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Biomedical subjects

M Schulz

Publications and source records attributed to M Schulz.

At least 91 records · Page 5Linked to original sources
PubMed1998

Evidence for CCK(B) receptors in the guinea-pig kidney: localization and characterization by [125I]gastrin binding studies and by RT-PCR.

Two types of receptors for gastrin and cholecystokinin (CCK) have been identified in the gastrointestinal tract and in the central nervous system: CCK(A) and CCK(B) receptors. Here we report evidence for the expression of CCK(B) receptors in the guinea-pig kidney. Specific binding sites for [125I]gastrin were detected in sections of the guinea-pig kidney: Binding was saturable, pH-, temperature- and time-dependent, and specific for gastrin-related peptides. The potencies for inhibition of binding of [125I]gastrin were CCK-8 > gastrin 17-I > CCK(B) receptor antagonist L-365,260 > des(SO3)CCK-8 > CCK(A) receptor antagonist L-364,718. Autoradiography demonstrated specific [125I]gastrin binding to medullary collecting ducts and to a much lesser extent to glomeruli, but not over other structures. CCK(B) receptor cDNA fragments were amplified by RT-PCR from total kidney, isolated tubuli and from tissues known to express CCK(B) receptors such as stomach and brain. The kidney might therefore be a previously unidentified site of action for gastrin and cholecystokinin-related peptides.

Aldosterone↗
PubMed1998

Immunohistochemical localization of the murine transferrin receptor (TfR) on blood-tissue barriers using a novel anti-TfR monoclonal antibody.

A novel monoclonal antibody (mAb), 8D3 (IgG2a), that specifically recognizes the murine transferrin receptor (TfR) was produced by immunizing a Lewis rat with a polyoma middle T oncogene-transformed endothelioma cell line. The 8D3 mAb was obtained by immunohistochemical screening for exclusive staining of vessels forming a blood-brain barrier (BBB), but not of other vessels. The anti-TfR mAb 8D3 recognizes the TfR also in FACS analysis and in western blots and should prove to be useful for affinity purification of the TfR. Whereas 8D3 brightly stains BBB-forming vessels in the central nervous system of mice, it does not stain the fenestrated capillaries within the choroid plexus and the circumventricular organs. In testis, where the blood-tissue barrier is located at the level of the Sertoli cells, the 8D3 mAb specifically stains Sertoli cells but not endothelial cells. Finally, in vitro, 8D3 does not interfere with iron uptake of lymphocytes as it does not influence their proliferation. Taken together, 8D3 represents a versatile new tool to study the tissue distribution of the murine TfR and TfR-mediated transcytosis across tissue barriers in the mouse.

Animals↗
PubMed1998

Analysis of 3D transient blood flow passing through an artificial aortic valve by Lattice-Boltzmann methods.

The development of flow instabilities due to high Reynolds number flow in artificial heart valve geometries inducing high strain rates and stresses often leads to hemolysis and related highly undesired effects. Geometric and functional optimization of artificial heart valves is therefore mandatory. In addition to experimental work in this field it is meanwhile possible to obtain increasing insight into flow dynamics by computer simulation of refined model problems. After giving an introductory overview we report the results of the simulation of three-dimensional transient physiological flows in fixed geometries similar to a CarboMedics bileaflet heart valve at different opening angles. The visualization of emerging complicated flow patterns gives detailed information about the transient history of the systems dynamical stability. Stress analysis indicates temporal shear stress peaks even far away from walls. The mathematical approach used is the Lattice Boltzmann method. We obtained reasonable results for velocity and shear stress fields. The code is implemented on parallel hardware in order to decrease computation time. Finally, we discuss problems, shortcomings and possible extensions of our approach.

Algorithms↗
PubMed1998

Ascending dose tolerance study of intramuscular carbetocin administered after normal vaginal birth.

OBJECTIVE: To determine the maximum tolerated dose (MTD) of carbetocin (a long-acting synthetic analogue of oxytocin), when administered immediately after vaginal delivery at term. MATERIALS AND METHODS: Carbetocin was given as an intramuscular injection immediately after the birth of the infant in 45 healthy women with normal singleton pregnancies who delivered vaginally at term. Dosage groups of 15, 30, 50, 75, 100, 125, 150, 175 or 200 microg carbetocin were assigned to blocks of three women according to the continual reassessment method (CRM). RESULTS: All dosage groups consisted of three women, except those with 100 microg (n=6) and 200 microg (n=18). Recorded were dose-limiting adverse events: hyper- or hypotension (three), severe abdominal pain (0), vomiting (0) and retained placenta (four). Serious adverse events occurred in seven women: six cases with blood loss > or = 1000 ml, four cases of manual placenta removal, five cases of additional oxytocics administration and five cases of blood transfusion. Maximum blood loss was greatest at the upper and lower dose levels, and lowest in the 70-125 microg dose range. Four out of six cases with blood loss > or = 1000 ml occurred in the 200 microg group. The majority of additional administration of oxytocics (4/5) and blood transfusion (3/5) occurred in the dose groups of 200 microg. All retained placentae were found in the group of 200 microg. CONCLUSION: The MTD was calculated to be at 200 microg carbetocin.

Abdominal Pain↗
PubMed1998

Gastrin/cholecystokinin type B receptors in the kidney: molecular, pharmacological, functional characterization, and localization.

BACKGROUND: Gastrin/cholecystokinin type B receptors (CCKBRs) can be found on parietal cells and smooth muscle cells and are the predominant brain CCK receptors. Recent cloning studies indicate that this is receptor type might also be expressed in the kidney. MATERIALS AND METHODS: We used Northern blot analysis in guinea pig. kidney and reverse transcriptase polymerase chain reaction (RT-PCR) in several murine kidney cells lines to evaluate this organ for the expression of the CCKBRs. The receptor was pharmacologically characterized by displacement experiments using [125I]-BH-CCKs and various agonists and antagonists. Polyclonal antibodies vs. the CCKBRs were raised in chicken, and immunohistochemistry on tissue sections was used to localize the receptor within the organ. The effect of gastrin on renal cell growth was measured using proximal tubulus (MCT) cells, which were cultured with gastrin (10-9 M) for 24-72 h. Cell counts and [3H]-thymidine incorporation experiments were performed. RESULTS: CCKBR transcripts can be detected in kidney RNA (tubules > glomeruli > interstitium). RT-PCR revealed CCKBR transcripts in proximal tubules (MCT cells) and in mesangium (MMC). The medullary thick ascending limb of Henle's loop and several control tissues such as liver and muscle were negative. Displacement experiments using [125I]-BH-CCK and various agonists and antagonists identified binding sites with typical CCKBR pharmacology. CCKBRs were localized in the proximal tubulus, distal collecting ducts and mesangium cells. Treatment of rested MCT cells with gastrin 17-1 induced cell proliferation and [3H]-thymidine incorporation by at least 40% compared with normal growth (P < 0.05). CONCLUSION: These results show for the first time that CCKBRs are present in selected areas of the kidney, and strongly confirm our previous observation that this organ expresses binding sites for [125I]-gastrin. Furthermore, gastrin might act as a growth factor in the kidney.

Animals↗
PubMed1998

Long-term survival of hamster islet xenografts in mice under short-course treatment with nondepleting versus depleting anti-CD4 monoclonal antibodies.

Xenogeneic grafts provide a potential alternative to the current shortage of human organs for transplantation. However, the prevention of rejection and tolerance induction of xenografts still remain to be further explored. Islet xenografts appear more promising than vascularized whole organ xenografts and additionally also more resistant to the recurrence of autoimmune disease than allografts. Recently, the nondepleting monoclonal antibody (mAb), which blocks the CD4 molecule on lymphocytes, was reported to be able to induce tolerance in allotransplantation and CD4 positive cells were further confirmed to be a major factor responsible for cellular xenograft rejection. Therefore, we hypothesize that anti-CD4 nondepleting mAb could also be effective in protecting cellular xenografts and inducing unresponsiveness of recipients. We studied the effect of the nondepleting anti-CD4 mAb YTS177.9 on islet xenograft survival by using the hamster-to-mouse islet transplantation model. Results were compared with that of the depleting anti-CD4 mAb GK1.5 that was shown to have similar binding sites on the CD4 molecule to mAb YTS177.9. Our data show that mAb YTS177.9 did effectively prolong the survival of islet xenografts and, in addition, also successfully did induce long-term acceptance of 40% grafts after only three perioperative injections of 0.5 mg mAb per mouse. The average survival of the graft was markedly prolonged to >66.8+/-37.1 days compared with controls (8.3+/-1.4 days) or with the depleting anti-CD4 mAb GK1.5 (25.7+/-5.5 days). However, the latter displayed a more profound inhibition in in vitro and ex vivo mixed lymphocyte xenoreaction than mAb YTS177.9. Moreover, the activity of this nondepleting mAb was found to be dose-dependent and 80% of grafts survived permanently when the dose was increased to six injections of 0.5 mg mAb. Like mAb GK1.5, mAb YTS177.9 also prevented rejection when given after a delay of two days posttransplant. In addition, we found that neither depleting nor nondepleting anti-CD8 mAb was effective in this model. Our results strongly suggest that an anti-CD4 nondepleting or blocking mAb alone is able to induce long-term acceptance of islet xenografts and that blocking the CD4 molecule is significantly superior to depleting CD4 positive cells for the protection of islet xenografts. This may indicate that CD4 cells play a major role in xenograft tolerance induction.

Animals↗
PubMed1998

Seasonal change in the incidence of preeclampsia in Zimbabwe.

BACKGROUND: The aim of our study was to evaluate the number of women with hypertensive complications during pregnancy in a southern province in Zimbabwe and to examine the annual change in the incidence of preeclampsia. METHODS: In three different hospitals the preeclamptic women who were treated between January 1992 and August 1995 were counted. This data was compared with the amount of rainfall obtained from the local meteorological stations. RESULTS: A distinctive change in the incidence of preeclampsia during the year could be observed. These changes go along with the seasonal variation in precipitation: at the end of the dry season and in the first months of the rainy season there is an increase in the incidence. CONCLUSIONS: The relationship between climate and occurrence of preeclampsia raises new questions in the pathophysiology of preeclampsia. Possible explanations could be the impact of humidity and temperature on vessels or the production of vasoactive substances. Dry and rainy seasons influence the agricultural yields and therefore the nutritional status could also play a role in the pathophysiology.

Adult↗
PubMed1997

E- and P-selectin are not involved in the recruitment of inflammatory cells across the blood-brain barrier in experimental autoimmune encephalomyelitis.

In experimental autoimmune encephalomyelitis (EAE) inflammatory cells cross the endothelial blood-brain barrier (BBB) and gain access to the central nervous system (CNS). Here we show that E- and P-selectin are not involved in the recruitment of inflammatory cells across the BBB. Neither expression of E- nor P-selectin is induced in BBB-forming endothelium at any time after initiation of EAE. Some of the inflammatory cells present in the CNS during EAE express ligands for E- or P-selectin. However, anti-E- and P-selectin antibodies influence neither immigration of inflammatory cells across the BBB nor the development of EAE. In general, suppression of E- and P-selectin expression on BBB endothelium is dependent on factors derived from the CNS microenvironment, eg, astrocytes. Our results suggest that during EAE suppression of E- and P-selectin expression on the BBB provides a CNS-specific mechanism to reduce leukocyte recruitment into the CNS.

Animals↗
PubMed1997

Influence of cycloheximide-mediated downregulation of glucose transport on TNF alpha-induced apoptosis.

Enhancement of cellular sensitivity to TNF alpha-induced apoptosis by cycloheximide (CX) has been attributed to its quality as an inhibitor of protein synthesis, presumably by prevention of the synthesis of short-lived death antagonists. CX is also known to interfere with glucose transport, which in turn influences cell death. Hexose uptake, expression of glucose transporter (Glut) mRNAs and proteins, and other related factors were therefore examined upon induction of apoptosis with TNF alpha and CX in breast cancer cell lines. In the early phase of apoptosis, a dramatic decrease in glucose transport was observed, preceded by stimulation of Glut 1 and 3 mRNAs. Transport downregulation was also detectable upon incubation with CX alone, albeit to a lesser extent. With the doses used, TNF alpha had no such effect. Protein synthesis was inhibited to the same degree in TNF alpha/CX-treated apoptotic cells compared to viable CX-treated cells. Diminished hexose uptake was associated with decreased Vmax, while Glut affinity remained unaffected. As there was no evidence for changes in total cellular Glut content or for Glut translocation from the plasma membrane, a diminished intrinsic activity of Gluts must be postulated. In conclusion, CX is proposed to contribute to TNF alpha-induced apoptosis predominantly by interference with glucose transport; the exact nature of this effect remains to be elucidated.

Adenosine Triphosphate↗
PubMed1997

Characterization of CCK receptors in stomach smooth muscle: evidence for two subtypes.

Cholecystokinin (CCK) and related peptides such as gastrin are important regulators of gastric smooth muscle contraction. Several studies have shown that these effects of CCK and gastrin are mediated by CCK(B) receptors. However, recent studies suggest the expression of an additional CCK receptor subtype distinct from CCK(B) receptors in this tissue. This study was designed to distinguish between CCK(A) and CCK(B) receptors on guinea-pig stomach smooth muscle cells and to evaluate these cells for additional receptor subtypes. We cloned these receptors by hybridization screening of a guinea-pig smooth muscle cDNA library using 32P random primed labeled cDNA probes from the recently cloned rat CCK(A) and CCK(B) receptor coding regions. In addition to clones representing the CCK(B) subtype, clones of CCK(A) receptor subtype, but no additional CCK receptor subtypes, could be identified. All isolated clones displayed highly homologous nucleotide sequences in comparison to previously characterized CCK(A) and CCK(B) receptors from different species. The results of cDNA hybridization at different levels of stringency and Southern blot analysis using guinea-pig genomic DNA suggest that it is unlikely that additional CCK receptors despite CCK(A) and CCK(B) receptors exist in stomach smooth muscle.

Animals↗
PubMed1997

SDZ RAD, a new rapamycin derivative: pharmacological properties in vitro and in vivo.

BACKGROUND: This report describes the preclinical pharmacological profile of the new rapamycin analog, SDZ RAD, i.e., 40-O-(2-hydroxyethyl)-rapamycin. METHODS: The pharmacological effects of SDZ RAD were assessed in a variety of in vitro and in vivo models, which included an autoimmune disease model as well as kidney and heart allotransplantation models using different rat strain combinations. RESULTS: SDZ RAD has a mode of action that is different from that of cyclosporine or FK506. In contrast to the latter, SDZ RAD inhibits growth factor-driven cell proliferation in general, as demonstrated for the in vitro cell proliferation of a lymphoid cell line and of vascular smooth muscle cells. SDZ RAD is immunosuppressive in vitro as demonstrated by the inhibition of mouse and human mixed lymphocyte reactions and the inhibition of antigen-driven proliferation of human T-cell clones. The concentrations needed to achieve 50% inhibition in all of these assays fall into the subnanomolar range. SDZ RAD is effective in the in vivo models when given by the oral route in doses ranging between 1 mg/kg/day and 5 mg/kg/day. When compared with rapamycin, the in vitro activity of SDZ RAD is generally about two to three times lower; however, when administered orally, SDZ RAD is at least as active in vivo as rapamycin. CONCLUSIONS: In conclusion, SDZ RAD is a new, orally active rapamycin-derivative that is immunosuppressive and that efficiently prevents graft rejection in rat models of allotransplantation. SDZ RAD has therefore been selected for development for use in combination with cyclosporine A to prevent acute and chronic rejection after solid organ allotransplantation.

Abdomen↗
PubMed1997

[Percutaneous dilatative tracheostomy as a new method in intensive medicine. Procedure, advantages and risks].

BACKGROUND AND OBJECTIVE: Percutaneous dilatational tracheostomy (PDT) is a recently developed method to obtain endotracheal access, also at the bed-side, in ventilated patients. The procedure is described and results are presented. PATIENTS AND METHODS: PDT was performed in 112 patients (82 men, 30 women, average age 50.7 years) between 1.5. 1994 and 31.5. 1996, in all cases expected to require more than 10 days of assisted ventilation. All complications, late sequelae and cosmetic results after decannulation were analysed. RESULTS: No serious complications were noted during the procedure. Erroneous puncture occurred in nine patients, but were corrected without problem. Complications necessitating temporary interruption of the tracheostomy consisted of accidental extubation and ventilatory problems (two patients each). There were no late sequelae and the cosmetic results were judged to be very good. CONCLUSION: PDT is a simple and relatively easily learned procedure. It has a low complication rate, late sequelae are very rare and cosmetic results after closure of the tracheostomy are excellent.

Critical Care↗
PubMed1997

[Follow-up of intermittent self-ventilation (ISB). Mortality and causes].

BACKGROUND: Intermittent positive pressure ventilation (IPPV) has an impact on morbidity and survival in patients with chronic respiratory failure. We analyse the causes of death in relation to the disease, the age, the effectiveness of and the compliance with IPPV. PATIENTS: The course of 108 patients, who were on IPPV for a mean of 24 (SD +/- 21) months, is analysed. RESULTS: Twenty-seven patients die (7/7 AIS, 2/17 muscular dystrophy, 8/45 kyphoskoliosis and TB sequelae, 2/7 other neurological diseases, 6/16 COPD bronchiectasis, 1/1 fibrosis of the lang). The cause of death is in 21 hypoventilation or respiratory infection due to progressive disease (9 patients), air leakage after occlusion of tracheostoma (2 patients), bronchitis (6 patients), discontinuation of IPPV (3 patients). Two patients develop pulmonary failure (atypical mycobacteriosis and asbestosis, pulmonary embolism). Non-pulmonary causes of death are present in 2 (rupture of aortic aneurysm, pleural carcinosis). CONCLUSIONS: A safe interface for IPPV is needed for longer survival. An efficient system of home-care has to be developed.

Adolescent↗
PubMed1997

[Oral manifestations in patients with systemic lupus erythematosus].

Forty-six patients with systemic lupus erythematosus underwent thorough dental examination to determine the frequency and severity of oral lesions and periodontal diseases. According to clinical criteria, disease was classified as severe (n = 26) or less severe (n = 20). The overall rate of mucosal involvement in the studied patients was 48%-from 54% in patients with severe disease, 40% in those with less severe disease. Patients with severe disease were found to have a higher rate of tooth loss and an increased rate of gingival inflammation. The severity of periodontal lesions correlated with alterations in the immunoglobulin pattern, particularly with an increase in gamma-immunoglobulins. Thus it is suspected that complex immunodysregulation in combination with immunosuppressive therapy is responsible for the high rate of oral and periodontal lesions in patients with systemic lupus erythematosus.

Adult↗
PubMed1997

Number, fixation properties, dye-binding and protease expression of duodenal mast cells: comparisons between healthy subjects and patients with gastritis or Crohn's disease.

There is an accumulation of evidence to suggest that mast cells may play a key role in gastrointestinal inflammation. We have investigated the numbers and heterogeneity in staining properties of mast cells in biopsies of the duodenum of normal subjects (n = 10), and of normal duodenum from patients with Crohn's disease of the ileum and/or colon (n = 7) or with Helicobacter-associated gastritis of the antrum/corpus (n = 6). In normal donors, two subsets of mast cells, one located in the duodenal mucosa and the other in the submucosa, were clearly distinguished by their morphology and dye-binding properties. Whereas submucosal mast cells stained metachromatically with Toluidine Blue after neutral formalin fixation and emitted a yellow fluorescence after staining with Berberine sulphate, those in the mucosa were invisible using these stains. In patients with gastritis or Crohn's disease, there were marked changes in the numbers of mucosal mast cells compared with control subjects even though the duodenal biopsies were from apparently uninvolved tissue. Gastritis was associated with increased mucosal mast cell numbers (controls: 187 +/- 23 cells mm-2; gastritis: 413 +/- 139 cells mm-2; p = 0.0004), but mean mucosal mast cell counts in the uninvolved duodenum of Crohn's patients were actually decreased (34 +/- 30 cells mm-2, p = 0.0147). The clear differentiation between mucosal and submucosal mast cells on the basis of metachromasia with Toluidine Blue was not seen in biopsies from the patients with gastritis or Crohn's disease. Previous studies which have suggested that there are no distinct mucosal and submucosal mast cell subsets in the human intestine may, therefore, have been affected by the use of tissue from diseased subjects. Heterogeneity in the expression of mast cell tryptase and chymase was seen by immunohistochemistry using specific antibodies, but the relative numbers of mast cell subsets were critically dependent on the methods used. Using a sensitive staining procedure, the majority of mucosal mast cells stained positively for chymase as well as for tryptase, an observation confirmed by immunoelectron microscopy and immunoabsorption studies. Our findings suggest that early stages in intestinal inflammation may be reflected in changes in mast cell numbers and in their staining properties, and call for a reappraisal of mast cell heterogeneity in the human intestinal tract.

Adult↗
PubMed1997

Therapeutic and toxic blood concentrations of more than 500 drugs.

In order to assess the significance of drug levels measured in clinical and forensic toxicology as well as for Therapeutic Drug Monitoring (TDM) it is essential that good collections of data are readily available. For more than 500 frequently used drugs therapeutic and, if data was available, toxic, and fatal plasma concentrations as well as elimination half-lives were compiled in a table. The compilation includes data for hypnotics like barbiturates and benzodiazepines, diphenhydramine, neuroleptics, antidepressants, sedatives, analgesics, antiinflammatory agents (e.g., NSAIDs), antihistamines, antiepileptics, betaadrenergic antagonists, antibiotics (penicillins, cephalosporins, aminoglycosides, gyrase inhibitors), diuretics, calcium-channel blockers, cardiac glycosides, antiarrhythmics, antiasthmatics, ACE-inhibitors, opiate agonists, and local anesthetics, among others. In addition, some toxicological relevant xenobiotics were listed. Data have been abstracted from published information, both compilations and primary sources and have been completed with data collected in our own forensic and clinical toxicology laboratories. Wherever possible, ranges for therapeutic plasma concentrations are expressed as trough concentration at steady state. The half-life values given for each drug are chosen to represent the terminal log-linear phase at most. It is the purpose to rapidly assess the significance of drug levels for the therapeutic monitoring of patients, and to facilitate the diagnostic assessment in case of intoxications.

Animals↗