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Biomedical subjects

T Zimmer

Publications and source records attributed to T Zimmer.

At least 55 records · Page 3Linked to original sources
PubMed1995

Proliferation of intracellular membrane structures upon homologous overproduction of cytochrome P-450 in Candida maltosa.

In an alkane-assimilating yeast, Candida maltosa, a cultivation on alkane causes both induction of endoplasmic reticulum (ER)-resident membrane proteins, such as cytochrome P-450, and proliferation of ER. In this study, individual genes for alkane-inducible forms of cytochrome P-450 (P-450alk) were homologously overexpressed in C. maltosa using a galactose-inducible expression system developed in this yeast. Immunoelectron microscopy revealed that, upon the overexpression, a dramatic proliferation of ER occurred, in which overproduced P-450alk protein accumulated. The proliferated membranes were mainly tubular forms and stacks of paired membranes were also observed after prolonged expression. The tubular forms were morphologically very similar to the proliferated ER in alkane-induced C. maltosa cells. The observed proliferation of ER membranes by homologous overproduction of P-450alk, here depicted, will provide a unique opportunity for investigating the mechanisms by which cells regulate ER biogenesis, in comparison with the intrinsic form of ER proliferation.

Candida↗
PubMed1995

Characterization of the major sialyl-Lex-positive mucins present in colon, colon carcinoma, and sera of patients with colorectal cancer.

The expression of the mucin-bound sialyl-Lewisx epitope is increased in the tissue of most colorectal carcinomas and in the sera of about 30% of tumor patients. In colon cancer, a portion of the sialyl-Lex groups detectable with the monoclonal antibody AM-3 is located on MUC1 (C. Hanski et al., Cancer Res., 53: 4082-4088, 1993). In order to characterize the major colon carcinoma-associated sialyl-Lex-positive glycoprotein components, the tissue- and serum-derived antigens were investigated. The buoyant densities of the sialyl-Lewisx-positive antigens from tumor and normal colonic tissues and from sera of patients with colon carcinoma and healthy donors correspond to that of mucins (1.40 g/ml). The sialyl-Lex-positive mucins purified from both tissues elute under nonreducing conditions in the void volume of a Sepharose CL-2B column, indicating a molecular mass more than 2 x 10(7) daltons. They yield in immunoblot after SDS gel electrophoresis under reducing conditions a main band at an apparent M(r) 880,000. Radioactive labeling revealed that the band at M(r) 880,000 is the major protein component in sialyl-Lewisx-positive mucins both from tumor and normal colonic tissue. In sera of colon carcinoma patients, the sialyl-Lex moiety is also detectable mainly on a M(r) 880,000 glycoprotein band and, additionally, on a M(r) 140,000 molecule as well as on alpha 1-acid glycoprotein. Sera from healthy donors exhibited only a sialyl-Lex-positive glycoprotein with the apparent M(r) 140,000. Sandwich ELISA as well as immunoblots of mucins purified from the colon carcinoma cell line LS174T indicated that the sialyl-Lex moiety migrating in the M(r) 880,000 band is located on MUC2 protein core. Together, these data suggest that sialyl-Lex antigen in colon, colon carcinoma, and the sera of patients with this tumor is located on the MUC2 molecule, consisting of several subunits with an apparent M(r) 880,000, linked via disulfide bridges. The increase of sialyl-Lex expression in colon carcinomas appears to be mainly due to a more frequent transfer of sialyl-Lex moieties onto the mucin core in tumor tissue.

Antibodies, Monoclonal↗
PubMed1995

[Somatostatin receptor scintigraphy and endoscopic ultrasound for the diagnosis of insulinoma and gastrinoma].

In a prospective study of 13 patients (three males and 10 females; mean age 53 [8-82] years) the value of somatostatin receptor scintigraphy (SRS) and endoscopic ultrasonography (EUS) was compared with transabdominal ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI) in the diagnosis of insulinoma (six patients) or gastrinoma (seven patients). There were ten separate primary lesions of each tumour type, proven histologically. For insulinoma the sensitivity of EUS was 90%, SRS 10% and CT, US and MRI together 20%. For gastrinoma the sensitivity of EUS was 90%, SRS 100%, and 30% for the other three methods together. Thus EUS had a high diagnostic localizing sensitivity for both tumours, while SRS was highly sensitive only in the diagnosis of gastrinoma, not insulinoma. The value of CT, MRI and conventional ultrasonography lies in their ability to visualize distant metastases.

Adolescent↗
PubMed1995

A deviation from the universal genetic code in Candida maltosa and consequences for heterologous expression of cytochromes P450 52A4 and 52A5 in Saccharomyces cerevisiae.

We demonstrate that serine instead of leucine is specified by the CUG codon in the yeast Candida maltosa. Evidence for this deviation from the universal genetic code was obtained by means of in vitro translation experiments. Depending on the cell-free system used, either serine, in the C. maltosa system, or leucine, in the control with the conventional wheat germ system, was found to be incorporated into the translation products of artificial CUG-containing mRNAs. Moreover, we were able to transfer the non-universal decoding of CUG to the wheat germ system by adding a tRNA fraction isolated from C. maltosa. This finding indicates the presence in C. maltosa of an unusual serine tRNA that recognizes CUG. As a consequence of the altered genetic code, expression in Saccharomyces cerevisiae of C. maltosa cytochrome P450 genes required an exchange of their CTG triplets by TCT encoding serine in order to produce the authentic proteins. In contrast, heterologous expression of the original C. maltosa genes resulted in the formation of still active but unstable enzymes probably subject to selective proteolysis in the host cells.

Base Sequence↗
PubMed1995

Spheric duodenal duplication in a 13-year-old child.

Duodenal duplications are rare. Modern imaging procedures demonstrate the relation of the duplication to the duodenum and the adjacent organs. Thus the surgical procedure can be selected preoperatively. Endoscopic ultrasound is an excellent technique for visualizing a duodenal duplication. A cystic duodenal duplication measuring 6 cm in diameter was resected in a 13-year-old boy.

Adolescent↗
PubMed1995

In vivo reconstitution of highly active Candida maltosa cytochrome P450 monooxygenase systems in inducible membranes of Saccharomyces cerevisiae.

To establish a system for functional characterization of individual Candida maltosa cytochrome P450 monooxygenases, the NADPH-cytochrome P450 reductase from this yeast species was co-expressed in Saccharomyces cerevisiae with each of the following cytochrome P450 forms; P450Cm1 (CYP52 A3), P450Cm2 (CYP52 A4), and P450AlK2A (CYP52 A5). For this purpose, a multicopy plasmid was constructed that contained two independent expression units controlled by the galactose-inducible GAL10 promoter. As shown by spectral and immunological methods, large amounts of the desired monooxygenase components could be simultaneously produced in the respective S. cerevisiae transformants. It was important, however, to adjust semi-anaerobic cultivation conditions during induction by galactose to minimize a mutual impairment of cytochrome P450 and NADPH-cytochrome P450 reductase formation. Compared to the specific cellular content of the host-own enzyme, a 75- to 100-fold overproduction of the reductase component was obtained resulting in P450/reductase molar ratios of about 1:3 in the microsomal fractions prepared from the co-expression strains. At the same time, the rates of cytochrome P450-dependent lauric acid hydroxylation increased more than 10-fold, showing a proper reconstitution of the C. maltosa monooxygenase systems in S. cerevisiae. Using intact cells, an efficient biotransformation of lauric acid to omega-hydroxylauric acid and dodecanedioic acid was found. S. cerevisiae cells coexpressing cytochrome P450 and NADPH-cytochrome P450 reductase were characterized by a marked proliferation of the endoplasmic reticulum. Immunoelectron microscopy revealed a colocalization of the monooxygenase components produced to these newly formed membrane structures.

Base Sequence↗
PubMed1995

[Imaging methods in diagnosis of neuroendocrine tumors of the gastrointestinal tract].

Neuroendocrine tumors of the gastroenteropancreatic system represent a group of tumors with various diagnostic problems. Especially detection of primary tumor lesions is often difficult. Endoscopic ultrasonography is a relatively new imaging procedure localizing insulinomas preoperatively in about 90% of cases. Thus, previously used invasive preoperative imaging methods are usually unnecessary. The combination of endoscopic ultrasonography and somatostatin receptor scintigraphy allows visualization of gastrinomas in 90% of cases. Somatostatin receptor scintigraphy can also visualize metastatic lesions of gastrinomas and carcinoids in the whole body with high accuracy. In surgical management of a gastrinoma, duodenal transillumination and intraoperative ultrasound should be performed in all cases to exclude small duodenal or periduodenal, extrapancreatic tumors. US, CT, and MRI should be mainly used to exclude local and distant metastases. Angiography is helpful in detecting anatomical variations of abdominal vessels preoperatively. Due to the excellent results of endoscopic ultrasonography and somatostatin receptor scintigraphy in localizing insulinomas and gastrinomas, transhepatic portal venous sampling appears to be obsolete.

Carcinoid Tumor↗
PubMed1994

Endosonography of neuroendocrine tumors of the stomach, duodenum, and pancreas.

Neuroendocrine tumors (NETs) of the foregut type are frequently smaller than 2 cm in diameter and mainly located in the pancreas or the gastric and duodenal wall. Conventional cross-sectional imaging techniques, such as transabdominal ultrasonography (US), computed tomography (CT), and magnetic resonance imaging (MRI) are limited by their inability to detect small tumors and especially those located within the gastrointestinal wall. Endoscopic ultrasonography (EUS) allows detailed visualization of the whole pancreas and almost all parts of the gastric and duodenal walls. Therefore, EUS is an important diagnostic tool for the preoperative localization of NETs of the foregut type. Several studies performed in a retrospective manner, as well as two studies performed in a prospective manner, indicate a clear superiority of EUS as compared to CT, US, MRI, and also angiography in detecting NETs of the foregut type. Somatostatin-receptor scintigraphy (SRS) also detects NETs of the foregut type in a very high percentage of cases, and the combination of EUS and SRS appears to increase the sensitivity even more. Thus EUS and also SRS should be employed early if NETs of the foregut type are suspected. Conventional imaging procedures such as US, CT, and MRI should be mainly used to exclude local and distant metastases.

Digestive System↗
PubMed1994

Localisation of neuroendocrine tumours of the upper gastrointestinal tract.

In order to localise neuroendocrine tumours of the foregut type (that is, of the stomach, duodenum, and pancreas), 18 patients were studied prospectively by endoscopic ultrasonography, computed tomography, transabdominal ultrasonography, magnetic resonance imaging, and somatostatin receptor scintigraphy. These 18 patients had a total of 25 primary tumour lesions which were verified histologically in tissue obtained by surgery or by ultrasound or endoscopy guided biopsy. Tumours were found in the stomach (n = 1), duodenum (n = 6), pancreas (n = 17), and liver (n = 1). Endoscopic ultrasonography had the highest sensitivity for tumour detection, followed by somatostatin receptor scintigraphy, computed tomography, transabdominal ultrasonography, and magnetic resonance imaging (88%, 52%, 36%, 32%, and 24% respectively). Endoscopic ultrasonography was especially sensitive in tumours smaller than 2 cm in diameter (88% v somatostatin receptor scintigraphy 35%; computed tomography 12%; transabdominal ultrasonography 6%; and magnetic resonance imaging 0%). Of 17 tumours located in the pancreas, endoscopic ultrasonography showed a sensitivity of 94% (somatostatin receptor scintigraphy 47%; computed tomography 47%; transabdominal ultrasonography 41%; and magnetic resonance imaging 29%). Of eight extrapancreatic tumours, six were identified by endoscopic ultrasonography, five by somatostatin receptor scintigraphy, and only one by computed tomography, transabdominal ultrasonography, and magnetic resonance imaging. One neuroendocrine tumour that was not detected by endoscopic ultrasonography was correctly identified by somatostatin receptor scintigraphy. Endoscopic ultrasound allowed correct determination of the tumour size and tumour spread into parapancreatic structures, especially the large vessels (T stage), in all 14 patients operated upon. The lymph node stage (N stage) was correctly determined in 10 of these 14 patients. In summary, endoscopic ultrasonography and somatostatin receptor scintigraphy were the most sensitive imaging methods for the localisation of these tumours and should be used as early diagnostic procedures to accurately stage neuroendocrine tumours of the foregut type.

Adolescent↗
PubMed1993

Comparison of computed tomography, endosonography, and intraoperative assessment in TN staging of gastric carcinoma.

From 1986 to 1990 a prospective comparative study was undertaken to compare the relative accuracy of computed tomography, endogastric ultrasonography, and intraoperative surgical assessment in evaluating the depth of invasion (T category) and involvement of lymph nodes (N category) of patients with gastric carcinoma. One hundred and eight consecutive patients, who were treated by total gastrectomy and previously evaluated with computed tomography, endogastric ultrasonography, and intraoperative surgical assessment, entered the study. Results (T and N category) were compared with those of histopathological staging (pT and pN category). T categories were correctly staged in 43% of cases with computed tomography, 86% with endogastric ultrasonography, and 56% with intraoperative surgical assessment. Computed tomography scanning correctly staged 51% of all N1 and N2 lymph nodes compared with 74% for endogastric ultrasonography and 54% for intraoperative surgical assessment. In general, computed tomography was more accurate for advanced stages of cancer and showed a tendency to overstage the T category and understage N category of gastric tumours. By contrast, endogastric ultrasonography was equally accurate for all T categories and showed an understaging for N categories. Intraoperative surgical assessment overstaged early T stages, understaged T4 tumours, and was equally accurate for all grades of N categories. Computed tomography scanning and intraoperative surgical assessment of T and N categories were of little value in staging of gastric carcinoma. Endogastric ultrasonography is more accurate than computed tomography scanning and intraoperative surgical assessment. Therefore endogastric ultrasonography should be introduced in the preoperative assessment of patients with gastric carcinoma.

Adult↗
PubMed1993

Lithotripsy of an impacted calcified stone in the cystic duct accompanied by cholecystitis in severe Crohn's disease.

A 35 year old women patient with Crohn's disease and previous multiple abdominal operations presented with a calcified stone of 12 mm diameter in the cystic duct giving rise to cholecystitis. The surgeons declined to operate because of extensive intra-abdominal adhesions caused by multiple intestinal resections and chronic enterocutaneous fistulas. It was possible to fragment the stone in three lithotripsy sessions. The fragments were excreted spontaneously through the ductus choledochus and the cholecystitis was cured by antibiotic treatment. The patient remained symptom free after 12 months.

Adult↗
PubMed1991

Evaluation of endosonography in sclerotherapy of esophageal varices.

During intravariceal sclerotherapy of esophageal varices with polidocanol in 32 patients with portal hypertension due to liver cirrhosis of various etiologies, endosonographic assessment of both esophageal and gastric intramural vessels was carried out in order to evaluate the usefulness of endosonography in the follow-up of the variceal status. In all cases endosonography demonstrated esophageal and gastric varices; in contrast, only five cases of gastric varices could be demonstrated by endoscopy. Furthermore, different stages of variceal obliteration following sclerotherapy could be demonstrated by means of endosonography, and it was possible to identify incomplete obliteration in about one-third of the patients in whom inadequate sclerotherapy was suspected endoscopically. In addition, the status of gastric varices during sclerotherapy was demonstrated by means of endosonography. Only in cases of adequate sclerotherapy of esophageal varices, as assessed by both endoscopic and endosonographic criteria, were gastric varices plugged. On the basis of these findings endosonography would appear to be a useful technique for the diagnosis and follow-up of esophageal and gastric varices during intravariceal sclerotherapy.

Esophageal and Gastric Varices↗
PubMed1990

Combined effects of tumor necrosis factor-alpha, prostaglandin E2, and corticosterone on induced Ia expression on murine macrophages.

Ia expression is an important marker of macrophage functional capacity. IFN-gamma induces Ia expression on perhaps all murine macrophages, whereas IL-4, granulocyte-macrophage CSF, and CSF-1 induce Ia on restricted sets of macrophages. Inhibitors of expression include PGE2, glucocorticoids, and IFN-beta. TNF has been found to augment Ia expression on several macrophage lineage cell lines but to inhibit expression on murine peritoneal macrophages. Our study shows that TNF can have opposite effects on Ia expression (induced by IFN-gamma) on thioglycollate-elicited peritoneal macrophages, depending on the length of time cells are treated and on the presence of other modulators. In particular, TNF augmented early expression induced by IFN-gamma but inhibited later expression. And although TNF synergized with PGE2 to markedly inhibit Ia induction on these cells, it partially antagonized the inhibition by corticosterone and IFN-beta. TNF and PGE2 also synergized to inhibit Ia expression induced on bone marrow-derived and splenic macrophages by either IFN-gamma or IL-4. In contrast to their effect on Ia expression, TNF and PGE2 had opposite effects on expression of gamma 2a FcR in macrophages. TNF blocked the increase in FcR expression due to any combination of PGE2, IFN-gamma, and IFN-beta. However, TNF and PGE2 both increased expression of gamma 2a FcR on WEHI-3 cells. If the different effects of TNF reflect the differentiation states of macrophages, its effects on Ia and FcR expression may vary with the progression of an immune response.

Animals↗
PubMed1990

[Joint status after prophylactic substitution. An investigation in hemophilic children and adolescents in the DDR].

The joint condition in 98 children and adolescents with severe or moderate types of haemophilia participating in a summer camp between 1987 and 1989 had been analyzed. This was done by the centers' report and on the other hand with testing the patients by aid of the score system recommended by the World Federation of Hemophilia. According to the centers' reports more than 50% of all patients seem to be free of joint contractures. But according to the more sensitive score system more patients are affected by discrete symptoms of the chronic arthropathy. There had been discovered big differences between the centers and an increase of the patient's score by age. Not seldom an impairment of the findings within a single year was recognized. The joint problems in haemophiliacs are solved by the prophylactic treatment in an incomplete manner only. Lacks in the sophisticated evaluation of joints, with the management of prophylactic treatment as well as adjustment to prevention lead to avoidable damage crippling the patient on later age.

Adolescent↗