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Biomedical subjects

S Kaufman

Publications and source records attributed to S Kaufman.

At least 325 records · Page 18Linked to original sources

Biosynthesis of biopterin by rat brain.

A method for the determination of [14C]biopterin biosynthesis from [14C]guanosine-5'-triphosphate by a desalted preparation from rat striatum, based on sequential reverse-phase and cation-exchange high performance liquid chromatography, is described. Synthesis of reduced forms of biopterin by this striatal extract was found to be dependent on enzymatic activity, guanosine-5'-triphosphate, magnesium ions, and a reduced pyridine nucleotide. As demonstrated by the technique of isotope dilution, isotope trapping, 6-lactyl-7,8-dihydropterin (sepiapterin) was found to be an intermediate in biopterin biosynthesis that is catalyzed by the striatal extract. Rat brain was also shown to synthesize biopterin in vivo from intraventricularly administered [14C]guanosine or sepiapterin. Intraventricular injection of sepiapterin increased dihydro- and 5,6,7,8-tetrahydrobiopterin levels in rat brain by more than eightfold. The temporal relationship between the appearance of dihydro- and 5,6,7,8-tetrahydrobiopterin following intraventricular injection of sepiapterin suggests that dihydrobiopterin is the immediate product of sepiapterin reduction which is then reduced further to the functional cofactor 5,6,7,8-tetrahydrobiopterin. Therefore, in contrast to previous reports, the biosynthesis of biopterin by rat brain does not appear to differ from that occurring in other, nonneural tissues.

Animals↗

Effect of stimulating right atrial receptors on renal blood flow.

This investigation was undertaken to determine the effect of stretching the superior vena caval--right atrial (SVC-RA) junction and the right atrial appendage on blood flow to the kidney (RBF) and to establish whether any changes observed were influenced by the input from the baroreceptors in the carotid sinus. The experiments were performed on seven dogs, anaesthetized with alpha-chloralose. The systemic arterial (i.e., renal perfusion) pressure was held constant. At a carotid sinus pressure (CSP) of 59.0 +/- 1.2 mmHg (1 mmHg = 133.322 Pa), the RBF increased from 218 +/- 16.1 to 231.7 +/- 18.4 mL/min per 100 g renal mass (p less than 0.025). At a CSP of 88.0 +/- 3.5 mmHg, the RBF increased from 230.1 +/- 19.2 to 237.1 +/- 19.2 mL/min per 100 g renal mass (p less than 0.05). At a CSP of 137 +/- 3.7 mmHg there were no significant changes in RBF. These responses were abolished by cutting (four dogs) or cooling the vagi (one dog only). In a subsidiary investigation it was shown that stretching the SVC-RA junction activated receptors in the endocardial surface of the right atrium which discharged into myelinated fibres in the vagi, having an average conduction velocity of 8.1 m/s (range 3.8-15). It is concluded that stimulation of right atrial receptors increases the RBF and that this response is influenced by the input from the baroreceptors in the carotid sinus.

Animals↗

Intrahepatic abscess as a complication of long-term percutaneous internal biliary drainage.

One hundred five patients with obstructive jaundice have undergone percutaneous transhepatic internal biliary drainage at the Johns Hopkins Hospital. Many of these patients subsequently underwent corrective or palliative surgery, whereas other died of malignant disease after relatively short periods of catheter decompression, Seven of these patients with percutaneous internal biliary drainage, however, have been followed for over 8 months. Three of these seven patients developed intrahepatic abscesses at a mean of 16 months after catheter placement. Two of the three patients died of sepsis. In two of the patients the abscesses communicated with the biliary tree, in the third it did not. Intrahepatic abscess formation may be a common complication of long-term percutaneous transhepatic internal biliary drainage, and it should be suspected in any patient with fever or signs of sepsis who has been followed with catheter drainage for over 6 months.

Adenoma, Bile Duct↗

Use of tetrahydropterins in the treatment of hyperphenylalaninemia due to defective synthesis of tetrahydrobiopterin: evidence that peripherally administered tetrahydropterins enter the brain.

Substantial amounts of tetrahydrobiopterin and 6-methyltetrahydropterin can be detected in CSF when these pterins are given peripherally to patients with hyperphenylalaninemia due to defective biopterin synthesis. Results of this study suggest that administration of either of these pterins in proper doses may prove to be a treatment not only for the impaired peripheral phenylalanine metabolism, but also for the neurologic disorders that are characteristic of the variant forms of hyperphenylalaninemia due to defective tetrahydrobiopterin synthesis or metabolism.

Biopterins↗

Biosynthesis of biopterin: adrenergic cyclic adenosine monophosphate-dependent inhibition in the pineal gland.

Pineal glands in organ culture synthesize and release biopterin and are able to maintain concentrations of biopterin occurring in vivo for up to 54 hours in vitro. The intracellular biopterin content is reduced 50 percent by treatment with l-norepinephrine or cyclic adenosine monophosphate derivatives, but not by d-norepinephrine. This is an indication that biopterin levels are regulated by an adrenergic cyclic adenosine monophosphate-dependent mechanism. The decline in tissue biopterin content, produced mainly by inhibited of biosynthesis, is maximal at 6 hours and is not associated with either an increase in biopterin release or a shift in the reduction state of the biopterin.

1-Methyl-3-isobutylxanthine↗

Rat liver phenylalanine hydroxylase. Activation by sulfhydryl modification.

Upon reaction with N-ethylmaleimide, a single sulfhydryl residue/Mr = 50,000 subunit of phenylalanine hydroxylase is modified. This modification is accompanied by a 20-30-fold increase in hydroxylase activity when the activity is measured with tetrahydrobiopterin as cofactor. The N-ethylmaleimide-modified enzyme exhibits many of the characteristics of phenylalanine hydroxylase activated by partial proteolysis or by exposure to phospholipids. For example, a change from sigmoid to hyperbolic kinetics with varying phenylalanine concentration is observed, in addition to broadened substrate specificity and a dependence on phenylalanine hydroxylase stimulator protein at pH 6.8. The binding of phenylalanine to phenylalanine hydroxylase in the absence of pterin cofactor has also been studied. The native enzyme exhibits a sigmoidal phenylalanine binding curve. The N-ethylmaleimide-modified enzyme shows a hyperbolic response to phenylalanine binding in addition to an apparent decrease in total phenylalanine binding.

Animals↗

Peripherally administered reduced pterins do enter the brain.

The content of tetrahydrobiopterin in rat brain was doubled by peripherally administered tetrahydrobiopterin, with the natural 1 diastereoisomer more effective than the unnatural d configuration. The model pteridine, 6-methyltetrahydropterin was ten times more efficient than tetrahydrobiopterin in crossing the blood-brain barrier, and striatal concentrations of 6-methyltetrahydropterin remained elevated for 2 hours, declining with a half-life of 3 hours. While no evidence for a specific uptake mechanism for concentrating 6-methyltetrahydropterin in cells containing tetrahydrobiopterin was detected, the pterin was found in ts presumed site of action, the nerve terminal. Replacement therapy with reduced pterins may therefore be effective in the treatment of the neurological disorders associated with the variant forms of hyperphenylalaninemia that result from defects in the biosynthesis or metabolism of tetrahydrobiopterin within the central nervous system.

Animals↗

Stretch-induced growth of skeletal myotubes correlates with activation of the sodium pump.

Skeletal myotubes responded to passive stretch by increased amino acid uptake (as measured with [3H]alpha-aminoisobutyric acid), increased incorporation of amino acids into total cellular protein and myosin heavy chains, and increased accumulation of total cellular protein and myosin heavy chains. These alterations were preceded by an increase in the uptake of ouabain-sensitive rubidium-86 (86Rb+), a potassium tracer used to measure membrane sodium pump activity (Na+K+ATPase). This stretch-induced stimulation of 86Rb+ uptake resulted from a 60-70% increase in the Vmax of the Na pump with little change in the Km. [3H] ouabain binding studies showed no stretch-induced change in the number of membrane Na pumps, indicating that stretch activates the Na pumps that are already present on the cell surface. Since the stretch-induced increases in amino acid transport and amino acid incorporation into proteins were inhibited by ouabain, Na pump activation may be involved in stretch-induced cell growth of skeletal muscle cells by hypertrophy.

Aminoisobutyric Acids↗

Parenteral hyperalimentation in surgical patients with head and neck cancer: a randomized study.

Sixty-nine patients were entered in a randomized study to determine the usefulness and practicality of parenteral hyperalimentation (TPN) in preparing and supporting patients with head and neck cancer undergoing radical resections. The patients were stratified by nutritional status and prognosis and randomization were done within each strata to TPN or control. Minimum full TPN was given at 35 calories/kgm/day for at least 14 days postoperatively. Eight patients received preoperative TPN also. Control patients received customary enteral alimentation by feeding tubes. Under the conditions of this particular study, the administration schedules, and type of solutions used, we were unable to demonstrate any superiority of TPN over conventional enteral nutrition in terms of immune parameters, wound healing, complications, and survival.

Body Weight↗

Leukocyte alkaline phosphatase in cancer patient.

Leukocyte alkaline phosphatase (LAP) activity in peripheral blood was determined in 113 patients with non-metastatic malignancies, 36 patients with metastatic spread, and 22 individuals who served as controls. The LAP score of the non-metastatic cancer patients was significantly higher (p less than 0.001) than the controls, and the score of the metastatic group was further increased significantly as compared to both control (p less than 0.001) and non-metastatic groups (p less than 0.001). The results of this survey suggest that the level of LAP score in peripheral blood might be used to differentiate between non-metastatic and metastatic disease and might serve as an aid in prognosis of the patients.

Alkaline Phosphatase↗

Factor XIII deficiency.

A girl and her newborn brother with factor XIII deficiency from a family, which has not previously been reported, as described; two other Israeli families are reviewed. The sexes are equally affected. In two of the three families there was consanguinity among the parents. The families fit autosomal recessive inheritance and rule out X-linked recessive mode of transmission. The proposita was born to unrelated healthy parents from the Bnei Israel Jewish community of Bombay. She was re-admitted to hospital at the age of 15 days after umbilical bleeding. Later in infancy there were repeated haematomata and the diagnosis of factor XIII deficiency was established at the age of 1 1/2 years.

Child↗

Effect of cyclic AMP-dependent protein phosphorylating conditions on the pH-dependent activity of tyrosine hydroxylase from beef and rat striata.

Tyrosine hydroxylase (TH, EC 1.14.16.2) from beef brain striata was purified 23-fold from an extract of an acetone powder. If this enzyme preparation is treated with a cyclic AMP[-dependent protein phosphorylation system, there is a change in the pH dependence of the enzyme activity. The pH optimum at saturating tetrahydrobiopterin (BH4) concentration is shifted from below pH 6 to about pH 6.7. At pH 7, activation is expressed mainly as an increase in Vmax, whereas at pH 6, activation is expressed mainly as a decrease in Km for the pterin cofactor. Further, even with the control enzyme the Km for pterin cofactor declines precipitously as the pH is increased from 6 toward neutrality. Similar data were obtained with G-25 Sephadex-treated rat striatal TH. Experiments in which rat striatal synaptosomes were used demonstrated that the in situ activation of TH by phosphorylating conditions is expressed primarily as an increase in the maximum rate of dopamine synthesis. These results indicate that changes in TH activity caused by cyclic AMP-dependent protein phosphorylation will depend to a large extent on the pH of the TH environment.

Animals↗

The dipsogenic activity of prolactin in male and female rats.

1. Ovine prolactin injected intravenously in doses of 10.0, 5.0, 1.0, 0.1 and 0 mg/kg body wt. caused neither drinking nor a change in urine output in normal water replete male and female rats. 2. The water intake of male rats subjected to 48 hr water deprivation was substantially increased after injection of prolactin. 3. The water intake of male and female rats injected I.P. with a hyperoncotic solution of polyethylene glycol (20 M) was significantly increased after injection of prolactin. 4. Prolactin ws found to act synergistically with a subthreshold dose of angiotensin II amide to cause significant drinking and fluid retention. 5. The drinking responses of male and female rats injected I.V. with hypertonic saline were not modified by prolactin. 6. It is concluded that prolactin may act to increase the net water gain of animals suffering a deficit of the extracellular fluid space but is without effect on stimuli arising from deficits in the intracellular fluid space.

Angiotensin II↗