Anterior urethral recurrence of superficial bladder cancer: its clinical significance

The aim of this study was to reveal the clinical features of anterior urethral recurrence in patients with superficial bladder cancer, and to determine the appropriate treatment. Three hundred and three patients with superficial bladder cancer, who were newly diagnosed and initially treated conservatively in our hospital between 1965 and 1990, were followed for at least 5 years and their clinical outcomes were analyzed. Clinical factors, including anterior urethral recurrence, were evaluated statistically regarding tumor progression. Eight patients (2.6%) had anterior urethral recurrence following superficial bladder cancer. Twenty-four patients (7.9%) had tumor progression and 149 (49.2%) had tumor recurrence. In a multivariate analysis using a logistic model, anterior urethral recurrence was the most important factor, followed by histological grade. Four of 5 patients who were treated for anterior urethral recurrent tumors by transurethral resection showed progression and died of the cancer within one year. Two of the remaining three patients who underwent radical cysto-urethrectomy at the time of anterior urethral recurrence survived. Anterior urethral recurrence following superficial bladder cancer is a predictor for rapid subsequent malignant progression. Once there is anterior urethral recurrence, radical intensive therapy, including radical cysto-urethrectomy, should be carried out immediately.     

Protective role of heme oxygenase-1 in renal ischemia

Oxidative stress, which has been implicated in the pathogenesis of ischemic renal injury, degrades heme proteins, such as cytochrome P450, and causes the elevation in the level of cellular free heme, which can catalyze the formation of reactive oxygen species. Heme oxygenase-1 (HO-1), the rate-limiting enzyme in heme degradation, is induced not only by its substrate, heme, but also by oxidative stress. In various models of oxidative tissue injuries, the induction of HO-1 confers protection on tissues from further damages by removing the prooxidant heme, or by virtue of the antioxidative, antiinflammatory, and/or antiapoptotic actions of one or more of the three products, i.e., carbon monoxide, biliverdin IXalpha, and iron by HO reaction. In contrast, the abrogation of HO-1 induction, or chemical inhibition of HO activity, abolishes its beneficial effect on the protection of tissues from oxidative damages. In this article, we review the protective role of HO-1 in renal ischemic injury, and its potential therapeutic applications. In addition, we summarize recent findings in the regulatory mechanism of ho-1 gene expression.     

Humanization of a mouse neutralizing monoclonal antibody against tumor necrosis factor-alpha (TNF-alpha)

An anti-human tumor necrosis factor-alpha (TNF-alpha) monoclonal antibody, designated as 3B10, inhibits the biological activity of human TNF-alpha. In the present study, we constructed humanized version of the antibody by grafting its complementarity-determining regions (CDRs) onto a human antibody, HBS-1. Using a molecular model of mouse 3B10, framework residues affecting the CDR conformation were identified. Thus, these residues were also introduced into the framework together with the CDRs in a stepwise manner, depending on the degree of the possible importance of the residues. As a result, one humanized version (h3B10-9) which possesses nine mouse framework residues showed the same binding activity as that of the chimeric version. This humanized anti-TNF-alpha antibody is expected to be less immunogenic and thus more suitable for possible clinical use.     

HLA-DR Antigens in Pemphigus among Japanese

The frequency of HLA-DR4 was significantly increased at P < 0.02 in 37 unrelated pemphigus patients (62.2%), when compared with unrelated 73 healthy controls (30.1%). This antigen was more frequently found in pemphigus foliaceus (70.6%) than pemphigus vulgaris (55.8%).     

Enhancement of thermal damage in murine tumors by hydralazine-induced modification of blood flow and oxygen tension

We investigated changes in blood flow in normal muscle and in SCC-VII tumors treated by hyperthermia combined with hydralazine, to evaluate the enhancement of thermal tumor damage by hydralazine. We studied SCC-VII tumor-bearing C3H/He mice. Hydralazine was administered by intraperitoneal injection, and tumors were heated by a water bath. We measured blood flow using the laser Doppler method, and oxygen tension using polarography. The response of tumors to therapy was assessed using a growth delay analysis. In tumors, blood flow and O-2 tension significantly decreased with increasing doses of hydralazine. Compared to tumors treated by hydralazine alone or by hyperthermia alone, tumor blood flow was significantly decreased in the group treated by hyperthermia with hydralazine. In tumors treated by hyperthermia with hydralazine, blood flow was significantly decreased with increasing Hyd doses, heat durations, and temperatures. In normal muscle, no decrease in blood flow was induced by hyperthermia, hydralazine, or their combination. In tumors treated by hyperthermia (43 degrees C, 20 min) with hydralazine, a maximum additional growth delay was observed. Our results suggest that a decrease in tumor blood flow caused by hydralazine plays an important role in enhancement of the hyperthermic antitumor effect.     

The medicine chest handed down in the Takaya family, doctors of Sendai-han

There is a medicine chest with design of Chrysanthemums in Makie made for Edo-era and handed down in the Takaya family, doctors of Sendai-han. Many kinds of crude drugs, named by one Chinese character, are kept in this chest. They were classified into three types, namely, [Japanese characters]. Identification of these crude drugs was carried out and the meaning of the classification was brought up as a question.