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Biomedical subjects

R D Johnson

Publications and source records attributed to R D Johnson.

At least 145 records · Page 8Linked to original sources
PubMed1987

Nifedipine hepatitis.

An 80-year-old woman developed acute hepatitis following her first exposure to nifedipine. This adverse effect was characterised by fever, chills, anorexia, nausea, liver tenderness, hepatitic liver function tests and peripheral blood eosinophilia. On liver biopsy the portal tracts were expanded with a mixed inflammatory cell infiltrate rich in eosinophils. The potential for the occurrence of this adverse effect must increase with the current expansion of indications for the use of nifedipine.

Aged↗
PubMed1987

Mechanoreceptor response to mechanical and thermal stimuli in the glans penis of the dog.

In the dog, we isolated 126 mechanoreceptive afferent fibers of the A-delta myelinated fiber class from the dorsal nerve of the penis using microdissection and extracellular electrophysiological techniques. Receptive fields on the glans penis were stimulated with a computer-controlled mechanostimulator and Peltier effect thermostimulator. The great majority of units were categorized as either rapidly adapting (RA) or slowly adapting (SA) and were located primarily proximally and distally, respectively, on the glans. In comparison to values from other glabrous skin regions in other species, mean displacement and force thresholds of penile mechanoreceptors were high, whereas the mean velocity thresholds were low. SA units, generally poor encoders of static displacement, were distinguishable into two types based on static response firing pattern but were not homologous to either the SA I or SA II mechanoreceptors found in other skin regions. Fifty-five units were given simultaneous mechanical and thermal stimulation. Very few units responded to pure thermal stimulation or increased their discharge frequency to skin cooling. Warm receptive-field temperatures between 35 and 43 degrees C increased mechanical sensitivity, measured by displacement and velocity coding functions, in almost all units tested. We conclude that canine penile mechanoreceptors, capable of encoding a variety of skin movements when the penis is warm, provide the spinal cord with the sensory input necessary to drive the spinal sexual reflexes. However, many appear to be at least physiologically different from mechanoreceptors native to other skin areas.

Animals↗
PubMed1987

Differentiation of alpha 1-adrenergic receptors linked to phosphatidylinositol turnover and cyclic AMP accumulation in rat brain.

Activation of alpha 1-adrenergic receptors in slices of rat brain increases inositol phosphate accumulation, increases basal cyclic AMP accumulation, and potentiates the increase in cyclic AMP caused by adenosine. We compared these three responses to determine whether they are mediated by the same receptors. The increase in inositol phosphates and the potentiation of cyclic AMP accumulation in cerebral cortex were largely blocked by chelation of extracellular calcium, whereas the increase in basal cyclic AMP was not affected. The magnitude of the increase in inositol phosphates in different brain regions correlated with the magnitude of the potentiation of cyclic AMP accumulation (r = 0.80), but neither of these correlated with the magnitude of the increase in basal cyclic AMP. Although other alkylating agents inactivated all of the alpha 1-adrenergic receptor-binding sites labeled with 125IBE 2254 in membrane preparations of cerebral cortex, chlorethylclonidine (CEC) potently and selectively inactivated only half of these sites. Pretreatment with CEC partially blocked the increase in basal cyclic AMP, but not the increase in inositol phosphates or potentiation of cyclic AMP accumulation in slices of cerebral cortex. Comparing different brain regions, there was a better correlation between the density of 125IBE 2254-binding sites not inactivated by CEC with the magnitude of the increase in inositol phosphates or potentiation of cyclic AMP accumulation than with the increase in basal cyclic AMP. Although the largest increase in inositol phosphates was observed in slices of hippocampus, there was only a small increase in basal cyclic AMP in this region, and CEC did not inactivate any 125IBE-binding sites in hippocampus. Phentolamine and WB 4101 were significantly more potent in inhibiting specific 125IBE 2254 binding in hippocampus than in cerebral cortex. After treatment of cerebral cortical membranes with CEC, however, these drugs had potencies similar to those observed in hippocampus. The results suggest that the alpha 1-adrenergic receptors mediating increases in basal cyclic AMP accumulation can be differentiated from those mediating increases in inositol phosphate accumulation and potentiating adenosine stimulated cyclic AMP accumulation by their binding properties, calcium dependency, regional distribution, and sensitivity to the alkylating agent CEC.

1-Methyl-3-isobutylxanthine↗
PubMed1987

Regulation of alpha-1 adrenergic receptor density and functional responsiveness in rat brain.

The effects of changes in norepinephrine availability on alpha-1 adrenergic receptor density and responsiveness were determined in several regions of rat brain. Receptor density was determined from specific 125I-BE 2254 binding, and responsiveness was determined by norepinephrine-stimulated increases in inositol phosphate accumulation and in cyclic AMP accumulation in the absence or presence of adenosine in slices where beta adrenergic receptors had been inactivated. Adrenergic input was reduced by destroying noradrenergic neurons with DSP-4, depleting amines with chronic reserpine treatment or blocking alpha-1 adrenergic receptors with chronic prazosin treatment. All three treatments caused similar increases in alpha-1 adrenergic receptor density in cerebral cortex but not in striatum or hippocampus. DSP-4 treatment increased the maximal cyclic AMP response to both norepinephrine and phenylephrine but did not alter the maximal inositol phosphate response or the maximal potentiation of the cyclic AMP response to adenosine. DSP-4 treatment also increased the potency of norepinephrine in activating all three responses in cerebral cortex. Adrenergic input was increased by chronic treatment with desmethylimipramine to block norepinephrine reuptake, chronic i.c.v. infusion of norepinephrine or chronic yohimbine treatment to block presynaptic autoreceptors. None of these treatments caused significant changes in alpha-1 adrenergic receptor density or functional responsiveness in any region studied. The results suggest that alpha-1 adrenergic receptor density and responsiveness in rat brain can be increased but not easily decreased. They also suggest that different brain regions are affected differently by alterations of adrenergic input and that the different responses are not coregulated.

Animals↗
PubMed1987

Influence of aetiology, clinical and histological features on survival in chronic active hepatitis: an analysis of 204 patients.

To determine which clinical and laboratory features may influence survival in patients with chronic active hepatitis, we undertook a retrospective study of 204 patients seen on this unit over a 15-year period and applied logistic regression analysis. One hundred and six patients had autoimmune chronic active hepatitis, 69 'cryptogenic' chronic active hepatitis (no autoimmune markers or other aetiological factors identified), and 29 were HBsAg-seropositive. Variceal haemorrhage, encephalopathy and ascites were common presenting features in the cryptogenic group while the presence of jaundice and other immunopathic diseases did not differ between the groups. Cirrhosis was more common at presentation in the cryptogenic group. Remission was induced with corticosteroids and azathioprine in 82 per cent of patients with autoimmune chronic active hepatis and in 77 per cent of patients with cryptogenic chronic active hepatitis and the annual relapse rate was similar in the autoimmune and cryptogenic groups. Five-year survival was 87 per cent in the autoimmune group, 65 per cent in the cryptogenic group, and 80 per cent in those with HBsAg-positive disease, and on logistic regression analysis, the presence of cirrhosis at presentation was the only independent factor which adversely affected survival. Overall survival in the cirrhotic patients at five and 12 years was 63 and 48 per cent respectively compared with 95 and 92 per cent in those without cirrhosis.

Adolescent↗
PubMed1987

Mineral content of market samples of fluid whole milk.

Results from the Food and Drug Administration's Total Diet Study on the nutrient element content of fluid whole cow's milk are presented and compared with previously published values. Whole milk was collected and analyzed yearly from 1975 through 1985. Yearly and overall means were similar for all elements except iron and iodine. The iron content of milk was generally low, but several samples had high levels. The distribution of iodine in whole milk was quite wide (0.002 to 0.094 mg/100 gm). The iodine content of milk is affected by the level of iodine added to cattle feed and by the use of iodophor sanitizing solutions used by the dairy industry. Overall mean levels of the elements in milligrams per 100 gm whole milk were: sodium, 42; potassium, 134; calcium, 106; phosphorus, 83; magnesium, 9.8; iron, 0.07; zinc, 0.37; copper, 0.009; manganese, 0.004; iodine, 0.034; and selenium, 0.001. Coefficients of variation were high (67% to 117%) for iron, copper, manganese, selenium, and iodine but ranged from 18% to 26% for the other elements. An 8-fl oz serving of whole milk is an excellent source of iodine, calcium, phosphorus, and potassium. It also provides some sodium, magnesium, zinc, and selenium but is not a reliable source of iron, copper, or manganese.

Adolescent↗
PubMed1987

Neurophysiologic maps of cutaneous innervation of the hind limb of sheep.

The area of skin supplied by afferent fibers in a peripheral nerve is called the cutaneous area (CA) of that nerve. The CA of hind limb nerves that were responsive to movement of wool/hairs were mapped neurophysiologically in 25 barbiturate-anesthetized sheep. The CA of the dorsal cutaneous branches of the caudal lumbar spinal nerves and of the sacral spinal nerves extended over the lateral aspect of the thigh. The CA of the lateral cutaneous femoral nerve was restricted to the stifle region, that of the saphenous nerve did not reach the digits, that of the deep peroneal nerve lay between the 3rd and 4th digits, and that of the lateral plantar nerve was confined to the lateral aspect of the 4th digit. The CA of the superficial peroneal nerve enveloped the dorsal, medial, and lateral aspects of the distal portions of the hind limb. In some sheep, the boundaries of the CA of the superficial peroneal nerve were juxtaposed caudally in such way that the medial plantar nerve did not have an autonomous zone. Differences in sizes of the CA resulted in corresponding differences in the overlap between adjacent CA and concomitant differences in the sizes of autonomous zones.

Animals↗
PubMed1986

Characterization of alpha 1-adrenoceptors which increase cyclic AMP accumulation in rat cerebral cortex.

The pharmacological properties of the alpha-adrenoceptors which increase cyclic AMP accumulation were studied in slices of rat cerebral cortex after inactivation of beta-adrenoceptors with bromoacetylalprenololmenthane. Norepinephrine increased basal cyclic AMP accumulation 2-fold, and potentiated the effect of adenosine 5-fold. The Ki and EC50 values for antagonists and agonists for both the basal and potentiated responses were generally similar to those for alpha 1-adrenoceptor-stimulated inositol phosphate accumulation in the same preparation. However, significant differences in the potencies of all agonists, and the antagonists phentolamine and BE2254 were observed between the basal and potentiated cyclic AMP responses. The differences in agonist potencies did not appear to be due to the existence of a receptor reserve. Norepinephrine, epinephrine, alpha-methylnorepinephrine and 6-fluoronorepinephrine were full agonists, while methoxamine and phenylephrine were partial agonists in both systems. The results suggest that norepinephrine increases cyclic AMP accumulation in rat cerebral cortex through alpha 1-adrenoceptors similar to those increasing phosphatidylinositol metabolism in the same tissue.

Adrenergic beta-Agonists↗
PubMed1986

Rapidly and slowly adapting mechanoreceptors in the glans penis of the cat.

Sixty-one single mechanoreceptive fibers were surgically isolated from the dorsal nerve of the penis in anesthetized, mature, and sexually intact male cats. Impulse activity was recorded extracellularly. Receptive fields on the glans penis were stimulated with an accurate computer controlled mechanostimulator. Thirty-four units were categorized as rapidly adapting (RA) based on the absence of a response to sustained skin displacement. The remaining were slowly adapting (SA) units responding to sustained displacement. Most of the SA units were located in the distal smooth glans whereas RA units predominated in the proximal spiny glans. Displacement thresholds were significantly lower for RA units. All units encoded indentation velocity although the SA units were better suited to discriminate slowly moving stimuli. In addition, SA units encoded sustained displacement amplitude. Male cats with a denervated glans penis display disoriented mounting behavior disabling intromission. The presence of distally located SA mechanoreceptors suggests they may be the primary penile proprioceptors, mediating, along with the RA mechanoreceptors, successful completion of intromission.

Animals↗
PubMed1986

Significance of serum bilirubin level in response of hepatocellular carcinoma to doxorubicin.

To determine which of several clinical and laboratory features could be of significance in the response of hepatocellular carcinoma to doxorubicin we have analysed the frequency of remission in 143 patients treated with this drug. Of those features investigated including age, sex, presence and aetiology of underlying cirrhosis, duration of symptoms, performance grade and liver function tests, a normal serum bilirubin level was shown to be the only one on logistic regression analysis to predict a greater change of response (response rate = 46% with serum bilirubin less than 20 mumol/l and 10% with bilirubin greater than 20 mumol/l). The most likely explanation is that reduction in doxorubicin dosage according to the serum bilirubin level, based on the view that the risk of myelosuppression is thereby lessened, may lead to suboptimal dose administration.

Adult↗
PubMed1986

Mineral content of foods and total diets: the Selected Minerals in Foods Survey, 1982 to 1984.

The 234 foods of the FDA's Total Diet Study were collected four times per year form mid-1982 to mid-1984 and analyzed for 11 essential minerals. Daily intakes of the minerals were estimated for eight age-sex groups of the U.S. population. Levels of calcium, magnesium, iron, zinc, copper, and manganese were low (less than 80% of the RDA or below the low end of the Estimated Safe and Adequate Daily Dietary Intake range) for some or all age-sex groups. Those most at risk of low intakes were young children, teenage girls, adult women, and older women. Non-discretionary sodium intake exceeded the upper Estimated Safe and Adequate Daily Dietary Intake range for two age-sex groups, and iodine was considerably above the RDA for all age-sex groups. Levels of potassium, phosphorus, and selenium were adequate for all groups.

Diet Surveys↗
PubMed1985

Alpha 1-adrenergic receptors and stimulation of [3H]inositol metabolism in rat brain: regional distribution and parallel inactivation.

The relationship between norepinephrine-stimulated phosphatidyl-inositol metabolism and alpha 1-adrenergic receptor density was examined in rat brain. Increases in phosphatidyl-inositol metabolism were determined by accumulation of [3H]inositol phosphates in the presence of lithium in brain slices, while receptor density was determined by specific binding of 125I-BE 2254 (125IBE) in membrane fractions. Treatment of slices of cerebral cortex with increasing concentrations of the irreversible alpha 1-adrenergic receptor antagonist phenoxybenzamine caused a parallel inactivation of specific 125IBE binding sites and norepinephrine-induced [3H]inositol phosphate accumulation, although approximately 20% of the binding sites remained after abolition of the inositol response. Comparison of the density of 125IBE binding sites and the magnitude of norepinephrine-stimulated [3H]inositol phosphate accumulation in 8 different brain regions did not show a particularly good correlation. The thalamus had the highest density of binding sites and an intermediate inositol response, while the hippocampus had the highest inositol response but an intermediate density of binding sites. However, the cerebellum had the lowest density of binding sites and no measurable inositol response. Treatment of slices of each region with 300 nM phenoxybenzamine abolished the inositol response and caused a 59-73% decrease in the density of 125IBE binding sites. The lack of correlation between receptor density and inositol response between brain regions could not be explained on the basis of receptor affinity, spare receptors, protein content, nor differences in slice size.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Risk factors in development of hepatocellular carcinoma in cirrhosis: prospective study of 613 patients.

In a prospective study of 613 patients with cirrhosis of different aetiological types increasing age, male sex, and non-UK nationality were found to be significant independent risk factors for the progression of cirrhosis to hepatocellular carcinoma. Seropositivity for hepatitis B surface antigen and the duration and aetiology of cirrhosis were not related to the development of the disease. Age and sex were also found to be significant risk factors when UK patients alone were considered. Seropositivity for hepatitis B surface antigen may be associated with hepatocellular carcinoma only because hepatitis B virus infection is a common cause of cirrhosis.

Adult↗
PubMed1985

Characterization of heme orientational disorder in myoglobin by proton nuclear Overhauser effects.

Freshly reconstituted sperm whale myoglobin is a mixture of two components distinguishable by proton nuclear magnetic resonance. The two species are interconvertible and the equilibrium composition is about 90% of one form, the form studied by X-ray methods. We have used the nuclear Overhauser effect to characterize the other (minor) component in its metcyano complex. Whereas in the major form there is dipolar contact between residue 99 and the heme pyrrole ring III, in the minor form the same residue is in contact with pyrrole IV, related to ring III by a 180 degrees rotation about the alpha-gamma meso axis. This interaction proves the validity of the heme rotational disorder proposition and confirms that the apoprotein does not discriminate between the two sides of the heme in the rapid insertion process. It is proposed that the differences in nuclear Overhauser effect between the protein matrix and the heme moiety can be used to define qualitatively the structural consequences of this heterogeneity. The altered heme-protein contacts could be related to the enhanced oxygen affinity in the minor form.

Animals↗