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Biomedical subjects

J Dietrich

Publications and source records attributed to J Dietrich.

At least 91 records · Page 5Linked to original sources
PubMed1994

Chloride channels in mast cells: block by DIDS and role in exocytosis.

In rat peritoneal mast cells, we have investigated the influence of the chloride transport blocker 4,4'-diisothiocyanato-stilbene-2,2'-disulfonic acid (DIDS) and the extracellular chloride concentration on the chloride current induced by intracellular application of cyclic AMP (cAMP) and on hexosaminidase secretion from intact cells stimulated with compound 48/80. The inhibition of the Cl-current by extracellular DIDS is voltage and time dependent. Upon depolarization from -10 to +70 mV, the outward current diminishes with millisecond kinetics. The size of the steady state current and the time constant of the decrease both decrease with increasing DIDS concentrations. The steady state current at +70 mV is blocked by DIDS with an IC50 of 2.3 microM. The number of open channels at -10 mV is reduced with an IC50 of 22 microM. The electrophysiological and pharmacological properties of this current are most similar to those of the Cl- current in T lymphocytes activated by osmotic stress (Lewis, R. S., P. E. Ross, and M. D. Cahalan. 1993. Journal of General Physiology. 101:801-826). Extracellular DIDS also inhibits exocytosis. At optimal stimulation with 10 micrograms/ml compound 48/80 secretion is inhibited with an IC50 = 50 microM and a Hill coefficient n = 10. At half optimal stimulation with 1 microgram/ml inhibition occurs with an IC50 = 10 microM and n = 1. Substitution of extracellular chloride by glutamate has only very small effects on secretion stimulated with 10 micrograms/ml compound 48/80. We conclude that activation of the chloride current in mast cells is not essential for stimulation of exocytosis but may enhance secretion at suboptimal stimulation. Alternatively, the channel may play a role in volume regulation following degranulation.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1994

Secondary fungal metabolites and their biological activities, V. Investigations concerning the induction of the biosynthesis of toxic secondary metabolites in basidiomycetes.

In cultures of the basidiomycetes Heterobasidion annosum, Gloeophyllum abietinum or Armillaria ostoyae, the biosynthesis of some of their toxic secondary metabolites is enhanced up to 400-fold when they grow in the presence of an antagonist. This stimulation is induced before any cell contact occurs. The "inducing signals" are not macromolecules, polypeptides or constituents of the cell membranes, but the same toxins which are synthesized already in monocultures in very low concentrations. After excretion and diffusion into the media, the fungi thus recognize the proximity of the antagonist in dualcultures. As a consequence, the enormous stimulation of toxin synthesis takes place. The increasing toxin concentrations in the fungal dual cultures finally cause the formation of mycel-free growth inhibition zones between the fungi, or sometimes one of the contrahents is killed. This stimulation of toxin synthesis is achieved by an enhanced de novo synthesis of enzymes of the corresponding secondary pathways.

Antibiosis↗
PubMed1994

Chemical reactivity of the toxin oosponol from Gloeophyllum abietinum with nucleophilic agents.

It is shown that contrary to most isocoumarins the antibiotic compound oosponol from the fungus Gloeophyllum abietinum reacts instantaneously with nucleophilic agents like thiol compounds. The reason for this high reactivity is due to the vinylogous acid anhydride character of the compound which is produced by a single oxidation step of the non toxic biological precursor oospoglycol. One must assume that reactions of oosponol with HS-groups of polypeptides form the basis for its toxicity. The ring-opening reactions were studied in detail with the synthetic analogue 4-acetyl-isocoumarin. The structures of some reaction products have been analysed mainly with H-1 and C-13 NMR spectroscopy.

Anti-Bacterial Agents↗
PubMed1994

[Intracranial 3-dimensional computerized tomography in preoperative diagnosis of brain tumor].

Three dimensional processing of cranial dynamic sequence computertomograms enables in cases of tumour enhancement the simultaneous imaging of vessels, bone structures and tumour in their relations. In our opinion, especially in tumours of the frontotemporal basal region, the method may frequently substitute angiography and gives serious information in planning operative treatment.

Brain Mapping↗
PubMed1993

Secondary fungal metabolites and their biological activities, IV. Synthesis of compounds with structural similarities to the toxic metabolites of the pathogenic fungus Heterobasidion annosum and investigation of their antibiotic activities.

A series of synthetic analogues of fomannoxin and fomajorin S, the toxic metabolites of the basidiomycete Heterobasidion annosum, was prepared in order to investigate which partial structures of the molecules are responsible for their biological activities. Of the compounds synthesized the five indane-2-acid derivatives 5-acetylindane-2-carboxylic acid (2), (+/-)5-formylindane-2-carboxylic acid (3), (+/-)indane-2,5-dicarboxylic acid (4), (+/-)formyl-2-methylindane-2-carboxylic acid (7) and 5-acetyl-indane-2,2-dicarboxylic acid (10) and 4-(2'-ethylbutyloxy)benzaldehyde (18) have not yet been described. Different biological test systems were employed to investigate the antibiotic activities of the synthesized analogues. The experimental results suggest that in the case of fomajorin S, the structural element essential for its toxicity is the 2-H- or 2-methylindane 2-acid. From the results obtained with the synthetic analogues of fomannoxin, it is now evident that the toxicity of this fungal metabolite can be attributed to an aromatic ring with a carbonyl or carboxyl substituent combined with a branched lipophilic side chain in p-substitution.

Antifungal Agents↗
PubMed1993

Secondary fungal metabolites and their biological activities, III. Further metabolites from dual cultures of the antagonistic basidiomycetes Heterobasidion annosum and Gloeophyllum abietinum.

In addition to a preceding publication (Sonnenbichler, J., Bliestle, I.M., Peipp, H. & Holdenrieder, O. (1989) Biol. Chem. Hoppe-Seyler 370, 1295-1303), six further metabolites formed in dual cultures of the antagonistic fungi Heterobasidion annosum and Gloeophyllum abietinum are described; three of them represent unknown structures. The producing organisms have been identified. The metabolites fommanoxin from H. annosum and oosponol from G. abietinum show that the toxins can be detoxified by metabolization by the antagonistic fungus. The newly-described compounds have been tested for their fungicidal properties.

Basidiomycota↗
PubMed1993

Detection of proopiomelanocortin-derived antigens in normal and pathologic human skin.

We investigated the presence of proopiomelanocortin (POMC) products in sections of skin from normal subjects and patients with neoplastic and non-neoplastic cutaneous disorders. Antibodies specific against adrenocorticotropin, beta-melanotropin, and beta-endorphin were used for detection and characterization of cell types bearing POMC peptides. POMC products were not observed in sections of normal skin from the corporal (non-scalp) areas (six cases), whereas the hair follicles of scalp skin exhibited positive immunostains that were readily apparent (four cases). POMC products were frequently detected in corporal skin affected by diseases (13 of 26 cases), for example, psoriatic keratinocytes, the inflammatory infiltrate in scarring alopecia, nevocytes, the epithelial cell nests of basal cell carcinoma, and melanoma cells. Further tests were performed in keloids, a primary reactive skin disorder, to evaluate whether POMC accumulation represented a disease-related phenomenon or an expression of normal cutaneous reactivity. POMC products were consistently detected (10 of 11 cases) in the keratinocytes and mononuclear cells at keloid lesions. Thus these observations indicate that POMC products may accumulate locally in lesional skin representing, presumably, a novel cutaneous response to injury. The broad spectrum of POMC products detected suggests that these arise from production in situ (expression of the POMC gene itself) by human skin.

Adrenocorticotropic Hormone↗
PubMed1992

Human fusion proteins between interleukin 2 and IgM heavy chain are cytotoxic for cells expressing the interleukin 2 receptor.

We have constructed a hybrid cDNA coding for a fusion protein between human interleukin 2 and a truncated heavy chain from human immunoglobulin M. The protein encoded by this cDNA contains the entire interleukin 2 sequence including its signal peptide, fused at its C terminus to domains 2 to 4 of the immunoglobulin heavy-chain constant region. Cells transfected with the hybrid cDNA secrete multimeric forms of the fusion protein, which bind specifically to cells bearing high-affinity interleukin 2 receptors. This binding leads either to T-cell proliferation or, if complement is added, to T-cell death. Multimeric forms of the fusion protein with a molecular mass above 500 kDa mediate complement-dependent lysis but trigger proliferation inefficiently when compared with forms with a low molecular mass (< 500 kDa). In contrast, the latter efficiently mediate T-cell proliferation without inducing complement-dependent lysis. The high molecular mass fusion proteins could thus constitute valuable tools for specific immunosuppression in humans.

Base Sequence↗
PubMed1992

Retinoic acid-induced differentiation of a nontumorigenic embryonal carcinoma cell mutant created through retroviral insertion.

A mutant embryonal carcinoma cell line, NR1-6, was created through retroviral insertion. We have previously reported that due to a single insertional event the mutant cell line is altered in regard to both its morphology and its tumorigenic capacity. We now report that this same cell line is also aberrant in its differentiative potential following exposure to the morphogen retinoic acid (RA). Unlike the parental NR1-0 cells, the NR1-6 cells apparently do not respond to RA by elaborating primitive endodermal derivatives in monolayer culture but rather appear morphologically to differentiate into mesodermal cells. This hypothesis is substantiated by the observation that RA treatment induces the transcription of both Endo A and B mRNA in parental but not mutant cells. No differences have been observed in the transcription of other RA sensitive markers such as c-myc, tissue plasminogen activator, collagen type IV, and laminin. In addition, the mutant cells are quantitatively much more sensitive to RA induction than are the parental cells, achieving full differentiation within 72 h of treatment with 10(-10) M RA. The parental cells, in contrast, will only differentiate at concentrations of 10(-5) or 10(-6) M RA, following 5 to 7 days of treatment. A spontaneous revertant cell line, which was isolated from an NR1-6 population and lacks the retroviral insert, is identical to the parental population in all parameters. Therefore, these data indicate that, in this case at least, a single genetic locus is involved in regulating both the qualitative and quantitative response of EC cells to RA-induced differentiation, as well as their morphology and tumorigenic potential.

Animals↗
PubMed1992

Laparoscopic cholecystectomy: technical performance, safety and patient's benefit.

Laparoscopic cholecystectomy seems to be the most promising new technique for the treatment of symptomatic gallstone disease. For different reasons, controlled clinical trials comparing comfort and trauma for the patient of conventional versus laparoscopic cholecystectomy are difficult to perform at our institution. We therefore report on the results of our first 400 laparoscopic cholecystectomies using a strict and detailed protocol on technical performance, safety and benefit for the patient. Data was obtained immediately after the operation and after a short-term follow-up. To analyze the technical performance and the safety of the procedure, we developed a new classification system (I-V) of adverse events, including both the patients' and the surgeons' viewpoints. Our results show that in nearly 80% of the cases an optimal result (no adverse events in any respect) was obtained. For different reasons, the surgical procedure had to be changed during the operation in 20 cases (5%). In 3 cases (0.8%), an injury of the common bile duct occurred; 2 patients died (mortality 0.5%). On the first post-operative day, vomiting occurred in only 8% and nausea in 19% of the patients. Pain intensity was always below the level where patients demand analgesic medication and declined near zero the day after the operation. Patients fatigue was measured on a scale from 0-10 and rose from 2.2 preoperatively to 3.3 postoperatively. Only a short hospital stay of 3 days median was required. At short-term follow-up 6 weeks after the operation, pain was only rarely reported, the patients were fit and only 20% avoided some kind of food. We conclude that laparoscopic cholecystectomy is the treatment of choice for this precisely defined patient population with symptomatic gallstone disease.

Cholecystectomy↗
PubMed1991

Recombinant baculoviruses expressing yellow fever virus E and NS1 proteins elicit protective immunity in mice.

Recently, we showed that yellow fever virus (YFV) E and NS1 proteins in Spodoptera frugiperda cells infected with a recombinant baculovirus are similar, if not identical to those produced during YFV infection. To study the role of E and NS1 in the induction of protective immunity against fatal YFV challenge, these viral antigens were expressed either alone or in tandem via recombinant baculoviruses Ac-E. NS1, Ac-E1 and Ac-NS1. Swiss mice were immunized with lysates of insect cells infected with the recombinant baculoviruses. Solid protection against lethal YFV encephalitis was achieved after immunization with cell lysates containing the E protein with or without the NS1 protein. Mice inoculated with recombinant protein NS1 alone were not significantly protected but showed an increased survival time. Recombinant E protein expressed alone or in tandem with NS1 elicited a low but significant level of neutralizing antibodies. Although protein NS1 synthesized by recombinant baculovirus expressing E plus NS1 was more immunogenic than that expressed alone, neither strategy induced NS1-specific antibodies with complement-mediated cytolytic activity.

Animals↗
PubMed1990

[Growth rate of glioblastoma multiforme].

The velocity of events in cases of glioblastomas is well known. In spite of modern methods of examination the perceivability can miss. By one's own experiences the value of the unchanged role of clinical and neurological examination is point out.

Brain Neoplasms↗
PubMed1989

Effects of elevated gonadotropin levels on thyroid function in the male rat.

In order to determine if thyroid disease in hypogonadal men is the result of chronic elevation of serum gonadotropins, thyroid histology and serum thyroid hormone levels were evaluated in male rats that had been castrated either 2 weeks or 15 months previously. Despite significantly elevating serum LH levels, castration did not affect thyroid structure or function. Serum total T4 levels were reduced with age in both short and long-term castrate animals but returned to the levels seen in young rats when testosterone was replaced. Testosterone replacement also increased free T4 levels in both the young and old castrate rats. Neither age nor testosterone replacement affected serum T3 or TSH levels.

Animals↗
PubMed1988

Ultrastructural characteristics of keloid fibroblasts.

Myofibroblasts abound in granulation tissue, where they play an important role in the healing process. We evaluated the characteristics of fibroblasts in ten patients with keloids, a disorder of skin wound repair. Keloid lesions uniformly exhibited numerous fibroblasts with prominent Golgi complexes and abundant rough endoplasmic reticulum. Although rare fibroblasts exhibited a convoluted nucleus and tangled microfilaments, none could be characterized as myofibroblast, as defined by cytoplasmic myofilaments and cell to cell junctions. We conclude that fibroblast density and activity are increased in keloids, but true myofibroblasts are not a component of these lesions.

Adult↗
PubMed1988

Metastatic thymoma to the head and neck.

Malignant thymoma is a mediastinal tumor which spreads primarily by local invasion. Spread to regional lymph nodes and distant organs is variable. The most common sites of metastasis in the head and neck region are the supraclavicular nodes and the brain. Cervical lymph node metastasis as the presenting symptom of malignant thymoma has not yet been reported in the otolaryngologic literature. We present three cases of metastatic thymoma to the neck from a series of 28 thymomas, ten of which were malignant. The clinical presentation, histopathological features, therapy, and prognosis of malignant thymomas are discussed.

Adult↗