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Biomedical subjects

M Johnson

Publications and source records attributed to M Johnson.

At least 667 records · Page 37Linked to original sources

Autoradiographic visualization of binding sites for [3H]somatostatin in the rat brain.

[4-3H][Phe6]somatostatin-14 was used to localize somatostatin binding sites in the rat brain by tritium-film autoradiography. The distribution of binding sites using 0.7 nM [3H]somatostatin confirmed that previously described for iodinated tyrosyl analogues of somatostatin, with highest densities of sites in the cerebral cortex (particularly in laminae III-V), amygdala, lateral septal nucleus, hippocampus and claustrum. Investigation of the pharmacological specificity of the binding sites showed that somatostatin-28, but not its N-terminal dodecapeptide, somatostatin-28 (1-12) or des-Ala1[Gly2,Lys4,Asn5,Thr12,Ser13]somatostatin displaced [3H]somatostatin. Further examination of the binding inhibition characteristics, using a homogenate assay, suggested the presence of two classes of binding sites in the cerebral cortex, hippocampus, midbrain and striatum. The existence of sub-populations of somatostatin binding sites in the rat brain has implications for future studies on the physiological and pharmacological significance of somatostatin receptors in the central nervous system.

Animals↗

Effects of amphetamine analogs on neurotensin concentrations in rat brain.

The present study investigates the effects of amphetamine-like analogs on neurotensin systems and compares the same to those of methamphetamine. Like methamphetamine, multiple high doses of each of the analogs examined significantly increased the concentrations of neurotensin-like immunoreactivity in the striatum, substantia nigra and nucleus accumbens; these effects were reversible and specific. The changes in the neurotensin systems developed rapidly and were evident within 6 h following a single administration of two of the analogs studied.

3,4-Methylenedioxyamphetamine↗

Role of the dopaminergic nigrostriatal pathway in methamphetamine-induced depression of the neostriatal serotonergic system.

The prevention of the decrease in neostriatal tryptophan hydroxylase (TPH) activity with a single dose of methamphetamine (MA) was attempted by lesioning the nigrostriatal dopaminergic projections with bilateral nigral injections of 6-hydroxydopamine (6-OHDA). The rats were injected with MA (10 mg/kg) 11 days later, and killed 3 h after the injection. The 6-OHDA lesions prevented the decrease of TPH activity in the neostriatum, while the decrease of enzyme activity was slightly attenuated in the hippocampus and unaffected in the frontal cortex. This study demonstrates: that the attenuation of TPH activity can be prevented in a selected brain area by destroying its dopaminergic afferents, and implicates central dopamine (DA), or its metabolite, in the decrease in central TPH activity observed after a single injection of MA.

Animals↗

A comparison of the neurotoxic potential of methylenedioxyamphetamine (MDA) and its N-methylated and N-ethylated derivatives.

Three psychoactive amphetamine congeners were evaluated for their ability to cause long-term changes in several neurochemical parameters indicative of central serotonergic function. Two weeks after multiple doses (10 mg/kg) of 3,4-methylenedioxyamphetamine (MDA) or its N-methylated derivative, 3,4-methylenedioxymethamphetamine (MDMA), selective and dramatic decreases were observed in regional brain tryptophan hydroxylase (TPH) activities, and in corresponding concentrations of 5-hydroxytryptamine (5-HT) and its primary metabolite, 5-hydroxyindoleacetic acid (5-HIAA). However, the N-ethylated derivative of MDA, N-ethyl-3,4-methylenedioxyamphetamine (MDE), was much less potent in its ability to lower brain hydroxyindoles, and in most regions examined did not significantly affect TPH activity. The neurotoxic implications of these results are discussed.

3,4-Dihydroxyphenylacetic Acid↗

MRI of sickle cell cerebral infarction.

Eleven patients with sickle cell disease and neurological symptoms underwent MRI examination. Cerebral infarcts of two types were found, those in the vascular distribution of the middle cerebral artery and those in the deep white matter. In the patient whose hydration and whose oxygenation of erythrocytes has been treated, MRI offers diagnostic advantages over arteriography and CT.

Adolescent↗

Systemic and renal hemodynamic consequences of manipulation of serum calcium and/or parathyroid hormone in the intact conscious mongrel dog.

Studies were undertaken in conscious mongrel dogs to separate the systemic and renal hemodynamic effects of alterations in serum calcium (Ca) from those of parathyroid hormone (PTH) in an intact conscious animal. Blood pressure was measured intra-arterially, cardiac output was determined by dye-dilution or thermodilution, total peripheral resistance (TPR) was calculated from standard formulae, and renal hemodynamics were estimated by the clearance of inulin and para-aminohippurate. Measurements were made before and after a 2 hour calcium chloride (CaCl2) infusion in 10 dogs (group 1). These animals had previously received a dose of PTH to prevent suppression of PTH during the CaCl2 infusion. Ionized calcium (Ca++) and TPR increased significantly. Blood pressure increased but not significantly. Administration of EDTA did not significantly change any systemic hemodynamic variable in eight thyroparathyroidectomized dogs (group 2). Chelation in seven dogs with intact parathyroid glands (group 3) reduced mean arterial blood pressure and total peripheral resistance. Renal hemodynamic measurements were not affected. Isolated acute elevation of serum Ca++, independent of suppression of PTH, increased total peripheral resistance. Decreased serum Ca++ required normal activity of parathyroids to reduce total peripheral resistance. The renal circulation was resistant to acute manipulation of ionized serum calcium and PTH. CaCl2 infusion to intact dogs (group 1) decreased serum magnesium significantly, increased urine flow rate, and decreased urinary PGE2 excretion. Comparisons between group 2 and group 3 revealed a greater decline in serum Mg and urinary prostaglandin E2 excretion in group 2 vs group 3. Elevation of peripheral resistance due to acute Ca elevations was accompanied by decreased serum Mg and decreased renal prostaglandin excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Comparative efficacy of ciprofloxacin, azlocillin, and tobramycin alone and in combination in experimental Pseudomonas sepsis.

Ciprofloxacin, azlocillin, and tobramycin, used alone and in combination, were studied in a model of lethal pseudomonas sepsis in rats. Ciprofloxacin alone at all doses studied and tobramycin alone at the highest dose reduced mortality significantly compared with saline controls. In contrast, survival was not improved with either azlocillin alone at all doses studied or lower doses of tobramycin alone. The combination of ciprofloxacin and azlocillin was synergistic in rats with systemic pseudomonas infection. Ciprofloxacin was rapidly absorbed, and effective levels persisted for 1-4 hr relative to the dose administered. These data suggest that ciprofloxacin may be a potent agent, either alone or in combination with azlocillin, in the treatment of severe pseudomonas infections.

Animals↗

Comparison of the daily lives of four young adults who are mentally retarded.

Least restrictive environments are assumed to be ones in which high-quality care is to be found. The quality of care provided for four adult males living in hospitals and hostels is described. The data indicate that there are not only differences in the quality of care provided between hospitals and hostels, but variation within both types of setting. Attention is drawn particularly to the differences in care provided within the hostel settings. The use of simple monitoring devices to assist in better practices is recommended.

Activities of Daily Living↗

Sodium-lithium countertransport in ambulatory hypertensive and normotensive patients.

Numerous studies have reported the mean value for Na+-Li+ countertransport to be increased in red blood cells from patients with essential hypertension. Although concomitant variables including age, body size, national origin, geographic location, gender, and family history of hypertension may affect Na+-Li+ countertransport values, most case-control studies have failed to assess the contribution of these factors to the differences in Na+-Li+ countertransport between hypertensive and normotensive groups. The present study was undertaken to provide estimates of Na+-Li+ countertransport in hypertensive and normotensive subjects after taking into account these potentially confounding sources of variation. In 187 subjects undergoing medical evaluation at the Mayo Clinic, Rochester, MN, the combined effects of variation in age, height, and weight accounted for 20.6% of the interindividual variability in Na+-Li+ countertransport. After adjustment to remove variability due to these concomitants, differences in national origin, region of birth, and place of current residence made no additional contribution to variability in this trait. There was no significant difference in mean adjusted Na+-Li+ countertransport between men and women (0.41 +/- 0.17 vs 0.40 +/- 0.12 [SD] mmol Li efflux/L red blood cells/hr; n = 107). The mean value for adjusted Na+-Li+ countertransport was significantly greater (p less than or equal to 0.001) in subjects with essential hypertension (0.44 +/- 0.15 mmol/L red blood cell/hr; n = 104) compared with normotensive subjects (0.31 +/- 0.07 mmol/L red blood cells/hr; n = 39) or subjects with borderline blood pressure elevation (0.35 +/- 0.11 mmol/L red blood cells/hr; n = 21). Subjects with a family history of hypertension in at least one parent or full sibling had significantly higher (p less than 0.02) Na+-Li+ countertransport values (0.42 +/- 0.16 mmol/L red blood cells/hr; n = 111) than those with no family history of hypertension (0.37 +/- 0.13 mmol/L red blood cells/hr; n = 76). These results suggest that increased mean Na+-Li+ countertransport in hypertensive subjects in this sample cannot be attributed to confounding effects of variation in age, body size, gender, national origin, birthplace, or residence. Forty-eight percent of subjects with essential hypertension had adjusted Na+-Li+ countertransport values above the range observed in normotensive controls.

Age Factors↗

The distribution and ontogeny of MHC antigens in murine ocular tissue.

The distribution of H-2 (Class I) and Ia (Class II) antigens in the mouse eye was determined with the use of monoclonal antibodies and found to be different. H-2 antigen was observed in the corneal epithelium, conjunctival epithelium, choroid, and inner and outer nuclear layer of the retina--in order of decreased intensity of staining. In contrast, Ia was detected most strongly, in a patchy distribution, in the choroid, limbus epithelium, and peripheral corneal stroma, followed by the iris and ciliary body. Thus, distinctively different patterns of distribution of H-2 and Ia were observed in the normal mouse eye. Surprisingly, adult eyes stained more intensely for both H-2 and Ia antigens than neonatal eyes, implying that the expression of MHC antigens varies with ontogeny. Since unique and important immunologic functions have been ascribed to class I and II antigens, their different distribution within the eye may indicate that various ocular structures can play distinctive roles in the immune response.

Animals↗

Analysis of the distribution of erythrocyte sodium lithium countertransport in a sample representative of the general population.

Numerous studies of sodium-lithium countertransport (Na-Li CNT) have reported higher rates in essential hypertensives versus normotensive controls. We studied the distribution and the mode of inheritance of Na-Li CNT using a sample of 238 unrelated individuals and a sample of 245 individuals in 50 pedigrees all sampled from the population at large. The distribution of Na-Li CNT is continuous and bimodal. Our results indicate that there is a large genetic contribution to the distribution of Na-Li CNT. The hypothesis that the effect that causes bimodality is transmitted from generation to generation is supported by the fit to these data of a restricted transmission model with tau 2 = 0.749. We hypothesize that this deviation of tau 2 from its Mendelian expectation may be attributable to heterogeneity in the etiology of the bimodality in the Na-Li CNT distribution in the population at large.

Adolescent↗

The effect of enkephalins and prostaglandins on O-2 release by neutrophils.

Derivatives of superoxide (O-2), produced by phagocytic cells, are thought to play a role in the adult respiratory distress syndrome (ARDS) and other disease states. Control of the release of O-2 may prove beneficial. Using human neutrophils as a source of O-2, and an assay for O-2 based upon the reduction of cytochrome C, we found that prostaglandin D2 (PGD2), leucine enkephalin (LE), and methionine enkephalin (ME) inhibited O-2 release. The Escherichia coli product, N-formyl methionyl leucyl phenylalanine (FMLP), was employed to stimulate O-2 release. PGD2 was most potent while there was no significant difference between LE and ME. Another peptide, thyrotropin releasing hormone (TRH), had no effect on O-2 release. There was no correlation between the potency of the inhibitory effect on O-2 release and the effect of these agents on the binding of [3H] FMLP to human neutrophils. Comparison of different but structurally related prostaglandins (PGD2, PGE2, and PGF2 alpha) revealed that PGD2 was more potent than PGE2 in inhibiting O-2 and that PGF2 alpha had no effect. This result suggested that the presence and position of the carbonyl group was an important determinant of the magnitude of inhibition.

Dinoprostone↗

Confounding and the dementia of schizophrenia.

Schizophrenia is often said to cause dementia, and previous studies have found cognitive impairment to be associated with schizophrenia. It is possible, however, that other causes of dementia and the study of patients not representative of all schizophrenics have contributed to these findings. The neuropsychological test scores of 26 schizophrenic outpatients were compared to those of 82 other patients with a history of psychosis. After other known causes of cognitive impairment were controlled for, the schizophrenics were not found to have cognitive impairment when compared to the other patients.

Adolescent↗

Treatment of metastatic malignant melanoma with recombinant interferon alpha 2.

Fifty-nine patients with metastatic malignant melanoma were entered into a phase II trial of recombinant alpha-2 interferon given in a dosage of 10 million IU/M2 subcutaneously three times per week for one year. Forty-five of these were evaluable for response. Of five evaluable patients with ocular primaries, none responded to interferon treatment. Four of 40 patients (10%) with cutaneous primaries achieved complete remission, and 6 further patients (15%) had partial remissions for a combined response rate of 25%. Two patients remain in complete remission 15+ and 32+ months after starting treatment. Responses were limited to subcutaneous, lymph node and lung metastases. The treatment schedule was well tolerated with the majority of patients receiving more than 70% of their predicted doses. Flu-like symptoms were the most common side effect. No evidence of cumulative toxicity was seen. We conclude that interferon is an active agent in metastatic malignant melanoma of cutaneous origin and that further trials are indicated.

Adult↗

Optimisation of indices of external pneumatic compression for prophylaxis against deep vein thrombosis: radionuclide gated imaging studies.

The amount and rate of blood expelled with different modes of intermittent external pneumatic compression applied to the lower leg were studied on a regional basis in a series of experiments on healthy human volunteers. Radionuclide imaging of the labelled blood pool, with acquisition of counts synchronised to the pressurisation cycle, provided data on regional blood volumes in the leg in relation to time. To determine the changes in blood volume of the lower leg resulting from external pneumatic compression labelled red blood cell counts were determined during 10 different types of compression cycle. Since venous stasis is considered to be a major cause of venous thrombosis the red blood cell counts were used to calculate regional values of the fraction of blood ejected as well as comparative indices proportional to regional flow rate, regional velocity, and regional wall shear stress. All these indices should be maximised for optimal prophylaxis against deep vein thrombosis. The four compartment cuff in each compression mode applied a mean pressure of 45 mm Hg, but different combinations of values were used for intercompartmental pressure gradation (delta p) and for intercompartmental time sequencing to the onset of compression (delta t). Uniform compression (delta p = 0; delta t = 0) was substantially inferior to cycles with gradation and sequencing. The optimal values of delta p were in the range 5-10 mm Hg and of delta t in the range 0-0.5 seconds.

Adolescent↗