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Biomedical subjects

R Fischer

Publications and source records attributed to R Fischer.

At least 505 records · Page 28Linked to original sources
PubMed1989

CA 50 and CA 19-9 antigen expression in normal, hyperplastic, and neoplastic thyroid tissue.

The occurrence of the tumor-associated carbohydrate antigens defined by the monoclonal antibodies (moabs) C 50 and 19-9 has been studied by immunoperoxidase staining of formalin-fixed and paraffin-embedded tissue specimens from normal, hyperplastic, adenomatous, and carcinomatous thyroid tissues. Epithelial expression of these antigens was observed neither in normal nor in hyperplastic thyroid tissue. The antigens were expressed in only 1 of 26 follicular adenomas and the staining in this case was weak and restricted to a few cells. In contrast, the expression of this antigens is marked and progressive in carcinomatous tissues. A high proportion, 48 of 52 papillary carcinomas demonstrated C 50 reactivity, whereas 25 of these tumors expressed the CA 19-9 antigen. Of 25 follicular carcinomas, 15 gave a positive staining for the CA 50 and 6 for the CA 19-9 antigen. CA 50 antigen expression was still detected in tumor cells lacking the CA 19-9 antigen and C 50 reactive material was found in all tissue specimens from medullary carcinomas tested, whereas CA 19-9 antigen staining was consistently negative. This indicates that the moab C 50 which reacts, like the moab 19-9, with the sialylated Lewisa (Lea) blood group determinant also binds to other antigens apart from the sialylated Lea in CA 19-9 antigen negative tumor cells. Although, the functional significance of CA 50 and CA 19-9 antigen expression remains to be investigated, these results suggest that the demonstration of these antigens could provide additional differential diagnostic parameters for the characterization of hyperplastic and neoplastic lesions of the thyroid gland. Further clinical studies will show whether these carbohydrate antigens are useful serum markers for the monitoring of thyroid carcinomas.

Adenocarcinoma↗
PubMed1989

[Results of 10 years' experience with peranal Parks and Stuart extirpation of villous and tubulo-villous adenomas of the rectum].

From 1973 to 1983 68 patients with villous and tubulovillous adenomas were operated by the peranal technique of Parks and Stuart. Seven patients had a circumferential adenoma and in ten patients (14.7%) an invasive cancer was found, four patients with Dukes A and six patients with Dukes B. The lethality of the 68 patients was 1.5% and the morbidity 4.5%. By a follow-up between 5 and 15 years the recurrence rate was 20.9%. There was no recurrence of cancer, especially not in the two patients with primary excision of an invasive carcinoma.

Adult↗
PubMed1989

[Incidence of abnormalities following the use of hormonal contraceptives].

In order to get evidence about the incidence of malformations as because of intrauterine exposition of steroids as after cessation of hormonal contraception in dependence on the time interval between the last intake of hormonale contraceptives (h.c.) and on different pills 5,866 pregnant women have been entered into a case-control-study. 2,834 pregnant women had taken h.c. during pregnancy or got pregnant within 6 menstrual cycles after discontinuation of pills (= cases). For control the data of 3,032 pregnant women were examined. These one had never taken pills or their pregnancy occurred after 7 menstrual cycles after cessation of pill ingestion. Perinatal mortality, Apgar-score (5 min) and incidence of twins were not different in cases and controls. The incidence of malformations was significant (p less than or equal to 0.01) higher in controls than in cases. It depended on age in form of an increase with rising age. The incidence of malformations in both groups increased significantly (p less than or equal to 0.01) with a rising cigarette consumption during pregnancy. The results of this study suggest that smoking regarding malformations represents a higher risk than the intake of h.c.

Abnormalities, Drug-Induced↗
PubMed1988

Multiple divergent mRNAs code for a single human calmodulin.

The isolation of a novel complementary DNA (cDNA) clone coding for human calmodulin (CaM) is reported. Although it encodes a protein indistinguishable from the only known higher vertebrate calmodulin, its nucleotide sequence varies extensively from that of two previously reported human CaM cDNAs (Wawrzynczak and Perham, 1984; SenGupta et al., 1987). Only 82 and 81% identity, respectively, is found between the newly isolated and the two known human mRNAs in their coding regions. No striking homology is present in their noncoding regions. Codon usage in the three CaM mRNAs is also surprisingly divergent. A 2.3-kilobase mRNA corresponding to the newly isolated clone is expressed to varying extents in several human tissues, together with an approximately 0.8-kilobase mRNA species presumably arising from alternative polyadenylation of the same primary transcript. The results indicate that the human genome contains at least three divergent CaM genes that are under selective pressure to encode an identical protein while maintaining maximally divergent nucleotide sequences. Partial characterization of a genomic clone specifying the 3' portion of the newly identified CaM mRNA shows that this gene contains introns at identical positions as the previously characterized bona fide vertebrate CaM genes. Evolutionary implications of the presence of a CaM multigene family are discussed.

Amino Acid Sequence↗
PubMed1988

Complete primary structure of a human plasma membrane Ca2+ pump.

cDNAs coding for a plasma membrane Ca2+ pump were isolated from a human teratoma library and sequenced. The translated sequence contained 1,220 amino acids with a calculated molecular weight of 134,683. All regions of functional importance known from other ion-transporting ATPases could be identified. The translated sequence also contained, near the carboxyl terminus, the calmodulin-binding domain and two domains which are very rich in glutamic acid and aspartic acid. These two domains resemble calmodulin somewhat and one of them may play a role in the binding of Ca2+. The enzyme also contains domains rich in serine and threonine, one of which has a sequence matching those of good cAMP-dependent protein kinase substrates. The carboxyl-terminal region is important for regulation by calmodulin, proteolysis, and phosphorylation. Near the amino terminus are two domains which are very rich in lysine and glutamic acid, as well as two domains resembling EF hands, one of which also has some resemblance to calmodulin. Comparison of the cloned sequence with peptide sequences from the erythrocyte Ca2+ pump showed that the two proteins have a very high proportion of identical residues but are not 100% identical, indicating that they represent different isozymes.

Amino Acid Sequence↗
PubMed1988

Prevention of enteral radiocesium absorption by hexacyanoferrates(II) in piglets.

The efficacy of different hexacyanoferrates(II) in preventing the enteral absorption of 134Cs was studied in piglets. As compared to the controls, oral application of 134Cs together with KFe[Fe(CN)6], NH4Fe[Fe(CN)6], or Fe4[Fe(CN)6]3 resulted in a strong reduction of the 134 Cs-uptake by more than 97%. The decrease in enteral absorption depends on the dose of administered hexacyanoferrate(II), whereas differences between the compounds under study were small. The biological half-life of 134Cs in non-hexacyanoferrate(II) treated piglets was 21.6 +/- 3.3 days (mean +/- SD).

Animals↗
PubMed1988

Identification and primary structure of a calmodulin binding domain of the Ca2+ pump of human erythrocytes.

Exposure of the purified Ca2+ pump of human erythrocytes to chymotrypsin led to the rapid loss of calmodulin activation. A fragment of about 12 kDa was removed from the ATPase in 1-2 min. Blotting experiments with 125I-labeled calmodulin showed that this fragment contains the calmodulin binding region. The remainder of the ATPase molecule was degraded to a number of fragments ranging from 3 to 120 kDa; none of them bound calmodulin. To isolate the calmodulin binding domain, calmodulin which had been coupled to the Denny-Jaffe reagent (a cleavable radioactive photoaffinity cross-linker) was allowed to bind to the Ca2+ pump. After illumination to couple the cross-linker to the pump, the cleavable bond was split and the calmodulin removed, leaving the pump radioactively labeled. This pump was digested with chymotrypsin, and the products were separated by gel permeation chromatography. The only radioactive peak (migrating at about 12 kDa) was further purified on reverse-phase high pressure liquid chromatography (HPLC). Amino acid analysis showed the fragment to have a minimal molecular mass of 12.4 kDa and to contain a single methionine. After attempts to sequence the peptide directly failed. CNBr digestion was carried out on the labeled ATPase, producing both soluble and insoluble labeled material. After reverse-phase HPLC purification of the soluble material, a single radioactive peak was collected. Its sequence was (Formula: see text). A portion of this peak was passed through a microcalmodulin column; it bound in the presence of Ca2+ and was eluted by EDTA, and by a mixture of EDTA and urea. Staphylococcal V8 protease digestion of the eluted peak produced the same sequence as shown above, but starting at Leu-2 and ending at Glu-32. Structural analysis of this peptide showed that it shares features with the calmodulin binding domains of other enzymes which are regulated by calmodulin.

Amino Acid Sequence↗
PubMed1988

Boerhaave's syndrome. Computed tomographic findings and diagnostic considerations.

Boerhaave's syndrome, or spontaneous rupture of the esophagus, may present with atypical chest pain mimicking an acute thoracic aortic dissection. We describe such a case and discuss the utility of a thoracic computed tomographic scan in arriving at a prompt diagnosis. The importance of early diagnosis is reviewed with particular attention to these roentgenographic findings.

Aortic Dissection↗
PubMed1988

Histomorphometry of bone marrow biopsies in chronic myeloproliferative disorders with associated thrombocytosis--features of significance for the diagnosis of primary (essential) thrombocythaemia.

A histomorphometric analysis was performed on trephine biopsies of the bone marrow in 55 patients with chronic myeloproliferative disorders (CMPDs) and marked thrombocytosis (platelet count exceeding 600 x 10(9)/l). This study aimed at discriminating primary (essential) thrombocythaemia (PTH) from the various other subtypes of CMPDs presenting with thrombocytosis. Following the diagnostic requirements postulated by the Polycythemia-vera-Study-Group for PTH and polycythaemia vera rubra (P.vera) and the generally accepted criteria for the establishment of chronic myeloid leukaemia (CML) and agnogenic myeloid metaplasia (AMM), our cohort of 55 patients was divided into the following subgroups: CML (16 cases), P.vera (11 cases), AMM (13 cases) and finally PTH (15 cases). Histomorphometric measurements revealed that PTH was distinguishable from the other subtypes of CMPDs with respect to several histological variables: patients with PTH had a normal amount of neutrophilic granulo- and erythrocytopoiesis as well as a non-increased content of reticulin (argyrophilic) fibers in contrast to the findings in CML, P.vera and of course AMM. Moreover, sizes of megakaryocytes and their nuclei were significantly greater in PTH and internalization of haematopoietic cells (emperipolesis) was more frequently encountered in comparison with the other subtypes of CMPDs. Deviation of the circular perimeter of megakaryocyte shape was most prominently expressed in CML and AMM, and consequently generated an increased number of a-nuclear cytoplasmic fragments. In contrast to this feature aberration of the nuclei from a circular outline occurred in a less pronounced way in CML, but was excessive in P.vera, AMM and PTH. Our morphometric evaluation demonstrates that certain histological features may serve as a valuable aid in discriminating PTH from the other occasionally thrombocythaemic subtypes of CMPDs.

Aged↗
PubMed1988

Differentiation of plasma cell infiltrates in the bone marrow. A clinicopathological study on 80 patients including immunohistochemistry and morphometry.

In 80 patients immunohistochemical, morphometrical and clinical studies were performed on routinely referred trephine biopsies of the bone marrow showing an abnormal increase in plasma cells. From the approximately determined density of plasma cell infiltrates two main groups were distinguished, the first with an involvement exceeding 20% and the second with less than 10% of the total marrow area involved. The first group (n = 30; 324 +/- 130 plasma cells per square millimeter bone marrow) consisted of patients with frank malignant myeloma (MM) by clinical and histomorphological diagnosis. The second group (n = 50; 132 +/- 54 plasma cells per square millimeter bone marrow) with plasmacytic differentiation of infiltrates, had to be further divided into one component with evidence for initial or residual MM following chemotherapy (n = 27), another with obviously monoclonal gammopathy of undetermined significance--benign monoclonal gammopathy (BMG, n = 6), and a final set of cases with a reactive plasmacytosis mostly associated with an inflammatory condition (n = 17). There was an excellent agreement between the intracellular immunoglobulin staining as defined by the immunoperoxidase technique and the serum or urinary M-component detected by immunoelectrophoresis. In MM significant correlations were found between osteoclastic activity (number of osteoclasts specifically stained by acid phosphatase) per trabecular bone area, presence of lytic bone defects and the density of plasma cell infiltrates in the marrow. This latter feature corresponded well with the titer of secreted serum M-components measured by quantitative immunoelectrophoresis. Using morphological data alone, BMG cases could not be discriminated with any certainty from initial or residual plasmacytic MM. They consequently need a prolonged clinical follow up to clarify the nature of the lesions.

Bone Marrow↗
PubMed1988

Immunohistochemical study of distribution of estrogen receptors in corpus and cervix uteri.

An immunohistochemical assay based on monoclonal antiestrophilin antibodies has been used to localize estrogen receptor (ER) in frozen sections of normal human endometrial, myometrial and cervical tissues from menstruating, hormonally treated, pregnant and postmenopausal women. Specific staining was confined to the cellular nuclei. In proliferative phase endometrium, postmenopausal emdometrium, and endometrium from patients treated with hormone ERs were easily detected in most glandular and stromal cells. After ovulation and in early pregnancy a quick and distinct decrease of ER expression was noted. This was especially the case with the more superficial layers of endometrium (endometrium functionalis), the majority of whose cells had either weak localization of ER or none at all. In the endometrium basalis, however, the reduction of ER localization turned out to be more moderate. More then half of the epithelial and stromal cells displayed nuclear staining, partly strong. The myometrium of the corpus uteri showed a similar ER localization and dependence on hormonal stage when compared with the endometrium functionalis. The endocervical mucosa displayed a high degree of ER expression in the proliferative phase, in postmenopausal women and in women who had been treated with hormones. Unlike the endometrium and myometrium, the endocervical glands underwent minimal changes in nuclear ER content during the menstrual cycle. Although the endocervical stroma showed cyclic alterations in ER levels, their reduction after ovulation was less marked than in the corresponding endometria. In cervical squamous epithelium ER localization was predominantly confined to the basal layers. In the course of cellular maturation, specific nuclear staining vanished. In the proliferative phase, after the menopause and in early pregnancy, the basal, parabasal and intermediate cells were specifically stained. In the postovulatory phase, However, nuclear staining was confined to the basal and parabasal cells. Hormonally treated squamous epithelia almost completely lacked nuclear ER localization.

Antibodies, Monoclonal↗
PubMed1988

Hepatic detoxification and hepatic function in chronic active hepatitis with and without cirrhosis.

The detoxification capacity of the liver in chronic active hepatitis (CAH) without liver cirrhosis (LC) is not sufficiently known. Therefore, we examined, in 156 patients with morphologically proven CAH of different stages, plasma ammonia, free phenols, indican, glucuronic acid and urea synthesis rate as parameters for liver detoxification. We found a significant increase of ammonia, phenols, and indican and a significant decrease of glucuronic acid and urea synthesis rate parallel to the stage of CAH without LC. In 34 CAH patients with complete recovery, a retrospective 10-year follow-up was possible. Parallel to the normalization of liver morphology and general liver tests, detoxification parameters also normalized. However, the detoxification disorders in CAH without LC are mild in nature and do not produce hepatic encephalopathy. Probably, they are caused by a reduced synthesis of the urea-cycle enzymes and of glucuronyltransferase in the liver.

Ammonia↗
PubMed1988

Prognostic features at diagnosis of chronic myeloid leukaemia with special emphasis on histological parameters.

A clinicopathological study was performed on 115 patients (56 males, 59 females; median age 48 yr) with chronic myeloid leukaemia (CML) to reveal initial clinical, but particularly histomorphological features of predictive value for survival. All patients had a trephine biopsy of the bone marrow and entered this study without prior selection. Overall survival was 36 +/- 27 months. In addition to multiple interactions between various disease features, multivariate regression analysis showed that of the clinical parameters age, liver size and level of LDH were primarily and most closely associated with prognosis. Of the histomorphological variables, megakaryocytes greater than 60 mm-2 bone marrow area and fibrosis displayed an unfavourable impact on survival on univariate calculation. On multivariate analysis, however, only pseudo-Gaucher cells remained significant, i.e. exerted an independent and favourable influence on prognosis. Histological features of predictive value were reviewed together with the different categories of a histopathological classification proposed for chronic myeloproliferative diseases by Georgii and co-workers.

Adolescent↗
PubMed1988

Iron absorption in man calculated from erythrocyte incorporation of the stable isotope iron-54 determined by fast atom bombardment mass spectrometry.

The methodology of precise isotope abundance determinations of erythrocyte iron by fast atom bombardment mass spectrometry and signal averaging is established. For the determination of the 54Fe/56Fe ratio a relative precision of 0.5% and an absolute precision of 0.03% is achieved. After oral loading with 54Fe-enriched samples in the range between 5 and 25 mg per subject, the 14-day erythrocyte incorporation of 54Fe has been determined in five individuals, namely, two adults, two children, and one infant. In the two adults, the oral dose of 54Fe was simultaneously labeled with a trace amount of carrier-free 59Fe. In these double-isotope loading tests, a good agreement was observed between the absorption data determined on the basis of whole body retention of 59Fe and on the basis of the 54Fe erythrocyte incorporation. The stable isotope methodology applied allows measurement of the iron absorption using highly enriched 54Fe at a dose of 25 mg for an adult or at a dose of 5 mg for infants of about 1 year of age.

Adult↗