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Biomedical subjects

R Reiter

Publications and source records attributed to R Reiter.

At least 37 records · Page 2Linked to original sources
PubMed1998

Plasma membrane phospholipid asymmetry precedes DNA fragmentation in different apoptotic cell models.

Biochemical alterations occurring in many cell types during apoptosis include the loss of plasma membrane phospholipid asymmetry and nuclear DNA fragmentation. Annexin V staining detects phosphatidylserine translocation into the outer plasma membrane layer occurring during cell death, while the in situ tailing (IST or TUNEL) reaction labels the DNA strand breaks typical of apoptosis. To compare the time course of these processes we investigated methylprednisolone-induced apoptosis of rat thymocytes, topoisomerase inhibitor-induced apoptosis in the human histiocytic lymphoma cell line U937, and serum deprivation-induced apoptosis in the rat pheochromocytoma cell line, PC12. At all time points, FACS analysis and quantitative fluorescence light microscopy showed a higher proportion of annexin V-positive than IST-positive cells, with significantly different time courses in the apoptotic cell models investigated (Anova test). Results were confirmed by confocal microscopy. Our data indicate that the exposure of phosphatidylserine, a potential phagocyte recognition signal on the cell surface of apoptotic cells in vivo, precedes DNA strand breaks during apoptosis in different cell types.

Animals↗
PubMed1997

CpG-containing synthetic oligonucleotides promote B and cytotoxic T cell responses to protein antigen: a new class of vaccine adjuvants.

Foreign DNA has been shown to impinge on immune cell function by an as yet unidentified mechanism. We and others have demonstrated that single-stranded (ss) DNA containing the motif CpG flanked by two 5' purines and two 3' pyrimidines are mitogenic for B cells and activate macrophages to release tumor necrosis factor-alpha, interferon-gamma, interleukin (IL)-6 or IL-12. Because of these pro-inflammatory responses we investigated if ssDNA would serve as a potential vaccine adjuvant. Here we show that CpG-containing oligonucleotides represent a powerful adjuvant for both humoral and cellular immune responses. When ssDNA was incorporated into inocula, specific antibody titers of the IgG2 isotype were enhanced by greater than 100-fold. Primary cytotoxic T lymphocyte responses generated to either unprocessed protein antigen or major histocompatibility complex class I-restricted peptide were exceedingly strong. Evidence is also provided that oligomers directly influenced T cell receptor-triggered T cell proliferation. Thus ssDNA oligomers may serve as inexpensive and safe vaccine adjuvants and, in addition, differential effects due to sequence may allow for directed responses.

Adjuvants, Immunologic↗
PubMed1997

Pharmacological actions of melatonin in oxygen radical pathophysiology.

Melatonin, the chief secretory product of the pineal gland, was recently found to be a free radical scavenger and antioxidant. This review briefly summarizes the published reports supporting this conclusion. Melatonin is believed to work via electron donation to directly detoxify free radicals such as the highly toxic hydroxyl radical. Additionally, in both in vitro and in vivo experiments, melatonin has been found to protect cells, tissues and organs against oxidative damage induced by a variety of free radical generating agents and processes, e.g., the carcinogen safrole, lipopolysaccharide, kainic acid, Fenton reagents, potassium cyanide, L-cysteine, excessive exercise, glutathione depletion, carbon tetrachloride, ischemia-reperfusion, MPTP, amyloid beta (25-35 amino acid residue) protein, and ionizing radiation. Melatonin as an antioxidant is effective in protecting nuclear DNA, membrane lipids and possibly cytosolic proteins from oxidative damage. Also, melatonin has been reported to alter the activities of enzymes which improve the total antioxidative defense capacity of the organism, i.e., superoxide dimutase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase, and nitric oxide synthase. Most studies have used pharmacological concentrations or doses of melatonin to protect against free radical damage; in a few studies physiological levels of the indole have been shown to be beneficial against oxidative stress. Melatonin's function as a free radical scavenger and antioxidant is likely assisted by the ease with which it crosses morphophysiological barriers, e.g., the blood-brain barrier, and enters cells and subcellular compartments. Whether the quantity of melatonin produced in vertebrate species is sufficient to significantly influence the total antioxidative defense capacity of the organism remains unknown, but its pharmacological benefits seem assured considering the low toxicity of the molecule.

Animals↗
PubMed1996

Cloning and characterization of a novel bicoid-related homeobox transcription factor gene, RIEG, involved in Rieger syndrome.

Rieger syndrome (RIEG) is an autosomal-dominant human disorder that includes anomalies of the anterior chamber of the eye, dental hypoplasia and a protuberant umbilicus. We report the human cDNA and genomic characterization of a new homeobox gene, RIEG, causing this disorder. Six mutations in RIEG were found in individuals with the disorder. The cDNA sequence of Rieg, the murine homologue of RIEG, has also been isolated and shows strong homology with the human sequence. In mouse embryos Rieg mRNA localized in the periocular mesenchyme, maxillary and mandibular epithelia, and umbilicus, all consistent with RIEG abnormalities. The gene is also expressed in Rathke's pouch, vitelline vessels and the limb mesenchyme. RIEG characterization provides opportunities for understanding ocular, dental and umbilical development and the pleiotropic interactions of pituitary and limb morphogenesis.

Abnormalities, Multiple↗
PubMed1995

Effect of nerve growth factor on peptide neurons in dorsal root ganglia after taxol or cisplatin treatment and in diabetic (db/db) mice.

In our study we have used morphological and radio-immunological methods for the investigation of calcitonin gene-related peptide (CGRP) and substance P in cervical dorsal root ganglia (DRGs) in mice after administration of taxol or cisplatin and in spontaneously diabetic animals (db/db mice). The results were compared to findings in animals receiving recombinant human nerve growth factor (rhNGF). Morphometric analysis did not reveal any significant changes of cell size distribution in diabetic and taxol-treated mice, whereas cisplatin induced a significant decrease in the number of large- and medium-sized neurons, indicating neuronal atrophy. This finding correlated with a highly significant loss of neuropeptides after cisplatin-application. Measurement of peptide levels in the taxol-treated groups and in diabetic mice demonstrated a decrease predominantly for CGRP. Application of 10 mg/kg NGF caused a significant elevation in peptide-immunoreactivity in control animals and in taxol-treated mice, i.e., statistically significant increase in peptide concentrations and in the number of substance P- and CGRP-immunoreactive DRG-neurons, suggesting a recruitment of additional peptide cells. In diabetic animals a restoration in CGRP-content was observed under NGF-treatment; however, in this model the quantitative parameters did not demonstrate further elevation above control levels. Our data support the hypothesis that NGF exerts a major effect on the metabolism of transmitters associated with nociception and sensation in "healthy" controls and in various models of toxic and metabolic neuropathy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Parenchymal sparing surgery in patients with hereditary renal cell carcinoma.

The von Hippel-Lindau syndrome is the most well known cause of familial renal cancer. Because affected individuals with renal lesions can have complex, multisystem manifestations of von Hippel-Lindau disease, our renal management strategy has included parenchymal sparing surgery whenever possible. From May 1988 to January 1993, 20 patients with hereditary renal cell carcinoma (19 with von Hippel-Lindau disease and 1 with hereditary papillary renal cancer) underwent renal exploration with the intent of performing parenchymal sparing surgery. A total of 7 nephrectomies and 27 parenchymal sparing procedures was performed. Additional procedures performed included 2 bilateral adrenalectomies for pheochromocytomas, 1 resection of a renal vein thrombus and 1 resection of a pancreatic islet cell tumor. Renal atrophy occurred in 3 of 27 kidneys (11%) treated by parenchymal sparing surgery. In 8 kidneys of 7 patients new solid lesions developed and in 14 kidneys of 12 patients no new solid lesions developed during a mean followup of 26 months (range 6 to 60 months). The use of parenchymal sparing surgery in patients with familial forms of kidney cancer is based on a desire to maintain renal function as long as possible while reducing the risk of metastases. The potential advantages and disadvantages of more ablative surgical treatment requiring subsequent dialysis or transplantation in patients with existing or potential central nervous system, eye, pancreas and/or adrenal tumors must be weighed against the possibility of renal cancer metastases or recurrence when deciding on the use of parenchymal sparing surgery.

Adult↗
PubMed1994

The murine decorin. Complete cDNA cloning, genomic organization, chromosomal assignment, and expression during organogenesis and tissue differentiation.

Decorin, a proteoglycan known to interact with collagen and growth factors, may play key roles during ontogenesis, tissue remodeling, and cancer. We have deciphered the complete protein sequence of the murine decorin by cDNA cloning, elucidated its gene structure and chromosomal location, and investigated its expression in the developing embryo. The decorin protein and the gene were highly conserved vis à vis the human counterpart; however, the murine gene lacked a leader exon, exon Ib, which was found only in the human. Using interspecific backcrossing, we assigned the gene to chromosome 10 just proximally to the Steel gene locus. In situ hybridization studies of developing mouse embryos showed a distinct pattern of expression with a progressive increase of decorin mRNA during ontogenesis. At early stages (day 11 postconception), decorin was detectable only in the floor plate region. Subsequently (days 13-16 postconception), decorin expression was especially prominent in the meninges and mesothelial linings of pericardium, pleura, and coelomic cavity, as well as in the dermis and subepithelial layers of the intestine and urinary bladder. In contrast, the major parenchymal organs were only weakly positive for decorin mRNA. These findings suggest that decorin may play a role in epithelial/mesenchymal interactions during organ development and shaping.

3T3 Cells↗
PubMed1993

Possible biological effects of electric and magnetic parameters in the environment.

The features and intensities of electric and magnetic fields in the environment are described. Natural as well as technical constant and variable fields are considered in the light of their possible biological effects. The upper limits of the various fields are discussed. Results of laboratory measurements and also of epidemiological investigations are presented. The question is raised whether atmospheric small ions can cause a biological effect.

Electricity↗
PubMed1993

Regression of metastatic renal cell carcinoma after cytoreductive nephrectomy.

Fewer than 1% of patients with renal cell carcinoma are reported to experience spontaneous regression of metastatic lesions after nephrectomy. We report on 4 of 91 patients (4.4%) with metastatic renal cell carcinoma who had spontaneous regression of all metastatic lesions after cytoreductive nephrectomy. These patients were carefully selected before surgery for the ability to receive high dose interleukin-2. One patient had recurrence at 2 months, 1 had recurrence at 11 months, and 2 had no evidence of disease at 3 and 4.5 years.

Carcinoma, Renal Cell↗
PubMed1992

Hospital records as a data source for occupational disease surveillance: a feasibility study.

To assess the feasibility of using hospital records for occupational disease surveillance and to evaluate the quality of the industry/occupation (I/O) information available in these records, the computer file of all discharge diagnoses from a large health maintenance organization during 1985 was reviewed. The frequencies of discharge diagnoses previously listed as Sentinel Health Events (Occupational), or SHE (O), were calculated and three possible SHE(O) diagnoses--lung cancer, bladder cancer, and toxic hepatitis--were selected for further review. Outpatient charts of patients discharged for each diagnosis were abstracted with regard to I/O information and the discharged patients were interviewed by telephone to obtain a lifetime occupational history. The accuracy of the I/O information obtained from the hospital chart was compared to that obtained by patient interview by number of digits matched on standard classification codes. The frequencies of matches for occupation and industry were greater for "usual" than for "last" categories with both cancer diagnoses, but were similar for "usual" and "last" categories with toxic hepatitis. To assess the proportion of each possible SHE(O) diagnosis that was related to workplace exposures, the I/O information obtained by interview was rated in a blinded fashion by an experienced occupational medicine physician. The highest probability ratings for work-relatedness were noted for lung cancer, primarily due to asbestos exposure. The results of this study suggest that hospital records can be used to identify possible SHE(O); if adequate I/O information is available, then work-relatedness can be assessed. However, the accuracy of I/O obtained from hospital charts is relatively low. The efficient and accurate collection of I/O information from hospital records will require the use of a simple, easily coded instrument to be routinely administered on admission.

Asbestos↗
PubMed1991

Fatal injuries at work in California.

We examined deaths due to injury on the job reported from three readily accessible data sources in California for a 1-year period. Of 682 deaths identified as of February 1990 as having occurred on the job in 1983, county coroners identified 607 (89.0%), workers' compensation records identified 294 (43.1%), and the California Occupational Safety and Health Administration investigated 141 (20.7%). Most fatal injuries at work resulted from events that are not covered by current California Occupational Safety and Health Administration standards: transportation vehicle accidents and homicides. Demographic patterns suggest that fatal injuries on the job are nonrandom events, which may be prevented by additions to existing standards or increased enforcement of workplace safety standards and by efforts to target groups at highest risk. Improved surveillance of fatal occupational injuries will require changes in existing reporting mechanisms, similar to those proposed by the US Bureau of Labor Statistics.

Accidents, Occupational↗
PubMed1990

Blood-glucose-lowering activity of 2-(3-phenylpropoxyimido)-butyrate (BM 13.677).

A single oral or intraperitoneal application of 2-(3-phenylpropoxyimido)-butyrate (BM 13.677) resulted in a dose-dependent blood-glucose-lowering effect in fasted guinea-pigs. The threshold dose and the EC50 were estimated as 25 mg/kg and 63 mg/kg, respectively, which is between that of the biguanides phenformin and metformin. A rise in blood lactate concentrations was observed only at high doses of BM 13.677, but was not related to an irreversible metabolic inhibition. Among several rodent species studied the potency of the drug decreased in the order guinea-pig much greater than mouse greater than rat = rabbit. Inhibition of hepatic gluconeogenesis by the drug was demonstrated in the perfused liver or hepatocytes of guinea-pigs. Inhibition of glucose production by the perfused liver in the presence of 0.1 mM BM 13.677 was dependent on the substrate and decreased in the order: lactate greater than pyruvate greater than alanine much greater than propionate greater than glycerol = fructose. This suggests a specific interaction of the drug with a mitochondrial key reaction of gluconeogenesis. Stimulation of glucose oxidation in rat diaphragm by the compound (EC50 = 0.85 mM) suggests that besides inhibition of gluconeogenesis also extrahepatic effects contribute to the blood-glucose-lowering effects of the drug.

Animals↗
PubMed1989

Adverse outcomes and lack of health insurance among newborns in an eight-county area of California, 1982 to 1986.

In this study of hospital discharge data on births to residents of an eight-county region of California, we found an increasing lack of health insurance that was associated with an elevated and increasing risk of adverse outcomes in newborns. Between 1982 and 1986, the percentage of newborns without health insurance increased overall by 45 percent (from 5.5 to 8.0 percent; P less than 0.001); the increases were larger among Asians (by 54 percent [from 7.8 to 12.0 percent]; P less than 0.001) and Latinos (by 140 percent [from 8.2 to 19.7 percent]; P less than 0.001). By 1986, the odds ratio for an adverse hospital outcome (defined as a prolonged hospital stay, transfer of the newborn to another institution, or death) was 1.31 (95 percent confidence interval, 1.17 to 1.46) in uninsured as compared with privately insured newborns, with control for race or ethnic group. There was a significant increase in risk over time (P less than 0.03); the comparable odds ratios in 1982 and 1984 were 1.11 (95 percent confidence interval, 0.93 to 1.33) and 1.19 (1.05 to 1.35), respectively. In 1986 the risks were especially elevated for uninsured as compared with privately insured blacks and Latinos (odds ratios, 2.24 [95 percent confidence interval, 1.60 to 3.13] and 1.56 [1.26 to 1.94], respectively); the increases in risk over time were the most marked in these groups. We believe that the elevated and increasing risks for uninsured newborns are explained at least in part by inadequate and diminishing access to care and that this burden is borne disproportionately by blacks and Latinos.

California↗
PubMed1989

Alterations in the protein-synthesis, -degradation and/or -secretion rates in hepatic subcellular fractions of selenium-deficient mice.

Single mouse livers were subfractionated by differential centrifugation and isopycnic centrifugation on sucrose or metrizamide gradients and separated into subcellular compartments. The fractionation procedure was highly reproducible and yielded essentially similar results in different preparations of livers from selenium-adequate (Se+) and selenium-deficient (Se-) mice that were fed on a Torula-yeast-based diet containing less than 10 parts per 10(9) of selenium for at least 16 weeks. Mice of both dietary groups were injected intraperitoneally with 370 kBq of L-[U-14C]leucine, and 48 h later 1.85 MBq of L-[4,5-3H]leucine was injected intraportally. After another 1 h, the livers were removed and subjected to subcellular fractionation. Incorporation of the 3H label into proteins of the subcellular fractions was taken as a measure of relative protein-synthesis rate. The ratio of the 3H to the 14C protein-bound label of the same fractions was used as an estimate of relative protein-degradation and/or -secretion rate. The results showed a statistically significant 180% increase in protein-synthesis rate in the endoplasmic reticulum and a 80% increase in relative protein-degradation and/or -secretion rate in the same compartment. A significant decrease in the 3H/14C ratio, by 40 and 30% respectively, was observed in the Golgi fraction and in liver homogenate. The observed changes suggest a highly regulated hepatic response to selenium deficiency.

Animals↗