Search

Heat shock proteins (Hsps) are overexpressed in many tumors, but are downregulated in some tumors. To check for a direct effect of Ha-Rasval12 on HSP70 transcription, we transiently expressed the oncoprotein in Rat1 fibroblasts and monitored its effect on HSP70b promoter-driven reporter gene. We show that expression of Ha-Rasval12 induced this promoter. Promoter analysis via systematic deletions and point mutations revealed that Ha-Rasval12 induces HSP70b transcription via heat shock elements (HSEs). Also, Ha-Rasval12 induction of HSE-mediated transcription was dramatically reduced in HSF1−/− cells. Yet, residual effect of Ha-Rasval12 that was still measured in HSF1−/− cells suggests that some of the Ha-Rasval12 effect is Hsf1-independent. When HSF1−/− cells, stably expressing Ha-Rasval12, were grown on soft agar only small colonies were formed suggesting a role for heat shock factor 1 (Hsf1) in Ha-Rasval12-mediated transformation. Although Ha-rasVal12 seems to be an inducer of HSP70's expression, we found that in Ha-rasVal12-transformed fibroblasts expression of this gene is suppressed. This suppression is correlated with higher sensitivity of Ha-rasval12-transformed cells to heat shock. We suggest that Ha-rasVal12 is involved in Hsf1 activation, thereby inducing the cellular protective response. Cells that repress this response are perhaps those that acquire the capability to further proliferate and become transformed clones.Oncogene (2006) 25, 1485–1495. doi:10.1038/sj.onc.1209193; published online 7 November 2005 [ABSTRACT FROM AUTHOR]

Ulcerative colitis is a chronic inflammatory bowel disorder of unknown etiology. Treatment of flare-ups is based on mesalamine and steroids. Treatment of moderate to severe ulcerative colitis with high-dose heparin and low-molecular-weight heparin was reported. The mechanism was assumed to be a combination of anti-coagulant and anti-inflammatory effects. Low-molecular-weight heparin is better and safer than unfractionated heparin. Studies of low-dose low-molecular-weight heparin in experimental models of inflammation and in inflammatory diseases demonstrated a beneficial effect. Our aim in this study was to evaluate the effect of low-dose, low-molecular-weight heparin in active ulcerative colitis. Twelve patients with flare-ups of colitis were prospectively enrolled. Subcutaneous injections of 5-mg enoxaparin were administered at weekly intervals for 12 weeks. Mesalamine doses remained unchanged. Clinical, laboratory, endoscopic, histologic, and quality-of-life scores were evaluated at the beginning and end of the study. Ten patients completed the study. Mean age was 40.1; the female–male ratio was 7:3. Mean Mayo scores were 9.0 ± 0.94 at baseline and 3.4 ± 2.0 at the end of the study (P = 0.0001). Endoscopic scores decreased from 2.2 ± 0.4 to 1.2 ± 1.0 (P = 0.049) and in 7 of 10 patients extent of disease shortened. A significant increase in IBDQL scores from 135.7 ± 37.17 to 179.6 ± 45.15 points was demonstrated (P = 0.0117). Adverse events were one hospitalization due to abdominal pain, arthralgia (1), transient peripheral edema (1), and elevation of alkaline phosphatase (1). During follow-up, one patient required colectomy and another experienced an exacerbation. In conclusion, low-dose low-molecular-weight heparin once a week, combined with mesalamine, may be an effective therapy for active ulcerative colitis. It may delay or preclude the need for steroid treatment. Controlled studies to evaluate efficacy are needed. [ABSTRACT FROM AUTHOR]

This report describes seven patients from three university hospitals whose native valve infective endocarditis was caused by Staphylococcus epidermidis. The literature on endocarditis caused by S. epidermidis is also reviewed and the clinical features of patients with native valve endocarditis due to this organism are compared with those of patients from a general series of infective endocarditis cases. Compared with infective endocarditis caused by other organisms, S. epidermidis endocarditis tends to occur more frequently in male patients. Patients with S. epidermidis endocarditis exhibit fewer embolic complications and skin manifestations. The frequency of congestive heart failure is lower in this group. The relative indolent course and apparent rarity of native valve S. epidermidis endocarditis necessitate a high index of suspicion for early diagnosis. [ABSTRACT FROM AUTHOR]

Hepatocytes are hypothesized to continually stream from the portal tract to the terminal hepatic vein. By this model, when a cell divides, one of its progeny replaces the dividing ancestor and the other is displaced into a more remote location. The present experiment aims to demonstrate that hypothyroidism affects liver cell turnover. Thirty male adult rats were divided into two groups. One received methimazole for two weeks and the other served as control. Each rat was injected intraperitoneally with 18.5 KBq [3H]thymidine/g body weight. Rats were killed after 1 hr and two and four weeks. Autoradiography was done. The distance of the labeled cells from the portal tract was measured. The mean TSH levels of the methimazole-treated group and controls were 1.45 and 0.25 mM/liter, respectively (P < 0.01). Hepatocyte streaming was lower in hypothyroid (1.8 microns/day) than in untreated rats (2.5 microns/day) (P < 0.01). The respective labeling indices 1 hr after labeling were 0.9% and 1.24% (P < 0.05). We conclude that hypothyroidism diminishes hepatocyte and littoral cell turnover and slows down their streaming. [ABSTRACT FROM AUTHOR]

- Thirty male adult rats, weighing 250-300 g, were injected with 0.5 μCi [3H]-thymidine. The rats were killed in groups of five, at the following times: 1 h, 14, 30, 60, 90 and 120 days. The livers were fixed in formalin, embedded in paraffin and cut into 5-μm-thick sections, which were then dipped into liquid emulsion for autoradiography. Bile ducts were evaluated in all portal tracts of a section. Obliquely cut bile ducts were excluded. The number of cells paving the duct lumen was defined as bile duct class. Class is roughly proportional to bile duct size. One hour after labelling, labelling index was 3.39 ± 0.06% (the second number is one standard error of the mean). With time it declined, reaching 0.22 ± 0.15 on day 60. Initially labelled cells were found in narrow bile ducts and the mean labelled cell was located at class 7.48 ± 0.63. With time, labelled cells proceeded into wider bile ducts advancing daily 0.122 ± 0.025 classes. Intra-hepatic bile duct epithelium renews its cells continuously in the same way as epidermis or gastro-intestinal mucosa do. It consists of two kinetic compartments, a progenitor (P) and a functional (Q) compartment. P feeds Q with cells. [ABSTRACT FROM AUTHOR]

ABSTRACT- In previous studies we have shown that hepatocytes stream from the portal tract toward the terminal hepatic vein. The present study provides evidence that littoral cells participate in the same cell stream and that the liver actually streams en masse. Littoral cells stand for sinusoidal endothelia and Kupffer cells. Thirty male adult rats, random bred, were injected with 0.5 μCi [3H]-thymidine, specific activity 5 Ci/mmol/g body weight. The rats were killed in groups of five, at the following times: 1 h, 14, 30, 60, 90 and 120 days. The livers were processed histologically and dipped into liquid emulsion for autoradiography. In each animal 50 labelled hepatocytes and 50 littoral cells were randomly selected and their distance from the nearest terminal portal tract rim was measured. Both cell populations renew their cells continuously. Each consists of two cell types, progenitors, residing around the portal tract up to the distance of 200 μm. and functional cells, which inhabit the rest of the acinus. The two regions where the different cell types reside are known respectively as progenitor (P) and functional (Q) compartments. Both cells are formed in the P-compartment and advance jointly along a trajectory, the tissue radius, toward the terminal hepatic vein where they die. They progress at a daily velocity of 2 μm. Since both advance at the same speed, as long as they exist they remain neighbours. Liver parenchyma and stroma thus stream en masse. It is proposed that hepatocytes and littoral cells are displaced as tissue quanta, or proliferons, which are assembled in the progenitor region near the portal tract, and gradually traverse the three acinus zones, changing their metabolic tasks as they go, until at the terminal hepatic vein they disintegrate, probably by apoptosis. [ABSTRACT FROM AUTHOR]

ABSTRACT- Thirty male adult rats, were injected with [3H]-thymidine, [3H]TdR. The animals were killed in groups of five, at the following times: 1 h, 14, 30, 60, 90 and 120 days. The livers were fixed in formalin, embedded in paraffin and cut into 5-μ-thick sections, which were then dipped into liquid emulsion and exposed for 3 weeks. The grain content of each sampled cell was counted and its distance from the nearest portal tract rim measured. Since the cells were labelled once and the label was available only for a short period, cell displacement could be followed with time. One hour after labelling, most labelled cells were confined within the 300 μm distance from the portal space rim. From then on, labelled cells advanced at a daily velocity of 2.5 μm toward the terminal hepatic vein. The liver acinus is composed of two compartments: a progenitor compartment extending up to 300 μm from the portal tract and a functional compartment covering the remaining acinus portion. Such an arrangement is known as a two-compartment cell renewal system, and is found in renewing tissues like cryptvillus and epidermis. The hepatocyte moves from the portal space toward the terminal hepatic vein, proceeding along a trajectory, denominated as tissue radius. Since cells move in one direction, the further a cell is from the portal tract, the older it is. One may therefore estimate cell age by measuring its distance from the origin. Since the tissue radius portrays cells of all ages, it describes the entire life history of one cell. The advancing hepatocytes traverse the three acinus zones. Each represents, therefore, a differentiation stage of one cell, and since in each zone cells perform different functions, the metabolic activity of the hepatocyte is age-dependent. When young it is engaged, among other activities, in gluconeogenesis, turning in old age to glycolysis. [ABSTRACT FROM AUTHOR]

Objectives: The seasonal variation of duodenal ulcer disease and its complications have been repeatedly demonstrated in Israel by several independent studies. The aim of this study was to determine possible seasonal variations in the occurrence of H. pylori infection among dyspeptic patients in Israel. Methods: All 14C-urea breath tests performed in dyspeptic patients at the gastroenterology department in the Tel Aviv Medical Center from January 1991 to December 1992 were reviewed. The monthly variation in the proportion of patients with H. pylori infection was determined, and compared with that of an unrelated 14C-cholyl-glycine breath test. Results: Altogether, 702 patients were examined, and 371 (52.8%) of them were found to be infected with H. pylori. During summer months (July-September), a significant decrease in the percentage of patients infected with H. pylori was found, compared with winter months (December-January, 42.3% vs. 60.9%, p < 0.007). No seasonal variation was found in the results of 14C-cholyl-glycine test. The fluctuations in H. pylori infection were highly correlated with the seasonal occurrence of peptic ulcer disease in Israel. Conclusions: The frequency of H. pylori infection in dyspeptic patients in Israel is significantly increased during the winter months and decreased in the summer. This seasonal variation is identical to that found in duodenal ulcer disease. Thus, the seasonal variation of peptic ulcer disease could be explained by H. pylori infection, as seen in other communicable infectious diseases. [ABSTRACT FROM AUTHOR]