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Biomedical subjects

R Fischer

Publications and source records attributed to R Fischer.

At least 271 records · Page 15Linked to original sources
PubMed1996

Intragastric pH and serum gastrin during administration of different doses of pantoprazole in healthy subjects.

OBJECTIVE AND DESIGN: The effect of increasing doses of pantoprazole, a newly developed proton pump inhibitor, given at once daily doses of 40, 80 and 120 mg, on intragastric pH and serum gastrin profiles was studied in 15 healthy subjects in a randomized, double-blind, crossover study and compared to recordings without therapy. Measurements of intragastric pH and serum gastrin were performed on the 7th day of treatment by continuous pH recording and radioimmunoassay in blood samples obtained in 1-h intervals, respectively. RESULTS: Pantoprazole significantly increased gastric pH above basal at all pantoprazole doses studied: median 24-h pH rose from 1.2 without therapy to 3.4, 3.3 and 3.6 at 40, 80 and 120 mg daily, respectively. The corresponding integrated 24-h gastrin output was 1632, 2338 and 2248 pg/ml x 24 h compared to 575 pg/ml x 24 h without pantoprazole. There was no interindividual correlation between values of 24-h median pH and 24-h gastrin output at any pantoprazole dose studied. However, fasting gastrin levels closely correlated with 24-h gastrin output (r = 0.789; P < 0.0001). The acid inhibitory effect was significantly (P < 0.01) augmented in Helicobacter pylori positive subjects. CONCLUSION: It is concluded that pantoprazole is an effective inhibitor of gastric acid secretion. Increasing a single pantoprazole dose above 40 mg does not lead to increased median pH elevation. The individual extent of acid inhibition does not predict the magnitude of gastrin elevation. Acid inhibition appears more efficient in Helicobacter pylori positive subjects.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1996

Distribution of lectin binding sites in human bone marrow. Identification by use of an ultrastructural postembedding technique.

The purpose of this ultrastructural study was to detect various carbohydrate residues on mature elements of the major human haematopoietic cell lines (granulopoiesis, erythropoiesis and megakaryopoiesis), sinus endothelium and plasma cells under comparable experimental conditions. Marrow specimens were processed according to a modified postembedding technique with Unicryl as embedding resin. A broad panel of 10 digoxigenin (dig)-conjugated lectins was applied for staining and specificity was evaluated by incubation with their corresponding inhibitory sugars. Lectins under study were derived from Canavalia ensiformis (Con A), Triticum vulgare (WGA), Ulex europaeus-I (UEA-I), Baubinia purpurea (BPA), Erythrina cristagalli (ECA), Glycine max (SBA), Helix pomatia (HPA), Arachis hypogaea (PNA), Griffonia simplicifolia-I (GS-I) and its isotype GS-I-B4. As a common feature WGA was shown to be a prominent marker of cytoplasmic membranes, except for plasma cells. On the other hand, Con A turned out to be reactive with the nuclear envelopes in all haematopoietic cells and, additionally, exhibited a strong labelling of the rough endoplasmic reticulum in plasma cells. Granules of eosinophilic granulocytes revealed staining of varying intensity with all lectins; however, inhibition was mostly incomplete. Several lectins (WGA, Con A, UEA, BPA, ECA, SBA and PNA) disclosed a clear cut differentiation of at least two subpopulations of granules in polymorphonuclear leukocytes. UEA-I (H type 2 specific) exhibited a high affinity to cytoplasmic membranes of erythropoietic precursor cells. In keeping with the blood group of our patient (O Rh+) membranes of red blood cells were completely negative with those lectins that are known to exhibit a group A or B specificity (HPA, GS-I-B4). As a remarkable finding the luminal and abluminal surfaces of sinusoidal endothelium revealed a specific reaction with UEA-I. Carbohydrate binding sites on the surface of endothelial cells may play a pivotal role in several functional processes such as cellular adhesion, traffic of mature cell elements across the marrow blood barrier and "homing' of haematopoietic stem cells.

Bone Marrow↗
PubMed1996

Results and prognostic factors of splenectomy in idiopathic thrombocytopenic purpura.

BACKGROUND: Splenectomy is the therapy of choice after relapse following different immunosuppressive treatments for idiopathic thrombocytopenic purpura, which is still the most frequent cause of thrombocytopenia. STUDY DESIGN: A prospective clinical study was undertaken to evaluate the rate of complete remission in idiopathic thrombocytopenic purpura after splenectomy, to reveal the influence of preoperative immunosuppression on the postoperative course in groups of patients with different responses to treatment, and to describe possible prognostic factors predicting the postoperative course of idiopathic thrombocytopenic purpura. Difino's classification of remission was used. After fulfilling criteria for admission into the study, 72 patients who had undergone splenectomy (male to female ratio, 1:1.4) were examined. RESULTS: Early postoperative mortality and morbidity rates were 3 percent each. The following degrees of remission were achieved: complete remission, 72 percent; partial remission, 15 percent; partial remission affording further medical support, 6 percent; and no remission, 4 percent. Platelet counts differed significantly between complete and partial remission, but not between patients who did or did not experience a response to different preoperative medical strategies (Tukey-Kramer test, p < .05; t test, not significant). The correlation of megakaryocytopoiesis and the site of thrombocytolysis to the stages of remission was significant (Fisher's exact test). Patients with hyperplasia of splenic follicles had significantly higher platelet counts 2 years after operation than did those without hyperplastic splenic follicles (Student-Newman-Keuls test). CONCLUSIONS: Splenectomy is a low morbidity and low mortality procedure. It is, therefore, a treatment of choice after relapse following immunosuppressive courses. Isolated splenic thrombocytolysis and hyperplasia of megakaryocytopoiesis and of splenic follicles correlated with better postoperative outcome (ie, stable remission and platelet counts) and could serve as possible prognostic factors for the postoperative course in idiopathic thrombocytopenic purpura.

Adolescent↗
PubMed1996

An improved postembedding technique for ultrastructural studies of lectin binding sites in bone marrow: a critical evaluation.

Little is known about the ultrastructural localization of lectin binding sites in human bone marrow tissue. This is probably due to the lack of suitable methods yielding both satisfactory tissue preservation and optimal labelling results. For this reason, we developed a modified postembedding technique for electron-microscopic studies of the glycosylation pattern of haematopoietic cells. Fixation with a 2.5% glutardialdehyde solution was shown to be an important prerequisite and could be even improved by postfixation with tannic acid and uranyl acetate. In particular, embedding with the acrylic resin UnicrylR (Bioacryl) resulted in an optimal ultrastructural preservation of bone marrow tissue. Employment of this hydrophilic resin in combination with a two-step labelling method which included digoxigenin-conjugated Concanavalin A (Con A) followed by ultrasmall anti-digoxigenin-gold and silver amplification, delivered a highly specific staining pattern. Our results with this lectin in different bone marrow cells revealed nuclear and cytoplasmic membranes, rough endoplasmic reticulum as well as granules to display reactivity of varying intensity. These findings underline the validity of our method, for they confirm and extend formerly reported histochemical and biochemical evaluations on the cellular binding sites of Con A.

Binding Sites↗
PubMed1996

Effects of interferon treatment on the macrophage population in the bone marrow of patients with Ph1+-CML.

In Ph1+-CML the abnormal function of bone marrow stroma was related to the presence of clonally transformed macrophages (MAs). Moreover, previous in vitro studies revealed that activation (phagocytosis, cytotoxicity) of MAs was associated with a pronounced increase in alpha-D-galactosyl residues on their membranes. Stimulation of this cell population has been shown to be easily accomplished by interferon (IFN) treatment. The latter caused an enhanced expression of binding sites for the lectin Griffonia simplicifolia isotype I-B4 (GSA-I), specific for this carbohydrate moiety. The present immuno- and lectinhistochemical study was designed to quantify MA subsets of the bone marrow in patients with Ph1+-CML under IFN therapy. For comparison a control group with monotherapy by busulfan (BU) was included. Identification of the total MA population was carried out by a monoclonal antibody against CD68 (PG-M1) and for the characterization of its activated fraction, the lectin GSA-I was employed. In both therapeutic groups morphometric analysis revealed a conspicuous increase in PG-M1-positive MAs in sequential trephine biopsies. However, following IFN therapy the relative amount of the GSA-I fraction was maintained or even increased and accompanied by enhanced apoptosis. On the other hand, BU generated a significant reduction of this subpopulation and the number of apoptotic cells as well. This finding is probably related to the immunomodulatory activity of IFN associated with MA activation and secretion of biogenic mediators. These are thought to belong partly to the so-called tumor necrosis factor superfamily, which is known to stimulate programmed cell death (apoptosis).

Adolescent↗
PubMed1996

Use of assisted reproductive techniques for treatment of ejaculatory disorders.

Ejaculatory disorders can interfere with the fertility of young adults who suffer from spinal cord injury, have type I diabetes mellitus or have undergone retroperitoneal or intrapelvic operations. Following an overview of causes and treatment of ejaculatory disorders, the data of our centre are presented. From a group of 37 patients with genuine loss of seminal emission, 15 men and their wives were offered a combined treatment of rectal probe electro-ejaculation and artificial reproductive techniques. No serious complications occurred. During 40 cycles with intracorporeal insemination and 11 cycles with extracorporeal fertilization techniques, seven pregnancies were achieved, representing a pregnancy rate of 46% per couple and 14% per cycle for all cycles. Five healthy children were born, all following extracorporeal insemination. The 'take-home baby rate' for this population and for this technique is 45%. In vitro fertilization (IVF) led to one birth, intracytoplasmic sperm injection (ICSI) achieved four live births out of three pregnancies, one being a twin gestation. Since our successes are due to the use of extracorporeal insemination techniques, these are now incorporated in a new, more rational treatment protocol.

Ejaculation↗
PubMed1995

Expression, purification and characterization of the enzyme II mannitol-specific domain from Staphylococcus carnosus and determination of the active-site cysteine residue.

The C-terminal B domain of mannitol-specific enzyme II (enzyme IIB) of the phosphoenolpyruvate-dependent phosphotransferase system for mannitol from Staphylococcus carnosus was subcloned, purified and characterized. In Staphylococcal cells, mannitol-specific enzyme II is composed of a soluble A domain (EIIA) and a transmembrane C domain transporter with a fused enzyme IIB (IIB) domain. We purified large amounts of the IIB domain as an in-frame fusion with six histidine residues. Here, we show that the domain is stable and can be phosphorylated by phosphoenolpyruvate and the phosphotransferase components. It is a dimer over a wide range of pH values and salt conditions. Differences between the published nucleotide sequence data and the mass-spectroscopic data obtained with the purified protein lead to anewed nucleotide sequencing of the gene. Two errors in the original proposed sequence were found, the correction of the second error leading to a frame shift that adds 10 amino acids to the deduced amino acid sequence. The mass of the phosphorylated domain is 20,068 Da, 80 Da more than the mass of the unphosphorylated domain, therefore, no other residues, such as COOH side chains, are directly involved in an additional phosphate linkage concerning the IIB domain. 31P-NMR experiments as well as chemical modification proved that Cys429 is the phosphoamino acid. Titration of the phosphorylated domain during 31P-NMR did not lead to the typical shift for the protonation of the thiophosphate in the resonance spectrum. Thus, the thiophosphate remains in the twofold negatively charged state.

Amino Acid Sequence↗
PubMed1995

Expression of alpha-3/4-monofucosylated polylactosaminoglycan epitope, as defined by monoclonal antibody FW6, is a marker of the colorectal adenoma-carcinoma sequence.

BACKGROUND: The expression of a distinct alpha-3/4-monofucosylated polylactosaminoglycan epitope, which is detected by monoclonal antibody FW6, was investigated by comparative immunohistochemical analysis of colorectal tissue specimens exhibiting different grades of premalignant and malignant transformation. The presence of this peculiar epitope was compared with different lewis type 2 blood group antigens. METHODS: Paraffin embedded specimens from 8 hyperplastic polyps, 46 adenomas, 27 colorectal carcinomas, and 10 corresponding liver metastases were studied. Staining reactions included monoclonal antibodies FW6, AM-3 (anti-sialosyl-Le(x)), LeuM1 (anti-Le(x)), and 12-4LE (anti-Le(y)) in a standard peroxidase-antiperoxidase method. RESULTS: Hyperplastic polyps were not reactive with FW6 or LeuM1, but showed a slight binding of AM-3 and 12-4LE in some cases. Approximately two-thirds of the adenomatous polyps displayed a pronounced staining activity by AM-3, and approximately half of them revealed FW6, LeuM1, and 12-4LE binding. Only the expression of the FW6 (P < 0.005) epitope correlated with the presence of severe dysplasia. All antibodies were more or less reactive with colorectal carcinomas and their liver metastases, and some showed correlating binding patterns. CONCLUSIONS: FW6 revealed a high specificity for adenomas with areas of severe epithelial dysplasia. Because this monoclonal antibody also detects the great majority of carcinomas, it is reasonable to postulate that the alpha-3/4-monofucosylated polylactosaminoglycan epitope is an important marker for malignant transformation in the colorectal adenoma-carcinoma sequence.

Adenoma↗
PubMed1995

Secretion of cytokines (interleukins-1 alpha, -3, and -6 and granulocyte-macrophage colony-stimulating factor) by normal human bone marrow megakaryocytes.

The effects of cytokine stimulation [recombinant human interleukin (rhIL)-1 alpha, rhIL-3, rhIL-6, rhIL-11, and rh granulocyte-macrophage colony-stimulating factor (GM-CSF)] on the secretory activity of normal human megakaryocytes were studied by means of the reverse hemolytic plaque assay (RHPA) in enriched cell preparations. This test facilitates an extremely sensitive determination of cytokine secretion at the single-cell level, together with the clear-cut identification of each immunostained (CD61) secretory active megakaryocyte. Moreover, the reverse transcriptase-polymerase chain reaction (RT-PCR) was used to investigate the expression of IL-6, IL-6 receptor (IL-6R), IL-9, IL-10, IL-12, and IL-13 mRNA in highly concentrated megakaryocyte preparations. In comparison with the spontaneous secretion rate, stimulation with rhIL-1 alpha, rhIL-6, and rhGM-CSF failed to induce a significant increase in the release of cytokines by CD61+ cells. On the other hand, both rhIL-3 and, in a less pronounced way, rhIL-11 exerted a marked effect on IL-6 secretion. Additionally, after stimulation with rhIL-3, a significant enhancement of the secretion of IL-3 and GM-CSF, but not of IL-1 alpha, could be observed. Using the RT-PCR, a significant induction of IL-6 expression could be appreciated in the enriched megakaryocyte population (60% to 80%) stimulated with rhIL-3. The results of this study provide persuasive evidence that a number of cytokines are synthesized and secreted by human megakaryocytes and not only by hematopoietic stroma cells. These data suggest the existence of autocrine and paracrine mechanisms that may influence maturation and differentiation of megakaryocytes as well as act on various stroma cells to sustain an appropriate hematopoietic micro-environment.

Base Sequence↗
PubMed1995

Clinical and histological features retain their prognostic impact under interferon therapy of CML: a pilot study.

In 55 patients with Ph1+ CML under interferon (IFN) monotherapy, an immunohistochemical and morphometric study on pretreatment bone marrow biopsies was performed to evaluate the prognostic impact of clinical as well as histological disease features. For identification of megakaryocytes we used the PAS stain and CD61 to calculate the subfraction of precursors (pro- and megakaryoblasts). Demonstration of macrophages and their different subsets was carried out by PG-M1 (CD68) and the GSA-1 lectin. The erythroid precursors were stained by Ret40f (anti-glycophorin C). Density of argyrophilic (reticulin plus collagen) fibers was determined by applying Gomori's silver impregnation method. Clinical variables like state of hematological response to IFN administration, age, spleen and liver size, myeloblasts plus promyelocytes, basophils as well as basophils and eosinophils exerted a predictive capacity by univariate statistical analysis. However, when entering these factors into previously published risk models, i.e., the so-called Sokal score and its modifications, to assess subgroups with different survival patterns or relative risk groups, a clear-cut discrimination was not feasible. Bone marrow features of prognostic value consisted of megakaryocytes and their precursors, fibers, and pro- and erythroblasts. Only when including histological variables into a formerly reported Cox model, could a significant separation of patients into the different categories or relative risk groups be computated. In conclusion, the present data emphasize the prognostic impact of histological parameters to be considered in all clinical trials on CML.

Adult↗
PubMed1995

Effects of excimer laser on healing of articular cartilage in rabbits.

This study examined healing of 1.0 mm diameter defects in rabbit knee articular cartilage for as long as 14 weeks after creation of the defects by either laser or drilling. The purpose of the research was to determine the effects of laser debridement of cartilage on the intrinsic biomechanical properties of the repair tissue. We therefore imitated chondral shaving and subchondral abrasion of cartilage by creating partial-thickness and full-thickness cartilage defects of standardized size with both excimer laser and drilling. Light and scanning electron microscopic examinations of the repair tissue showed that healing of osteochondral defects created by laser may be delayed compared with defects created by drilling, for at least 6 weeks postoperatively. Even though there initially was a considerable delay in healing in the laser group, neither laser nor drilling had any appreciable effects on the mechanical properties of the repair tissue, as demonstrated by biomechanical testing at 14 weeks. Specifically, the repair cartilage in the defects in the laser group had the following material properties (mean +/- SD): aggregate modulus, 0.40 +/- 0.24 MPa; Poisson's ratio, 0.37 +/- 0.08; permeability, 3.72 +/- 4.28 x 10(-15) m4/N.s; and thickness, 0.20 +/- 0.06 mm. The corresponding values for the defects in the drilling group were 0.39 +/- 0.23 MPa, 0.34 +/- 0.09, 3.82 +/- 3.44 x 10(-15) m4/N.s, and 0.22 +/- 0.09 mm. The repair tissue from both types of defects was pooled, and the values were compared with those for contralateral (control) tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Blood group antigen expression in malignant tumors of the thyroid: a parallel between medullary and nonmedullary carcinomas.

Blood group antigen (BGA) expression has been described in many fetal, adult, and tumorous tissues. Synthesis of BGA in the thyroid gland is regarded as oncofetal due to blood group structures that are detected in fetal and carcinomatous tissues but not in the normal adult organ. This study examined the prevalence of type 1 (CA-50, CA-19-9, Lea, Leb, A, B, H type 1) and type 2 (Le(x), Le(y), A, B, H type 2) antigens in normal thyroid (n = 25), papillary (n = 104), follicular (n = 52), anaplastic (n = 33), and medullary (n = 48) carcinomas of the thyroid. While normal thyroid tissue expressed no BGA, there was a significant increase of BGA expression in carcinomas of the thyroid gland. There are two theories about the possible origin of C cells, from which the medullary carcinomas arise. Some authors postulate that C cells belong to the amine precursor uptake and decarboxylation system and therefore derive from the neural crest, while others believe that C cells originate from the fifth pharyngeal pouch, as do the follicular cells. The results obtained in this study show that medullary and nonmedullary carcinomas correspond to one another in their BGA expression profile. Therefore it is concluded that medullary carcinomas may have the same origin as nonmedullary tumors of the thyroid.

Adenocarcinoma, Follicular↗
PubMed1995

The bcl-2/JH gene rearrangement is undetectable in Hodgkin's lymphomas: results from the German Hodgkin trial.

Ninety-one Hodgkin's lymphomas (HD), 52 non-Hodgkin lymphomas (NHL) and 33 specimens of non-neoplastic lymphatic tissues were investigated by polymerase chain reaction (PCR) for the presence of the bcl-2/JH gene rearrangement. The majority of the HD cases were drawn from the files of the German Hodgkin trial where diagnoses are established by a panel of four independent histopathologists. Using the very sensitive PCR method which detected 1 positive among 10000 negative cells, the bcl-2/JH gene rearrangement was found in 7/52 NHL and 3/16 tonsils with follicular hyperplasia, but in none of the 91 HD. The bcl-2 protein, however, was expressed by malignant cells of B and T cell lymphomas and by the giant tumour cells in 2/13 HD lymphocyte predominant, 11/28 HD nodular sclerosing I, 14/17 HD nodular sclerosing II, 10/27 HD mixed cellularity and 3/3 HD lymphocyte depleted. The bcl-2/JH rearrangement is thus independent of protein over-expression, the latter being found in all types of lymphomas. Our results do not confirm the findings of others who have detected the bcl-2/JH rearrangement in HD. These discrepancies may be explained by differences in choice of material, the gene rearrangement actually occurring in bystander cells but not in Reed-Sternberg or Hodgkin cells, or by contamination.

Chromosomes, Human, Pair 18↗
PubMed1995

Complete reversion and prevention of rectal adenomas in colectomized patients with familial adenomatous polyposis by rectal low-dose sulindac maintenance treatment. Advantages of a low-dose nonsteroidal anti-inflammatory drug regimen in reversing adenomas exceeding 33 months.

PURPOSE: This nonrandomized, controlled Phase II pilot study aims at the lowest effective dose of rectally applied sulindac to achieve and maintain adenoma reversion in colectomized patients with familial adenomatous polyposis (FAP). METHODS: The study group (n = 15) underwent proctoscopic and laboratory follow-up for polyp reversion every 6 to 12 weeks. Polyp reversion was followed by dose reduction in predefined steps. Proliferating cell nuclear antigen/cyclin (PCNA) and KI-67 proliferation indices (PI) were performed by point counting. Prostaglandin (PG)E2 and PGF2 alpha were quantified by time-resolved competitive fluorescence immunoassay. RESULTS: All patients responded to therapy within 6 to 24 weeks. Sixty and 87 percent of patients achieved complete adenoma reversion after 48 weeks at 53 and 67 mg of sulindac per day per patient on average, respectively. Reversion was evident compared with the control group. Dose reduction by one-sixth to one-eighth of the usual oral dose was significant (Mann's trend test, P < 0.05). PCNA and KI-67 PIs of adenomatous and flat mucosa were significantly reduced (Wilcoxon's test, P < 0.05). Correlation of PCNA and KI-67 PIs indicate similar reaction of different tissue structures (Spearman's rank correlation test, P < 0.01). Nonsteroidal anti-inflammatory drug-induced redifferentiation from high-grade to low-grade dysplasia occurred in all but two patients. Tissue-PGE2 levels were greatly reduced. Unwanted, curable side effects were rare (gastritis, n = 2), and laboratory controls are within detection limits. CONCLUSIONS: Low-dose rectal sulindac maintenance therapy is highly effective in achieving complete adenoma reversion without relapse in 87 percent of patients after 33 months. Rectal FAP phenotype should be crucial for the surgical decision. Colectomy with ileorectal anastomosis and regular chemoprevention might proceed to be a promising alternative to pouch procedures. Chemoprevention with lower incidence of FAP-related tumors via dysplasia reversion may be possible in the future.

Adenomatous Polyposis Coli↗
PubMed1995

[Hematopoietic stem cells of the human. Function and morphology].

Pluripotential haematopoietic stem cells and their progeny, the so-called committed precursor cells, i.e., progenitor cells which are already lineage-restricted, may be identified by the membrane-bound expression of CD34. In accordance with this peculiar property it became possible to enrich and characterize primitive precursor cells by using different methods of cell separation techniques, which involved fluorescence staining or ferro-magnetic particles bound to CD34 antibodies. Recently conducted studies demonstrate that CD34-positive (CD34+) stem cells of the peripheral blood represent a relatively uniform cell population with almost round nuclei, a finely dispersed chromatin pattern and a small portion of weakly basophilic cytoplasm. From the cytological viewpoint they resemble so-called large stimulated lymphocytes (virocytes). Ultrastructural studies are compatible with a paucity of organelles and a lymphoid character of these progenitors. In comparison, the stem cell population, derived from the bone marrow consists of more heterogeneous elements. These are generally larger and reveal an admixture of fairly immature as well as more differentiated cells, sharing bean-shaped or indented nuclei with prominent nucleoli and a more extended cytoplasm. CD34+ progenitors from the peripheral blood and those from the bone marrow display a co-expression of CD43 (MT1) and CD45 (LCA). Furthermore, different subpopulations exhibit--dependent on their origin (blood/bone marrow) and to a various extent--lineage-restricted markers like CD33, CD38, CD61, CD20, CD11a/c, glycophorin C und CD15 (LeuM1). The recently developed immuno- and ferromagnetic enrichment methods for CD34+ progenitor cells are considered innovative tools for modern oncology. These techniques play an important role in the treatment of haematological malignancies and advanced tumours in the context of autologous and, although so far rarely applied, heterologous stem cell transplantation procedures.

Antigens, CD↗