It has already been demonstrated that the Notch signaling system is essential for gametogenesis in the adult germ line of Caenorhabditis elegans. However, the role of the Notch signaling system in mammalian spermatogenesis has not been well investigated. Recently, it has been revealed that this signaling system is expressed in the mammalian testis by showing coexpression of Jagged 2 and its receptor, Notch 1, is consistent with Notch 1 being a cognate receptor for Jagged 2 in the mammalian testis. Therefore, we investigated expressions of messenger RNAs of Notch 1 and Jagged 2 in the testicular tissues of developing Sprague-Dawley rats by reverse transcription-polymerase chain reaction and Northern blot analysis, expressions of their proteins in the testicular tissues of developing rats, fertile human controls and infertile human patients with maturation arrest by immunohistochemistry, and effects of antibodies to this system by culturing rat testicular tissues with these antibodies. Transcripts of Notch 1 and Jagged 2 in the rat testis were positive throughout the examined period; these intensities became higher at day 13 after birth, coincidence with the formation of spermatocytes, and peaked at day 19 after birth. Expressions of Notch 1 and Jagged 2 were recognized at first in the perinuclear regions of spermatocytes in the rat testis as a round structure at day 19 after birth and thereafter in further differentiated germ cells as meiosis proceeded. In the adult rat testis, positive staining was present as a round structure in spermatocytes, as a typical horseshoe-shaped structure in round spermatids, and as a covering structure spreading around the nucleus of elongated spermatids, but not in spermatozoa. Notch 1 was recognized in the vacuole of the Golgi complex of primary spermatocytes and the acrosome of elongated spermatids with electron microscopy. When rat testicular tissues were cultured with anti-Notch 1 or anti-Jagged 2 antibody, round and elongated spermatids decreased after 5 and 7 days of culture, respectively, and disappeared at around 9 and 12 days of culture, respectively, with shrinkage of the diameter of seminiferous tubules. Spermatocytes, however, increased after 11 days of culture. Expressions of both proteins have been detected in the testicular tissues of human fertile controls as in the rat testicular tissues. However, Notch 1 expression has not been detected in testicular tissues of 11 patients with maturation arrest, whereas Jagged 2 expression has been recognized in all of them. In conclusion, the results presented in this study offer the possibility that Notch 1/Jagged 2 signaling system plays an important role for male germ cells to differentiate or at least to survive in the rat testis and fails to express in the testis of spermatogenic maturation arrest patients.

Actins↗

PubMedDate not supplied

Early post-operative hyperbaric oxygen therapy modifies neutrophile activation.

BACKGROUND/AIMS: To investigate the effect of acute hyperbaric oxygen therapy (HBOT) on post-operative sinusoidal endothelial cell (SEC) damage caused by activated neutrophils. METHODOLOGY: 12 non-cirrhotic patients (Group H), who underwent elective hepatectomy for liver cancer, were given 2 courses of HBOT: 2.0 atm with inhalation of 100% oxygen, for 60 min, at 3 hours and 24 hours after hepatectomy; they were then compared with the 12 patients (Group C) who had been treated to maintain normal hemodynamic values. RESULTS: In group H, peak levels of polymorphonuclear leukocyte elastase (PMNE) and thrombomodulin (TM) were clearly diminished and delayed compared to Group C. All subjects in Group C showed more than a 10% increase in CD18 12 hours after surgery; however, in Group H, the elevation of CD18 expression was clearly suppressed compared to Group C. No patient in Group H had post-operative hyperbilirubinemia or hepatic failure; however, 3 had post-operative hyperbilirubinemia and 1 had intraperitoneal infection in Group C. CONCLUSIONS: Our results provide direct evidence that HBOT, especially at 3 hours after hepatectomy, has favorable effects on the activation of neutrophiles decreasing SEC injury.

CD18 Antigens↗

PubMedDate not supplied

Inhibitory effect of N-acetylcysteine on invasion and MMP-9 production of T24 human bladder cancer cells.

BACKGROUND: MMPs play a crucial role in the process of cancer invasion and metastasis. METHODS: The influence of NAC on invasion and MMP-9 production of human bladder cancer cell line T24 was investigated using an in vitro invasion assay, gelatin zymography, Western and Northern blot analyses and RT-PCR assays. RESULTS: TPA increased the number of invading T24 cells through reconstituted basement membrane more than 10-fold compared to basal condition. NAC inhibited TPA-enhanced invasion dose-dependently. TPA increased the MMP-9 production by T24 cells without altering expression of TIMP-1 gene, while NAC suppressed TPA-enhanced production of MMP-9. Neither TPA nor NAC altered TIMP-1 mRNA level in T24 cells. In vitro experiments demonstrated that MMP-9 was directly inhibited by NAC but was not influenced by TPA. CONCLUSION: NAC limits invasion of T24 human bladder cancer cells by inhibiting the MMP-9 production in addition to a direct inhibition of MMP-9 activity.

Acetylcysteine↗

PubMedDate not supplied

Favorable quality of life after repeat hepatic resection for recurrent hepatocellular carcinoma.

BACKGROUND/AIMS: The appropriate choice of treatment for recurrent hepatocellular carcinoma after hepatic resection remains controversial. The aim of this study is to clarify prognostic factors and quality of life in patients with tumor recurrence after hepatic resection for hepatocellular carcinoma. METHODOLOGY: We retrospectively analyzed 188 patients with hepatocellular carcinoma who underwent curative hepatic resection between 1988 and 1997. Statistical analysis was performed to identify prognostic factors involved after recurrence. Furthermore, quality of life after treatment for recurrence was compared between patients with repeat hepatic resection or hepatic arterial infusion chemotherapy. RESULTS: In 123 patients with recurrence, unfavorable predictors after recurrence are pTNM Stage III/IV at initial surgery, receiving chemotherapy before initial surgery and presence of extrahepatic recurrence. In contrast, favorable predictors are 3 years or more of disease-free interval and repeat hepatic resection. The incidence of deteriorated performance status in the repeat hepatic resection group was lower than in the hepatic arterial infusion chemotherapy group because of better psychological function in patients undergoing repeat hepatic resection. CONCLUSIONS: Repeat hepatic resection provides a good prognosis and a favorable quality of life in patients with recurrence after hepatic resection for hepatocellular carcinoma.

Adult↗

PubMedDate not supplied

Myocardial free fatty acid metabolism of the ischemic heart treated by left ventricular assist device.

Three-beta-methyl-iodophenyl-pentadecanoic acid (BMIPP), a newly developed radiographic probe of metabolic processes in tissue free fatty acid (FFA), was applied to a study analyzing the effect of a left ventricular assist device (LVAD) on impaired dog hearts. The radiographic image obtained with BMIPP was compared with 201thallium chloride (TL) imaging, which indicates tissue perfusion. In the myocardial infarction (MI) model, the BMIPP and TL uptake were equally increased with the use of LVAD in the marginal area of the MI. In another model using the reperfused myocardium after ischemia, the BMIPP and TL uptake were increased in the reperfused area by LVAD pumping. On the other hand, BMIPP uptake in the residual myocardium of both models was decreased by LVAD pumping when compared with TL uptake. This discrepancy between these radiographic tracers in the residual myocardium suggests that tissue metabolic processes may be suppressed as result of a decrease in the energy demand by the myocardium caused by LVAD pumping. The results of this study showed that use of LVADs for the impaired heart improved cell function of "stunned" myocardium and also unloaded the excess work from the residual myocardium as judged by FFA metabolism.

Animals↗