release from the superfused rat pituitary gland.

The effects of 2-hydroxyoestradiol (2OH-OE2), dopamine, oestradiol-17 beta and 2OH-OE2 plus dopamine on prolactin and LH release from the male rat pituitary gland were examined in vitro. 2-Hydroxyoestradiol reduced prolactin secretion by 51% at 10(-10) mol/l and by 34% at 10(-7) mol/l, while oestradiol-17 beta had no effect at these doses. Dopamine alone (5 x 10(-7) mol/l) decreased prolactin released by 58%, 2OH-OE2 plus dopamine produced a similar inhibition of 60%. No significant effect on LH release was observed throughout.

Animals↗
PubMed1980

Evidence for existence of two types of massive obesity.

The responses of growth hormone, cortisol, and prolactin to symptomatic hypoglycaemia during an intravenous insulin tolerance test were measured in 20 massively obese subjects and six lean volunteers. In 11 subjects, who had been obese since early childhood, an impaired growth-hormone response and an absent prolactin response were found. In the nine other obese subjects, however, the growth-hormone and prolactin responses were not significantly impaired. Seven of these subjects had become obese either as a teenager or during adult life. These findings suggest the existence of two types of human obesity similar to those found in rodent models. In one the disorder of hypothalamic function may be due to a basic, possibly genetic abnormality, while in the other it is acquired.

Adult↗
PubMed1980

Ultrastructural localization of TRH-like immunoreactivity.

With the peroxidase-antiperoxidase (PAP) method TRH-like immunoreactivity (TRH-LI) was observed in certain neurons of the central nervous system. Their distribution agreed well with findings previously obtained with the indirect immunofluorescence technique. At the ultrastructural level electron-dense precipitates representing TRH-LI were observed in so-called large dense core vesicles, which were localized both in the cytoplasm of some hypothalamic neuronal cell bodies, as well as in boutons in the hypothalamus and spinal cord. The boutons often seemed to form axo-somatic or axodendritic synapses.

Animals↗
PubMed1980

Abnormal sex steroid secretion and binding in massively obese women.

We have measured the plasma concentrations of sex steroids and sex hormone-binding globulin (SHBG) in twenty-three massively obese women and ten age-matched lean female volunteers. In the obese women increased plasma testosterone (obese 3.2 +/- 0.5 nmol/l controls 1.7 +/- 0.5 nmol/l, P less than 0.3) and androstenedione concentrations (obese 9.7 +/- 1.2 nmol/l, controls 4.4 +/- 0.6 nmol/l, P = less than 0.01) an increased ratio of oestrone:oestradiol (obese 2.4 +/- 0.4, controls 1.0 +/- 0.1, P = less than 0.1) and decreased SHBG levels (obese 30 +/- 4 nmol/l, controls 60 +/- 8 nmol/l, P = less than 0.001) were found. Obesity differed from the polycystic ovary syndrome (in which a similar pattern of changes of sex steroid concentrations and binding are seen) in that it was associated with normal increases in serum luteinizing hormone (LH) follicle stimulating hormone (FSH) levels in response to the administration of LHRH. We conclude that the common occurrence of menstrual abnormalities in obesity results from abnormal secretion and binding of sex steroids. In addition, the unaltered secretion of LH and FSH in the presence of such changes is evidence for a disorder of hypothalamic function.

Adult↗
PubMed1980

Further studies on the inactivation of thyrotrophin releasing hormone (TRH) by enzymes in the rat hypothalamus.

Thyrotrophin-releasing hormone (TRH) is known to be inactivated by enzymes present in the rat hypothalamus. To make a further study of the enzymes' action on the tripeptide, synthetic TRH was incubated with two hypothalamic subcellular fractions. By using a direct radioimmunoassay for TRH, the tripeptide was shown to be rapidly degraded by both supernatant and particulate fractions, with higher enzyme activity in the particulate fraction. Of several biologically-active peptides tested, only luteinizing hormone-releasing hormone was found to inhibit TRH inactivation; bacitracin, a polypeptide antibiotic, was also effective in inhibiting inactivation. Enzyme activity was highest in the middle hypothalamic area and lowest in the posterior hypothalamic area. Thin layer chromatography of the products of enzyme cleavage revealed the formation of only deamidated TRH in the supernatant fraction and the constitutent amino acids (pyroGlu, His, ProNH2) and histidylproline-diketopiperazine by the particular fraction, suggesting the presence of an amidase in the supernatant and two peptidases in the particulate fractions. These properties of the enzymes inactivating TRH may indicate that the enzymes could be of importance in regulating the endocrine and other functions attributed to this hypothalamic regulatory hormone.

Animals↗
PubMed1980

Age-related changes in the degradation of thyrotrophin releasing hormone by human and rat serum.

Changes in the rate of in-vitro degradation of thyrotrophin releasing hormone (TRH) in serum as related to age have been investigated in the rat and man. In rats, no inactivation was found up to the age of 15 days but therafter an age-related increase in inactivation was detected with approximately 75% inactivation in 60 min at 40 days and reaching a maximum of 88-93% inactivation in adult male and female animals. The human serum samples studied (both male and female) showed a similar but less clear-cut pattern of inactivation of TRH compared with that found in the rat. A physiological role for these age-related changes in the degradation of TRH remains to be established but it has been concluded that the changes observed in both rat and man may be associated with growth and development, possibly by facilitating feedback control of thyrotrophin secretion through the degradation of TRH.

Adolescent↗
PubMed1979

HLA-DR specificities among black Americans with juvenile-onset diabetes.

To study the association of histocompatibility (HLA) genes in black persons with juvenile-onset diabetes, we determined HLA-A, HLA-B, HLA-C and HLA-DR specificities in 40 black Americans with this disease and in 67 unaffected black Americans. Marked increases in the frequencies of HLA-DRw3 and HLA-DRw4 were found in the patients as compared with the unaffected persons: DRw3 was found in 72.5 per cent of patients versus 29.9 per cent of unaffected persons and DRw4 in 72.5 per cent versus 25.4 per cent (corrected P values each less than 0.0007). DRw2 was not found in any of the patients but was present in 26.9 per cent of unaffected persons (P corrected less than 0.035). There is thus a negative correlation between this specificity and juvenile-onset diabetes. By contrast, no meaningful differences were found in the frequencies of A, B, or C locus antigens. Studies in white persons with juvenile-onset diabetes have suggested that the reported HLA-B associations are due to HLA-D region specificities, and our results also support the premise that D region specificities are the primary associations with juvenile-onset diabetes.

Adult↗