Malignant fibrous histiocytoma of the right spermatic cord: a case report.

The patient was a 47-year-old male, who visited Hidaka Hospital with a chief complaint of swelling in the right inguinal region and the scrotum. With a diagnosis of a right spermatic cord tumor, right high orchiectomy was performed. Since an inflammatory type of malignant fibrous histiocytoma (MFH) was diagnosed from histopathological findings, chemotherapy and radiation therapy were performed as postoperative treatment. Malignant fibrous histiocytoma with the primary focus of the spermatic cords is a rare disease. To our knowledge, this is the 20th case of MFH of the spermatic cord in Japan (the 42nd in the world) and it is the second case of inflammatory type of MFH in Japan.

[Clinical study on prostate cancer initially presenting with disseminated intravascular coagulation syndrome].

We experienced five patients with prostate cancer with disseminated intravascular coagulation syndrome (DIC) at the first presentation at Gunma University Hospital and affiliated institutions between 1991 and 1997. Their average age was 68 years, average DIC score at the first presentation was 10 and prostate specific antigen (PSA) level was more than 700 ng/ml. All of them had multiple bone metastases. The therapy for DIC and hormonal therapy for prostate cancer were simultaneously started at the first presentation before prostate needle biopsy, but all patients died. The average number of days from the start of DIC to death was 685 days. The patients initially showed a good response to therapy, but their conditions soon aggravated. The prognosis was extremely poor, but some proper therapies lead to the prognosis which was equal to that of prostate cancer in Stage D2 without DIC.

Modulation of apoptotic cell death by extracellular matrix proteins and a fibronectin-derived antiadhesive peptide.

Cell adhesion to the extracellular matrix (ECM) has been implicated in apoptosis in anchorage-dependent cell types. We recently found that a peptide derived from fibronectin (termed III14-2) inhibits the integrin-mediated cell adhesion to ECM. Using this antiadhesive peptide and a variety of ECM proteins, we show here a critical role of the integrin-ECM protein interaction in apoptotic regulation of human umbilical vein endothelial cells (HUVEC). HUVEC in suspension underwent apoptosis under the serum-free conditions, as judged by nuclear and DNA fragmentations. This apoptosis was suppressed to varying degrees when alpha 5 beta 1, alpha v beta 3, and alpha 2 beta 1 integrins were occupied with either soluble or immobilized ECM proteins such as fibronectin, vitronectin, and type I collagen, respectively. Peptide III14-2, which had no effect by itself on the HUVEC apoptosis, disrupted the ligation of alpha 5 beta 1 and alpha v beta 3 but no alpha 2 beta 1 and ultimately led the cells to apoptosis, indicating that this antiadhesive peptide indirectly induces apoptosis by blocking cell survival signal delivered from alpha 5 beta 1 and alpha v beta 3 integrins. Genistein, a protein tyrosine kinase inhibitor, slightly reduced the rescuing effect of fibronectin, whereas sodium orthovanadate and bombesin, which increase in the level of protein tyrosine phosphorylation, made HUVEC less susceptible to apoptosis and blocked the effect of peptide III14-2. HUVEC adhesion to fibronectin substrate raised the tyrosine phosphorylation level of focal adhesion kinase and the expression of cytoprotective Bcl-2 protein, both of which were reversed by the antiadhesive effect of peptide III14-2. Thus, the opposing effects of ECM proteins, including fibronectin and vitronectin, and peptide III14-2 on HUVEC apoptosis appear to be due to the opposing effects of these factors on the signaling pathway which includes tyrosine phosphorylation of FAK and Bcl-2 expression.

Leuprorelin acetate blood levels and dialysance after the administration of sustained-release leuprorelin acetate in a dialysis case complicated by prostate cancer.

BACKGROUND: The objective of this study is to determine whether in a dialysis patient with prostate cancer leuprorelin acetate blood levels were abnormally high or low due to kidney failure or because of dialysis. METHODS: Sustained-release leuprorelin acetate 3.75 mg was given every 4 weeks for prostate cancer in a 79-year-old dialysis patient. Changes in serum level of leuprorelin acetate in this patient were measured before and after dialysis. RESULTS: Leuprorelin acetate appeared to have a dialysance close to that of vitamin B12, which has a similar molecular weight. The amount dialyzed did not exceed 8.3% of the amount released per day. Mean blood levels of leuprorelin acetate, as measured in this patient, were higher (0.64 to 1.31 ng/ml) than those in prostate cancer patients with normal kidney function (mean +/- SD, 0.24 +/- 0.12 to 0.50 +/- 0.32 ng/ml). CONCLUSIONS: Sustained-release leuprorelin acetate can be used safely in dialysis patients with prostate cancer.

Testosterone replacement therapy for male hypogonadism with a radiation-polymerized testicular prosthesis.

BACKGROUND: The effect of an artificial testicular prosthesis on sexual disturbance in hypogonadal men was investigated. METHODS: Twelve hypogonadal men were treated with testosterone replacement therapy delivered via radiation-polymerized testicular prostheses surgically implanted in their scrotums. RESULTS: An average serum testosterone level of over 200 ng/dL was maintained for 48 months. Most patients treated with this prosthesis were satisfied with the improvement of their sexual activity. Moreover, the patients were psychologically more satisfied with the enlarged scrotum achieved with the implanted prosthesis. CONCLUSION: We recommend this prosthesis as the first choice among testosterone-replacement therapies for hypogonadal men.

N-nitroso compounds in two nitrosated food products in southwest Korea.

Gastric cancer is the commonest malignant neoplasm in Southwest Korea. The possibility of carcinogenic dietary factors led to the investigation of exposure to N-nitroso compound precursors among residents of the City of Chonju and of two outlying rural townships in North Cholla Province. Two traditional and widely consumed home-prepared food products, salted pickled cabbage (kimchi) and salted seafood sauce (chut-kal) were analysed (a) for nitrite, nitrate, total secondary amines and pH in these food products prior to nitrite incubation and (b) for volatile nitrosamines and total N-nitroso compounds before and after incubation with nitrite in simulated human stomach conditions. Nitrate levels were significantly higher in kimchi (median 1550 mg/kg) than in chut-kal (median 140 mg/kg) (P < 0.001). Secondary amine levels in non-nitrosated samples of kimchi (median 5.5 mg/kg) were significantly lower than secondary amine levels in non-nitrosated chut-kal (median 56 mg/kg) (P = < 0.001). Analyses of nitrite-incubated kimchi revealed high levels of total N-nitroso compounds (median 1173 micrograms/kg); the increase with nitrosation was significant (P = 0.001). The concentration of N-nitroso compounds in nitrite-incubated kimchi was significantly greater than that found in nitrite-incubated chut-kal (P = 0.015). The combination of high levels of nitrate in the kimchi, the demonstration of high levels of total N-nitroso compounds in this food after nitrosation, and the volume of kimchi consumed in the traditional diet suggest that salted pickled cabbage may play a role in gastric carcinogenesis in Southwest Korea.

Molecular genotyping for N-acetylation polymorphism in Japanese patients with colorectal cancer.

BACKGROUND: N-acetylation polymorphism has been documented as a representative pharmacogenetic trait, and also has been implicated ecogenetically in an individual's susceptibility to cancer. However, there still remains controversy concerning the association between colorectal cancer and N-acetylation polymorphism. METHODS: A newly established molecular genotyping method using polymerase chain reaction-based restriction fragment length polymorphism to analyze the distribution of polymorphism in a large group of Japanese patients with colorectal cancer was used. RESULTS: Based on an analysis of 234 Japanese patient with colorectal cancer and 329 healthy control subjects, no significant difference was observed in either the distribution of acetylator phenotypes or of allele frequencies between the two groups. In addition, no significant difference in their distribution was found based on the age at which cancer was first detected, the location of tumors, or the histopathologic features. CONCLUSIONS: N-acetylation polymorphism does not appear to be implicated crucially as a genetic trait affecting an individual's susceptibility to colorectal cancer.

Hot spots on liver scans associated with superior or inferior vena caval obstruction.

Although hot spots on hepatic scintigrams have been reported in association with superior and inferior vena caval obstruction, these studies were not clinically correlated, and are hampered by the poor resolution of earlier scintillation cameras. In this report, a modern scintillation camera was used to study the formation of hot spots associated with superior and inferior vena caval obstruction. Moreover, radionuclide cavography was performed in 70 patients with superior vena caval (SVC) obstruction and in 95 patients with inferior vena caval (IVC) obstruction. As a result, 13 cases of hot spots in the liver were observed. In cases of SVC obstruction, hot spots were seen in the quadrate lobe, the medial segment, and the bare area of the liver. In IVC obstruction, a hot spot was seen in the quadrate lobe in all cases. In rare instances, in cases of both SVC and IVC obstruction, a hot spot was seen in the wide area. For these hot spots to develop, it appears necessary to have systemic-portal venous blood flow through the internal thoracic vein and the paraumbilical vein.

Molecular genotyping of N-acetylation polymorphism to predict phenotype.

N-acetylation polymorphism is one of the representative pharmacogenetic traits that underlie interindividual and interethnic differences in response to xenobiotics. To develop a practical genotyping method to predict acetylator phenotype, we studied the conditions for accurate phenotyping, and identified the phenotype in 51 Japanese. Then we performed Southern blot analysis of genomic DNA from these subjects using 32P-labeled cDNA for polymorphic N-acetyltransferase in the liver, and found that four N-acetyltransferase alleles generated six genotypes. The present genotyping method predicted the rapid, intermediate, and slow acetylators correctly in 48 of 51 overall subjects (96%) and in all of 4 slow acetylators.

Possible role of the hormonal form of vitamin D3 in the granuloma-associated angiotensin-converting enzyme activity.

We studied effects of the hormonal form of vitamin D3 on the angiotensin-converting enzyme (ACE) activity of hepatic granulomas in mice infected with Schistosoma mansoni. During 7 to 11 weeks after infection, mice were given orally 0.1 or 1.0 microgram/kg of 1 alpha (OH)D3 or only medium solution every other day. Granulomatous livers were removed at 7, 9 and 11 weeks after infection, and ACE activity was measured in the granulomas isolated from each liver tissue using a fluorometric method. Oral administration of 0.1 or 1.0 microgram/kg/2 days of 1 alpha (OH)D3 for 4 weeks significantly enhanced ACE activity in the granuloma tissue. Since the DNA content relative to a unit weight of protein in the granulomas did not change with the 1 alpha (OH)D3 treatment, it is suggested that the elevated tissue ACE activity is due to an actual increase of the enzyme activity in each granuloma cell. The present observation may have relevance to sarcoid granulomas characterized by an increased tissue ACE activity, since macrophages from patients with sarcoidosis synthesize a biologically active hormonal form of vitamin D3. Namely hormonal form of vitamin D3 locally produced by macrophages is involved not only in systemic Ca++ metabolism but also in the stimulation of macrophages themselves to produce ACE in the granulomas.

Correlation between acetylator phenotypes and genotypes of polymorphic arylamine N-acetyltransferase in human liver.

Southern blot analysis was performed with genomic DNAs from 86 human subjects using the 32P-labeled cDNA for polymorphic arylamine N-acetyltransferase (EC 2.3.1.5) in human liver recently cloned in our laboratory. Three types of N-acetyltransferase gene were identified. Gene 1 contains a 5.5-kilobase (kb) KpnI fragment with a BamHI site; gene 2 contains a 5.5-kb KpnI fragment without a BamHI site; and gene 3 contains a 5.0-kb KpnI fragment with a BamHI site. The combination of these three genes generated five genotypes. Acetylator phenotypes were determined in 29 healthy volunteers by isoniazid loading tests, and they were classified as rapid (10 subjects), intermediate (16 subjects), or slow (3 subjects) acetylators. Rapid acetylators were homozygotes of gene 1. Intermediate acetylators were heterozygotes of either genes 1 and 2 or genes 1 and 3. There were two exceptional cases who were classified as intermediate acetylators but were homozygotes of gene 1. Slow acetylators were either heterozygote of genes 2 and 3 or homozygotes of gene 3. These results indicate that gene 1 corresponds to high N-acetyltransferase activity, while gene 2 and gene 3 give rise to low N-acetyltransferase activity.