Biomedical subjects

W Schmidt

Publications and source records attributed to W Schmidt.

At least 487 records · Page 27Linked to original sources

PubMed1987

Preparation and properties of GnRH-loaded multilamellar liposomes.

Binding of the decapeptide gonadotropin releasing hormone (GnRH) to multilamellar liposomes was investigated with variation of the lipid matrix and of the medium conditions. It is demonstrated, that binding capacity of liposomes may be varied within wide limits if negatively charged phosphatidic acid is made a constituent part of the liposomes. Binding to liposomes is protecting GnRH against enzymatic hydrolysis by proteases, if structural integrity of liposomes is maintained. These properties are in favour of the application of liposomes as a drug carrier system for GnRH. The determination of the binding capacity and of the association constant for a definite system GnRH/lipid and, additionally, comparison of these data with analogous results concerning substance P [Pharmazie 39, 765 (1984)] furnish some new information with respect to the interaction of oppositely charged peptides and lipids.

Chemistry, Pharmaceutical↗

PubMed1987

Pharmacokinetics of gonadotropin-releasing hormone and stimulation of luteinizing hormone secretion after single dose administration of GnRH incorporated into liposomes.

The properties of liposomes as a carrier for sustained release of gonadotropin-releasing hormone (GnRH) was investigated. A mixture of egg-phosphatidylcholine/egg-phosphatidic acid, binding GnRH with high capacity, was used for preparation of GnRH-carrier liposomes, which were of the multilamellar type in most experiments. As test animals we used rabbits and pigs, the last mentioned for checking the LH4 response to GnRH-injections, which was via the i.m. route throughout in this investigation. By measuring the kinetics of removal of GnRH from the injection site and by following the GnRH invasion into the circulation, it was demonstrated that GnRH release from liposomal depots is strongly slowed down, compared with injections of the free hormone. Further, plasma levels of GnRH were detectable up to 8 h generally, sometimes up to 20 h after injection. However, a considerable portion of GnRH bound to multilamellar liposomes was released so slowly in our case, that the concentration decreased even below the RIA detection limit. This appears clearly from our kinetic data. For this reason the resorption of GnRH from liposomes seems to be less efficient than after i.m. injections of the free hormone. With pigs also the LH response to the injection of GnRH-liposomes was relatively poor. Apparently, biological activity is missing with very low GnRH concentrations. The results furnish good information on how to modify the liposome carrier in order to produce preparations with changed rates of GnRH release.

Animals↗

PubMed1987

[Cometabolic degradation of the herbicide nitrofen by mixed bacterial cultures].

The herbicide nitrofen undergoes microbial degradation by mixed bacterial populations isolated from arable soil, and with a supply of acetate, within 4 to 5 weeks. The degradation proceeds endogenously after an ATP-dependent uptake of the agent followed by a temporary accumulation. This cometabolic degradation, however, shows two peculiarities, (a) the occurrence of a lag-phase and (b) the possible use of endogenous storage products. In the case of application of glucose as a substratum for growth the degradation is blocked in consequence of a catabolic enzyme reprisal. If there are used more complex organic substrates, i.e. peptone and algal biomass, respectively, the degradation is retarded compared with acetate.

Acetates↗

PubMed1987

Autocrine growth stimulation of thymocyte precursors in the thymus.

A thymocyte specific growth peptide (TGP) has previously been purified from bovine thymus. In the present study TGP activity is demonstrated in the conditioned medium from a murine thymic leukemia cell line with prothymocyte phenotype, but is absent from media of cultured thymic epithelium. This murine TGP shows specificity for immature thymocytes and growth-stimulating kinetics identical to bovine TGP. Murine and bovine TGP show different chromatographic behaviour which may indicate biochemical differences. The results suggest that the immature thymocyte population includes both TGP-producing and TGP-responding cells. Our finding of TGP activity in fresh homogenates of normal mouse thymocytes supports this interpretation. We propose that TGP acts as an autocrine growth factor for rapidly cycling immature cortical thymocytes.

Animals↗

PubMed1986

[Genetic studies in etiologically different chronic liver diseases].

In 198 patients with chronic liver diseases of different etiology 16 genetic feature systems were investigated (blood groups, erythrocytic enzymes, immunoglobulin allotypes, proteins). In comparison to a representative normal population significant differences of the frequency of the distribution of phenotypes of various systems were found. In these cases is remarkable that association between genetic markers and hepatopathies were above all proved in their classification according to etiopathogenetic criteria. We evaluate our findings as a reference to the importance of genetic factors in the development of chronic liver diseases.

Blood Group Antigens↗

PubMed1986

Prenatal diagnosis of autosomal dominant polycystic kidney disease with a DNA probe.

A highly polymorphic DNA probe genetically linked to the locus of autosomal dominant polycystic kidney disease was used in linkage studies for prenatal diagnosis in a nine-week fetus at risk for the disease. The fetus was judged to have inherited the polycystic kidney disease mutation, and this was confirmed by microscopic examination of the fetal kidneys at necropsy.

Abortion, Therapeutic↗

PubMed1986

[Rational procedures in the differential diagnosis of jaundice].

In jaundice after exclusions of prehepatic and functional hepatogenic hyperbilirubinaemias the sonography should pre-eminently be used as a riskless, economical and qualified investigation method, taking into consideration clinical and laboratory-chemical data. If sonographically the findings of an intrahepatic cholostatis are shown, in therapeutic relevance the histological clarification must follow. Only in unequivocal focal changes of the liver (perhaps thin needle puncture) further investigations are unnecessary. If there are findings of an extrahepatic cholostasis, in a not unequivocal sonographic result or before a surgical intervention further aimed investigations, such as ERCP, PTC and CT, are necessary for the exact clarification of the cause of the obstruction of the bile ducts.

Bile Duct Diseases↗

PubMed1986

Cytotoxic T cell lysis of H-2-negative murine sarcoma cells.

The DOH cell line was established from C3H.OH (H-2Kd,Dk) embryonic fibroblasts transformed with Rous sarcoma virus (RSV) in vitro. When injected into syngeneic mice, DOH cells were very weakly tumorigenic and induced a cytotoxic immune response. Cytotoxic T lymphocytes (CTL) specifically lysed DOH cells but not other RSV-induced sarcoma cells, which shared the H-2Kd or H-2Dk antigen, respectively, with DOH. Serological and immunochemical analysis of H-2 antigens subsequently showed that DOH sarcoma cells did not express syngeneic H-2K and H-2D antigens. Surprisingly, a H-2Kk-specific monoclonal antibody (100-5) bound to DOH cells and was inhibitory for syngeneic CTL specific for DOH. In addition, DOH cells were lysed by alloreactive H-2Kk-specific CTL. The demonstration of immunogenic H-2-negative sarcoma cells suggests that either the H-2K antigens have been extensively altered or that hitherto unidentified major histocompatibility complex class I molecules are expressed on DOH sarcoma cells surfaces, acting as target antigens for tumor-specific CTL.

Animals↗

PubMed1986

Resistance to cellular immune response in AKR leukemias.

Spontaneous AKR leukemias express murine leukemia virus (MuLV) gag and env gene-encoded structural proteins on their cell surface. Cytotoxic T lymphocytes (CTL) induced in AKR mice by syngeneic leukemia 369 which expressed high amounts of H-2 antigens recognized viral gag polyproteins in association with H-2K antigens as target antigens. H-2K-negative leukemias were resistant to lysis by AKR/Gross MuLV-specific CTL and did not induce a cellular immune response. However, they became susceptible after stimulation with interferon. H-2K-positive leukemias induced CTL which were cytotoxic for 369 cells. However, the majority of H-2K-positive leukemias was not lysed by CTL induced by autologous immunization. These leukemias were also resistant to lysis by anti-369 CTL, but could restimulate AKR/Gross-specific CTL in vitro, and were susceptible to lysis by H-2Kk-restricted CTL against AKR minor histocompatibility antigens. Thus, there could be specific defects of the H-2Kk antigens of these tumors. However, there were also qualitative and quantitative differences in antigenic determinants of the gag target antigens in these leukemias. Therefore, in addition to quantitative reduction of the H-2K restriction elements, qualitative alterations of H-2 antigens or of the viral target antigens may impair T cell cytotoxicity and thus influence leukemogenesis of AKR spontaneous leukemia.

AKR murine leukemia virus↗

PubMed1986

Is prenatal ultrasonography of any advantage?

With the percentage of prenatally diagnosed malformations rising, there is a growing need for the contribution of the pediatric surgeon regarding prognostic and therapeutic aspects for the unborn child. An important risk factor for the validity of any statement is the possible presence of undetected, associated malformations. In spite of all advantages prenatal diagnosis offers regarding carefully planned therapy, etc., doubt and uncertainty always remain.

Congenital Abnormalities↗

PubMed1986

2-ketoglutarate generation in pancreatic B-cell mitochondria regulates insulin secretory action of amino acids and 2-keto acids.

The various neutral amino acids and aliphatic 2-keto acids exhibit differential effects on insulin secretion. The common denominator for all these effects is the 2-ketoglutarate generation in the pancreatic B-cell mitochondria. The neutral amino acids L-leucine and L-norvaline and the aliphatic ketomonocarboxylic acids 2-ketoisocaproate, 2-ketocaproate, 2-ketovalerate, and 2-keto-3-methylvalerate all stimulate insulin secretion and increase 2-ketoglutarate generation in pancreatic B-cell mitochondria through activation of glutamate dehydrogenase and transamination with L-glutamate and L-glutamine, respectively. The neutral amino acids L-valine, L-norleucine, and L-alanine and the aliphatic 2-keto acids 2-ketoisovalerate and pyruvate do not stimulate insulin secretion and do not increase 2-ketoglutarate generation in pancreatic B-cell mitochondria. Inhibition of 2-keto acid induced insulin secretion by L-valine and L-isoleucine is accompanied by reduced 2-ketoglutarate generation in pancreatic B-cell mitochondria. Thus intramitochondrial 2-ketoglutarate generation in pancreatic B-cells may regulate the insulin secretory potency of amino acids and 2-keto acids.

Amino Acids↗

PubMed1986

Cytogenetic studies on human breast carcinomas.

Cytogenetic studies were performed on cell material obtained from surgical specimens of 50 human breast carcinomas and from 61 cancerous effusions of 46 patients. Classical cytogenetic analyses of numerical chromosome changes and marker chromosomes revealed the non-random involvement of chromosomes #X and #22 as monosomics, of chromosomes #3, #7, and #19 as trisomics, and chromosome #1 (particularly p 13 to q 12) in marker formation. Karyotypic evolution was followed in vitro and in vivo and showed a highly individualistic pattern of stability and variability. In addition, a systematic screening for the presence of cytogenetic equivalents of gene amplification (double minutes 'DM', homogeneously staining regions 'HSR') was carried out. A high incidence of DM-positive cases was detected in primary tumors (48%) as well as in metastatic cells from effusions (40%), with the frequency of DM-containing metaphases ranging from 1 to 100% in the positive cases. This finding supports the assumption of the fundamental biological importance of gene amplification in human solid tumors. Furthermore, chromosome breakage and micronuclei were observed in breast carcinoma cells as an apparent consequence of therapy-independent mutability.

Breast Neoplasms↗

PubMed1986

[A new study method: the perineal scan in obstetrics and gynecology].

For gynecological/obstetrical ultrasound examination the abdominal wall constituted the first and for a long time the only acoustical window that could be used to visualize the female reproductive organs. Only recently transvaginal/transrectal endosonography has opened new approaches in this diagnostic field. Apart from the above-mentioned procedures, the female perineum can be regarded as a useful window to demonstrate the cervix uteri, the bladder and the urethra. At the Universitäts-Frauenklinik Heidelberg this examination procedure was used since June, 1985, to evaluate its clinical reliability in obstetrics and gynecology.

Female↗

PubMed1986

[Sonographic evaluation of the quantity of amniotic fluid. II. Oligohydramnios--significance for the course of pregnancy and labor].

3,274 pregnant women were examined sonographically in this study, with particular emphasis on the quantity of amniotic fluid present. In 8% of the patients a reduced amount of amniotic fluid was seen. If the largest pocket of amniotic fluid was less than 2 cm that particular case was classified as oligohydramnios. If the largest pocket of amniotic fluid was between 2 cm and 3 cm, it was assumed to be in the lower standard range. These cases were compared with a randomly selected control group with normal amounts of amniotic fluid, in respect of the occurrence of complications during gestation and delivery and of the incidence of fetal malformations. Patients with reduced amounts of amniotic fluid showed signs and symptoms of gestosis more often (p less than 0.001) and delivered more often before the 36th week of pregnancy (p less than 0.001) and growth-retarded children (p less than 0.001) than women with standard amounts of amniotic fluid. The incidence rate of Caesarean section was 42%, and hence far above the standard level (p less than 0.001). In oligohydramnios, 13% (p less than 0.001) of the children had severe fetal malformation, whereas, with an amount of amniotic fluid in the lower standard range, only 5.5% (not significant) showed severe foetal malformation. The stated sonographic criteria are suitable as an objective measure for quantifying the amount of amniotic fluid.

Adult↗

PubMed1986

[Pathological insertion of the placenta after the 20th week of pregnancy--its importance in the course of pregnancy and delivery].

The present paper reports on the results of sonographic diagnosis of a pathologic insertion of the placenta after the 20th week of pregnancy and its importance with regard to the course of pregnancy and birth. The conversion of a primarily pathologic placental insertion to a "normal" insertion at term depends on the severity of the placental insertion disorder and the date of diagnosis. The frequency of pathologic insertions after the 20th week of pregnancy amounted to 4.2% of the patients examined. The rate of conversion from pathologic to normal placental insertion was 91%, if marginal/partial and total placenta previa are accepted as definitive diagnoses at term. The insertion remained unchanged up to term in approximately 90% of the cases in which total placenta previa was sonographically diagnosed. The sonographic diagnosis of "pathologic insertion of the placenta" after the 20th week of pregnancy is associated with severe complications in the subsequent course of pregnancy and birth. There is a significant cluster of vaginal hemorrhage in the last trimester of pregnancy; cesarean deliveries are common; there are more cases of transfer to pediatric clinics, and the incidence of retarded fetal growth and perinatal mortality is higher. The present authors believe that where the diagnosis of placenta previa has been confirmed sonographically, prophylactic measures and, in the last resort, a planned cesarean delivery can contribute to a reduction in maternal morbidity and also to a decrease in perinatal morbidity and mortality.

Abortion, Spontaneous↗

PubMed1986

[Sonographic evaluation of the amount of amniotic fluid. I. Polyhydramnios--significance for the course of pregnancy and labor].

In this study, 3,274 pregnant patients were sonographically examined. Special attention was paid to the classification of the quantity of amniotic fluid according to sonographic criteria. An increase in amniotic fluid was observed in 6% of the patients examined. Cases in which the largest sonographically demonstrable amniotic fluid was significantly larger than the transverse thoracoabdominal diameter were classified as polyhydramnios. An amniotic fluid depot that was either as large as or up to 10% larger than the transverse thoracoabdominal diameter of the fetus was regarded as the upper normal range for the amount of amniotic fluid. These cases were compared with a randomly chosen control group with normal quantities of amniotic fluid with regard to the occurrence of complications during pregnancy and birth and to the incidence of fetal malformation. Patients with increased quantities of amniotic fluid more frequently had symptoms of toxemia (p less than 0.01). In patients with manifest diabetes mellitus the quantity of amniotic fluid was frequently in the upper normal range (p less than 0.01), while women with gestation diabetes frequently suffered from polyhydramnios (p less than 0.001). Fifteen percent of women with quantities of amniotic fluid in the upper normal range beared macrosomatic children (p less than 0.001). Twenty-seven percent of cases with polyhydramnios (p less than 0.001) and 8% of cases with a quantity of amniotic fluid in the upper normal range (p less than 0.01) were associated with serious fetal malformation.

Adult↗

PubMed1986

[Diagnosis of holoprosencephaly with cyclopia in the fetus].

The typical ultrasound findings in cases of fetal holoprosencephaly with hypotelorism and cyclopia are explained with reference to a case history. Hypotelorism was confirmed by measurement of the distance between the orbits of the fetus.

Abnormalities, Multiple↗

PubMed1986

[Delivery planning and interdisciplinary management of large coccygeal teratomas].

Prenatal sonographic screening and a growing experience of examiners with regard to possible congenital malformations such as large coccygeal teratomas have induced the request for an early interdisciplinary consultation between obstetrician, human geneticist, paediatric surgeon, neonatologist and psychologist. It should aim at a careful information and counselling of the parents with regard to the mode of delivery and possibilities of operative management. The prerequisites for far sighted planning and performance of delivery are demonstrated by the example of large coccygeal teratomas. The availability of equipment, facilities and manpower at the time of delivery guarantees a course of delivery at reduced risk and is, together with the psychological guidance of the parents, a basic element of optimal care for the newborn.

Coccyx↗