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Biomedical subjects

S Kaufman

Publications and source records attributed to S Kaufman.

At least 271 records · Page 15Linked to original sources
PubMed1986

Cerebrospinal fluid biopterin is decreased in Alzheimer's disease.

Tetrahydrobiopterin is the cofactor in the hydroxylation of phenylalanine, tyrosine, and tryptophan leading to the eventual synthesis of the monoaminergic neurotransmitters, dopamine, norepinephrine, and serotonin, respectively. Total biopterin (90% of which is in the tetrahydro form) was measured in cerebrospinal fluid (CSF) and plasma of 30 patients with Alzheimer's disease and of 19 healthy controls. Plasma and CSF biopterin concentrations were not significantly correlated, but the mean CSF biopterin concentration in patients with Alzheimer's disease was significantly less than in age-matched controls, 13.5 pmol/mL as compared with 18.9 pmol/mL. The CSF biopterin concentration was not correlated with ventricular volume, as estimated by quantitative computed tomography, nor with the severity of dementia, as measured by various cognitive tests. The results suggest that a central biopterin deficiency exists in Alzheimer's disease.

Adult↗
PubMed1986

Regulation of the activity of hepatic phenylalanine hydroxylase.

Rat liver phenylalanine hydroxylase catalyzes the tetrahydropterin-dependent oxidation of phenylalanine to tyrosine, according to equation 1. In addition to the naturally-occurring coenzyme, tetrahydrobiopterin (BH4), certain synthetic analogs of BH4 such as 6-methyltetrahydropterin (6MPH4) have high cofactor activity. (formula; see text) The hydroxylase can be activated by a variety of reversible and irreversible modifications, including those caused by partial proteolysis, by interaction with phospholipids such as lysolecithin, by alkylation of a single sulfhydryl group, by phosphorylation catalyzed by cAMP-dependent protein kinase, and by preincubation with its substrate, phenylalanine. All of these modes of activation greatly increase the hydroxylase activity in the presence of BH4, whereas the activity in the presence of 6MPH4 is increased only slightly. The ratio of hydroxylase activity in the presence of BH4 compared to the activity in the presence of 6MPH4, therefore, is a useful index of the state of activation of the enzyme. Of the various activation mechanisms listed above, only phosphorylation of the enzyme and phenylalanine-activation appear to operate in vivo. The evidence indicates that these two regulatory mechanisms act synergistically. Thus, phosphorylation of the enzyme by cAMP-dependent protein kinase is stimulated by phenylalanine, especially in the presence of BH4, (which by itself inhibits), whereas phosphorylation sensitizes the enzyme to activation by phenylalanine. One of the consequences of these interlocking control mechanisms is to enhance the responsiveness of the activity of the hydroxylase to alterations in tissue levels of phenylalanine. As a result, elevated concentrations of phenylalanine can be rapidly metabolized, thereby protecting the fetal and neonatal brain from possible damage by excess phenylalanine.

Animals↗
PubMed1986

A modified ferrozine method for the measurement of enzyme-bound iron.

A general procedure for the determination of the iron content of enzymes by digestion with methanesulfonic acid to release protein-bound iron has been developed. This procedure replaces the tedious and potentially hazardous method of wet ashing with concentrated nitric-sulfuric-perchloric acids. The method has been used to determine the stoichiometry of iron for nanomole quantities of heme-iron proteins, iron-sulfur proteins, complex iron-sulfur proteins, as well as in phenylalanine hydroxylase, an enzyme with iron in an undetermined coordination.

Catalase↗
PubMed1986

Stroke: health care on the periphery.

A study of decision-making among health providers who work with stroke patients provided information concerning stroke rehabilitation ideology and practice. Data collected from 32 professionals on the meaning of rehabilitation in relation to stroke revealed that stroke rehabilitation is considered to be on the periphery of American health care. Three factors contribute to the peripheral status of stroke rehabilitation: the health care system devalues rehabilitation; stroke rehabilitation differs from acute care medicine; and stroke is viewed as a geriatric problem.

Attitude of Health Personnel↗
PubMed1986

Gaucher's disease associated with chronic lymphocytic leukaemia.

The association of Gaucher's disease with chronic lymphocytic leukaemia (CLL) is very rare. To our knowledge only five cases have been reported (Chang-Lo, Yam & Rubenstone 1967; Chang-Lo et al. 1975; Fox et al. 1984; Lee 1982; Mark, Dominguez & Rywlin 1982). We report a patient with this association, the CLL had been diagnosed 12 years after the demonstration of Gaucher's disease.

Bone Marrow Cells↗
PubMed1986

Primary pulmonary Hodgkin's disease with air bronchogram.

A 30-year-old woman presented with a large pulmonary mass and air bronchogram. Hodgkin's disease of the nodular sclerosing type was diagnosed. Survival was short despite aggressive treatment. Primary pulmonary Hodgkin's disease is extremely rare. This is the first reported case of its presentation with an air bronchogram.

Adult↗
PubMed1986

Induction of suppressor cells in normal lymphocytes by uremic serum.

Sera of patients on chronic hemodialysis induced suppressor cell activity (SCA) in normal peripheral blood mononuclear cells, which significantly impaired blastogenic response to PHA. This SCA is statistically not different from Con A induced SCA. Both SCAs are however additive. Speculations concerning the modes of action of this induced SCA are discussed.

Adult↗
PubMed1986

Immunoregulatory defect in patients with autoimmune thrombocytopenic purpura (ATP).

Con A-induced suppressor cells were studied in 20 patients with autoimmune thrombocytopenic purpura and 20 normal controls. Percentage of suppression was determined on autologous and allogenic lymphocytes during blast transformation with phytohemagglutinin (PHA). In 10 patients and 10 controls helper (T4) and suppressor (T8) subsets were also determined, using monoclonal antibodies. We found a significant decrease in patients' suppressor cell activity both with autologous and allogeneic lymphocytes. Patients' responder lymphocytes were also impaired when tested with normal suppressor cells. The numbers of T4 and T8 in patients was found to be normal although the ratio T4/T8 was somewhat lower than in normal controls. There was a significant direct correlation between the numbers of T4 of patients and their suppressor cell activity on allogeneic lymphocytes suggesting an immunoregulatory defect at the level of induction of suppressor cells.

Adolescent↗
PubMed1986

The effects of uremic serum and 3'-5' cyclic AMP on blastogenesis of normal lymphocytes.

Phytohemagglutinin (PHA) induced lymphocyte blast transformation is impaired both in uremic lymphocytes and in normal lymphocytes exposed to uremic serum. Cyclic AMP is known to inhibit blast transformation in normal and uremic lymphocytes. This investigation was undertaken to assess quantitatively the effects of uremic serum and cyclic AMP on blastogenesis of normal lymphocytes. Uremic serum or cyclic AMP significantly inhibited blast transformation of normal lymphocytes. These effects were statistically similar and cumulative. We conclude that the inhibition imposed by uremic serum on normal lymphocyte blastogenesis is predominantly mediated by a mechanism(s) different from cyclic AMP.

Cells, Cultured↗
PubMed1985

K-Sol corneal preservation.

K-Sol, a new cornea preserving solution which contains no calf serum of foreign protein and is used for refrigerated storage of donor tissue, has storage procedures identical to those currently used for tissue preservation in McCarey-Kaufman medium. K-Sol can keep corneas alive and usable for penetrating keratoplasty for at least two weeks. The clinical results in a series of 17 patients indicated that tissue preserved in K-Sol for as long as two weeks, even when used by inexperienced surgeons in difficult or unfavorable cases requiring extensive anterior segment reconstruction, including reoperations or retained intraocular lenses, gave results virtually identical to those obtained with tissue preserved in McCarey-Kaufman medium for only two or three days.

Adult↗
PubMed1985

Biosynthesis of tetrahydrobiopterin: conversion of dihydroneopterin triphosphate to tetrahydropterin intermediates.

It is known that the first step in the de novo synthesis of tetrahydrobiopterin from GTP is the conversion of GTP to dihydroneopterin triphosphate. Recent evidence supports the conclusion that beyond this first step, the pterin intermediates in the pathway are all at the tetrahydro level of reduction. We have now shown that partially purified fractions from rat liver, rat brain and bovine adrenal medulla catalyze the conversion of dihydroneopterin triphosphate to tetrahydrobiopterin, as well as to the putative intermediates in the pathway, 6-pyruvoyl-tetrahydropterin and 6-lactoyl-tetrahydropterin. Results of both enzymatic and chemical studies support the assigned structures for the latter two tetrahydropterins. We have also purified extensively from brain an enzyme, distinct from sepiapterin reductase, that catalyzes the TPNH-dependent reduction of 6-pyruvoyl-tetrahydropterin to 6-lactoyl-tetrahydropterin. The role of this reductase in tetrahydrobiopterin synthesis has not yet been established.

Adrenal Medulla↗
PubMed1985

Studies on the primary structure of rat liver phenylalanine hydroxylase.

The primary structure of phenylalanine hydroxylase purified from rat liver was investigated with high speed gel filtration chromatography, cyanogen bromide cleavage and end group analyses of polypeptides derived from the enzyme. On gel filtration in the presence of 6M guanidine hydrochloride, the enzyme gave a single peak corresponding to a molecular weight of 52,000. In the same system the enzyme that had been cleaved with cyanogen bromide gave two peptides (CB1, Mr = 32,800 and CB2, Mr = 20,400). Sequence studies showed that the alignment of these two peptides was CB1 - CB2. Furthermore, in experiments using 32P phosphorylated enzyme, the site of phosphorylation by cAMP-dependent protein kinase was found to be located on the CB1 peptide. The NH2-terminus of this enzyme, which was found to be blocked, was shown to be N-acetylalanine. By both carboxypeptidase A digestion and hydrazinolysis, the carboxyl terminus was identified as serine. These data indicate that the phenylalanine hydroxylase molecule from rat liver is composed of subunits which are homogenous or, at least, very similar in their primary structure.

Amino Acids↗
PubMed1985

Hyperphenylalaninaemia caused by defects in biopterin metabolism.

The hepatic phenylalanine hydroxylating system consists of three essential components, phenylalanine hydroxylase, dihydropteridine reductase and the non-protein coenzyme, tetrahydrobiopterin. The reductase and the pterin coenzyme are also essential components of the tyrosine and tryptophan hydroxylating systems. Recent studies have shown that there are three distinct forms of phenylketonuria or hyperphenylalaninaemia, each caused by the lack of one of these essential components. The variant forms of the disease that are caused by the lack of dihydropteridine reductase or tetrahydrobiopterin are characterized by severe neurological deterioration, impaired functioning of tyrosine and tryptophan hydroxylases and the resultant deficiency of tyrosine- and tryptophan-derived monoamine neurotransmitters in brain.

Amino Acid Metabolism, Inborn Errors↗
PubMed1985

The effect of several uremic parameters on uremic serum inhibition of lymphocyte blastogenesis.

Uremic sera are known to inhibit thymidine incorporation of normal lymphocytes. The nature of the factor(s) responsible for this inhibitory effect has not been completely elucidated. In this study a possible correlation was investigated between a number of uremic blood constituents altered with the progression of the disease and the immunoinhibitory effect of the respective sera. No such correlation was found with the values of hematocrit, urea, creatinine, calcium and phosphorus. On the other hand a significant negative correlation emerged between H+ and Mg2+ ion levels and the inhibition imposed on normal lymphocyte thymidine incorporation. This apparently paradoxical result would indicate that with regard to these two parameters the greater the severity of renal failure the smaller would be the immunoinhibitory effect of the respective serum. The inhibition imposed by uremic serum on immune functions is probably a multifactorial phenomenon, in which H+ and Mg2+ might play a role antagonistic to inhibitory factors.

Adult↗
PubMed1985

Functions of polymorphonuclear (PMN) leukocytes of patients with lymphoproliferative diseases.

PMN leukocytes from untreated patients with multiple myeloma (MM), Hodgkin's disease (HD) and non-Hodgkin lymphoma (NHL) were studied in vitro for their phagocytic and chemotactic function. Alkaline phosphatase score and the reduction of nitroblue tetrazolium (NBT) in these leukocytes were also determined. Most of the functions of PMN leukocytes from untreated patients with MM were impaired, compared to control leukocytes, while those from patients with HD and NHL were impaired only in their chemotactic response to casein and endotoxin-activated serum (EAS).

Adolescent↗