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Biomedical subjects

R Hertz

Publications and source records attributed to R Hertz.

At least 37 records · Page 2Linked to original sources
PubMed1989

Effects of ovarian tissue reduction on the menstrual cycle: persistent normalcy after near-total oophorectomy.

These experiments were designed to evaluate whether removal of approximately 95% visible ovarian tissue would interrupt the short- or long-term regulation of cyclic ovarian function. On cycle Days 2 4 (onset of menses = Day 1), the entire left ovary and approximately 90% of the right ovary were removed from three cycling cynomolgus monkeys. After approximately 95% ovariectomy, there was an acute elevation of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which lasted 11 +/- 2 days. A midcycle-like gonadotropin surge occurred 20 +/- 3 days following approximately 95% ovariectomy; the next menses occurred 19 +/- 1 days later. Follicular phase patterns of estradiol preceded the midcycle gonadotropin surge, and luteal phase progesterone levels indicated subsequent ovulation. Two of three monkeys resumed normal menstrual cyclicity in the following cycle with follicular phase, luteal phase, and menstrual cycle lengths similar to pretreatment levels. Histological examination of the ovarian remnant removed on Day 21 of the next cycle revealed a morphologically normal corpus luteum and many small follicles. A second group of 6 rhesus monkeys also underwent approximately 95% ovariectomy for long-term evaluation of menstrual cyclicity; typical 28-day menstrual cycle patterns were observed in 4 of the 6 monkeys for 5 mo, with 2 of these 3 animals maintaining regular menstrual cycles for 1 yr. In summary, our data suggest that normal ovarian function, i.e. recruitment, selection, and dominance of the ovulatory follicle, ovulation, and subsequent corpus luteum function, is maintained with only approximately 5% of functional ovarian tissue remaining.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1988

The induction of liver peroxisomal proliferation by beta,beta'-methyl-substituted hexadecanedioic acid (MEDICA 16).

Treatment of rats by beta,beta'-methyl-substituted hexadecanedioic acid (MEDICA 16) resulted in a dose- and time-dependent increase in liver peroxisomal enoyl-CoA hydratase and cyanide-insensitive palmitoyl-CoA oxidation with a concomitant increase in the volume density of peroxisomes as determined by morphometry. The induced peroxisomal proliferation was sustained as long as treatment was maintained and was accompanied by an increase in liver weight. Incubation of cultured rat hepatocytes in the presence of MEDICA 16 added to the culture medium resulted in a dose-dependent increase in peroxisomal beta-oxidation activities with a concomitant elevation of the volume density of peroxisomes. The induction of peroxisomal proliferation by MEDICA 16 in culture could be prevented in the presence of carnitine palmitoyltransferase inhibitors added to the culture medium, e.g. 2-bromopalmitate, 2-tetradecylglycidic acid or 2-[5-(4-chlorophenyl)-pentyl]oxirane-2-carboxylate. The induction of liver peroxisomes by MEDICA 16 conforms to the previously defined requirement for an amphipathic carboxylate in initiating peroxisomal proliferation. The prevention of peroxisomal proliferation by carnitine acyltransferase inhibitors may implicate the involvement of this acyltransferase in the induction of peroxisomal proliferation by xenobiotic or native amphipathic carboxylates.

Animals↗
PubMed1988

The acylation of proteins by xenobiotic amphipathic carboxylic acids in cultured rat hepatocytes.

Three xenobiotic amphipathic carboxylates, namely MEDICA 16, nafenopin and bezafibrate, which differ remarkably in their hydrophobic backbones, were found to acylate membrane and cytosolic liver proteins in cultured rat hepatocytes. The acylation patterns observed were time- and dose-dependent, and the acylated residue consisted of the original xenobiotic. The acylation patterns generated by the three xenobiotic carboxylates included common proteins which were acylated by the three xenobiotics (e.g. proteins of 32, 52, 56 and 72 kDa) as well as unique proteins which were specifically acylated by the respective xenobiotics. The acylation of liver proteins by either MEDICA 16 or nafenopin remained unaffected under conditions where protein synthesis was completely inhibited by cycloheximide. Protein acylation thus offers a common mode of action of xenobiotic amphipathic carboxylates, which may, however, result in diverse xenobiotyl-protein adducts. The xenobiotyl-acylated proteins might be involved in triggering some of the biological effects exerted by xenobiotic amphipathic carboxylates employed as hypolipidaemic effectors, peroxisomal proliferators or preadipocyte convertors.

Acylation↗
PubMed1988

The hypochylomicronemic effect of beta,beta'-methyl-substituted hexadecanedioic acid (MEDICA 16) is mediated by a decrease in apolipoprotein C-III.

Treatment of rats fed a balanced Purina Chow diet with beta,beta'-tetramethyl-substituted hexadecanedioic acid (MEDICA 16) (Bar-Tana, J., Rose-Kahn, G., and Srebnik, M. (1985) J. Biol. Chem. 260, 8404-8410) resulted in an acute 70-80% decrease in plasma chylomicrons-triacylglycerols which was sustained as long as the drug was administered. The hypochylomicronemic effect resulted from an enhanced plasma clearance of chylomicrons whereas their intestinal production and absorption remained unaffected. Chylomicrons-triacylglycerols clearance in MEDICA 16-treated rats was characterized by a fast initial phase lasting for 1-2 min and consisting of elimination of 50-60% of the injected chylomicrons' tracer at a fractional clearance rate of 0.77 +/- 0.27 min-1 as compared to 0.08 +/- 0.01 min-1 in nontreated rats. The fractional clearance rate of chylomicrons-cholesterol ester was similarly affected by MEDICA 16 treatment and amounted to 0.48 +/- 0.05 and 0.05 +/- 0.01 min-1 in MEDICA 16-treated and nontreated rats, respectively. The increased fractional clearance rate of plasma chylomicrons in MEDICA 16-treated rats presumably reflects the primary action of the drug rather than being secondary to the hypochylomicronemic state, since it was similarly observed in MEDICA 16-treated animals made transiently normolipemic by loading them with intestinal lipid. The increase in the fractional clearance rate of plasma chylomicrons resulted from their enhanced uptake by the liver complemented with their activated extrahepatic catabolism. The activation of both catabolic modes in MEDICA 16-treated rats could be accounted for by a 10-fold decrease in the apoC-III content of plasma chylomicrons. No increase was observed in hepatic apoB,E or apoE receptors, nor in the maximal capacity of lipoprotein lipase. The pharmacological reduction of plasma apoC-III may thus offer a treatment mode of choice for selected hyperlipidemic states.

Animals↗
PubMed1987

Prevention of peroxisomal proliferation by carnitine palmitoyltransferase inhibitors in cultured rat hepatocytes and in vivo.

1. The induction of peroxisomal beta-oxidation activities by bezafibrate in cultured rat hepatocytes and in the rat in vivo was prevented by inhibitors of carnitine acyltransferase, e.g. 2-bromopalmitate, 2-[5-(4-chlorophenyl)pentyl]oxirane-2-carboxylate or 2-tetradecylglycidic acid. 2. The prevention of peroxisomal proliferation by carnitine palmitoyltransferase inhibitors could not be accounted for by inhibition of mitochondrial beta-oxidation, since 2-bromo-octanoate, acting as an inhibitor of beta-oxidation, did not prevent the induction of peroxisomal activities in cultured rat hepatocytes. 3. The putative role of the acylcarnitine derivative of bezafibrate was analysed by studying the formation of bezafibroylcarnitine with bezafibroyl-CoA as substrate. However, no bezafibroylcarnitine formation was demonstrated in the presence of rat liver preparations capable of catalysing transfer to carnitine of medium- or long-chain fatty acids. 4. The prevention of peroxisomal proliferation by carnitine acyltransferase inhibitors may help in dissecting the causal relationship between the multiple effects mediated by peroxisomal proliferators.

Acyltransferases↗
PubMed1987

Adipocyte conversion of cultured 3T3-L1 preadipocytes by bezafibrate.

Transient exposure of cultured 3T3-L1 preadipocytes to hypolipidemic fibrate drugs results in extensive adipocyte conversion. Adipocyte conversion in culture was characterized by an increase in neutral lipids content and in adipocyte marker enzymes like hormone-sensitive lipase and glycerol-3-phosphate dehydrogenase. Adipocyte conversion in culture was also accompanied by induction of cyanide-insensitive peroxisomal palmitoyl-CoA oxidation. The conversion pattern exerted by fibrate drugs in 3T3-L1 cells was similar to that reported previously for primary cultured epididymal preadipocytes (R. Brandes, R. Arad and J. Bar-Tana, Biochim. Biophys. Acta, 877, 314-321 (1986)), and seems to refute clonal selection in the conversion sequel initiated by fibrate drugs in primary cultured preadipocytes.

1-Methyl-3-isobutylxanthine↗
PubMed1987

Increased response to peroxisomal proliferators in starved rats.

The induction of liver peroxisomal beta-oxidation activities by bezafibrate or Wy 14,643 was 2-4-fold higher in starved rats than in fed animals. The increased response to peroxisomal proliferators in starved rats was independent of the mode of administration of the proliferator, given either orally or by intraperitoneal injection. Inhibitors of carnitine acyltransferase I could prevent the induction of peroxisomal activities in starved rats but not in fed animals. In contrast to fasted rats, the induction of liver peroxisomal activities in streptozotocin-diabetic rats was not susceptible to bezafibrate. The higher sensitivity to peroxisomal proliferators under conditions of starvation may allow for the detection of xenobiotic peroxisomal proliferators of low proliferative potency.

Acyl Coenzyme A↗
PubMed1987

Clofibrate does not induce peroxisomal proliferation in human hepatoma cell lines PLC/PRF/5 and SK-HEP-1.

The potential of fibrate drugs to induce peroxisomal proliferation in human liver cells was evaluated in athymic nude mice transplanted with human hepatoma cells and treated by clofibrate in vivo as well as in cultured human hepatoma cells in the presence of fibrate drugs added to the culture medium. Clofibrate did not induce peroxisomal activities and neither acted as a peroxisomal proliferator in human PLC/PRF/5 or SK-HEP-1 heterotransplants under conditions of induction of peroxisomal activities in the host rodent liver. Similarly, clofibric acid or bezafibrate did not induce peroxisomal activities in cultured human PLC/PRF/5 or SK-HEP-1 cells under conditions of induction of peroxisomal activities in cultured primary rat liver cells. The lack of response of the human cells to peroxisomal proliferators of the fibrate type may indicate a species specificity with respect to induction of peroxisomal activities by xenobiotic peroxisomal proliferators.

Carcinoma, Hepatocellular↗
PubMed1987

Should all pregnant women be screened for hepatitis B?

To assess the sensitivity of historical risk factors for identification for hepatitis B surface antigen (HBsAg)-positive parturients, 4399 pregnant women were consecutively screened for HBsAg. Information regarding risk for hepatitis B infection was obtained from each HBsAg-positive parturient. Twenty-three HBsAg-positive subjects were identified (5.2/1000 deliveries). The HBsAg carrier rate (18/2231, or 8.1/1000 deliveries) was significantly higher in women of black, Asian, or Hispanic origin than in the remaining ethnic groups (non-Hispanic whites plus all others, 5/2168, or 2.3/1000 deliveries) (chi square, 5.95; p = 0.016). Risk factors for identification of HBsAg-positive women were present in 10 of 22 asymptomatic subjects (sensitivity, 45%; 95% confidence interval, 24% to 68%). Much of the information required to assess one of these risk factors, previous infection, involved detailed questioning and is unlikely to be obtained in the context of conventional obstetrical care. Routine maternal HBsAg screening programs may be needed if transmission of hepatitis B from mother to infant is to be prevented.

Carrier State↗
PubMed1987

Malignant neoplasms of decidual origin (deciduosarcomas) induced by estrogen-progestin-releasing intravaginal devices in rabbits.

A combination of estrogen and levonorgestrel was continuously delivered to 23 adult rabbits for up to 2 years via a Silastic ring device sutured into the vagina. Twenty-one control rabbits were given similar rings devoid of drugs. A marked decidual reaction of the endometrium occurred in 16 of 23 test rabbits. In 14 test rabbits (61%) malignant tumors developed of decidual type cells not heretofore described. The deciduosarcomas were composed of anaplastic cells that invaded the uterine walls, uterine lymphatics, and in 4 of 13 (31%) rabbits that survived 2 years of treatment, the tumors metastasized to the lungs. Several deciduosarcomas appeared to arise within the spleen or other abdominal organs. Other drug-related lesions included uterine or vaginal polyps, endometrial atrophy, and focal necrosis and mineralization of the uterine wall. Cells from several deciduosarcomas failed to produce tumors in nude mice or to colonize on soft agar. No decidualization or decidual neoplasms were seen in the controls.

Animals↗
PubMed1986

Hypothesis: menstruation is a steroid-regulated, cyclic, autoimmune process.

There is presented an hypothesis that menstruation occurs when estrogen or progesterone withdrawal permits a previously hormone-blocked interaction between an endometrial autoantigen and its specific autoantibody, thereby inducing the characteristic necrosis and sloughing of the endometrium. Experimental and clinical studies are outlined to test this hypothesis.

Autoantibodies↗
PubMed1986

Reductive repression in Escherichia coli K-12 is mediated by oxygen radicals.

Cyclic AMP (cAMP) content and the expression of cAMP-dependent phenotypes were positively correlated with respiration capacity in respiration-deficient mutants of Escherichia coli K-12 ("reductive repression," R. Hertz, and J. Bar-Tana, (1982) Arch. Biochem. Biophys. 213, 193-199). Reductive repression in respiration-deficient mutants could not be accounted for by respective changes in either the energy charge of adenine nucleotides or the redox state of pyridine nucleotides but could be ascribed to an increased formation of oxygen radicals under conditions of limited respiration. Scavengers of superoxide radicals eliminated reductive repression in respiration-deficient mutants with a concomitant increase in cAMP content. Such scavengers also effected a partial escape from permanent glucose catabolite repression, thus indicating a possible role played by oxygen radicals in both repression modes.

Adenine Nucleotides↗
PubMed1985

The effect of bezafibrate and long-chain fatty acids on peroxisomal activities in cultured rat hepatocytes.

Peroxisomal activities have been evaluated in cultured rat hepatocytes in the presence of bezafibrate or long-chain fatty acids added to the culture medium. All activities decreased continuously over a time period of 100 h in culture but selected activities were relatively increased as a function of the added effectors. This relative increase in peroxisomal activities was dose-dependent, discernible within the first 24 h in culture and consisted of activities related specifically to peroxisomal fatty acyl beta-oxidation, e.g., cyanide-insensitive palmitoyl-CoA oxidation, H2O2-forming palmitoyl-CoA oxidase and heat-labile enoyl-CoA hydratase. Peroxisomal catalase or mitochondrial fatty acyl beta-oxidation (cyanide-sensitive) remained relatively unchanged. The relative increase in peroxisomal activities was accompanied by a respective increase in the number of peroxisomes as well as in thymidine incorporation rate.

Animals↗
PubMed1983

Expression of gastric-associated antigens by human premalignant and malignant colonic epithelial cells.

A rabbit antiserum prepared to 2nd-trimester fetal organ extracts and absorbed with adult tissue (anti-STFa) was used to detect antigens common to 2nd-trimester fetal large bowel, normal adult stomach, several colon carcinoma cells (in primary and established cultures) and epithelial cells cultured from benign colonic polyps. The frequency of anti-STFa-positive cells was highest in cultures derived from benign tumors known to be associated with a greater degree of premalignancy. Thus, the percentage of antigen-positive cells increased from 18 and 43% to 70% of cultures from tubular, villotubular and villous adenomas, respectively. Considerable heterogeneity in the distribution of antigen-containing cells was evident within any given area of a positive culture. Absorption experiments, using a spectrum of fetal and normal adult tissue extracts, indicated that the adenoma-carcinoma specificity resides in fetal, but not adult, large bowel and normal adult stomach.

Adenoma↗