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Biomedical subjects

D S Robinson

Publications and source records attributed to D S Robinson.

At least 19 recordsLinked to original sources

Plasma tricyclic drug levels in amitriptyline-treated depressed patients.

In a double-blind phenelzine controlled clinical trial, 49 depressed outpatients were treated with a fixed dose of amitriptyline (AMI) 150 mg/day for 6 weeks. No significant relationships were found between steady-state plasma levels of AMI and its metabolite, nortriptyline, at 4 weeks and therapeutic response at 6 weeks or side effects. In the patient subgroup with more severe endogenous symptoms, there was a general trend for a weak positive association between AMI plasma levels and clinical improvement. Plasma tricyclic determinations appear to have little if any predictive value for antidepressant effect in outpatients treated with AMI.

Adult

Hydroxylase cofactor activity in cerebrospinal fluid of normal subjects and patients with Parkinson's disease.

A method for measuring hydroxylase cofactor activity in human cerebrospinal fluid is described. The hydroxylase cofactor content of cerebrsopinal fluid from Parkinsonian patients is approximately 50 percent that of normal subjects. A significant correlation between hydroxylase cofactor and the concentration of homovanillic acid in the cerebrospinal fluid was observed.

Biopterins

The metabolic conversion of very-low-density lipoprotein into low-density lipoprotein by the extrahepatic tissues of the rat.

1. The work reported was designed to provide quantitative information about the capacity of the extrahepatic tissues of the rat to degrade injected VLD lipoproteins (very-low-density lipoproteins, d less than 1.006) to LD lipoproteins (low-density lipoproteins, d 1.006--1.063) and to study the fate of the different VLD-lipoprotein apoproteins during the degradative process. 2. Rat liver VLD lipoproteins, radioactively labelled in their protein moieties, were produced by the perfusion of the organ and were either injected into the circulation of the supradiaphragmatic rats or incubated in rat plasma at 37 degrees C. At a time (75 min) when approx. 90% of the triacylglycerol of the VLD lipoproteins had been hydrolysed the supradiaphragmatic rats were bled and VLD lipoproteins, LD lipoproteins and HD lipoproteins (high-density lipoproteins, d 1.063--1.21) were separated from their plasma and from the plasma incubated in vitro. The apoproteins of each of the lipoprotein classes were resolved by gel-filtration chromatography into three main fractions, designated peaks I, II and III. 3. Incubation of the liver VLD lipoproteins in plasma in vitro led to the transfer of about 30% of the total protein radioactivity to the HD lipoproteins. The transfer mainly involved the peak-II (arginine-rich and/or apo A-I) and peak-III (apo C) proteins. There was also a small transfer of radioactivity (about 5% of the total) to the LD lipoproteins. 4. Injection of the liver VLD lipoproteins into the circulation of the supradiaphragmatic rat resulted in the transfer of about 15% of the total VLD-lipoprotein radioactivity to the LD lipoproteins. The transfer involved mainly the peak-I (apo B) proteins and accounted for about 20% of the total apo B protein radioactivity of the injected VLD lipoproteins. When the endogenous plasma VLD lipoprotein was taken into account the transfer of apo B protein was about 35%. 5. The transfer of peak-II protein radioactivity from the VLD to the HD lipoproteins was greater in the plasma of the supradiaphragmatic rat than in the incubated plasma suggesting that there was a net transfer of peak-II apoproteins during the VLD lipoprotein degradation. The transfer of peak-III protein radioactivity was not greater in the plasma of the supradiaphragmatic rat, but there was a loss of this radioactivity from the circulation.

Animals

Multiple primary melanoma.

From a series of 712 patients with melanoma, 38 patients (5.3%) had more than one primary melanoma. Twenty-four patients had two primaries, 11 patients had three, 2 patients had four, and 1 patient had eight. Twelve patients (32%) had one or more synchronous primaries. Forty-five percent of all multiple primaries were diagnosed within the first year. Microstaging by level and depth was determined prior to treatment and in patients with nonsynchronous primaries, 83% had a subsequent melanoma equal or less advanced than the original. Twenty-six patients with Stage I primaries were skin-tested with DNCB prior to therapy. No significant differences in delayed cutaneous hypersensitivity reactions were found between multiple primary and matched controls with only a single melanoma. Four of 10 patients with multiple primaries treated with adjuvant BCG or BCG-tumor cell vaccine developed subsequent melanomas suggesting that immunotherapy with BCG will not prevent the development of a new primary melanoma. Survival in patients with Stage I and II multiple primary melanomas was improved compared to Stage I and Stage II patients with a single primary. This study suggests that prognosis in multiple primary melanomas is better reflected by the most advanced primary based on microstaging and the presence or absence of regional lymph node metastases than by multiplicity.

Adult

The degradation of very low density lipoprotein by the extrahepatic tissues of the rat.

The supradiaphragmatic rat was used to investigate the metabolism by the extrahepatic tissues of endogenous plasma VLDL of d less than 1.006 g/ml. The demonstration that, at 20, 30 and 40 min after the isolation of the supradiaphragmatic rat, the VLDL lose respectively 29, 54, and 63% of their triglyceride provides evidence for the suitability of this preparation for the investigation of VLDL degradation. At all time intervals after the isolation of the supradiaphragmatic rat, VLDL triglyceride loss was accompanied by similar losses of cholesterol, protein and phospholipid, with the result that the percentage by weight composition of the residual VLDL remained unaltered. By subfractionation of the VLDL, a group of particles with an Sf range of 20--60 were isolated that, when compared with total VLDL, were enriched in their cholesterol (P less than 0.02), protein (P less than 0.001) and phospholipid (P less than 0.01) content. However, these particles represented only a small percentage of the total VLDL mass. Furthermore, their amount was not increased in the circulation of the supradiaphragmatic rat. The amount of IDL (d = 1.006--1.019 g/m) and of LDL (d = 1.019--1.063 g/ml) was increased in the supradiaphragmatic rat and a part of the total cholesterol and protein lost from the VLDL could be accounted for by the increases in these constituents in the IDL and LDL fractions. It is suggested that, although the liver probably takes up partial degradation products of VLDL in the intact animal, the extrahepatic tissues alone can metabolize VLDL to LDL of d = 1.019--1.063 g/ml. The lipoprotein particles taken up by the liver in the intact animal appear most likely to be those of Sf greater than 100.

Animals

Clinical pharmacology of phenelzine.

There is renewed interest in the clinical pharmacology of phenelzine sulfate and other monoamine oxidase (MAO) inhibitors. Newer clinical and analytic techniques recently have been applied to investigations of this class of drugs in man. The results show that drugs such as phenelzine are effective in nonendogenous depression and phobic disorders. Clinical response to phenelzine is related to platelet MAO inhibition and dosage per unit body weight. High percent MAO inhibition in platelets at two weeks is associated with greater improvement after a six-week course of treatment. Our data show that a safe, effective phenelzine dose in 1 mg/kg body weight per day. These results have delineated the pharmacologic and therapeutic effects of phenelzine and support a continuing role for MAO inhibitors in psychopharmacology.

Acetylation

Monoamine metabolism in human brain.

Norepinephrine (NE), dopamine (DA), tyrosine hydroxylase (TH), catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO) levels were measured in human brain tissue obtained at autopsy from a series of 39 patients dying of various medical and accidental causes. The nine following brain areas were studied: globus pallidus, thalamus, hypothalamus, hippocampus, substantia nigra, floor of the fourth ventricle, orbital cortex, caudate nucleus, and mammillary bodies. Enzyme activity correlated positively with age in all brain areas for MAO (with both benzylamine and tryptamine substrates) but no consistent pattern of correlation was found for COMT and TH. Mean MAO activity was significantly higher in women than men. There is increased brain MAO activity during late childhood and adolescence. These data are consistent with previous evidence suggesting that age and sex are important determinants of amine metabolism in the human central nervous system.

Adolescent

Clearing factor lipase (lipoprotein lipase) activator. A method for the measurement of the net activating ability of human sera.

The hydrolysis of an emulsified triglyceride substrate by clearing factor lipase (lipoprotein lipase) normally requires the presence of particular activating polypeptide species. These are present in serum, together with other inhibitory species, as part of the serum lipoproteins. The paper describes a method whereby the net activating ability of individual human sera may be measured routinely. In a normal population, this activating ability is shown to be correlated positively with the fasting serum triglyceride concentration. As the fasting triglyceride concentration increases, there is a rise in the proportion of the total activating ability that is associated with the very low density lipoproteins. A dietary fat load does not raise the total activating ability but does increase the proportion of the total that is associated with the serum lipoproteins of lowest density.

Animals

A study of the interrelationship between the triacylglycerol and protein components of very-low-density lipoproteins using the perfused rat liver.

High and low rates of very-low-density-lipoprotein triacylglycerol release from the perfused rat liver were achieved by using livers taken respectively from animals that had been given fructose for 48h or from animals that had been starved for 18h. 2. The higher rates of very-low-density-lipoprotein triacylglycerol release by the livers of the fructose-fed rats were associated with higher rates of very-low-density-lipoprotein protein release. 3. When the livers were perfused in the presence of [3H]leucine, radioactivity was incorporated into the very-low-density-lipoprotein apoproteins. The higher rates of very-low-density-lipoprotein triacylgycerol and protein release by the livers of fructose-fed rats were associated with a greater total incorporation of radioactivity into those apoproteins that entered the running gel during polyacrylamide-gel electrophoresis. However, the distribution of radioactivity among the various apoproteins was not significantly changed by the dietary treatments used.

Acrylamides