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Biomedical subjects

S Kaufman

Publications and source records attributed to S Kaufman.

At least 361 records · Page 20Linked to original sources
PubMed1980

Chronic, nonocclusive, and maintenance-free central venous cannula in the rat.

To provide a means of taking repeated blood samples from conscious, stress-free rats, we devised a method to chronically cannulate the inferior vena cava. The rat was anesthetized with pentobarbital sodium plus methoxyflurane. The inferior vena cava was exposed through a midline abdominal incision. Silastic tubing (0.020 in. ID, 0.037 in. OD) was pushed through a tiny hole punctured in the wall of the vein; it remained in place without leaking due to the elasticity of the vessel wall. The cannula was advanced towards the heart until its tip lay at the level of the xiphisternum at which point blood could be aspirated. A series of silk (4-0) sutures to the psoas muscle and body wall held the cannula secure without compromising blood flow. The cannula ran subcutaneously to the back of the neck where it was ligated to the underside of the skin (prolene 4-0 suture), plugged with a short metal obturator, and exteriorized through a small stab wound. The cannula was filled with heparinized saline, but it was not necessary to regularly flush it through to maintain patency. Sepsis did not occur and animals autopsied several months after cannulation showed no tissue reaction around the cannula.

Animals↗
PubMed1980

Regulatory drinking in the pigeon Columba livia.

Pigeons were subjected to stimuli known to induce regulatory drinking in mammals. Water-satiated birds drank in response to intravenous (iv) hypertonic NaCl, intraperitoneal (ip) hyperoncotic polyethylene glycol (PEG) (20 M), iv infusions of angiotensinamide, subcutaneous (sc) isoprenaline, and iv chicken kidney extract. Intravenous porcine renin failed to elicit a major drinking response. Drinking after water deprivation was reduced by an iv preload of isotonic saline. Water intake after iv hypertonic NaCl equaled the volume required for dilution to isotonicity. Water intake in response to ip PEG was larger than in rats and resulted in a parallel increase in body weight. Sensitivity to isoprenaline and angiotensinamide was less than or equal to that of rats although pigeons drank much more. Drinking responses to iv hypertonic NaCl plus ip hyperoncotic PEG were additive. Small (5 ml/kg body wt) blood losses induced delayed (after 4 h) drinking; larger blood losses were ineffective. There was no simple additive relationship between the responses to hemorrhage and hypertonic saline. In summary, the dipsogenic response of pigeons was much greater than that of mammals although sensitivity was sometimes higher and sometimes lower.

Angiotensin Amide↗
PubMed1980

Recurrent traumatic hyphema due to increased local fibrinolysis.

A 20-year-old male was injured in his right eye by the stopper of a bottle filled with carbonated fruit juice. The contusion caused a recurrent hyphema which lasted approximately 6 weeks and responded to epsilon-aminocaproic acid treatment. Among the investigations for coagulation and fibrinolysis, the only pathological laboratory finding was a shortened plasma euglobulin clot lysis time (1.5 h) which returned to normal (4--5 h) following the epsilon-aminocaproic and treatment.

Adult↗
PubMed1980

Symptomatology in head and neck cancer: a quantitative review of 385 cases.

Symptom durations in head and neck cancer patients analyzed as a function of tumor stage suggest a reversal of the "common sense" notion that patients with early disease generally present with a shorter symptomatic period. A possible explanation is that variation in stage at diagnosis is primarily due to intrinsic differences in tumor aggressiveness rather than patient delay. This would imply that early detection programs may be incapable of realizing the potential for improved survival commonly ascribed to them.

Head and Neck Neoplasms↗
PubMed1980

Hyperphenylalaninemia due to dihydropteridine reductase deficiency: diagnosis by measurement of oxidized and reduced pterins in urine.

Hyperphenylalaninemia due to dihydropteridine reductase deficiency results from the inability to maintain the aromatic amino acid hydroxylase cofactor, tetrahydrobiopterin, in its reduced or active form. Diagnosis of the disease is usually made by direct enzymatic assay on liver biopsies or in cultured skin fibroblasts. Evidence is presented that normal children and classic phenylketonuric children excrete mainly tetrahydrobiopterin in their urines, whereas children with dihydropteridine reductase deficiency excrete only oxidized forms of biopterin. Details of a rapid high performance liquid chromatographic assay for the measurement of the various forms of biopterin in urine are presented. This assay can be used to screen for suspected dihydropterine reductase mutants.

Adult↗
PubMed1980

Effect of jogging on serum low density lipoprotein cholesterol.

The effects of jogging on serum lipids were assessed in 16 normolipidemic males who ran an average of 5.8 miles (9.3 kilometres) per week for 6 weeks. There was no change in serum triglyceride concentration or clearance nor in HDL-cholesterol, but both total and LDL-cholesterol concentrations decreased significantly, by 5.7 and 8.3% respectively. Individual decreases in LDL-cholesterol were correlated with the distance run and it seems probable tht a stimulatory effect of exercise on LDL catabolism was responsible. These findings suggest a possible explanation for the known protective effect of exercise against coronary heart disease, even when taken in amounts insufficient to raise HDL-cholesterol.

Adult↗
PubMed1979

The activity of 2,4,5-triamino-6-hydroxypyrimidine in the phenylalanine hydroxylase system.

The pyrimidine moiety of a pterin, 2,4,5-triamino-6-hydroxypyrimidine, has been found to be active in the phenylalanine-hydroxylating system. The phenylalanine-dependent, phenylalanine hydroxylase-catalyzed reaction in the presence of the pyrimidine is largely, but not completely, uncoupled; the ratio of DPNH oxidized to tyrosine formed is about 20 to 1. In addition to the pyrimidine having activity with phenylalanine hydroxylase, a product of the pyrimidine is also a substrate for dihydropteridine reductase. The activity of the pyrimidine with the hydroxylase indicates that neither carbon atoms 6 or 7 of the pterin ring is involved in activation of oxygen during the hydroxylase-catalyzed reaction.

Animals↗
PubMed1979

The mechanism of the irreversible inhibition ofrat liver phenylalanine hydroxylase due to treatment with p-chlorophenylalanine. The lack of effect on turnover of phenylalanine hydroxylase.

The administration of a single dose of p-chlorophenylalanine (360 mg/kg) to rats leads to the irreversible loss of 90% of hepatic phenylalanine hydroxylase activity after 24 h. This loss of activity is not the result of either an alteration in the overall structure of the enzyme, as determined by its antigenicity, or in the total immunologically reactive protein in the liver, as tested with a specific antiserum prepared against native phenylalanine hydroxylase. Neither the rate of synthesis nor the rate of degradation of phenylalanine hydroxylase is changed by p-chlorophenylalanine (pClPhe) treatment. The half-life for the enzyme is about 2 days in control and in pClPhe-treated rats. In addition, there is no detectable incorporation of pClPhe into the phenylalanine hydroxylase molecule itself.

Animals↗
PubMed1979

In vitro model for stretch-induced hypertrophy of skeletal muscle.

Mechanical stretch of embryonic chicken skeletal myotubes developed in vitro leads to many of the biochemical changes seen in skeletal muscle hypertrophy. These include increased amino acid accumulation, increased incorporation of amino acids into general cellular proteins and myosin heavy chains, and increased accumulation of total protein and myosin heavy chains. This model system should aid in understanding how the growth rate of skeletal muscle is regulated by its activity.

Amino Acids↗
PubMed1979

5-drug adjuvant chemotherapy for breast cancer.

A series of 41 patients at the MGH who received 5-drug chemotherapy, cyclophosphamide, methotrexate, 5-fluorouracil, vincristine and prednisone, (CMF VP) as adjuvant to surgical treatment of operable breast cancer with 4 or more positive axillary nodes is compared to an analogous group of patients treated with cyclophosphamide, methotrexate and 5-fluorouracil (CMF) reported by Bonadonna et al. in an effort to assess the contribution of the treatment program to disease control. The MGH pattern of disease free survival closely parallels that of Bonadonna. Median disease-free survival among the 24 patients who have not recurred is 27 months; among those who recurred 18 months. The analogous medians for treated patients in the Bonadonna study are 24 months and 16 months, as compared to 27 months and 8 months for his nontreated controls. The treatment program, carried out over a two year period, was well tolerated with excellent patient compliance. There was no significant impact, however, in the disease-free survival of postmenopausal patients. While use of this regimen improved disease-free survival in premenopausal individuals, it is clear that a great deal of room for improvement exists, and newer regimens should be investigated.

Antineoplastic Agents↗
PubMed1979

A prospective study of the course of Crohn's disease.

To better define the course of Crohn's disease, certain clinical, laboratory, and radiological features were studied prospectively in a representative group of 25 patients at intervals of up to 77 months. Eleven variables of potential use in assessing the course were analyzed for clinician preference, and the statistical relationship of one variable, the Crohn's disease activity index, to the other 10 was determined. Modest improvement was documented in three clinical variables, as well as in anemia, serum albumin, intestinal protein loss, and radiological extent of disease. Variables most frequently ranked high as reflections of the course of Crohn's disease were hematocrit and extent of disease, followed by body weight, stools per day, B12 absorption, serum albumin, and intestinal protein loss. The highest intervariable correlation was between improvement in protein loss and decrease in radiological extent (r = 0.75).

Adolescent↗
PubMed1979

Dihydropteridine reductase deficiency associated with severe neurologic disease and mild hyperphenylalaninemia.

A deficiency of hepatic dihydropteridine reductase (DHPR) activity was found in a neurologically impaired infant with mild hyperphenylalaninemia and normal levels of hepatic phenylalanine hydroxylase. DHPR is required for the regeneration of tetrahydrobiopterin, an essential cofactor in aromatic amino acid hydroxylation, a necessary step in the biosynthesis of the neurotransmitters, dopamine and serotonin. Evidence for decreased synthesis of these transmitters in this patient was provided by the finding of reduced levels of homovanillic acid and 5-hydroxyindole acetic acid, metabolites of dopamine and serotonin, respectively, in the cerebrospinal fluid and urine. Treatment with dopamine and serotonin precursors, L-3,4 dihydroxyphenylalanine and 5-hydroxytryptophan, respectively, was associated with improvement in temperament and motor tone and less frequent seizures. However, there was no improvement in gross motor function or language development.

5-Hydroxytryptophan↗
PubMed1978

Glucagon stimulation of rat hepatic phenylalanine hydroxylase through phosphorylation in vivo.

Phenylalanine hydroxylase activities in extracts of livers from rats pretreated with glucagon are higher than in controls. This time-dependent activation is seen when the hydroxylase is assayed in the presence of tetrahydrobiopterin, but not in the presence of 2-amino-4-hydroxy-6,7-dimethyltetrahydropterin. A maximum 4-fold stimulation of hydroxylase activity was correlated with a conversion of the multiple forms of the enzyme to a single form. This form is characterized by an increased extent of phosphorylation compared to the unactivated enzyme. Incorporation of radioactive inorganic phosphate into phenylalanine hydroxylase following administration of glucagon was determined after specific immunoprecipitation of the enzyme from partially purified preparations. Sodium dodecyl sulfate disc gel electrophoresis showed that stimulation of enzyme activity is accompanied by incorporation of 32Pi into the protein to the extent of 0.7 mol/mol of hydroxylase subunit. These results demonstrate the phosphorylation of hepatic phenylalanine hydroxylase in vivo and strongly support the idea that the activity of this enzyme can be hormonally regulated through a phosphorylation mechanism.

Animals↗
PubMed1978

Hyperphenylalaninemia due to a deficiency of biopterin. A variant form of phenylketonuria.

We studied the components of the hepatic phenylalanine hydroxylating system in a child with phenylketonuria who showed substantial neurologic impairment despite early dietary control of elevated blood phenylalanine levels. Phenylalanine hydroxylase, dihydropteridine reductase and dihydrofolate reductase activities were normal. In contrast the level of hydroxylation cofactor, tetrahydrobiopterin, in liver was only 10 per cent of normal. In addition to this hepatic deficiency, serum and urinary levels of biopterin-like compounds were low, and the serum biopterin did not increase in response to a phenylalanine load as it does in normal and phenylketonuric subjects. The phenylalanine hydroxylase activity in this child, as determined by an in vivo tritium-release assay, was 2.3 per cent of the normal value. These results indicate that the child suffers from a variant form of phenylketonuria--a deficiency of a functional phenylalanine hydroxylating system secondary to a defect in biosynthesis of biopterin.

Administration, Oral↗
PubMed1978

Hyperphenylalaninaemia due to dihydropteridine reductase deficiency.

Two siblings with increased levels of serum phenylalanine were detected by newborn screening. The older sibling deteriorated neurologically and mentally, despite early dietary control, and died at the age of 6 1/2 years. In the younger sibling phenylalanine hydroxylase activity in liver tissue was normal. Further investigations revealed increased concentrations of biopterin derivatives in the blood, a low excretion of 5-hydroxyindole acetic acid in the urine, and a dihydropteridine reductase deficiency as the cause of hyperphenylalaninaemia. The parents of the siblings showed 50% of the normal dihydropteridine reductase activity in their fibroblasts grown in culture. Neurotransmitter therapy was started in the second child at the age of 6 months and this was followed by distinct neurological and mental improvement.

Amino Acid Metabolism, Inborn Errors↗