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Biomedical subjects

L Braun

Publications and source records attributed to L Braun.

At least 91 records · Page 5Linked to original sources
PubMed1990

Differential response of nontumorigenic and tumorigenic human papillomavirus type 16-positive epithelial cells to transforming growth factor beta 1.

The transforming growth factor (TGF) beta s are multifunctional polypeptide growth factors with diverse biological effects, including inhibition of epithelial cell proliferation both in vitro and in vivo. To investigate the possible role of TGF beta 1 in the regulation of papillomavirus infection and papillomavirus-associated transformation, we compared the response to TGF beta 1 of normal keratinocytes, human papillomavirus, type 16 (HPV 16)-positive-immortalized keratinocytes (nontumorigenic), and HPV 16-positive cervical carcinoma cells (tumorigenic) with respect to DNA synthesis and protooncogene expression. All HPV 16-immortalized cell lines were nearly as inhibited by TGF beta 1 as normal keratinocytes, whereas two cervical carcinoma cell lines (Caski and Siha) were refractory to growth inhibition by TGF beta 1. Cell surface receptors for TGF beta 1 were present on both normal and carcinoma cell lines. In all cases, growth inhibition by TGF beta 1 was accompanied by suppression of Steady-state levels of c-myc mRNA. In contrast, TGF beta 1 induced the expression of c-jun mRNA transcripts in normal, immortalized, and tumorigenic cells. We also studied the effect of TGF beta 1 on HPV 16 mRNA expression. Steady-state levels of HPV 16 mRNA transcripts were suppressed by TGF beta 1 in the nontumorigenic HPK cells but were unaffected in the tumorigenic lines. These findings suggest that TGF beta 1 may be an in vivo modulator of HPV infection and that loss of responsiveness to this growth inhibitory signal may be involved in HPV-associated malignant transformation.

Cell Division↗
PubMed1990

Induction of replicative competence ("priming") in normal liver.

We have used a system of nutritional manipulation to investigate whether hepatocytes of the normal liver can be primed for replication in vivo. In this system, rats that are denied protein for 3 days undergo a burst of hepatic DNA synthesis and mitosis when they are refed amino acids, while normally fed or starved rats do not respond. To determine if hepatocytes of protein deprived (PD) rats have been "primed" for replication, we examined changes in protooncogene expression in livers of PD rats to see if they would mimic the pattern of gene expression that is induced early after partial hepatectomy. c-jun, c-myc, and p53 mRNAs were elevated in livers of PD rats, while c-fos and c-ras genes were not expressed. The administration of amino acids to PD rats stimulated hepatic DNA synthesis in a shorter period than is required after partial hepatectomy and induced p53 and c-ras expression. In culture, hepatocytes from PD rats had higher levels of c-myc mRNA, underwent morphological changes more rapidly, and reached maximum rates of DNA synthesis earlier than normal hepatocytes. In both normal and primed hepatocyte cultures, transforming growth factor alpha stimulated DNA synthesis more effectively than epidermal growth factor. We conclude that hepatocytes pass through a priming stage before they proliferate and that replicative competence without DNA synthesis can be induced in hepatocytes in the normal liver.

Amino Acids↗
PubMed1990

Expression of hepatocyte and oval cell antigens in hepatocellular carcinomas produced by oncogene-transfected liver epithelial cells.

We have established an in vivo/in vitro system in which epithelial cells ("oval cells") isolated from livers of rats fed a carcinogenic diet for a very brief period are placed in culture and transfected with an oncogene. Injection s.c. into nude mice of oval cells transfected with the activated c-Ha-ras (EJ oncogene) produces tumors with morphological features of differentiated hepatocellular carcinomas. Using monoclonal antibodies that can recognize hepatocyte, oval cell, and tumor antigens, we investigated the expression of these antigens in oval cells in culture, transfected with either the EJ oncogene or the normal c-Ha-ras allele and in tumors derived from the oncogene-transfected cells. We show that EJ-transfected cells and most particularly the tumors they produce expressed hepatocyte and oval cell antigens not detectable in untransfected cells or cells transfected with the normal c-Ha-ras gene. Furthermore, we found that in cloned tumor cells, the expression of hepatocyte antigens could be induced by changes in culture conditions and was accompanied by a decrease in the expression of oval cell markers. Trabecular hepatocellular carcinomas had higher reactivity toward monoclonal antibodies recognizing hepatocyte antigens while tumors with glandular architecture reacted predominantly with monoclonal antibodies against oval cells. We conclude that, in addition to its tumorigenic effect, the EJ oncogene induced the differentiation of tumor cells toward the hepatocyte lineage. In addition, the data provide further confirmation that oval cells can serve as progenitors of differentiated hepatocellular carcinomas.

Animals↗
PubMed1990

Null alleles of human complement C4. Evidence for pseudogenes at the C4A locus and for gene conversion at the C4B locus.

The two genes for the C4A and C4B isotypes of the fourth component of human complement are located in the MHC class III region. Previous studies have demonstrated the unusual expression of C4 genes in the form of aberrant or duplicated haplotypes. Null alleles of C4A or C4B (AQ0 or BQ0) have been defined by the absence of gene products and occur at frequencies of 0.1-0.3. However, only some C4 null alleles are due to gene deletions, the remainder were thought to be nonexpressed genes. We have analyzed the C4 gene structure of 26 individuals lacking either C4A or C4B protein. The DNA of individuals with apparently nonexpressed C4 genes was tested for the presence of C4A- and C4B-specific sequences using restriction fragment analysis and isotype-specific oligonucleotide hybridization of DNA amplified by polymerase chain reaction. All nondeleted AQ0 allels had C4A-specific sequences and may thus be described as pseudogenes, whereas the nondeleted BQ0 alleles had C4A-instead of C4B-specific sequences. Gene conversion is the probable mechanism by which a C4A gene is found at the second C4 locus normally occupied by C4B genes.

Alleles↗
PubMed1990

[Surgical treatment of gastric carcinoma: complications and results].

Between 1974 and 1989 468 patients with gastric cancer were operated upon. The correlations between age, tumour staging, operability, postoperative complications, and perioperative mortality are analyzed. The further course of the disease was followed carefully in all patients. Therefore it is possible to correlated survival with tumour stage and operability.

Adult↗
PubMed1990

Transforming growth factor beta 1 in liver carcinogenesis: messenger RNA expression and growth effects.

Transforming growth factor beta 1 (TGF-beta 1) is a potent inhibitor of hepatocyte proliferation. Since loss of sensitivity to growth inhibition is thought to contribute to the development of neoplasia, we analyzed the expression of TGF-beta 1 mRNA during hepatocarcinogenesis in vivo and in cultured liver epithelial cells (oval cells) obtained from carcinogen-treated animals. We found that TGF-beta 1 mRNA increases in the liver during carcinogenesis and that, at the early stages of the process, oval cells but not hepatocytes contain the growth factor mRNA. Moreover, immortalized, nontumorigenic oval cells (LE/6 cell line) continued to produce TGF-beta 1 mRNA in culture. TGF-beta 1 message markedly decreased upon cell transformation, but message levels, although generally low, were variable in various tumor cell clones. A consistent feature of the tumorigenic cell lines was a loss of sensitivity to TGF-beta 1 growth inhibition. Tumor cells could bind TGF-beta 1 with similar capacity as normal cells and had the same type of receptors (Mr 280,000, 85,000, and 65,000) capable of binding iodinated TGF-beta 1, suggesting that the loss of sensitivity to TGF-beta 1 in transformed liver epithelial cells involves postreceptor mechanisms. Further studies showed that c-myc is not a target for TGF-beta 1 in liver epithelial cells and that TGF-beta 1 no longer induces fibronectin mRNA in transformed cells. The data presented are consistent with the hypothesis that TGF-beta 1 secreted during liver carcinogenesis may inhibit the proliferation of normal cells while providing a selective advantage for the growth of cells that are "partially transformed" and are unresponsive to the factor.

Animals↗
PubMed1989

Production of hepatocellular carcinoma by oval cells: cell cycle expression of c-myc and p53 at different stages of oval cell transformation.

In rats maintained on a carcinogenic diet (choline deficient containing 0.1% ethionine), the levels of c-myc and p53 mRNAs increased by 4 wk after animals were placed on the diet. Cell isolation studies showed that the change in c-myc takes place in oval cells, while p53 increases predominantly in oval cells but also in hepatocytes. To determine whether this increase is a consequence of cell proliferation or is associated with transformation, we have developed an in vitro model of hepatocarcinogenesis using epithelial cells isolated from the livers of rats fed the carcinogenic diet. When maintained in vitro with infrequent subculture, this cell line (LE/6) undergoes spontaneous transformation. Inoculation s.c. of the transformed cells into nude mice yields tumors histologically identified as hepatocellular carcinoma. We have used these cell lines to compare the cell cycle expression of c-myc and p53 mRNAs in untransformed, partially transformed, and tumorigenic LE/6 cells. We find that the expression of both genes is under cell cycle control in untransformed and partially transformed cells. However, complete transformation of this cell line is associated with constitutive expression of myc but not p53 transcripts. On the basis of this work we suggest that constitutive expression of c-myc may be a late event in hepatocarcinogenesis.

Animals↗
PubMed1989

Possible association of sudden infant death with partial complement C4 deficiency revealed by post-mortem DNA typing of HLA class II and III genes.

Based on evidence of an increased rate of respiratory infections in sudden infant death (SID) infants as well as the observation of familial occurrence, we analysed in a retrospective study class II and class II genes of the major histocompatibility complex in 40 cases of SID by Southern blot analysis of DNA obtained post mortem from tissue samples. In 24 cases, the parents were interviewed and confirmatory human lymphocyte antigen (HLA) and DNA typing was carried out. Using HLA-DR beta and -DQ beta probes, no evidence of an abnormal HLA-DR frequency distribution in SID infants was detected (P = 0.97). Using DNA probes for the tandemly arranged complement C4 and steroid 21-hydroxylase genes, an increased number of C4B gene deletions in SID cases was found. The increase in C4 gene deletions was significant (P = 0.0125) in infants with recurrent infections. These data indicate a possible role of partial C4 deficiency as a genetically predisposing risk factor in SID.

Complement C4↗
PubMed1989

[The role of gastrectomy in the treatment of hemorrhaging stomach ulcers].

It is reported about 6 patients whose bleeding gastric ulcers required gastrectomy as ultima ratio. The operative technique depends on the individual case. Gastrectomy is indicated in patients with diffuse bleeding from erosions or multiple ulcers especially combined to coagulation disorders or in patients with recurrence bleeding after previous gastric resection. We saw no letal complication in spite of unfavourable initial conditions and major operating trauma. There were no essential postoperative complications except of one patient. The definite hemostasis seems to be most important for the prognosis of such critically ill patients.

Aged↗
PubMed1989

[Gallstone ileus. Incidence, clinical aspects, therapy].

Between 1974 and 1987 11 patients - 9 females and 2 males - have been treated operatively. Their mean age was 75.0 years. In only 5 cases cholecystolithiasis was known at the time of hospital admission. In 9 cases 1 gallstone, in 2 cases 2 resp. 6 stones were removed operatively. The stones were located in the ileum in 7, in the jejunum in 2 and in the sigmoid colon in 2 instances. Beside removal of the stones in two patients a simultaneous cholecystectomy, in two patients segmental resection of small intestine, in one patient a sigmoid resection and in one the resection of a Meckel diverticulum were performed. All patients survived and were followed-up after dismissal from the hospital for 10-114 months. Only 1 out of 9 patients, in whom the gallbladder was not removed, suffered 3 years postoperatively from choledocholithiasis. The other patients remained free of symptoms until now resp. their death.

Aged↗
PubMed1988

[Prognosis in stomach carcinoma].

Between 1974 and 1981, laparotomies were performed on 233 patients with histologically proven gastric carcinoma. Lymph-node metastases were found in 72.6%, distant metastases in 14.2%. The condition was found to be inoperable in 18.9%, a palliative procedure was performed in 17.6%, a questionably curative operation in 33.5% and a curative one in 30.0%. Postoperative mortality was 15.9%, highest in case of inoperability and palliative operations. During the follow-up period of 5-13 years 137 patients (58.8%) died of metastases or recurrence, two (0.9%) of another malignancy and 30 (12.9%) of other illnesses. The five-year survival rate was 13.3%. There was no difference in prognosis between carcinoma in a residual stomach (after previous partial resection) and a previously unoperated one. Carcinoma of the cardia gave the worst results. No patient with an early cancer died of it.

Adenocarcinoma↗
PubMed1988

Transforming growth factor beta mRNA increases during liver regeneration: a possible paracrine mechanism of growth regulation.

Transforming growth factor beta (TGF-beta) is a growth factor with multiple biological properties including stimulation and inhibition of cell proliferation. To determine whether TGF-beta is involved in hepatocyte growth responses in vivo, we measured the levels of TGF-beta mRNA in normal liver and during liver regeneration after partial hepatectomy in rats. TGF-beta mRNA increases in the regenerating liver and reaches a peak (about 8 times higher than basal levels) after the major wave of hepatocyte cell division and mitosis have taken place and after the peak expression of the ras protooncogenes. Although hepatocytes from normal and regenerating liver respond to TGF-beta, they do not synthesize TGF-beta mRNA. Instead, the message is present in liver nonparenchymal cells and is particularly abundant in cell fractions enriched for endothelial cells. TGF-beta inhibits epidermal growth factor-induced DNA synthesis in vitro in hepatocytes from normal or regenerating liver, although the dose-response curves vary according to the culture medium used. We conclude that TGF-beta may function as the effector of an inhibitory paracrine loop that is activated during liver regeneration, perhaps to prevent uncontrolled hepatocyte proliferation.

Animals↗
PubMed1988

[Not Available].

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Europe↗
PubMed1988

Demonstration of glucose-6-phosphatase and peroxisomal catalase activity by ultrastructural cytochemistry in oval cells from livers of carcinogen-treated rats.

Oval cells isolated from livers of carcinogen-treated rats have morphologic and biochemical features of immature hepatocytes but seem to lack glucose-6-phosphatase (G6Pase) activity. The authors reinvestigated this question using histochemical methods for visualization of G6Pase activity by light and electron microscopy and the polyene antibiotic filipin to facilitate the penetration of the substrate. Oval cells that proliferate in the liver of animals receiving a carcinogenic diet (choline-deficient, containing 0.05% ethionine) contained G6Pase activity; 50-60% of nonparenchymal epithelial cells isolated from these livers by centrifugal elutriation contained G6Pase activity; and oval cell cultures displayed intense G6Pase activity at confluence but did not have detectable enzyme activity during exponential growth. These results and the demonstration that clofibrate induces peroxisomal proliferation in cultured oval cells strengthen the view that oval cells (or some subpopulation of cells in this compartment) are part of the hepatocyte lineage.

Animals↗
PubMed1988

[Early and late results following implantation of an aortic bifurcation prosthesis].

Aorto-iliacal or aortofemoral bifurcation grafts were implanted to 351 patients for stenotic or occlusive diseases of pelvic and femoral arteries, between 1974 and 1986. The average age of patients was 62.7 years, and perioperative lethality amounted to 7.4 per cent. The average age of patients who died was 68.2 years. Intraoperative complications occurred in 18 cases, early postoperative problems in 103, and complications over more extended periods of time in 37 instances. Postoperative amputation was necessary for eight patients (2.3 per cent) with pre-existence of gangrene. Another 30 patients (9.2 per cent) had to undergo amputation later on. Second, third and more interventions were required in 75 patients. Postoperative follow-up periods were between three months and 13 years during which 51 patients died of cardiovascular diseases, 21 of malignoma, and 14 of other diseases. Adequate surgical results were established by follow-up checks in 80 per cent of the above cases. Twenty-four per cent complained about continued or recurrent claudication. Forty-six per cent of all survivors have continued to be smokers.

Adult↗