Hypertonicity-induced cation channels.

Whenever studied in a quantitative fashion, hypertonicity-induced cation channels (HICCs) are found to be the main mediators of regulatory volume increase. In most instances, these channels are either inhibited by amiloride (but insensitive to Gd3+ and flufenamate) or they are efficiently blocked by Gd3+ and flufenamate (but insensitive to amiloride). Of note, however, from two preparations so far a mixed type of pharmacology has also been reported. Whereas the ion selectivity of amiloride-sensitive HICCs has not been studied in much detail yet, amiloride-insensitive channels are either equally permeable to Na+, K+, Cs+ and Li+ but impermeable to N-methyl-D-glucamine (NMDG+) or they exhibit a permeability to Li+ and NMDG+ that amounts to some 50% when compared with that of Na+. Also in this respect, however, some peculiarities do exist. Concerning the actual molecular correlate, evidence was reported that HICCs may be related to the (amiloride-sensitive) epithelial Na+ channel and/or to transient receptor potential channels. Recent findings suggest that HICCs may contribute to cell proliferation, just as the K+ channels that are employed in regulatory volume decrease are mediators of the opposing process, i.e. apoptosis.

[Simultaneous papillary carcinoma in a thyroglossal duct remnant and the thyroid gland]. / Simultanes papilläres Schilddrüsenkarzinom in einer medianen Halszyste und Zweitkarzinom der Schilddrüse.

BACKGROUND: In 1 % of the thyroglossal duct cysts malignant transformation is found with predomination of the papillary carcinoma (80 %). CASE REPORT: We present the case of a 51 year old man with a synchronic papillary carcinoma in a thyroglossal duct remnant and a microcarcinoma of the thyroid gland. After exstirpation of a thyroglossal duct cyst histological examination identified a papillary carcinoma. Postoperative staging uncovered enlarged lymph nodes but no abnormalities in the thyroid gland. Cervical lymphadenectomy and total thyroidectomie was performed. On histological examination a synchronic microcarcinoma of the thyroid was shown. CONCLUSION: Only 7 similar cases have been published in literature before. Because of the rare incidence no therapeutic standard could be established so far. We discuss our therapeutic approach as well as the relevant literature.

[Malignant course of pigmented villonodular synovitis of the flexor tendon sheath of the small finger--case report and review of the literature]. / Maligner Verlauf einer pigmentierten villonodulären Synovialitis der Beugesehnenscheide des Kleinfingers--Fallbericht und Literaturübersicht.

The case of a 55-year-old patient is described, presenting the clinical sign of a chronic infection of the tendon sheath. Upon incision a mass of brown synovial tumor was found. The X-ray showed a circumscript bone erosion. MRI demonstrated tumor involvement of all flexor tendons up to the forearm. Under radiation the tumor initially was diminished. Half a year later, pulmonary metastases were found. The destruction of the whole skeleton of the hand led to a forearm amputation. Later, a metastasis was found in the tongue. The patient died with the clinical signs of pulmonary insufficiency. Autopsy showed diffuse pulmonary metastases. This case is discussed together with other rare cases of malignant pigmented villonodular synovialitis arising from joints and tendon sheaths.

[Complicated intestinal tuberculosis of the mesenteric root]. / Die komplizierte intestinale Tuberkulose der Mesenterialwurzel.

HISTORY AND CLINICAL FINDINGS: In the course of 2 1/2 years a 72-year-old man had five episodes of intestinal bleeding with anaemia, but no cause was at first found by routine diagnostic tests. After the fourth episode a diagnostic laparotomy was performed at which a diffusely infiltrating growing tumour was found. As it encircled the mesenteric vascular axis resection was not possible. But because of threatened ileal obstruction by the tumour a segmental ileal resection was performed, but no intraoperative diagnosis could be established. INVESTIGATIONS: Repeated oesophago-gastro-duodenoscopies and a coloscopy all revealed blood, especially in the upper gastrointestinal tract, but no bleeding source was found. Angiography suggested bleeding in the terminal ileum. Computed tomography demonstrated a tumour in the region of the mesenteric root. DIAGNOSIS, TREATMENT AND COURSE: At a second laparotomy because of another bleeding, which required a blood transfusion, tuberculosis was diagnosed. Triple drug treatment was initiated and the patient has been free of symptoms and bleedings since then and fully active for 1 1/2 years. CONCLUSION: This case clearly demonstrates the difficulty of diagnosis and the long delay until specific treatment, because the combination of "tumour", bleeding and stenosis of the small intestine by an infiltrative lesion at first pointed to malignant process.

Immunohistochemical detection of MAGE tumor-associated antigens in esophageal squamous cell carcinoma.

Genes of the MAGE family encode tumor-specific antigens recognized by cytotoxic T-lymphocytes in a variety of neoplasms. We investigated the protein expression of these antigens as related to the gene expression, in esophageal squamous cell carcinoma by using monoclonal antibodies recognizing MAGE gene products. Esophageal squamous cell carcinomas were found to express both MAGE-1 (4 out of 15 samples) and MAGE-3 (7 out of 15 samples) genes, by RT-PCR. Immunoblotting revealed MAGE-1 and MAGE-3 gene products in 2 and 6 out of 15 samples, respectively. Immunohistochemistry performed on 12 samples showed MAGE-1 protein expression, limited to single tumor cells, in 2 cases. MAGE-3 gene product was detectable in 7 cases: in 5 of them over 50% of neoplastic cells were positive. Considering the high percentages of tumor cells expressing MAGE-3 antigen, the use of epitope-based vaccines could be envisaged in patients displaying appropriate HLA-class I phenotype.

Activation and analysis of cryptic crt genes for carotenoid biosynthesis from Streptomyces griseus.

Genes encoding enzymes with sequence similarity to carotenoid biosynthetic enzymes of other organisms were cloned from Streptomyces griseus JA3933 and transformed into the colourless (non-daunorubicin producing) mutant Streptomyces griseus IMET JA3933/956/2. Cells harbouring these genes showed an orange-red pigmentation, caused by the strongly hydrophobic, membrane-bound lycopene. The cloned fragment (9 kb) contained seven genes, four transcribed in one direction (crtEIBV) and three (crtYTU) transcribed convergently to them. Three of these genes encode polypeptides that resemble geranylgeranyl-pyrophosphate (GGPP) synthases (CrtE), phytoene synthases (PS) (CrtB) and phytoene dehydrogenases (PDH) (CrtI), respectively, of various bacteria. These enzymes are sufficient for the formation of lycopene. crtE alone was sufficient to induce zeaxanthin formation in an Escherichia coli clone containing the crt gene cluster from Erwinia herbicola deleted for crtE. The combination of crtE and crtB led to formation of phytoene in S. griseus. The putative crtEp promoter region was cloned and mapped by primer extension analysis. In a gel retardation experiment, this fragment was specifically shifted by an unknown protein. CrtY shows similarity to lycopene cyclases that convert lycopene into beta-carotene, CrtT resembles various methyltransferases and CrtU a dehydrogenase. We conclude that these genes are functionally intact, but not expressed (cryptic) in the wild-type S. griseus strain.

[Is splenectomy "en principe" necessary for radical gastrectomy with systematic lymphadenectomy?]. / Ist die Splenektomie "en principe" für die Radikalität der Gastrektomie mit systematischer Lymphadenektomie beim Magenkarzinom notwendig?

SUMMARY: In order to screen the necessity of splenectomy "en principe" we evaluated all patients suffering from gastric carcinoma between Jan. 1988--Apr. 1993 retrospectively. In total a group of 318 patients were treated and from these 261 patients were operated (resection rate 82%). In 30% of the patients (77 pat.) we performed a subtotal distal gastrectomy and in 70% (184 pat.) a radical gastrectomy with a D 2-lymphadenectomy. The splenectomy rate in the group of gastrectomy was 94% (173 pat.). In total 13% of the lymph nodes of the hilus of the spleen were infiltrated and an additional metastasis of the spleen was found in 1%. In carcinomas located at the minor curvature 13% had an infiltration of the lymph node station 10, in carcinomas located at the greater curvature in 17% and in carcinomas with a diffuse tumor growth in 10% respectively. Patients with a tumor located in the proximal stomach had an infiltration of the lymph nodes in 14% and in carcinomas of the antrum in 7% respectively. None of the patients having a UICC stage I/II had an infiltration of the lymph nodes at the hilus of the spleen, but 25% of the patients having a UICC stage III/IV. 2 patients from the latter group had an additional metastasis of the spleen. CONCLUSION: The indication of splenectomy is given only in advanced proximal tumor locations, especially in tumors of the greater curvature. In the early tumor stages and in the distal locations of gastric carcinoma it might be useful to perform a selective lymph node dissection of the hilus of the spleen in order to increase the completeness of the radical gastrectomy.

[Surgical therapy of esophageal cancer--early results]. / Die operative Therapie des Osophaguskarzinoms--Frühergebnisse.

PATIENTS AND METHOD: A prospective study was undertaken in 230 patients with carcinoma of the esophagus and of the cardia with infiltration of the distal oesophageal part from 1988 to 1993. RESULTS: According to postoperative UICC-classification 3% of patients had stage 0, 43% stage I/II and 54% stage III/IV. 162/230 were resected (resection rate 70.4%). 55% (89/162) of resected patients had thoracoabdominocervical, 38% (62) thoracoabdominal and 8% (11) transhiatal esophagectomy. Rate of anastomotic break-down was 1.9% (3/162). Clinical mortality decreased from 32% in 1988/89 to 11% in 1990/91 to at least 0% in 1992/93 (total 13%). CONCLUSION: Control of the postoperative phase is of decisive importance in decreasing mortality after esophageal resection, while surgical-technical problems seem to be solved. Esophagectomy is possible even as palliative measure in the presence of low mortality.

[Experiences with reliability and rate of complications in collar or thoracic anastomosis after subtotal esophagectomy]. / Erfahrungen zur Sicherheit und Komplikationsrate bei kollarer oder thorakaler Anastomosierung nach subtotaler Osophagektomie.

In the period from 1988-1992 we performed 148 subtotal esophagectomies. In 69% (102 cases) the operation was carried out because of squamous cell carcinomas of the esophagus, in 27% (40 cases) because of adenocarcinomas and in 4% (6 cases) because of other indications. In 97% (143 cases) the passage was reconstructed by means of a tubulized gastric pull-up established by Akiyama and in of a tubulized gastric pull-up established by Akiyama and in 3% (5 cases) by means of a colon interposition, whereby all interponates were pulled up through the posterior mediastinum. The esophago-gastrointestinal anastomosis was performed in 98% (145 cases) by a hand made suture end-to-side. In 2% (3 cases) we performed the anastomosis by a mechanical EEA device. The collar anastomoses (n = 88) on the posterior wall were covered with the remainder of the gastric fundus, the thoracal anastomoses (n = 60) on the anterior wall were secured by means of a plication. Postoperative surgical complications occurred in 22.7% of the collar and in 25.0% of the thoracal anastomoses. Insufficiencies (n = 3) were observed with thoracic anastomoses only 2 of the 3 insufficiencies were lethal. Postoperative paralysis of the n. recurrens, disturbance of swallowing coordination and aspiration occurred in 29.5% of the collar and in 13.4% of the thoracal anastomoses. In contrast to other reports we were able to show that the collar esophago-enteroanastomosis after subtotal esophagectomy is safer than the thoracic anastomoses with regard to anastomotic insufficiencies.(ABSTRACT TRUNCATED AT 250 WORDS)

[Results of preoperative radio-chemotherapy in locally advanced squamous epithelial cancer of the esophagus]. / Ergebnisse der präoperativen Radio-Chemotherapie beim lokal fortgeschrittenen Plattenepithelcarcinom des Oesophagus.

In a 4-year period (1988-1991) 122 patients with a squamous cell carcinoma of the esophagus were studied prospectively and analysed. 64 patients of them could be primary resected (primary resectability rate 52%), 36 patients were in general inoperable and 22 patients had an advanced stage of cancer with local inoperability. Due to a preoperative combined radiotherapy and chemotherapy 16 of the 22 patients with local inoperability had a clinical remission of the tumor (73%). 11 patients (50%) showed a histological verified down staging and 3 cases of them a complete remission (no primary tumor was found, no infiltration of the regional lymphnodes and no metastatic disease). Curative resection was possible in 14 of 16 patients with clinical remission (2 patients refused surgical treatment). So the resectability rate now increases from 52 to 63%. We conclude that there was no increased rate of postoperative complications or mortality in the combined radio-/chemotherapy group compared with the primary resected patients.

[Synthesis of a highly branched nonasaccharide sequence of the "bisected"structure of N-glycoproteins]. / Synthese der verzweigten Nonasaccharid-Sequenz der "bisected" Struktur von N-Glycoproteinen.

A highly branched nonasaccharide, beta-D-Galp-(1----4)-beta-D-GlcpNAc-(1----2)-alpha-D-Manp-(1----3) -[beta-D- Glcp-NAc-(1----4)-[beta-D-Galp-(1----4)-beta-D-GlcpNAc-(1----2)-alpha-D- Manp- (1----6)]-beta-D-Manp-(1----4)-D-GlcNAc, that represents the carbohydrate chain of the "bisected" structure of lactosamine-type N-glycoproteins was synthesized by a block synthesis approach. The activated trisaccharide block beta-D-Galp-(1----4)-beta-D-GlcpNAc-(1----2)-D-Man was coupled first with the low reactive OH-3 group and, in a second step, with the reactive OH-6 group of the central beta-D-mannopyranosyl residue within the suitably protected trisaccharide block beta-D-GlcpNAc-(1----4)-beta-D-Manp-(1----4)-D-GlcNAc. During these coupling steps, the alpha-glycosidic linkages of D-mannopyranosyl residues were formed without neighboring-group participation, which is only successful by use of the imidate procedure.

[The value of thoracic computed tomography in the intensive care diagnosis of blunt thoracic trauma]. / Die Wertigkeit der Thorax-Computertomographie in der Intensivdiagnostik des stumpfen Thoraxtraumas.

92% of all patients with a thorax-trauma suffer from a blunt chest trauma. In the early diagnosis by plane chest X-ray only a quarter of all pathological findings in comparison to the CT of the thorax are found. In addition to that the special deviations and imaging of the thoracic organs in the plane chest X-ray have to be noted. With the demonstration of same examples the special value of the thorax-CT in early diagnosis and patient control was demonstrated. Specially in showing the grade of lung contusion, the volume of bilaterally hemato-serothoraces, ventral pneumothoraces and additional injuries CT was more sensitive. The main disadvantage is the possibly long way of transportation and a contraindication is a severe trauma of the upper extremities and an instable fracture of the spine column.

The genetic relationship between the Döhne- and the Walrich-merino.

The Döhne- and the Walrich Sheep breeders' societies amalgamated in 1982 to form an enlarged Döhne Merino Breed Society. Both breeds are dual-purpose, polled breeds with high fertility as well as good wool and mutton characteristics. Apparently they have a similar genetic background, both being developed out of local Merino ewes and dual-purpose Merino-type sheep from Europe. Studies of biochemical polymorphisms in the blood of 224 Döhne and 204 Walrich Merino established a close relationship between these two breeds.

[Biological testing of biomaterials in the framework of permitted procedures. 2]. / Zur biologischen Prüfung von Biomaterialien im Rahmen des Zulassungsverfahrens. 2. Mitteilung.

Submitted is the revised version of a proposal for a guideline for biological testing of materials (biomaterials) which remain temporarily or permanently, resp., at or in the human body or have contact with drugs or body fluids outside the human body.

[Summarized presentation of studies on the toxicology of 3-carbethoxyamino-5-dimethylamino-acetyl-10,11- dihydrobenz[b,f]azepine hydrochloride (Bonnecor, GS 015, AWD 19-166)]. / Zusammenfassende Darstellung der Untersuchungen zur Toxikologie von 3-Carbethoxyamino-5-dimethylamino-acetyl-10,11-dihydrodibenz- [b,f]azepin-hydrochlorid (Bonnecor, GS 015, AWD 19-166).

To ensure toxicologically the potential antiarrhythmic agent 3-carbethoxyamino-5-dimethylamino-acetyl-10,11-dihydro-dibenz[b,f] azepine hydrochloride (Bonnecor, GS 015, AWD 19-166), the following preclinical studies have been made up to the present: Determination of the acute toxicity on mice and rats, toxicity test on the rat by repeated applications, study as to the action of GS 015 on the prenatal development of the rat, diverse toxicologic studies on reproduction, mutagenity tests by using the DNA repair test and the Ames test. The results of these studies are represented in a summarized form. A good tolerance of GS 015 can be derived from the results of the preclinical studies gained up to now.