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Biomedical subjects

S Kaufman

Publications and source records attributed to S Kaufman.

At least 235 records · Page 13Linked to original sources
PubMed1988

Effect of alkaline pH on the activity of rat liver phenylalanine hydroxylase.

The pH optimum of rat liver phenylalanine hydroxylase is dependent on the structure of the cofactor employed and on the state of activation of the enzyme. The tetrahydrobiopterin-dependent activity of native phenylalanine hydroxylase has a pH optimum of about 8.5. In contrast, the 6,7-dimethyltetrahydropterin-dependent activity is highest at pH 7.0. Activation of phenylalanine hydroxylase either by preincubation with phenylalanine or by limited proteolysis results in a shift of the pH optimum of the tetrahydrobiopterin-dependent activity to pH 7.0. Activation of the enzyme has no effect on the optimal pH of the 6,7-dimethyltetrahydropterin-dependent activity. The different pH optimum of the tetrahydrobiopterin-dependent activity of native phenylalanine hydroxylase is due to a change in the properties of the enzyme when the pH is increased from pH 7 to 9.5. Phenylalanine hydroxylase at alkaline pH appears to be in an altered conformation that is very similar to that of the enzyme which has been activated by preincubation with phenylalanine as determined by changes in the intrinsic protein fluorescence spectrum of the enzyme. Furthermore, phenylalanine hydroxylase which has been preincubated at an alkaline pH in the absence of phenylalanine and subsequently assayed at pH 7.0 in the presence of phenylalanine shows an increase in tetrahydrobiopterin-dependent activity similar to that exhibited by the enzyme which has been activated by preincubation with phenylalanine at neutral pH. Activation of the enzyme also occurs when m-tyrosine or tryptophan replace phenylalanine in the assay mixture. The predominant cause of the increase in activity of the enzyme immediately following preincubation at alkaline pH appears to be the increase in the rate of activation by the amino acid substrate. However, in the absence of substrate activation, phenylalanine hydroxylase preincubated at alkaline pH displays an approximately 2-fold greater intrinsic activity than the native enzyme.

Animals↗
PubMed1988

Cerebrospinal fluid neurochemistry in the myoclonic subtype of Alzheimer's disease.

Monoamine metabolites, biopterin, acetylcholinesterase (AChE) activity, and somatostatin-like immunoreactivity (SLI) were determined in the lumbar cerebrospinal fluid (CSF) of 24 patients with dementia of the Alzheimer type (DAT) without myoclonus or extrapyramidal signs, in 8 patients with DAT and myoclonus, and in 14 age-matched healthy control subjects. In patients with DAT with myoclonus as compared with both DAT patients without myoclonus and control subjects, the concentrations of homovanillic acid and biopterin were significantly decreased. 5-Hydroxyindoleacetic acid was significantly lower in patients with myoclonic DAT as compared to patients with nonmyoclonic DAT, but not significantly lower than in control subjects. CSF AChE and SLI were significantly reduced in patients with DAT with or without myoclonus, as compared with control subjects, but AChE and SLI were not significantly different between dementia groups. These results suggest that DAT patients with myoclonus represent a distinct clinical and neurochemical DAT subtype.

Acetylcholinesterase↗
PubMed1988

Effect of venom sac extract of the Oriental hornet (Vespa orientalis) on coagulation factors.

Venom sac extract of the Oriental hornet significantly prolongs the prothrombin time and the activated partial thromboplastin time both in vitro in human plasma and in vivo in cats. Activity of factors VIII and IX in plasma is reduced to less than 1% within 5 min even with 1 microgram of venom sac extract per ml. The activity of purified factor VIII, as well as semipurified factors IX and X, in factor IX complex was also significantly reduced after incubation with the venom. The decrease of factors II, V, VII, X, XI and XII activity to 9%, 11%, 11%, 29%, 1.7% and 0.7% of normal, respectively, is dose- and time-dependent. Thrombin time, plasma fibrinogen and fibrin degradation products are not affected. The anticoagulant activity is not reversed by dialysis and is abolished completely by heating; it resides mainly in fractions with mol.wts above 5000. The venom has a proteolytic activity on 14C-globin which is partially inhibited by trasylol and ethylenediaminetetraacetic acid. Thus, the venom sac extract exhibits both serine and metaloprotease activities which may affect the activity of the plasma coagulation factors.

Bee Venoms↗
PubMed1988

Effect of peripherally administered atriopeptin III on water intake in rats.

1. Extracellular fluid deficits of 33% were produced in male Long-Evans rats by peritoneal dialysis. The conscious, unrestrained animals were then infused I.V. for 30 min with atriopeptin III at doses of 0.01, 0.1, 0.5 and 1.0 micrograms/min. At 5 min into the infusion, the rats were offered water and subsequent intakes were monitored. Since atrial natriuretic peptide (ANP) causes hypotension, one group of control animals was given an injection of diazoxide sufficient to match this fall in blood pressure. 2. A similar group of rats was prepared for measurement of plasma ANP achieved by infusion. 3. Relative to the saline-infused controls, atriopeptin III did not reduce water intake. Indeed, intake was increased at the highest dose of 1.0 micrograms/min. 4. Relative to the diazoxide controls, water intake was influenced by atriopeptin III in a dose-dependent manner, the greatest attenuation being observed at infusions of 0.1 microgram/min. 5. Infusion of atriopeptin III at 0.1 microgram/min caused plasma ANP levels to rise from 252 +/- 21 to 532 +/- 136 pg/ml (n = 9, P less than 0.05) at 15 min. The lowest dose (0.01 microgram/min) caused no detectable increase in plasma levels. 6. It is concluded that, in groups of hypovolaemic rats matched for blood pressure, atriopeptin III caused a dose-related reduction in water intake.

Animals↗
PubMed1988

Influence of right atrial stretch and atrial natriuretic factor on rat intestinal fluid content.

1. Studies were made on the effects of right atrial stretch and atrial natriuretic factor (ANF) infusion on fluid movement into the intestinal tract. 2. Stimulation of the atrial volume receptors by inflation of an intracardiac balloon in the conscious, unrestrained rat did not change intestinal fluid content under normovolaemic conditions. 3. When the rat was rendered hypovolaemic by peritoneal dialysis (34% deficit in extracellular fluid volume), right atrial stretch significantly increased intestinal fluid content. Under these conditions, inflation of the balloon restored large intestinal fluid content to the pre-dialysis state, i.e. right atrial stretch completely abolished that component of fluid absorption attributable to the extracellular fluid volume deficit. 4. These data suggest that stimulation of the right atrial receptors inhibits intestinal fluid reabsorption but probably does not initiate fluid secretion. 5. There was no evidence that this might be mediated by ANF since rat ANF (twenty-eight residue peptide, Ser-99-Tyr-126), infused for 1 h at doses of 0, 0.05, 0.1 and 0.5 microgram/min, did not cause any detectable changes in the fluid content of the large or small intestine of similarly prepared hypovolaemic rats.

Animals↗
PubMed1988

Stretch-induced reduction in atrial content of natriuretic factor is locally mediated.

Two groups of male Wistar rats were chronically implanted with small inflatable balloons at the right superior vena caval (SVC)-atrial junction. The balloons were inflated for 60 min in one-third of the rats in each group; the remainder served as noninflated controls. Extract was prepared from the right atria of the first and from the left atria of the second group and bioassayed in male Wistars to determine the content of atrial natriuretic factor (ANF). The bioassay rats received either two injections of sham extract (control) or an initial injection (I1) of sham extract followed by an injection (I2) of balloon-inflated extract (experimental). For right atrial extract, the incremental response to the experimental injection (I2/I1) was significantly less than the response to the control injection (experimental, 1.15 +/- 0.09 mueq/min, n = 14; control, 1.59 +/- 0.15 mueq/min, n = 13; P less than 0.01). However, in the case of left atrial extract, there was no such difference between the control group (1.35 +/- 0.13 mueq/min, n = 19) and the experimental group (1.25 +/- 0.11 mueq/min, n = 11; Student's t test). We conclude that right atrial distension causes release of ANF from the right atrium, but not the left, and that this release is probably locally mediated.

Animals↗
PubMed1988

Effect of levamisole on chemotaxis of granulocytes from uremic patients.

Uremic granulocyte chemotaxis was assessed in the presence of four different concentrations of levamisole. Chemotactic responsiveness of uremic granulocytes was significantly decreased compared to normal, both in the absence of levamisole and with all levamisole concentrations tested. However, with 10(-3) and 10(-4) M levamisole concentrations, uremic granulocyte chemotaxis was similar to that of normal granulocytes without levamisole. Defective chemotactic activity of granulocytes may play a role in the increased susceptibility of uremic patients to infections. Pharmacological correction of this defect may improve the patients' ability to cope with infections.

Adult↗
PubMed1988

1,25-Dihydroxyvitamin D-induced suppressor cells in uremic versus normal lymphocytes.

1,25-Dihydroxyvitamin D3 (DHD) has been shown to suppress mitogen-induced blast transformation. This inhibition is abolished by prior elimination of adherent cells. Chronic renal failure is an immunodeficiency state on the one hand and is associated with abnormalities in vitamin D metabolism on the other. The effect of DHD on the induction of suppressor cells in uremic vs. normal peripheral blood mononuclear cells was investigated. Study groups included 16 chronically uremic patients and 16 age- and sex-matched controls. DHD induced suppressor cell activity in normal lymphocytes. However, no suppressor cell activity was observed in lymphocytes from the uremic patients preincubated with DHD. The origin of the responder cells (normal or uremic) did not affect the outcome. The results would suggest that monocyte-adherent suppressor cells from uremic subjects are either incapable of binding DHD or fail to mount a normal post-receptor intracellular chain of events culminating in suppressor activity.

Adult↗
PubMed1988

Cerebrospinal fluid monoamine markers are decreased in dementia of the Alzheimer type with extrapyramidal features.

We measured monoamine metabolites and biopterin in the CSF of 37 patients with dementia of the Alzheimer type (DAT), with or without extrapyramidal signs, and in 14 age-matched healthy controls. Compared with concentrations in DAT and controls, the concentrations of homovanillic acid (HVA) and biopterin were significantly decreased in DAT with extrapyramidal signs (EDAT). CSF 3-methoxy-4-hydroxy-phenethyleneglycol and 5-hydroxyindoleacetic acid did not differ significantly among these groups. Age at onset of dementia was positively correlated with CSF HVA (r = 0.49, p less than 0.05). The two dementia groups did not differ significantly in the extent of ventricular dilation as measured by quantitative CT, but EDAT patients had lower Mini-Mental State Examination scores than did DAT patients. When patients were matched for age and dementia severity, CSF HVA and biopterin concentrations remained significantly lower in EDAT than in DAT patients. These results indicate that EDAT patients form a distinct subgroup of DAT with evidence of central monoamine dysfunction.

Aged↗
PubMed1988

Heavy- and free light-chain myeloma associated with peripheral polyneuropathy.

Peripheral polyneuropathy, a rare complication of multiple myeloma, is generally associated with heavy-chain M-proteins and, in very rare instances, with free light-chain myeloma proteins. Here we describe a case of multiple myeloma and polyneuropathy with both monoclonal IgG and free lambda light chains in the blood. The patient also had free lambda light chains in the cerebrospinal fluid and urine.

Female↗
PubMed1987

Activation of rat caudate tyrosine hydroxylase phosphatase by tetrahydropterins.

Tyrosine hydroxylase phosphatase activity in rat caudate nucleus was separated into three peaks by chromatography on DEAE-cellulose. [32P]Tyrosine hydroxylase phosphorylated by cyclic AMP-dependent protein kinase was dephosphorylated only by the major peak eluting at 0.3 M NaCl, while tyrosine hydroxylase phosphorylated by Ca2+-calmodulin-dependent protein kinase was also dephosphorylated by two calcium-inhibited phosphatases. The Vmax of the enzyme in the major DEAE peak was increased by 10 microM tetrahydrobiopterin (BH4) from 0.78 to 5.0 fmol min-1 mg-1 while the Km was only slightly affected, increasing from 45 to 62 pM. The activation could not be reversed by dilution. On Sephadex G-200, the enzyme was found to consist of two major forms with molecular masses of 420 and 100 kDa. In contrast to the activation of liver phosphatases by freezing with beta-mercaptoethanol, activation by tetrahydrobiopterin was not associated with a shift in the molecular weight of the phosphatase to lower molecular weight forms. Other reduced pterins, including tetrahydroneopterin, 6-methyltetrahydropterin, and 5-methyltetrahydrofolate, also activated the enzyme, while oxidized pterins had no effect. GTP, the metabolic precursor of tetrahydrobiopterin, was a potent inhibitor of the phosphatase reaction, inhibiting by 65% at a concentration of 1 microM. These findings suggest a close regulatory interrelationship between the tetrahydrobiopterin synthetic pathway and catecholamine biosynthesis.

Animals↗
PubMed1987

Interaction of tyrosine hydroxylase with ribonucleic acid and purification with DNA-cellulose or poly(A)-sepharose affinity chromatography.

Tyrosine hydroxylase in bovine adrenal medulla was activated up to fourfold by incubation with low concentrations (15 micrograms/ml) of ribonucleic acids. At higher RNA concentrations, enzyme activity was inhibited. This interaction with RNA was exploited with the use of poly(A)-Sepharose and DNA-cellulose to effect a rapid purification of stable tyrosine hydroxylase from rat brain and bovine adrenal medulla in high yield (up to 58%). With the purified rat brain enzyme, RNA acted as an uncompetitive inhibitor, a concentration of 15 micrograms/ml lowering the Vmax of tyrosine hydroxylase from 1050 to 569 nmol min-1 mg-1 and lowering the Km for tyrosine from 6.1 to 3.6 microM. With the natural cofactor, tetrahydrobiopterin (BH4), two Km values were obtained, indicating the presence of two forms of the enzyme. Both Km values were decreased only slightly by RNA. The purified brain and adrenal enzymes both contained about 0.07 mol of phosphate/63,000-Da subunit; in both cases, cyclic AMP-dependent protein kinase catalyzed the incorporation of an additional 0.8 mol of phosphate/subunit. The purified enzyme also contains ribonucleic acid, which comprises about 10% of the total mass and appears to be important for full activity.

Animals↗
PubMed1987

The oxidation of apomorphine and other catechol compounds by horseradish peroxidase: relevance to the measurement of dihydropteridine reductase activity.

It has been reported by Shen et al. (Shen, R.-S., Smith, R.V., Davis, P.J. and Abell, C.W. (1984) J. Biol. Chem. 259, 8894-9000) that apomorphine and dopamine are potent, non-competitive inhibitors of quinonoid dihydropteridine reductase. In this paper we show that apomorphine, dopamine and other catechol-containing compounds are oxidized rapidly to quinones by the horseradish peroxidase-H2O2 system which is used to generate the quinonoid dihydropterin substrate. These quinones react non-enzymatically with reduced pyridine nucleotides, depleting the other substrate of dihydropteridine reductase. When true initial rates of dihydropteridine reductase-dependent reduction of quinonoid dihydropterins are measured, neither apomorphine nor any other catechol-containing compound that has been tested has been found to inhibit dihydropteridine reductase.

Animals↗
PubMed1987

Physical and genetic localization of quinonoid dihydropteridine reductase gene (QDPR) on short arm of chromosome 4.

A portion of a cDNA clone corresponding to the 3' end of the human quinonoid dihydropteridine reductase (QDPR) mRNA was used as a probe to physically map the QDPR gene by analysis of somatic cell hybrid lines. The provisional assignment of QDPR to chromosome 4, based on expression of the human enzyme in hybrids, was confirmed. The gene was further regionally localized on the short arm to 4p16.1----4p15.1. This physical localization places QDPR in the same area of the genome that contains the defect causing Huntington's disease (HD). The QDPR probe revealed a restriction fragment length polymorphism with the enzyme BanII, permitting determination of its genetic proximity to D4S10, an anonymous DNA marker tightly linked to HD. QDPR is only loosely linked to D4S10, excluding any primary role for the gene in HD.

Animals↗