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[Effect of recombinant human basic fibroblast growth factor (rh-bFGF) on wound healing of the corneal epithelium].

Prior to a possible clinical trial in humans, we studied the wound-healing effect of RH-bFGF in vivo. Healing-rate measurements on 24 deepithelialized rabbit corneas were performed by means of computer-assisted image analysis. A significantly increased healing rate (P = 0.004) was revealed for the 200 ng FGF treated group (rate 1.57 mm2/h) compared to the control group (1.12 mm2/h). To assess the long-term (side) effects of FGF (50 ng topically applied, 2 times daily), 7 rabbits were involved in a model with repeated epithelial scraping of an anterior keratectomy wound (performed with Draeger's rotokeratom to a depth of 0.15 mm). Light and transmission electron micrographs of treated corneas showed an increased fibrogenesis in the anterior stroma with more pronounced activation of keratocytes. No evidence of abnormal neovascularization or inflammation was observed when compared to control corneas. We suggest that topical RH-bFGF promotes corneal wound healing with virtually no detectable adverse reactions. These results seem to be of considerable interest for the possible therapeutic use of rh-bFGF in patients with superficial corneal epithelial lesions.

Animals↗

Rhesus incompatibility as a risk factor for schizophrenia in male adults.

BACKGROUND: Rhesus (Rh) incompatibility is a cause of hemolytic disease of the fetus and newborn. Hemolytic disease results from the transplacentally transmitted maternal antibodies against Rh factor D and can cause permanent neurological damage in the affected newborn. This study examines the hypothesis that Rh incompatibility may be a risk factor for schizophrenia. METHODS: A sample of 1867 male subjects was divided into two groups, 535 Rh incompatible and 1332 Rh compatible, and compared on rate of schizophrenia. RESULTS: The rate of schizophrenia was significantly higher in the Rh-incompatible group (2.1%) compared with the Rh-compatible group (0.8%) (P < .03). In addition, since the risk for Rh hemolytic disease increases with second and later Rh incompatible pregnancies, it is noteworthy that the second- and later-born incompatible offspring exhibited a significantly higher rate of schizophrenia than second- and later-born compatible offspring (P < .05). Also, as predicted, the rate of schizophrenia among firstborn incompatible subjects was not significantly different from that of firstborn compatible subjects (1.1% vs 0.7%). CONCLUSION: Rh incompatibility may be a risk factor for schizophrenia.

Adult↗

Chronobiology in endocrinology.

Temporal endocrine structure (TES). It can be defined as a combination of predictable hormonal changes that are time-related. Regarding their frequency, endocrine rhythms may be circadian, ultradian and infradian. In this context, the endocrine circadian time structure (ECTS), that is closely dependent of some areas of the hypothalamus, is of particular interest. Long and short loop feedback link together the various components: central nervous system (CNS), hypothalamus and anterior pituitary with target glands and tissues. The hypothalamic neuropeptides (releasing hormones or factors - RH or RF - or inhibiting hormones or factors IH or IF) presently known are: thyrotropin releasing hormone (TRH); luteinizing releasing hormone (LH RH); prolactin releasing factor (PRF); Prolactin Inhibiting Factor (PIF); Corticotropin Releasing Factor (CRF); Growth Releasing hormone (GH RH). Some general remarks on endocrine rhythms should be noted: the circadian changes in hormones may depend on each other; even an apparently subordinate rhythm should be considered a true independent rhythm; accurate studies have shown that hormonal secretion occurs in all cases according to a rhythmic organization at many levels; these rhythms may not be evident at a first analysis. The hormone secretion is basically pulsating which makes it difficult to draw standard reference values. Although an ECTS is present at the cell level, in organs etc., it is evident that a rhythm hierarchy exists. Hormonal secretion and sleep-wake cycle. Although several reports state that no rhythm is totally dependent on the sleep-wake cycle, from a general point of view the hormone secretion rhythms can be divided in: sleep-dependent rhythms and sleep-independent rhythms. Meal-timing and hormonal secretion. In animals, meal-timing is a powerful synchronizer; however, there are no definitive and conclusive data to prove that meal-timing is a true synchronizer also in humans, although there have been some reports suggesting it. Endocrine rhythms. Data regarding the endocrine rhythms (circadian-ultradian-infradian) of the numerous hormones as GH; prolactin; aspects of temporal pattern of CRF-ACTH-corticosteroid and of hypothalamic - pituitary - thyroids axis; hypothalamic - pituitary - ovaric steroid and testosterone axis are reported. The study of a possible rhythmic pattern of insulin has been approached from many points of view as the basal rhythmicity of insulin; the diurnal variation of efficacy of injected insulin and of insulin responsiveness to insulinogenic stimuli.

Chronobiology Phenomena↗

Colony inhibitory effect of recombinant human tumor necrosis factor (rH-TNF) and/or recombinant human interferon (rH-IFN)-alpha, -beta and -gamma on human lung cancer cell lines.

This study was conducted to assess, by continuous exposure, the inhibitory effects of rH-TNF and rH-IFN-alpha, -beta and -gamma, either alone or in combination, on the colony formations of human lung cancer cell lines. The cell lines tested were PC-7 and PC-9 (adenocarcinoma), PC-10 (squamous cell carcinoma) and PC-13 (large cell carcinoma). Additional experiments were performed with L929 (transformed murine fibroblast), because of its known high sensitivity to TNF. rH-TNF inhibited the colony formations of PC-10 and L929 even at a low concentration (10 U/ml). However, PC-7, PC-9 and PC-13 were resistant to rH-TNF. rH-IFN-alpha, -beta and -gamma inhibited the colony formation of PC-10 (less than 50% of control) at the highest concentration tested (10(4) U/ml), but only rH-IFN-beta inhibited that of PC-7. PC-9, PC-13 and L929 were insensitive to all three rH-IFNs, even at the highest concentrations tested. Combination effects of rH-TNF and rH-IFN-alpha or -gamma were synergistic only at the highest concentration combinations tested in PC-9. However, the maximum inhibition of colony formation of PC-7, PC-9 or PC-13 in any concentration combination treatment was less than 50%.

Antineoplastic Combined Chemotherapy Protocols↗

Blood group frequencies in multiple sclerosis populations in the United States.

Multiple sclerosis (MS) patients (332) and controls (305) selected from Caucasian populations in the New York City area and in Tucson, Arizona, were tested for ABO blood group factors A and B, and Rh factors C, D, E, c, and e. There was no significant difference in the distribution frequencies of these factors in MS patients and controls.

ABO Blood-Group System↗

[Prevention of hemolytic disease in newborn infants using anti-D immunoglobulin G].

The authors have analyzed the prevention of Rh-immunization from 1972 to 1983. Results are presented in two six-year periods, i.e. from 1972 to 1977 and from 1978 to 1983. Prevention was applied to all rh-negative women, who have been delivered from a rh-negative baby in their first childbirth (with negative sensibilization tests). Anti D IgG was also applied to all women after their second, third, fourth or subsequent delivery, if they were willing to have more children. Women with Du variant of the Rh factor and having a Rh-positive child were also protected. Preparations containing 250 to 300 micrograms of IgG anti-D were used. During the first period we found rh-negative mothers in 18.41 per cent, in 63.48 per cent of them the newborn was Rh-positive. During the second period 17.89 per cent of our women were rh-negative with 58.45 per cent Rh-positive babies. During the first period, protection was afforded to 60.26 per cent of the rh-negative women with incompatible babies, and in the second period to 79.11 per cent, respectively (P less than 0.05). During the second period, 99.70 per cent of women were protected after their first delivery (except of one case with immunization already during pregnancy), in contrast to the first period, where this percentage amounted only to 84.66 per cent (P less than 0.05). During both periods, a total of 69.51 per cent of the rh-negative women having Rh-positive babies received anti-D-immunization.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Anti-Idiotypic↗

Idiotypic and anti-idiotypic determinants on lymphocytes during anti-Rh immunization.

Evolution of idiotypic determinants on lymphocytes membrane and presence of other lymphocytes carrying anti-idiotypic determinants, were studied in Rh negative human volunteer blood donors during immunization towards Rh factor. For this purpose E-Rh Rosettes, direct immunofluorescence, inhibition of E-Rh Rosettes by anti-idiotypic sera as well as EA-Rh Rosettes--induced with Fab'2 fragments from anti-Rh antibodies and lymphocytes from the same subject--were examined and compared to the evolution of circulating antibodies. E-Rh Rosettes preceded or accompanied production of anti-Rh antibodies; their frequency decreased after the fifth month following immunization, meanwhile EA-Rh Rosettes increased in parallel with antibody decrease. The direct immunofluorescence and the inhibition of E-Rh Rosettes, by anti-idiotypic sera, show the presence of idiotypic determinants on lymphocyte membranes; the presence of EA-Rh Rosettes, coinciding with the decrease in antibodies demonstrate the existence of lymphocytes bearing auto-anti-idiotypic determinants.

Antibodies, Anti-Idiotypic↗

[Specificity of antibodies formed in people with Rh-negative blood in response to administration to antigens C(rh', Rh2) and Cw(rhwf, Rh8)].

Anti-C, -Ce, -CD sera and monoclonal anti-C-antibodies with red cells varying by Rh-phenotypes comprising antigen C(w) have been studied. Four Rh-negative volunteer donors were reimmunized with antigens C and C(w). As shown by reactions of anti-C-sera, monoclonal antibodies anti-C with C(w)-positive cells, results of immunisation of the Rh-negative donors with antigen C(w) of Rh system, red cels containing Rh antigen C(w) contain also factor rh(C).

Antibody Formation↗

Perinatal risk factors for childhood type 1 diabetes in Europe. The EURODIAB Substudy 2 Study Group.

OBJECTIVE: To explore whether perinatal factors are associated with the development of childhood type 1 diabetes. RESEARCH DESIGN AND METHODS: We studied hospital records from 892 cases of childhood type 1 diabetes compared with 2,291 population-based control subjects in seven study centers in Europe. RESULTS: In a pooled analysis incorporating stratification by center, we confirmed the previous findings that older maternal age, maternal preeclampsia, neonatal respiratory disease, and jaundice caused by blood group incompatibility are significant risk factors for type 1 diabetes, whereas being a firstborn child, having a low birth weight, or having a short birth length were protective. Cesarean section delivery and neonatal infectious diseases were not significantly associated with the risk of type 1 diabetes in this study. The strongest association was found for blood group incompatibility (AB0 and Rh factor) with an odds ratio (OR) of 2.96 (95% CI 1.88-4.65). AB0 incompatibility (OR = 3.92) was a more common and also a stronger risk factor than Rh incompatibility (OR = 1.62). The effect of AB0 blood group incompatibility was independent of treatment effects in logistical regression analysis. CONCLUSIONS: Different perinatal events are associated with an increased risk of type 1 diabetes. The effect of maternal-child blood group incompatibility is strong and indicates a true effect that must be further explored.

ABO Blood-Group System↗

Cutaneous side effects in breast cancer patients treated with cytostatic polychemotherapy and rh GM-CSF: immune phenomena or drug toxicity?

The application of recombinant colony stimulating factors for chemotherapy induced granulocytopenia is becoming common in clinical oncology. Here we report on localized cutaneous side effects after subcutaneous administration of recombinant human granulocyte-macrophage colony-stimulating factor (rh GM-CSF) in 11 patients with breast cancer receiving cytostatic treatment. Seven patients suffering from inflammatory breast cancer received cytostatic chemotherapy with mitoxantrone/cyclophosphamide, whereas four patients suffering from noninflammatory breast cancer received high-dose epirubicin/cyclophosphamide, respectively. rh GM-CSF was applicated subcutaneously in a dose of 5 micrograms/kg/d for at least ten days. In all patients, sharply demarked, maculous itching and burning erythemas restricted to the injection sites occurred after three to four injections of rh GM-CSF. These eruptions cleared within 2 to 3 weeks, but reappeared after reexposure to rh GM-CSF. In contrast to previous sporadic reports, no generalized erythemas were observed. Because of this unexpected and subjectively intolerable side effect, rh GM-CSF administration had to be interrupted in all patients. Histopathological findings revealed skin infiltration with lymphocytes, monocytes/macrophages, neutrophils, and occasionally eosinophils, respectively. Since GM-CSF is known to alter immune functions, it seems likely that the eruptions were at least in part due to local immune reactions.

Adenocarcinoma↗