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Biomedical subjects

L Braun

Publications and source records attributed to L Braun.

At least 109 records · Page 6Linked to original sources

Growth in culture and tumorigenicity after transfection with the ras oncogene of liver epithelial cells from carcinogen-treated rats.

Two epithelial cell lines designated LE/2 and LE/6 were established from cells isolated by centrifugal elutriation from the livers of carcinogen-treated rats. Both cell lines exhibit some characteristics of fetal liver cells, such as the expression of the 2.3-kilobase alpha-fetoprotein mRNA, aldolase A, and lactate dehydrogenases 4 and 5. Primary cultures contain gamma-glutamyl transferase-positive cells which do not proliferate in vitro. After the first passage, the LE/2 and LE/6 cell lines are uniformly gamma-glutamyl transferase negative. Neither cell line is transformed as assayed by morphology, anchorage-independent growth, or tumor formation in nude mice. By the 50th passage, LE/6 cells form numerous colonies in soft agar in the presence of epidermal growth factor, while no colonies grow in medium lacking this growth factor. Clonal cell populations derived from five epidermal growth factor-induced soft agar colonies were not tumorigenic in nude mice. This indicates that, although epidermal growth factor-responsive late passage cells had acquired some of the phenotypic properties commonly associated with tumor cells, these cells were not fully transformed. Transformation of LE/6 cells was accomplished by transfection of the rasH oncogene (EJ). Subcutaneous inoculation of rasH (EJ)-transfected LE/6 cells produced tumors at the site of injection with histological features of moderate to well-differentiated trabecular hepatocellular carcinomas. Tumor cell lines derived from the nude mouse tumors are gamma-glutamyl transferase positive and express alpha-fetoprotein mRNA. One clonal cell line expresses both alpha-fetoprotein and albumin mRNA. These results show that nonparenchymal liver epithelial cells transfected with an activated oncogene can give rise to differentiated hepatocellular tumors similar to those induced in livers of rats fed a carcinogenic diet.

Animals↗

Na+, K+, and BP homeostasis in man during furosemide: effects of prazosin and captopril.

Furosemide increases sodium (Na+) and potassium (K+) excretion but if dietary salt is provided, a compensatory reduction in Na+ and K+ excretion follows which restores neutral balances within 18 to 24 hours. This compensation is not interrupted by blockade of the renin-angiotensin-aldosterone system (RAA) alone with captopril. Since plasma norepinephrine concentration increases after furosemide and alpha 1 adrenoreceptors can mediate enhanced Na+ reabsorption, we administered prazosin (2 mg 6 hr-1) to six normal volunteers consuming a daily intake of 270 mmol of Na+ and 75 mmol of K+, and added captopril (25 mg 6 hr-1) for an additional day to block the RAA system concurrently. Furosemide (40 mg day-1) was given for the last four days. Prazosin given alone before the diuretic reduced (P less than 0.05) BP and plasma angiotensin II (AII) concentration and increased body weight and heart rate. However, when given with furosemide, neither prazosin nor prazosin with captopril modified the short-term natriuretic or kaliuretic responses to furosemide, or the ensuing compensatory reductions in Na+ and K+ excretion. Accordingly, cumulative balances for Na+ and K+ remained neutral over four days of diuretic administration. Neither drug altered the renal responsiveness to the diuretic which was assessed from the relationship between renal Na+ and K+ excretion and diuretic elimination. Although the BP was maintained when furosemide was given alone, when given with prazosin and captopril, the mean BP fell by 13 +/- 5 mm Hg (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

On-line literature searching: comparison of PaperChase and National Library of Medicine data bases.

Two computerized retrieval systems--the National Library of Medicine (NLM) data bases (MEDLINE, TOXLINE, and their respective backfiles) and PaperChase (PC), a subset of the NLM data base, were compared. Comparative parameters of retrieval and costs for literature searching performed on each system were evaluated. Objective measures were used in the evaluation, as well as a subjective assessment of user satisfaction with each system. Data indicate that NLM is a faster and more direct search procedure for a trained individual, making it a more favorable choice in a drug information center. PC is a valuable tool for sites requiring or offering on-line access to many different people searching infrequently. Because P & T Committees must have access to comprehensive and timely literature, knowledge of various retrieval systems is beneficial.

Boston↗

[Risk of surgical interventions on the gallbladder and bile ducts].

Between 1974 and 1986 2702 patients with benign disorders of the gallbladder or biliary tract have been treated operatively. The following procedures were preformed: cholecystectomy in 70.6%, choledochotomy and T-tube in 18.8%, biliodigestive anastomosis in 5.6%, transduodenal papillotomy in 3.3%, recurrent operation in 1.3%, and operation for gallstone ileus in 0.4%. 38 patients (1.4%) died within 30 days postoperatively. Mortality rates were: 0.6% for cholecystectomy, 2.6% for choledochotomy, 5.3% for biliodigestive anastomosis, 2.2% for transduodenal papillotomy, 8.8% for reoperations, and 0% for treatment of gallstone ileus. Postoperative mortality increased from 0.5% in patients younger than 50 years (0.1% for cholecystectomies) to 4.4% in patients older than 70 years (3.0% for cholecystectomies). With advancing age more complicated procedures were mandatory, while the female/male ratio declined significantly. An immediate operation for acute cholecystitis is indicated only in cases with perforated gallbladder or impending perforation.

Adolescent↗

[Prognosis of colorectal cancer in patients over 80].

A comparison of 149 patients aged over 80 years with a group of 49 under 50 years demonstrated that colorectal carcinoma is more frequent in older persons and more frequently in the right and middle third of the colon. Ileus and perforation are more common in the elderly and are usually diagnosed at a more advanced stage making curative surgery less likely. Perioperative mortality in the over-80s totalled 18.8%. Re-operations had to be performed in 4.7%, an external stoma was needed in 28.1%. Postoperative complications occurred in 25.5% of the older age group, compared with 16.3% in the under-50s. Five-year survival rate was 19.1% in the over-80s. The late mortality rate was 36.2% in the older and 30.0% in the younger age group, after an average postoperative period of 14 and 21.1 months, respectively. Treatment results even in the higher age groups can be improved by earlier diagnosis and treatment.

Aged↗

[Age as a risk factor].

Risk factors like myocardial infarction, hypertension, and diabetes are increasing with age and cause higher perioperative mortality and morbidity. Advanced and complicated stages of various malignant and benign diseases of colon, gall bladder and bile ducts, stomach and great vessels are also more common in the aged population and therefore enlarge the risks of surgery. There is no dependency between age and frequency of intraoperative complications. No difference could be proven in regard to the malignancy of colorectal cancer in patients younger than 50 and older than 80 years.

Adolescent↗

Proto-oncogene expression and growth factors during liver regeneration.

When growth is stimulated in normally quiescent hepatocytes, steady-state levels of c-fos, c-myc, and p53 mRNAs increase sequentially and transiently before DNA replication. C-fos mRNA increases almost immediately after partial hepatectomy and decreases by 2 hr; c-myc mRNA reaches maximal levels between 30 min and 2 hr. In contrast, the p53 mRNA increase corresponds to the G1/S transition, and mRNAs from c-ras genes are elevated later, coinciding with DNA replication and mitosis. p53 and p21 proteins are elevated when their mRNAs are more abundant. This regulated response suggests that these genes either control key steps in the cell cycle or are responding to humoral or internal growth factors acting at specified growth stages. We propose that hepatocytes go through a "priming" stage during the first four hours after partial hepatectomy and that their progression through late G1, is likely to be controlled by autocrine or paracrine mechanisms, which may account for the precisely regulated growth of the liver after partial hepatectomy. Transforming growth factor beta (TGF beta) is a potent inhibitor of DNA synthesis in normal hepatocytes in vitro. We show that TGF beta mRNA increases in the regenerating liver at the time of hepatocyte DNA synthesis and mitosis. In normal or regenerating liver, the mRNA for this growth factor is contained in nonparenchymal cells but not in hepatocytes. We suggest that TGF beta may be a component of a paracrine regulatory loop that controls hepatocyte replication.

Animals↗

Sequential protooncogene expression during rat liver regeneration.

When growth is stimulated in the normally quiescent adult rat liver by partial hepatectomy, steady state levels of messenger RNAs (mRNAs) for c-fos, c-myc, and p53 increase sequentially during the prereplicative phase which precedes DNA synthesis. Levels of c-fos mRNA are elevated at least 4-fold within 15 min after partial hepatectomy and decrease rapidly by 2 h; c-myc mRNA reaches maximal levels (5-fold over normal) between 30 min and 2 h after the operation. A second, transient phase of expression for both c-fos and c-myc occurs around 8 h after partial hepatectomy. p53 mRNA levels increase between 8 and 12 h after the operation (5-fold over normal) and are reflected in an elevation of steady state levels of p53 protein between 12 and 15 h after partial hepatectomy. The levels of ras p21 protein increase much later at a time of active DNA replication and cell division. Actinomycin D injected at the time of partial hepatectomy blocks the increase in c-myc at 2 h but has no effect on c-fos mRNA levels. Actinomycin D injected at 6 h only partially blocks the increase in c-myc and p53 mRNA at 8 h but does not affect c-fos mRNA. Our results suggest that the transient and sequential expression of protooncogenes during the prereplicative stage of liver regeneration is likely to reflect events associated with entry and progression of hepatocytes into the cell cycle and can serve as markers for identifying specific humoral factors involved in liver regeneration.

Albumins↗

[Hemorrhaging gastroduodenal ulcer--clinical aspects, therapy, prognosis].

Between 1974 and 1985 208 patients with acutely bleeding gastroduodenal ulcers have been treated operatively. Postoperative mortality rate was 14.4% and mainly influenced by age, intensity of bleeding, pre- and intraoperative blood pressure, amount of blood transfusions, and duration of ulcer disease. Results after resections were distinctly better than those achieved by ligation of the bleeding vessel with or without vagotomy. In 2.9% recurrent hemorrhage necessitated an early relaparotomy. During a close follow-up from 1 to 12 years reoperation had to be performed because of recurrent ulcers in 4.5%. In 88% of all cases a good long-term result was obtained.

Adolescent↗

Measuring regression in hospitalized medical patients: the BUMP scale.

This article describes the construction and initial validation of a brief rating scale designed to measure behavioral regression or upset in hospitalized medical patients (the BUMP scale). The scale consists of 32 items representing various psychologic reactions to illness. Nurses completed questionnaires on 213 hospitalized patients. Corrected item-total score correlation coefficients averaged 0.53. Factor analysis revealed four factors measuring behavioral regression, poor patient--staff relations, depression/anxiety, and passivity/withdrawal. Alpha reliabilities revealed a high degree of internal consistency of scale items for total score and the four factor subscales. Cluster analysis revealed four clinically meaningful patient groups that were discussed in terms of various typologies in the literature. Potential uses of the BUMP scale and the need for further validating studies were discussed.

Adult↗

[Acute mesenteric artery occlusion--clinical aspects, therapy, prognosis].

During the last 10 years 52 patients with acute mesenteric artery occlusion underwent surgery. There were 19 males and 33 females with a mean age of 73.0 years. 33 patients (63.5%) died postoperatively within 30 days. In 12 cases laparotomy demonstrated inoperability. Resections of the necrotic small intestine were performed in 21 cases, in 6 cases also of the colon. Resections of the intestine were combined in 16 cases with vascular procedures (embolectomy or thrombendarterectomy of the mesenteric superior artery or implantation of aorto-mesenterial or iliaco-mesenterial bypass). In 5 patients a second look - operation was performed with 2 survivors. In 3 cases the clinical diagnosis of mesenteric artery occlusion was proven by preoperative angiography. The prognosis of acute intestinal ischemia can only be improved by early diagnosis and operative treatment. Surgery is aimed at removing the necrotic tissue and restoring an adequate blood flow to the remaining bowel.

Abdomen, Acute↗

Genital warts and cervical cancer. VI. The relationship between aneuploid and polyploid cervical lesions.

Human papillomaviral infection is now widely implicated in the causation of cervical neoplasia. Genotype analysis provides the best guide to biologic outcome; most polyploid lesions regress and most aneuploid ones persist or progress. This prospective survey examined the relationships between cell ploidy and 24 objectively validated criteria of human papillomaviral infection or premalignant change in 52 biopsies from a dysplasia clinic. Histologic evidence of benign warty expression and human papillomaviral capsid antigen production decreased steadily as DNA content ranged from diploidy to polyploidy to aneuploidy. In contrast, premalignant change increased with progressive distortion of nuclear DNA content. No absolute discriminants were found between polyploidy and aneuploidy, as evidenced by the detection of human papillomaviral proteins in three of 21 aneuploid epithelia and the recognition of abnormal mitotic figures in five of 17 polyploid lesions. Polyploid and aneuploid lesions differed only in severity, and it appears that some polyploid epithelia may be transition forms between diploidy and aneuploidy.

Animals↗

Genital warts and cervical cancer. V. The tissue basis of colposcopic change.

Histologic differences between subclinical papillomaviral infection and cervical intraepithelial neoplasia are quantitative rather than qualitative. Both entities are characterized colposcopically by acetowhite epithelium and aberrant surface capillaries. This study correlates five new colposcopic signs (variations in contour, thickness, color, vascular patterns, and iodine staining) with 12 histologic signs of human papillomaviral infection and 12 features of premalignant change. Acetowhitening and capillary abnormalities in minor colposcopic lesions are attributable to human papillomaviral disturbance of cell growth and maturation, seen histologically as parabasal layer proliferation, papillomatosis, koilocytosis , and dyskeratosis. Alteration in cell ploidy is usually minimal. Major colposcopic abnormalities reflect extensive disorganization of cell phenotype and tissue architecture, increased DNA content, and aneuploid stem cell populations. Intermediate colposcopic patterns generally denote polyploid lesions in which tissue changes are a composite of two reciprocal events: the extent of benign warty expression and the severity of premalignant change.

Animals↗

[Early and late results following simple suturing of the perforated stomach ulcer and duodenal ulcer].

Between 1968 and 1983, 1077 patients with gastric or duodenal ulcer underwent surgery in our department. 207 patients presented with perforation of the ulcer, which in all cases was closed by oversewing . They comprised 137 men and 70 females with a mean age of 55.7 years. 26.1% of the patients were aged over 71 years. Postoperative mortality was 15.9%. The prognosis was mainly influenced by age, time interval between perforation and surgery, and--probably--duration of ulcer disease. Follow-up (at least 3 years after surgery) demonstrated no symptoms of ulcer disease in 58.2%. In 21.9% a second and definitive operation had been performed in patients with persistent symptoms or complications of the ulcer.

Age Factors↗

Koilocytotic lesions of the cervix. The relationship of mitotic abnormalities to the presence of papillomavirus antigens and nuclear DNA content.

It has been reported that abnormal mitotic figures (AMFs) occur principally in aneuploid lesions and that aneuploidy is a diagnostic feature of non-endocrine-dependent epithelial cancer precursors and cancers. Recently, AMFs have been reported in cervical lesions interpreted as flat condylomata, and it has been suggested by several authors that AMFs may not be diagnostic or aneuploidy or neoplasia, particularly in human papillomavirus-(HPV)-induced lesions. Although it is conceivable that AMFs may be a regular feature of HPV infection, their association with cytologic atypia and their presence in higher grades of cervical intraepithelial neoplasia (CIN) suggests that AMFs may herald the presence of a different lesion than the pure flat condyloma. In the current study, koilocytotic cervical lesions thought to be HPV-induced were examined microscopically for the presence of AMFs, and the findings were correlated with the presence of HPV as determined by immunoperoxidase and nuclear DNA distribution patterns as measured by Feulgen microspectrophotometry. In unselected lesions originally diagnosed as flat cervical condylomata, AMFs were surprisingly common (22.6%), and did not correlate with the extent of koilocytosis. Immunoperoxidase (IMPO) stains were performed in 35 cases with AMFs, and were negative for HPV in 74.3% and positive in 22.8%. However, among the cases evaluated by IMPO, there was an inverse relationship between the presence of mitotic abnormalities and the expression of HPV antigen. Nine of 11 (81.8%) lesions containing AMFs were aneuploid, and 2 of 11 (18.2%) were polyploid. Abnormal mitotic figures have a range of morphology and frequency in koilocytotic cervical lesions. Although the biology of these lesions is not well-defined, the presence of AMFs may identify a subgroup of HPV-induced cervical atypias which represent a transition between flat cervical conylomata and CIN.

Animals↗

Genital warts and cervical cancer. III. Subclinical papillomaviral infection and cervical neoplasia are linked by a spectrum of continuous morphologic and biologic change.

Human papillomaviral (HPV) infection is now widely advanced as an important etiologic factor in cervical cancer. This study was undertaken to clarify morphologic relationships within the biologic spectrum linking subclinical papillomaviral infection (SPI) to cervical intraepithelial (CIN). Two pathologists analyzed 72 colposcopic biopsies, using a semi-objective rating scheme that scored 24 different histologic criteria. Each individual criterion was checked for reproducibility, and validated against an objective measure of papillomaviral infection (immunoperoxidase staining) or premalignant change (microspectrophotometry). The individual criteria were then combined into histologic indices of benign warty change, presumed viral atypia, abnormal cell phenotype, and disturbed tissue maturation. Histologic expression of papillomaviral infection decreased with increasing degrees of premalignant change. Plotting the index of abnormal cell phenotype against that of disturbed tissue maturation produced a linear plot in which cases clustered into four diagnostic groups. The histologic indices of papillomaviral infection displayed significant curvilinear correlations with genotypic distortion, benign warty change being maximal in the CIN 1 range and presumed viral atypia in the CIN 2 range. Disturbance of nuclear DNA content also increased with worsening diagnosis; diploidy being most common in SPI (67%), polyploidy in CIN 1 (59%), and aneuploidy in CIN 2 (65%) and CIN 3 (82%). Conversely, capsid antigen production decreased from 36% in SPI to 9% in CIN 3. Three aneuploid epithelia were immunoperoxidase positive. These inverse relationships between late viral expression and nuclear distortion fit experimental models of viral oncogenesis. The gradual transition and morphologic overlap between diagnostic groups support the postulate that SPI and CIN are a single disease spectrum, in which differences are those of degree rather than of kind.

Adolescent↗

Bowenoid papulosis. Demonstration of human papillomavirus (HPV) with anti-HPV immune serum.

Two cases of bowenoid papulosis (BP) occurred. The presence of human papillomavirus was demonstrated in one patient. In the other patient, condyloma acuminatum developed after initial spontaneous improvement in his lesions. The discovery of a possible oncogenic virus in BP and the epidemiologic behavior of carcinoma in situ and multicentric carcinomas suggest the need for a very careful follow-up evaluation of such lesions. Bowenoid papulosis may be a chronic dysplasia with a variable long-term prognosis linked to a cocarcinogenic factor.

Adult↗