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Biomedical subjects

G Weiss

Publications and source records attributed to G Weiss.

At least 163 records · Page 9Linked to original sources
PubMed1995

Heterogeneity of deletions involving RB-1 and the D13S25 locus in B-cell chronic lymphocytic leukemia revealed by fluorescence in situ hybridization.

Recently, the D13S25 locus, which is in close proximity to the retinoblastoma gene (RB-1) on chromosome band 13q14, was discussed to play a role in the pathogenesis of B-CLL. In the present study, we isolated two overlapping genomic DNA clones (termed c13S25) containing the D13S25 DNA segment and used them as probes to analyze 85 B-CLL cases by fluorescence in situ hybridization; of the 55 cases with two RB-1 copies, 13 exhibited hemizygous (n = 7) or homozygous (n = 6) deletion of D13S25. Of 29 cases with hemizygous deletion of RB-1, all but two also showed loss of D13S25 (hemizygous, n = 25; homozygous, n = 2). One case had a homozygous deletion of both loci. We conclude that deletion of D13S25 occurs in a substantial number of B-CLL without deletion of RB-1. However, in some cases there is deletion of RB-1 without loss of D13S25, suggesting that D13S25 is not the locus of the putative tumor suppressor gene. According to our data, such a gene is most likely located within the genomic region between D13S25 and RB-1.

Chromosome Deletion↗
PubMed1995

The effect of multifetal pregnancy reduction on serum relaxin.

OBJECTIVE: To determine the effect of multifetal pregnancy reduction on circulating relaxin levels. METHODS: Patients with multifetal pregnancies had relaxin levels determined on the day of multifetal pregnancy reduction, after the procedure, and late in pregnancy. RESULTS: Forty-eight women (26 presenting with three fetuses and 22 with four or more) were studied. All pregnancies followed some form of ovulation induction. All pregnancies (except for one, which was reduced to a singleton) were reduced to twins. Pre-procedure, post-procedure and late-pregnancy relaxin levels were significantly higher in the in vitro fertilization (IVF)-gamete intrafallopian transfer (GIFT) group compared with the human menopausal gonadotropin (hMG)-alone group (P < .05). The initial number of fetuses had no significant effect on relaxin levels. Although post-procedure relaxin levels were significantly lower than pre-procedure levels (P = .002), relaxin levels continued to decrease throughout pregnancy, as evidenced by even lower levels later on (P = .0001). CONCLUSIONS: Serum relaxin levels were significantly higher in the IVF-GIFT group than in the hMG-alone group, which probably reflects more aggressive ovulation induction in the former. Because relaxin levels continued to decrease throughout pregnancy, the difference observed between pre- and post-procedure levels are not considered to be due to the procedure itself.

Female↗
PubMed1995

Linkage of cell-mediated immunity to iron metabolism.

Iron is essential for growing microorganisms and tumour cells, and is also crucial for the proliferation of immune cells. In this review, Günter Weiss, Helmut Wachter and Dietmar Fuchs focus on the complex network of interactions that link iron metabolism with cellular immune effector functions involving cytokines and nitric oxide, and draw a suitable model for the pathogenesis of anaemia of chronic disease.

Animals↗
PubMed1995

Modeling the polymerase chain reaction.

We introduce a mathematical model to treat the polymerase chain reaction (PCR), where we regard the accumulation of new molecules during a PCR cycle as a randomly bifurcating tree. This model enables us to compute an approximate formula for the distribution of the number of replications that have occurred between a pair of molecules, which depends on the efficiency lambda of the reaction, the number N0 of template molecules at the beginning of the PCR and the number c of PCR cycles. The reliability of the approximation is tested by computer simulations. Finally, to model the effect of the intrinsic error rate of the polymerase, we superimpose a substitution process on the tree. The resulting closed formula for the distribution of pairwise differences of sequences as a function of error rate mu and efficiency lambda can be used to estimate the error rate, if lambda is known.

Base Sequence↗
PubMed1995

Relaxin used to produce the cervical ripening of labor.

Important progress has been made in understanding the physiology of relaxin in human pregnancy. The structure of relaxin and its genetics have been elucidated. Progress has been made into understanding the control of relaxin secretion. Many actions of relaxin have been defined. Some of the effects of too much or too little relaxin have been described. However, the cellular mechanisms of relaxin action must still be determined, and the relationship of relaxin to diseases of pregnancy must be clarified. Although relaxin affects the human cervix, its physiologic role is not clear. Pregnancies can proceed uneventfully in the absence of circulating relaxin. Thus circulating relaxin is not critical for maintaining pregnancy or for cervical ripening. The mechanisms by which pregnancy is maintained and the mechanism of the timely onset of labor at full term are not well understood. There is a plethora of data suggesting many parallel overlapping control mechanisms for uterine control. Most of these systems are not critical because their actions can be compensated for by other systems. Understanding the physiology of human pregnancy must account for these multiple systems. Within this context, the role of relaxin in the physiology of labor must be understood.

Animals↗
PubMed1995

Sex-selective abortion: a relational approach.

A critical application of Ruddick's model of maternal thinking is the best way to grapple with the ethical dilemmas posed by sex-selective abortion which I view as a "moral mistake." Chief among these is the need to be sensitive to local cultural practices in countries where sex-selective abortion is prevalent, while simultaneously developing consistent international standards to deal with the dangers posed by the use of sex-selective abortion to eliminate female fetuses.

Abortion, Induced↗
PubMed1995

Predictive value of urinary neopterin in patients with lung cancer.

Concentrations of neopterin, which is produced by human monocytes/macrophages when stimulated by gamma-interferon, were measured in urine specimens from 72 patients with lung cancer at diagnosis. Other routine clinical and laboratory variables were concomitantly determined. Neither neopterin nor any other laboratory variable studied showed a significant correlation with clinical indicators of the disease (morphologic type, tumour stage, grading, lymph node status, presence of distant metastases). The cancer patients were followed up for up to 10 years, and the abilities of all variable to predict fatal outcome were assessed. In univariate survival analyses, all clinical indicators except morphologic type (P = 0.86) were significant predictors of survival (P < 0.002), but of all the laboratory variables studies, only neopterin was significantly predictive (P = 0.0013). By multivariate survival analysis, a combination of four variables was found to jointly predict survival: lymph node status (P = 0.003), multivariate model), tumour stage (P = 0.0006), grading (P = 0.0047) and neopterin (P = 0.0047). The data suggest that certain aspects of immune activation may have adverse consequences for the prognosis of patients with lung cancer.

Adult↗
PubMed1995

Pharmacokinetics of ibuprofen following a single administration of a suspension containing enteric-coated microcapsules.

The relative bioavailability of ibuprofen (CAS 15687-27-1) was investigated following a single administration of a suspension containing enteric-coated microcapsules (A) in comparison to a rapid-release film-coated tablet (B) and a sustained-release tablet (C). The study was carried out in a three-way crossover design in 9 healthy male volunteers. Each formulation contained 800 mg ibuprofen. Plasma concentrations of ibuprofen were determined with a specific HPLC method. A mean relative bioavailability of 0.96 (B) and 1.01 (C) was determined for the test formulation. Since the corresponding 90% confidence intervals were within the recommended limits, bioequivalence for the extent of bioavailability of the test formulation can be concluded. Differences in pharmacokinetics were observed for the rate-dependent parameters. For the test formulation, the highest mean maximum plasma concentration (54.3 micrograms/ml) was measured with a corresponding tmax of 1.9 h. For the reference formulations, mean peak plasma concentrations of 45.2 micrograms/ml after 2.6 h (B) and 25.7 micrograms/ml after 5.6 h (C) were observed. Despite the enteric coating of the microcapsules, a very short lagtime of 0.03 h was determined for the suspension. For the other rapid release formulation (B), the lagtime was in a similar magnitude (0.11 h), while the absorption from the sustained-release tablet was clearly decelerated (tlag = 0.97 h). In comparison to the other rapid-release formulation (B), significant higher amounts of the drug were absorbed from the test formulation (A) within the first hour.

Adult↗
PubMed1995

Relaxin and its role in pregnancy.

Relaxin is a 6000-d polypeptide, structurally related to insulin and the insulin-like growth factors. Unlike insulin, the structure of which is remarkably well conserved among the vertebrates, relaxin sequences can vary by more than 50% between different species. Despite these large sequence variations, relaxins (with few exceptions) have very similar biologic activities in animal test systems. The reason for this has recently come to light: the receptor binding region of the B chain, in contrast to the rest of the molecule, is highly conserved between species. Relaxin is measured by bioassays employing interpubic ligament formation in mice and guinea pigs, and by inhibition of uterine motility. A more sensitive and efficient bioassay is urgently needed. In women, the target organs for relaxin are the uterine cervix, myometrium, endometrium, and decidua. Other presumptive but unproven targets are the pubic symphysis and sacroiliac joints, mammary glands, and pituitary gland. Circulating relaxin is secreted by the corpus luteum. The placenta, decidua, or both also produce relaxin, which does not enter the circulation but may act in an autocrine or paracrine fashion. hCG is a stimulus to luteal relaxin secretion. Other regulatory factors are poorly defined. Aluteal women are hyporelaxinemic, and yet are capable of normal vaginal delivery of their infants. Local effects of placental or decidual relaxin cannot be discounted in such subjects. Hyperrelaxinemia may occur in women with multiple gestations and ovarian stimulation, and may be associated with increased premature births. Serum relaxin also is elevated in pregnant diabetics, but its role in this condition has not been defined. Clearly, further investigations are needed to delineate the precise role of relaxin in human pregnancy.

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

Iron regulates nitric oxide synthase activity by controlling nuclear transcription.

Recently, it was reported that nitric oxide (NO) directly controls intracellular iron metabolism by activating iron regulatory protein (IRP), a cytoplasmic protein that regulates ferritin translation. To determine whether intracellular iron levels themselves affect NO synthase (NOS), we studied the effect of iron on cytokine-inducible NOS activity and mRNA expression in the murine macrophage cell line J774A.1. We show here that NOS activity is decreased by about 50% in homogenates obtained from cells treated with interferon gamma plus lipopolysaccharide (IFN-gamma/LPS) in the presence of 50 microM ferric iron [Fe(3+)] as compared with extracts from cells treated with IFN-gamma/LPS alone. Conversely, addition of the iron chelator desferrioxamine (100 microM) at the time of stimulation with IFN-gamma/LPS increases NOS activity up to 2.5-fold in J774 cells. These effects of changing the cellular iron state cannot be attributed to a general alteration of the IFN-gamma/LPS signal, since IFN-gamma/LPS-mediated major histocompatibility complex class II antigen expression is unaffected. Furthermore, neither was the intracellular availability of the NOS cofactor tetrahydrobiopterin altered by treatment with Fe(3+) or desferrioxamine, nor do these compounds interfere with the activity of the hemoprotein NOS in vitro. We demonstrate that the mRNA levels for NOS are profoundly increased by treatment with desferrioxamine and reduced by Fe(3+). The half-life of NOS mRNA appeared not to be significantly altered by administration of ferric ion, and NOS mRNA stability was only slightly prolonged by desferrioxamine treatment. Nuclear run-off experiments demonstrate that nuclear transcription of cytokine-inducible NOS mRNA is strongly increased by desferrioxamine whereas it is decreased by Fe(3+). Thus, this transcriptional response appears to account quantitatively for the changes in enzyme activity. Our results suggest the existence of a regulatory loop between iron metabolism and the NO/NOS pathway.

Amino Acid Oxidoreductases↗
PubMed1994

Increased production of immune activation marker neopterin by colony-stimulating factors in gynecological cancer patients.

Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) have recently been introduced in the treatment of chemotherapy-induced neutropenia. Effects of these CSFs on the cellular immune system were evaluated in 38 neutropenic gynecological cancer patients during chemotherapy. In addition to restoring the leukocyte count, GM-CSF--to a greater extent than G-CSF--also induced neopterin, a sensitive marker of macrophages activated by interferons. This effect was confirmed in vitro by investigating the effects of these CSFs on interferon-gamma-mediated pathways in THP-I human myelomonocytic cells. The results suggest activation of immune effector cells by GM-CSF.

Adult↗
PubMed1994

Immune activation and enhanced urinary zinc concentrations in allograft recipients.

OBJECTIVES: Zinc metabolism is frequently abnormal in renal allograft recipients. These abnormalities may be immune mediated because zinc metabolism is affected by inflammation. METHODS: We determined urinary zinc and neopterin concentrations in 24 allograft recipients (18 kidney, 3 combined kidney-pancreas and 3 liver allografts) daily for 1-41 days. In addition, serum zinc concentrations were measured in 11 patients. RESULTS: Serum zinc was decreased and urinary zinc concentrations were increased in kidney as well as liver transplant recipients when compared with healthy controls. Urinary zinc concentrations were only slightly elevated in patients with uncomplicated post-transplant course, but the increase was more pronounced in renal allograft recipients with acute tubular necrosis. Urinary zinc concentrations were drastically increased during rejection of various organs. In addition, significant associations between urinary zinc and neopterin concentrations were observed. CONCLUSION: Our results suggest that enhanced urinary zinc excretion in allograft recipients is due to immune activation. The data indicate that cytokines play a role in zinc metabolism.

Adolescent↗