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Biomedical subjects

S Orloff

Publications and source records attributed to S Orloff.

At least 37 records · Page 2Linked to original sources
PubMed1981

Synovial fluid hydroxyproline fractions before and after osmic acid treatment in rheumatoid arthritis.

Synovial fluid total, dialysable and non-dialysable hydroxyproline were determined in patients with Rheumatoid Arthritis before intra-articular osmic acid injection and on days 2 and 4 after this local treatment. On day 2 the increase in dialysable hydroxyproline paralleled the increase in non-dialysable hydroxyproline. Patients with the highest pre-treatment dialysable hydroxyproline levels also had the highest levels of this fraction on day 2 suggesting that articular damage proceeds after osmic acid injection. However, on day 4 dialysable hydroxyproline levels were consistently lower than before the treatment; the same pattern was observed with non-dialysable hydroxyproline, except for all the joints but one, where effusion recurred 6-12 months after osmic acid treatment. This study suggests that the determination of synovial fluid non-dialysable levels 4 days after osmic acid injection may provide a clue to the prediction of recurrent joint effusion and possibly justify a complementary injection either with osmic acid or with a beta-emitting isotope.

Adult↗
PubMed1980

Cystinotic and normal fibroblasts: differential susceptibility to cysteine toxicity in vitro.

Extracellular cysteine concentrations between 0.5 and 2.5 mM resulted in death of normal but not cystinotic cells grown in Eagle's minimal essential medium containing supplemental fetal bovine serum and antibiotics. Differential cell survival was determined by viable cell counting using Trypan Blue dye exclusion. In cocultivation experiments of [3H]thymidine-labelled cystinotic fibroblasts with nonradioactive normal fibroblasts, autoradiography confirmed the selective survival of cystinotic cells in medium containing 1 mM cysteine. At this concentration of 1 mM cysteine, intracellular cystine content increased slightly in surviving normal cells but not in cystinotic cells, which normally contain a high level of intracellular cystine. This comparative resistance of cystinotic fibroblasts to elevated extracellular cysteine concentrations forms the basis for an in vitro selective system for these mutant human cells. Further exploration of this resistance phenomenon may well expand the understanding of the molecular defect in cystinotic cells.

Cell Count↗
PubMed1980

Synovial fluid beta 2 microglobulin and hydroxyproline fractions in rheumatoid arthritis and nonautoimmune arthropathies.

Fourteen patients with classical and definite seropositive rheumatoid arthritis (RA), 5 patients with microcrystalline arthritis, and 7 patients with osteoarthrosis were studied with respect to markers of newly synthesised collagen (synovial NDOH pro levels); markers of connective tissue resorption (synovial DOH pro and NBH levels); markers of lymphoid tissue activity (synovial and plasma beta 2m levels). Higher amounts of NDOH pro in RA synovial fluid are compatible with the hypothesis of a local connective tissue production as suggested by Uitto et al. on basis of a higher protocollagen proline hydroxylase activity in RA synovial tissue. DOH pro and NBH do not differ significantly in synovial fluid from RA or gouty patients, but the correlations between these forms of OH pro and, respectively, synovial lymphocytes and polymorphonuclear leucocytes are indicative of different processes of connective tissue remodelling in the 2 conditions. Synovial beta 2m levels are a direct function of total synovial lymphocyte counts independently of the type of arthropathy being explored. The ratio of synovial to plasma beta 2m is systematically above unity in RA patients only.

Arthritis, Rheumatoid↗
PubMed1980

Pituitary resistance to thyroid hormone in cystinosis.

Eleven children with nephropathic cystinosis without clinical features of hyperthyroidism or hypothyroidism had elevated serum levels of immunoreactive TSH. The mean TSH level (+/- SE) was 37.4 +/- 12.3 microM/ml. Serial determinations of thyroid function during 1 yr were: mean (+/- SE) serum T4, 10.8 +/- 0.7 microgram/dl; free T4, 2.1 +/- 0.2 ng/dl; and T3, 239 +/- 6 ng/dl. After 500 microgram TRH iv, the peak TSH level exceeded 100 microU/ml in 6 of 10 patients, whereas T3 responses were variable. Studies of parameters influenced by thyroid hormone, including red cell sodium content, serum cholesterol, and 24-h urinary hydroxylysine excretion, were consistent with euthyroidism. On the other hand, the mean pulse wave arrival time was significantly reduced, consistent with hyperthyroidism. Three control patients, 2 with Lowe's syndrome and 1 with benign cystinosis, had normal thyroid studies. Eight of the patients were given either exogenous L-T4 or T3 in doses which were increased at weekly intervals. The serum TSH concentrations were suppressed to normal only after elevation of serum levels of thyroid hormones and with high exogenous thyroid replacement doses. The data suggest abnormal pituitary resistance to feedback by thyroid hormone in patients with cystinosis. We believe this to be the first description of the association of a heritable metabolic disease with such pituitary resistance.

Child↗
PubMed1980

Effect of bioflavonoids on lysosomal acid hydrolases and lysosomal stability in adjuvant-induced arthritis.

In rats with adjuvant-induced arthritis, the effect of (+)-catechin (CA) and 0-(beta-hydroxyethyl) rutosides (HR) on the activity of certain lysosomal acid hydrolases, viz., beta-glucuronidase, beta-N-acetyl glucosaminidase and cathepsin D in serum, liver, kidney and spleen and the stability of liver lysosomes was studied. The activity of these enzymes in arthritic tissues and serum increased significantly. The total activity of beta-glucuronidase in the lysosome-rich fraction from arthritic liver was appreciably decreased, while its release was significantly increased. These results demonstrate the fragility of lysosomes in arthritic tissues. Administration of CA or HR to the arthritic animals was found to have a prophylactic action by stabilizing liver lysosomes and reducing the free lysosomal enzyme activities in serum, liver, kidney and spleen. CA was more effective than HR.

Animals↗
PubMed1979

Ineffectiveness of ascorbic acid therapy in nephropathic cystinosis.

Because high concentrations of ascorbic acid (0.57 mM) lower the free (nonprotein) cystine content of cultured cystinotic skin fibroblasts by over 50 per cent, we did a double-blind clinical trial to establish whether this drug would benefit cystinotic children. Sixty-four patients were randomized into the study; 32 received ascorbic acid (200 mg per kilogram of body weight per day), and 32 placebo. The study was terminated after approximately two years because there was no indication that vitamin C was beneficial and accumulating evidence that it might be harmful. Of 11 patients who left the study because of death or the requirement for dialysis or renal transplantation, eight were receiving ascorbic acid. The estimated relative risk (treatment vs. control) of an adverse event was R = 2.7, with a 90 per cent confidence interval of (0.8, 11.5). The serum creatinine concentration increased 0.53 mg per deciliter per year in patients receiving vitamin C and 0.24 mg per deciliter per year in patients receiving placebo (P = 0.08).

Ascorbic Acid↗
PubMed1979

Intrauterine growth retardation in renal insufficiency: an experimental model in the rat.

Experiments described here with partially nephrectomized pregnant rats with pair-fed controls and controls fed at will indicate that decreased maternal food intake is a major factor in the intrauterine growth retardation associated with moderate renal insufficiency during the last trimester of gestation. Although renal disease in human pregnancy is often associated with vascular insufficiency, the possibility that maternal undernutrition may also play a contributory role in the fetal growth failure associated with certain cases of human renal compromise merits further study.

Animals↗
PubMed1979

A comparison of essential and general amino acid infusions in protein-depleted patients receiving parenteral alimentation.

Six malnourished patients were studied during intravenous nutrition therapy to compare the efficiency of essential and general amino acids when given as the sole nitrogen source during intravenous nitrogen therapy. A cross-over design was used so that each patient received both essential amino acids plus arginine and histidine and a general amino acid solution in random order. Glucose provided the remainder of the energy and both infusions contained 2 g of amino acid per 100 kcal. Each patient's daily urea nitrogen production was greater during infusion of the general amino acid solution. Consequently, nitrogen intake minus urea nitrogen production was significantly greater when the essential amino acid solution was infused. Plasma amino acid levels were determined on each patient during both essential and general amino acid infusion. Abnormalities tend to reflect the composition of the amino acid solutions as well as their administration directly into the systemic circulation bypassing the portal circulation.

Adult↗
PubMed1979

Placental transfer of analogs of glucose and amino acids in experimental intrauterine growth retardation.

We have employed the model in which one uterine artery is ligated to study maternofetal transport and tissue uptake of glucose and amino acids in the intrauterine growth-retarded rat. On the 18th day of gestation, the artery supplying one uterine horn was ligated. Two days later the rats received [3H]2-deoxyglucose and [14C]alpha-aminoisobutyric acid iv. One hour later the growth-retarded and control fetuses were delivered by Cesarean section and appropriate blood samples were obtained. The growth-retarded fetuses had an average weight reduction of 27%, significantly increased placental to fetal weight ratio and brain to body ratio, and a significantly reduced liver to body body ratio. Total radioactivity derived from tritiated deoxyglucose in whole fetal tissues, placenta, liver, and brain were significantly decreased in the intrauterine growth-retarded (IUGR) fetuses; this was also true per gram of tissue except for liver. Liver to plasma, brain to plasma, and whole fetal tissue to plasma 3H ratios were significantly increased in the IUGR group. The radioactivity derived from [14C]alpha-aminoisobutyric acid was significantly reduced in whole fetal tissues, placenta, liver, and brain in the IUGR fetuses whether expressed per whole organ or per gram of tissue. Significant differences in liver to plasma, brain to plasma, and whole tissue to plasma 14C ratios were not observed.

Aminoisobutyric Acids↗
PubMed1979

Synovial fluid and serum hydroxyproline fractions in rheumatoid arthritis.

In rheumatoid arthritis (RA) the synovial fluid lymphocyte count closely parallels the synovial fluid dialysable hydroxyproline, a marker of collagen resorption. This observation stresses the primordial role of lymphocytes in RA joint injury. The actual and eventually potential destruction of any single joint, as expressed by synovial fluid dialysable hydroxyproline levels, seems to reflect the general picture of disease activity as evaluated by the number of active joints (joint count), ESR and rheumatoid factor titres (latex fixation). Although urinary hydroxyproline levels are generally within the normal range in RA, they can be used as index of articular tissue destruction and as a parameter of overall disease activity when groups of patients are studied longitudinally in detail. The present study sheds no further light on the significance of synovial fluid and blood non-dialysable hydroxyproline levels.

Arthritis, Rheumatoid↗
PubMed1979

Serum and synovial fluid hydroxyproline fractions in microcrystalline arthritis and osteoarthritis.

Synovial fluid and serum hydroxyproline fractions were investigated in patients with osteoarthritis and microcrystalline arthritis. Synovial fluid dialysable hydroxyproline levels are higher than serum levels in both conditions. Synovial fluid total and dialysable hydroxyproline are higher in microcrystalline arthritis than in osteoarthritis, while non-dialysable hydroxyproline values are similar in both conditions. In microcrystalline arthritis, synovial fluid dialysable hydroxyproline and polymorphonuclear leukocyte counts closely parallel each other. Irrespective of the type of arthropathy, synovial fluid dialysable hydroxyproline levels correlate with urinary hydroxyproline excretion. While the data suggest overproduction of dialysable hydroxyproline by joints in both conditions, the overproduction appears to be mediated by polymorphonuclear leukocytes in microcrystalline arthritis only. The ratio of serum to synovial total hydroxyproline are further suggestive of a possible differentiation between osteoarthritis and microcrystalline arthritis. In the conditions governing the present study, urinary hydroxyproline may be used as an index of joint tissue collagen resorption. Finally the significance of synovial fluid and serum non-dialysable hydroxyproline is discussed.

Chondrocalcinosis↗
PubMed1979

[Osteomalacia in hyperphosphoethanolaminuria without hypophosphatasia (author's transl)].

Increased urinary excretion of phosphorylethanolamine (P.E.A.) is one of the salient features of hypophosphatasia. This inherited disorder is generally transmitted as an autosomial recessive trait and is characterized by abnormal mineralization of bone, premature loss of deciduous teeth and reduced tissue and serum alkaline phosphatases (A.P.) levels. The authors report a series of patients presenting with pains of skeletal origin attributed to an osteomalacia syndrome on the ground of a bone biopsy. These patients had no history of rickets during childhood but complained of early severe caries of the permanent dentition before the age of twenty. They had neither malabsorption nor renal tubular abnormalities. Their serum 25 OH vitamin D was normal and their serum A.P. levels were within the normal range with a normal isoenzyme distribution. All these patients had increased excretions of urinary P.E.A. and the latter correlate significantly with the degree of osteomalacia. Control patients with a malabsorption syndrome, showing osteomalacia and serum A.P. of the same degree of magnitude as the patients of the first group, have a normal P.E.A. excretion and no correlation appears between the degree of osteomalacia and the P.E.A. excretion. The cases with increased P.E.A. excretion may correspond to adult pseudohypophosphatasia. The signification of increased P.E.A. excretion is discussed.

Alkaline Phosphatase↗
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

Entrapment of metaphase chromosomes into phospholipid vesicles (lipochromosomes): carrier potential in gene transfer.

Transfer of genes from one type of cultured mammalian cell to another by using isolated metaphase chromosomes has been reported with a frequency of one per 10(6)-10(8) cells. Very recently a rate of 16/10(6) has been reported with Chinese hamster ovary cells [Spandidos, D. A. & Siminovitch, L. (1977) Proc. Natl. Acad. Sci. USA 74, 3480-3484]. To increase the frequency of gene transfer, we isolated metaphase chromosomes from hypoxanthine guanine phosphoribosyltransferase (HGPRT) positive cells, entrapped them in liposomes, and fused the lipochromosomes with HGPRT-negative cells. Lipochromosomes were prepared with cholesterol and egg lecithin, using isolated metaphase chromosomes from a mouse-human somatic hybrid cell line (A9/HRBC2); the entire X chromosome, including the HGPRT, glucose-6-phosphate dehydrogenase, and phosphoglycerate kinase genes, is the only recognizable human genetic material retained by the hybrids. Enclosure of the chromosomes in the lipid envelope was confirmed by electron and fluorescence microscopy and differential centrifugation. These lipochromosomes were fused with HGPRT(-) mouse cells (A9) in the presence or absence of polyethylene glycol and transferents were selected in hypoxanthine/aminopterin/thymidine (HAT) medium. The frequency of transfer was at least once per 10(5) cells, a minimum 10-fold improvement over previous methods. The selected cells contained HGPRT activity similar to the amount found in the A9/HRBC2 cells. Starch gel electrophoresis verified that the observed HGPRT activity in the transferents is due to the human enzyme. Human glucose-6-phosphate dehydrogenase and phosphoglycerate kinase were also identified electrophoretically in the transferents. Karyotyping with C and Q banding did not reveal the presence of the whole human X chromosome or a visible extra fragment of a human chromosome associated with the mouse genome. The biochemical data strongly suggest, however, that transfer of a portion of the human X chromosome has occurred in these transferents. Thus, at least three X-linked genes have been transferred from one cell to another with high frequency, using metaphase chromosomes.

Cell Line↗
PubMed1978

Plasma and urinary levels of beta2 microglobulin in rheumatoid arthritis.

Plasma and urinary levels of beta2 microglobulin have been investigated in 21 patients suffering from rheumatoid arthritis (RA). Despite a normal renal glomerular function in all patients 50% of them had supranormal plasma beta2 microglobulin levels and 30% had a higher than normal urinary output of beta2 microglobulin generally related to the high plasma level. Plasma beta2 microglobulin levels paralleled closely the lymphocytosis and the 'joint count' both indexes of the severity of the disease. beta2 Microglobulin was normally secreted by the lymphoid tissue and it is suggested that it reflects the increase of the total mass and/or membrane turnover of the lymphoid tissue in RA. beta2 Microglobulin may be considered as a good parameter of the degree of severity of the joint and extra-articular involvement as well as a useful tool for the evaluation of drug efficacy in rheumatoid arthritis.

Adult↗