Search PubMed⌕ Search

Biomedical subjects

L Braun

Publications and source records attributed to L Braun.

At least 73 records · Page 4Linked to original sources
PubMed1996

Ascorbate synthesis-dependent glutathione consumption in mouse liver.

Ascorbate synthesis causes glutathione consumption in the liver. Addition of gulonolactone resulted in an increase of ascorbate production in isolated murine hepatocytes. At the same time, a decrease in reduced glutathione (GSH) level was observed. In hepatic microsomal membranes, ascorbate synthesis stimulated by gulonolactone caused an almost equimolar consumption of GSH. This effect could be counteracted by the addition of catalase or mercaptosuccinate, indicating the role of hydrogen peroxide formed during ascorbate synthesis in the depletion of GSH. The observed phenomenon may be one of the reasons why the evolutionary loss of ascorbate synthesis could be advantageous.

Amitrole↗
PubMed1995

Effects of 12-O-tetradecanoylphorbol-13-acetate on human papillomavirus type 16-positive keratinocytes at different stages of transformation.

Normal human keratinocytes grown under serum-free conditions can be triggered to differentiate by exposure to serum or to the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). We found that TPA treatment of human papillomavirus (HPV) type 16-immortalized cells in culture induced formation of cornified envelopes indicative of squamous differentiation. Concurrent with differentiation, TPA inhibited the expression of HPV 16 E6 and E7 mRNA transcripts. Adaptation of the immortalized cells to growth in serum-containing medium led to the selection of a subpopulation of HPV-transformed cells that was resistant to TPA-induced differentiation. In this cell line, a transient suppression of HPV transcripts was observed at 5 h, whereas in differentiation-resistant, carcinoma-derived lines, TPA had little effect on HPV oncogene expression. c-myc transcripts were suppressed for the duration of exposure to TPA in only the differentiation-competent cells; c-fos and c-jun were transiently induced in all cell lines. Transforming growth factor-alpha mRNAs were also increased approximately eightfold as HPV 16-immortalized cells were induced to differentiate. These results demonstrate that, in HPV 16-immortalized keratinocytes, acquisition of resistance to inducers of squamous differentiation is accompanied by altered regulation of cell growth and gene expression.

Cell Differentiation↗
PubMed1995

Entry of Listeria monocytogenes into hepatocytes requires expression of inIB, a surface protein of the internalin multigene family.

The intracellular bacterium Listeria monocytogenes can invade several types of normally non-phagocytic cells. Entry into cultured epithelial cells requires the expression of inIA, the first gene of an operon, comprising two genes: inIA, which encodes internalin, an 800-amino-acid protein, and inIB, which encodes a 630-amino-acid protein. Several genes homologous to inIA are detected in the genome of L. monocytogenes; InIB is one of them. We have assessed the role of inIB in invasiveness of L. monocytogenes by constructing isogenic chromosomal deletion mutants in the inIAB locus. Our findings indicate that: i) inIB is required for entry of L. monocytogenes into hepatocytes, but not into intestinal epithelial cells; ii) inIB encodes a surface protein; iii) internalin plays a role for entry into some hepatocyte cell lines. These results provide the first insight into the cell tropism displayed by L. monocytogenes.

Amino Acid Sequence↗
PubMed1995

Inhibition of p-nitrophenol glucuronidation by calcium mobilizing hormones.

1. Vasopressin and phenylephrine markedly inhibited the glucuronidation of p-nitrophenol in isolated murine hepatocytes. 2. After longer preincubation of hepatocytes in the presence of vasopressin or phenylephrine the rate of conjugation began to return to the control values indicating the reversibility of the inhibition caused by these agents. 3. The inhibitory effect of both agents was dependent on the Ca2+ filled state of the intracellular stores. 4. The inhibition caused by the alpha 1 receptor agonist phenylephrine was receptor mediated because it could be prevented by the addition of alpha 1 antagonist prazosin. 5. The data support the theory that the maintenance of the intralumenal Ca2+ concentration is necessary for the optimal activity of p-nitrophenol UDP-glucuronosyl-transferase.

Adrenergic alpha-1 Receptor Agonists↗
PubMed1994

Ascorbic acid synthesis is stimulated by enhanced glycogenolysis in murine liver.

Ascorbic acid synthesis was stimulated by glucagon, dibutyryl cyclic AMP, as well as phenylephrine vasopressin or okadaic acid, in hepatocytes prepared from fed mice. However, no such effect was observed in glycogen-depleted cells from starved animals, either in the presence or absence of glucose. The rate of ascorbate synthesis showed close correlation with the glucose release by hepatocytes. In mice the injection of glucagon increased plasma ascorbate concentration fifteenfold, and caused a sixfold elevation of the ascorbate content of the liver. These results show that hepatic ascorbate synthesis is dependent on glycogenolysis, and indicate a regulatory role of ascorbate released by the liver.

Animals↗
PubMed1994

Methylglyoxal and cell viability.

Methylglyoxal by depleting glutathione stores increased Trypan-blue uptake by the cells incubated in glucose, pyruvate and amino acids free medium. Only a transient fall of glutathione concentration without any effect on cell viability was caused by methylglyoxal when the medium was supplemented with above-mentioned compounds. The role of gamma-glutamyl-transpeptidase is discussed.

Amino Acids↗
PubMed1994

Role of human immunodeficiency virus infection in the pathogenesis of human papillomavirus-associated cervical neoplasia.

Although many basic questions about the relationship between HIV and HPV infection remain unresolved, epidemiological studies have consistently shown a strong association between HIV infection and the development of HPV-related squamous intraepithelial neoplasia. This work indicates that HIV infection may promote the clinical manifestation of subclinical or latent HPV infection. Recent technical advances localizing virus DNA and gene products in situ will provide new avenues for investigation, allowing us to go beyond correlations and to clarify the mechanisms of interaction between the two viruses in individual patients. With improved antiretroviral therapy and prophylaxis for HIV-associated opportunistic infection and prolonged survival of women with HIV, HPV infection and its most serious consequence, cervical cancer, are likely to assume greater significance in the clinical management of HIV-infected women throughout the world. A better understanding of the role of HIV in promoting the clinical manifestation of HPV infection will be essential to the control of this disease.

Female↗
PubMed1993

Analysis of the growth properties and physical state of the human papillomavirus type 16 genome in cell lines derived from primary cervical tumors.

We have established three cell lines from keratinizing and nonkeratinizing cervical carcinomas with distinct growth properties in vitro and in vivo. Each cell line contained human papillomavirus type 16 DNA sequences, but the lines differed in the physical state of the viral genome present in the cells. A high copy number of episomal human papillomavirus type 16 DNA sequences was detected in the TC-140 line derived from a keratinizing cervical cancer. This cell line had an aneuploid karyotype, did not grow in soft agarose, and formed benign cystlike nodules in nude mice, similar in morphology to well-differentiated areas of the primary tumor. Only integrated human papillomavirus type 16 sequences were detected in the TC-146A and TC-146B lines established from a nonkeratinizing large-cell cervical carcinoma. These cell lines exhibited reduced sensitivity to transforming growth factor-beta 1 and produced invasive, but not progressively growing, tumors in nude mice. These cell lines should complement existing in vitro models of cervical carcinogenesis and provide useful tools for understanding the importance of virus integration in the transformation process as well as the cellular and molecular basis for tumor progression.

Adult↗
PubMed1993

[Aorto-enteric fistula].

Between 1974 and 1991 six patients with an aortoenteric fistula were treated. A primary aorto-jejunal fistula was successfully operated. The other 5 cases were suffering from secondary fistulas due to aortoiliac reconstructions. None of these patients survived. The diagnostic procedures, therapy and prophylaxis are discussed.

Aged↗
PubMed1992

Regulation of growth and gene expression in human papillomavirus-transformed keratinocytes by transforming growth factor-beta: implications for the control of papillomavirus infection.

Cervical carcinogenesis is a multistep process that appears to be initiated by infection of squamous epithelial cells in the cervix with one of a limited number of human papillomavirus (HPV) types. However, the mechanisms involved in the evolution of benign, HPV-induced lesions to malignancy have not yet been fully elucidated. Transforming growth factor-beta (TGF-beta), a multifunctional growth factor produced by cells in the skin, inhibits the proliferation of foreskin and cervical keratinocytes in vitro. We examined the effects of TGF-beta on growth and virus early-gene expression in cell lines immortalized by two HPV types associated with cervical carcinogenesis as well as the expression of TGF-beta 1 mRNA transcripts in normal and HPV-positive cells in vivo and in vitro. We found that normal and HPV-positive cells expressed similar levels of TGF-beta 1 mRNAs and exhibited similar patterns of responsiveness to three isoforms of TGF-beta in both monolayer and modified organotypic cultures. Of particular interest is our finding that the expression of the E6 and E7 early viral transforming regions of both HPV16 and HPV18 was reversibly and rapidly inhibited by TGF-beta. In one HPV16-positive cell line examined in detail, inhibition of HPV expression required protein synthesis and occurred at the level of transcription. HPV-immortalized cells selected for resistance to in vitro differentiation signals remained sensitive to TGF-beta-mediated growth inhibition. These results, showing that both growth and virus gene expression in HPV-transformed cells were responsive to TGF-beta, suggest that endogenous growth factors produced by different cell types in squamous epithelium may play a role in the progression of cervical neoplasia.

Blotting, Northern↗
PubMed1991

A role for transforming growth factor-beta 1 in regulating natural killer cell and T lymphocyte proliferative responses during acute infection with lymphocytic choriomeningitis virus.

The role of transforming growth factor beta 1 (TGF-beta 1) in regulating NK and T cell proliferation during acute viral infections was investigated. After infection of mice with lymphocytic choriomeningitis virus, NK cell proliferation peaks on day 3 and subsides by days 5 to 7 postinfection, whereas T cell proliferation peaks on day 7 and declines by days 9 to 14 postinfection. As TGF-beta 1 has been shown to inhibit lymphocyte proliferation in culture, the production and function of TGF-beta 1 during infection was evaluated in this model. Northern blot analysis demonstrated that the accumulation of TGF-beta 1 transcripts remained relatively constant in total splenic leukocytes during infection. The Mv 1 Lu mink lung cell bioassay was modified and used to evaluate the production of biologically active TGF-beta 1 during infection. Media conditioned with splenic leukocytes isolated from infected mice contained factors that inhibited DNA synthesis by the Mv 1 Lu cells. Low levels of inhibition were observed with conditioned media prepared on day 3 postinfection and high levels of inhibition were observed with conditioned media prepared on days 5 through 14 postinfection. Neutralization with antibodies specific for TGF-beta 1 demonstrated that TGF-beta 1 contributed to the inhibitory activity. As TGF-beta 1 was produced at times coinciding with the decline in NK cell proliferation, the TGF-beta 1 sensitivity of in vivo-elicited NK cells was evaluated. In vitro and in vivo studies demonstrated that NK cell proliferation was extremely sensitive to inhibition by TGF-beta 1. In culture, TGF-beta 1 had an ID50 of 8 pg/ml for inhibiting DNA synthesis by blast NK cells. In vivo, administration of a total of 0.18 micrograms of TGF-beta 1 resulted in a 93% inhibition of NK cell-mediated lytic units per spleen on day 3 postinfection. The inhibition was a result of a block in NK cell proliferation, as administration of TGF-beta 1 profoundly suppressed the appearance of blast size NK cells and the incorporation of [3H] thymidine by NK cell-enriched, blast lymphocyte populations on day 3 postinfection. In contrast to NK cell proliferation, T cell proliferation was not inhibited by up to 100-fold higher concentrations of the factor in vitro or in vivo. Taken together, these data demonstrate that TGF-beta 1 is an important regulator of NK cell proliferation in vivo. Furthermore, the results indicate that differential sensitivity to TGF-beta 1 may contribute to the coordination of NK and T cell responses during viral infections.

Acute Disease↗
PubMed1991

Growth arrest induced by transforming growth factor beta 1 is accompanied by protein phosphatase activation in human keratinocytes.

Protein phosphorylation and dephosphorylation are involved in regulation of cell growth. We tested the hypothesis that the growth inhibitory effect of transforming growth factor beta 1 (TGF-beta 1) involves activation of protein phosphatases. Exposure of human keratinocytes in culture to 400 pM TGF-beta 1 for 48 h led to 80% inhibition of DNA synthesis as measured by nuclear labeling. Incubation of cultured keratinocytes with 400 pM TGF-beta 1 rapidly activated (within 30 min) protein serine/threonine phosphatase, measured using phosphorylase as a substrate. Based on several criteria, including neutralization of activity with specific antibodies and inhibitor-2, TGF-beta 1-activated phosphorylase phosphatase was identified as protein phosphatase 1. TGF-beta 1 did not have rapid effects on protein serine/threonine phosphatase activity (type 2A) measured with histone phosphorylated by protein kinase C or on protein tyrosine phosphatase activity. However, protein tyrosine phosphatase was activated at 48 h, coincident with growth arrest. Differentiation, induced by the combination of TGF-beta 1 plus calcium or by serum, was not accompanied by further serine/threonine or tyrosine phosphatase activation. We conclude that induction of growth arrest in keratinocytes by TGF-beta 1 involves acute activation of protein phosphatase 1, while activation of protein tyrosine phosphatase may represent an additional mechanism for maintaining cells in a growth-arrested state.

Cell Differentiation↗
PubMed1991

[Rectal carcinoma. Analysis of 10-year results].

Between 1974 and 1979 139 patients with rectal cancer have been operated. Operative mortality was 14.4%. The fate of all patients was followed during 10 to 16 years. 46.8% of of patients died from recurrencies and metastases after a medium of 27.5 months. 3.6% died from another malignancy, 15.8% from other unrelated diseases. The 10-year survival rate is 22.3%; 19.4% of all patients are still alive with a mean survival time of 155 months. Prognosis depends mainly on tumour stage. No patient with recurrencies or metastases survived 10 years or longer.

Adult↗
PubMed1991

[Surgical therapy of ulcer disease. Early and late results of elective and emergency interventions].

Between 6/1974 and 12/1988 910 patients with peptic ulcer disease have been treated operatively. In 523 cases a resection, gastroenterostomy resp. ligation of a bleeding ulcer, in 160 cases with duodenal ulcers a vagotomy, and in 227 cases with perforated ulcers simple closure or primary resection have been performed. During this study the percentage of female patients rose from 32.0 to 39.7. There was also an increase of the mean age of the patients. Operative mortality rate was 7.3% for resection, GE resp. ligation of a bleeding vessel, 0.6% for vagotomies, and 16.3% for perforated ulcers. The fate of all patients was followed regularly. In patients operated before 1985--with a follow-up of 5-16 years--reoperations were necessary in 6.0% following resection, gastroenterostomy resp. ligation, in 7.7% following vagotomy, and in 21.3% following simple closure or primary resection of a perforated ulcer.

Adult↗
PubMed1991

[Preventive operations in hernia].

Between 1986 and 1990 1311 inguinal or femoral, 215 abdominal-wall, and 20 hiatal hernias were treated operatively at the Department of Surgery in Detmold. The operations were classified as follows: elective in 87.1%, in conjunction with other operations in 6.1%, and as emergency in 6.9%. Postoperative mortality was 0.1% in elective surgery, but rose 85-fold to 8.5% in emergencies. Hernias therefore should nearly always be treated by elective surgery.

Adolescent↗
PubMed1991

[Incidence of ulcer disease among patients of the Detmold Surgical Clinic 1949-1989].

Between 1949 and 1989 2,042 patients with peptic ulcer disease were treated operatively. The incidence of operations increased markedly after 1949, reached a summit from 1964 to 1978, and decreased thereafter steadily. Different from this trend there was a continuous rise in operations for peptic ulcers in women since 1949 in particular in ulcus perforations. Moreover it could be demonstrated that the need for surgery because of severe complications of ulcus disease effects mainly elderly patients.

Aged↗