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Biomedical subjects

K Shiraiwa

Publications and source records attributed to K Shiraiwa.

At least 19 recordsLinked to original sources

Familial nesidioblastosis in two sisters.

We herein present two female siblings with persistent hyperinsulinemic hypoglycemia in the neonatal period who were diagnosed as having familial nesidioblastosis. Despite both the administration of diazoxide and the intravenous infusion of glucose, one of the affected infants died of severe metabolic acidosis at about 1 month of age, before pancreatectomy could be performed. The other, in whom the disorder was diagnosed early, also failed to respond to conservative medical treatment and ultimately required a 99% pancreatectomy for control of hypoglycemia. A third female sibling was normal. The possibility of familial nesidioblastosis should thus be considered in the case of neonatal intractable hypoglycemia to ensure a prompt diagnosis and allow for early surgical intervention when indicated. The relevant literature on this life-threatening disorder is also reviewed.

Adenoma, Islet Cell

Selective 8-hydroxyguanine formation in pancreatic DNA due to a single intravenous administration of 4-hydroxyaminoquinoline 1-oxide in rats.

8-Hydroxyguanine (8-OHG) formation, a possible initiating event, was determined in pancreatic and liver DNA and compared with the genesis of acinar cell and hepatocyte necrosis in male Wistar rats given a single intravenous administration of 4-hydroxyaminoquinoline 1-oxide (4-HAQO). At the non-necrotic but tumorigenic dose of 7.0 mg/kg body weight, 8-OHG was selectively generated in pancreatic DNA, in the absence of acinar cell necrosis, at the 6 and 24 h time points and repaired by the 48 h time point. When rats were exposed to 4-HAQO at a necrotic dose of 14.0 mg/kg body weight, 8-OHG was also selectively formed in pancreatic DNA with the same time-dependence of generation and repair, while acinar cell necrosis became evident at the 24 h time point and progressed thereafter. Whereas no hepatocyte necrosis was detected in any rats, 8-OHG values for liver DNA merely expressed slight increases only at the 24 and 48 h time points in rats given 14.0 mg/kg body weight of 4-HAQO. The present data suggest that formation of oxidative DNA damage, assayed by 8-OHG, in pancreatic DNA is independent from toxicity and may be involved, along with quinoline adducts, in mutational events underlying 4-HAQO-induced rat acinar cell carcinogenesis.

4-Hydroxyaminoquinoline-1-oxide

A solid and cystic tumor of the pancreas in a 10-year-old girl: report of a case and review of the literature.

We report herein the unusual case of a 10-year-old girl in whom a neoplasm developed in the head of the pancreas. Complete extirpation of the tumor was performed, which was histologically classified as a "solid and cystic tumor of the pancreas." Postoperative DNA analysis revealed a diploid pattern. The patient remains well with no sign of tumor recurrence 2 years after her operation. Thus, complete tumor extirpation without pancreatectomy is recommended for pediatric patients when there is no direct invasion to the adjacent organs or distant tumor metastasis.

Carcinoma, Acinar Cell

Different roles of 8-hydroxyguanine formation and 2-thiobarbituric acid-reacting substance generation in the early phase of liver carcinogenesis induced by a choline-deficient, L-amino acid-defined diet in rats.

The present study was performed to assess the roles of hepatocellular oxidative damage to DNA and constituents other than DNA in rat liver carcinogenesis caused by a choline-deficient, L-amino acid-defined (CDAA) diet by examining the effects of the antioxidant N,N'-diphenyl-p-phenylenediamine (DPPD). The parameters used for cellular oxidative damage were the level of 8-hydroxy-guanine (8-OHGua) for DNA and that of 2-thiobarbituric acid-reacting substance (TBARS) for constituents other than DNA. A total of 40 male Fischer 344 rats, 6 weeks old, were fed the CDAA diet for 12 weeks with or without DPPD (0.05, 0.10 or 0.20%) or butylated hydroxytoluene (BHT, 0.25%). In the livers of the rats, the numbers and sizes of glutathione S-transferase (EC 2.5.1.18) placental form (GSTP)- and/or gamma-glutamyltransferase (GGT, EC 2.3.2.2)-positive lesions and levels of 8-OHGua and TBARS were determined. The GSTP-positive lesions of 0.08 mm2 or larger were all stained positively for GGT as well in cross-sectional area, whereas the smaller lesions were generally negative for GGT. DPPD and BHT reduced the size of the GSTP-positive lesions without affecting their total numbers. At the same time, they reduced TBARS generation without affecting 8-OHGua formation in DNA. The present results indicate that oxidative DNA damage (represented by 8-OHGua formation) and damage to constituents other than DNA (represented by TBARS generation) may play different roles in rat liver carcinogenesis caused by the CDAA diet; the former appears to be involved in the induction of phenotypically altered hepatocyte populations while the latter may be related to the growth of such populations.

Animals

High incidence of hepatocellular carcinomas induced by a choline deficient L-amino acid defined diet in rats.

The carcinogenicities of a choline deficient L-amino acid defined (CDAA) diet and a semipurified choline deficient diet were comparatively examined. A total of 60 male Fischer 344 rats, 6 weeks old, were divided into 5 experimental groups each consisting of 12 rats. Group 1 received the CDAA diet chronically to the end of the 52-week experiment while Group 2 was given the same diet for the first 24 weeks and then a basal diet for the following 28 weeks. Groups 3, 4, and 5 received a choline supplemented L-amino acid defined diet, the semipurified choline deficient diet, and a semipurified choline supplemented diet, respectively, throughout the experimental period. All surviving rats were subjected to complete macroscopic examination at Week 52. Histopathologically diagnosed hepatocellular carcinomas were induced in Group 1 at an incidence of 100%; multiple metastatic nodules were seen in the lungs of one of the animals. Hepatocellular carcinomas were also induced in Group 4 rats at a significantly lower incidence of 20%. No hepatocellular carcinomas were observed in rats in Groups 2, 3, and 4. The results indicate that the CDAA diet exerts more potent carcinogenicity for the livers of rats than does the semipurified choline deficient diet. However, limited exposure for 24 weeks may have not been sufficient for hepatocellular carcinoma induction by the CDAA diet at Week 52 although a high incidence of hyperplastic nodules and slight cirrhosis were evidence of persistent lesions.

Amino Acids

Expression of the transin, c-fos, and c-jun genes in rat transplantable osteosarcomas and malignant fibrous histiocytomas.

The expression of the transin, c-fos, and c-jun genes was assessed in transplantable osteosarcomas and malignant fibrous histiocytomas, as well as in pancreatic duct adenocarcinomas and hepatocellular carcinomas of rats and hamsters. Northern blot analysis revealed that both an undifferentiated osteosarcoma of spontaneous origin (SOS) and 4-hydroxyaminoquinoline 1-oxide (4-HAQO)-induced malignant fibrous histiocytomas with metastatic potential to the lung showed remarkably increased expression of transin mRNA transcripts. This was not the case for the other tumors. Interestingly, levels of transin mRNA were lower in lung metastatic lesions than in primary subcutaneous SOS tumors. The primary SOS and MFH expressed both c-fos and c-jun genes in conjunction with the transin gene, whereas the non-transin expressers, a 4-HAQO-induced osteosarcoma (COS) and the pancreatic duct adenocarcinomas, demonstrated one or the other, but not both. These results suggest a possible involvement of transin expression in the progression of spontaneous osteosarcomas and 4-HAQO-induced malignant fibrous histiocytomas in rats. Expression of the c-fos and c-jun genes may play a regulatory role in this process.

4-Hydroxyaminoquinoline-1-oxide

Chronic toxicity carcinogenicity studies of triethanolamine in B6C3F1 mice.

The chronic toxicity and carcinogenic potential of triethanolamine was examined in B6C3F1 mice. Triethanolamine, dissolved in distilled water at levels of 0 (control), 1, and 2%, was given to groups of 50 males and 50 females ad libitum in drinking water for 82 weeks. Neoplasms developed in all groups, including the control group, but no dose-related increase of the incidence of any tumor was observed in treated groups of both sexes. There were no adverse effects as regards survival of the mice, organ weights, and specific incidence of neoplasms in the treated, compared to the control group. This chronic toxicity test provides no evidence of carcinogenic potential of triethanolamine in B6C3F1 mice.

Animals

Metastatic potential of malignant fibrous histiocytoma of myxoid or giant-cell subtype in rats.

We have previously reported on the induction of rat malignant fibrous histiocytomas by 4-hydroxiaminoquinoline 1-oxide. The present study describes cell number- and time-related formation of metastatic lung nodules after i.v. injection of cell suspensions containing various numbers (10(3) to 10(5)/ml) of myxoid or giant-cell subtype malignant fibrous histiocytoma cells. The metastatic potential of the myxoid subtype of rat malignant fibrous histiocytoma was significantly enhanced by i.v. injection of tumor cells selected from metastatic lung nodules and was further increased by repeating the selection procedure more than 7 times. In contrast, the growth activity of subcutaneous transplants of tumor fragments obtained from metastatic lung nodules derived from myxoid subtype did not differ from that of parent malignant fibrous histiocytomas.

4-Hydroxyaminoquinoline-1-oxide

[Treatment with extracorporeal shockwave lithotripsy (ESWL), endourology and dissolution for staghorn calculi composed of cystine: report of two cases].

Two cases of complete staghorn calculi composed of cystine that were treated with ESWL, endourology and dissolution are reported. After successful dissolution in vitro using tromethamine (pH 8-10), the same solution was used to irrigate the renal collecting system via nephrostomy tube for residual fragments after ESWL and/or endourology. One patient was treated with dissolution for 60 days, the other patient for 6 days. After this therapy, these patients became almost stone-free. Our experience demonstrates that the residual fragments after ESWL and/or endourology with staghorn calculi composed of cystine can be dissolved by tromethamine.

Adult

[Prophylaxis of recurrence of superficial bladder tumor by intravesical chemotherapy].

During the past 10 years, we have experienced 110 bladder tumor cases. Among them, 70 patients were diagnosed superficial bladder tumor. Of these 70 cases, 30 were treated with intravesical adriamycin (ADR) and peplomycin (PEP), 13 with ADR only and one case with PEP and remaining 26 with TUR and hydrostatic pressure technique. We studied the efficacy of combination intravesical chemotherapy with ADR and PEP and other treatments in the prevention of recurrence in the superficial bladder tumor cases. The recurrence rate during 3 years of each group, was 25% in the group treated with ADR and PEP, 35% with ADR and 55% in remaining group. 3 years recurrence rate in the group treated with ADR and PEP was significantly low than that in the group tread with TUR and hydrostatic pressure technique alone (Wilcoxon test). Side effects was pollakisuria, pain after micturition and others. Anaphylactic shock appeared in one case. From these results we concluded that intravesical chemotherapy with combined agents is more effective than that with a single one or no treatment after TUR.

Administration, Intravesical

[Transplantable osteosarcomas in rats. I. The growth behavior of spontaneous and 4-HAQO induced osteosarcomas in rats].

While there are a number of experimental animal models for osteosarcoma development, the available rat systems are limited both in number and applicability. The present report concerns our attempts to establish an appropriate rat model to allow development of new experimental approaches to human osteosarcoma. A spontaneously occurring osteosarcoma (J. H. 1-OS) was found in a 35 week old male rat. The tumor could be transplanted and grew well and although the bone forming activity decreased after the 18th generation, the growth potential remained high.

4-Hydroxyaminoquinoline-1-oxide

[Second generation shock wave lithotripsy: experience with the Siemens Lithostar].

In 1980, extracorporeal shock wave lithotripsy (ESWL) was incorporated as a nonsurgical method of stone removal in the cases of nephrolithiasis and rapidly found worldwide acceptance. Several devices commonly designated "second generation" lithotripters vs "first generation" Dornier HM3 are now under experimental or clinical trial. We report our clinical experience of ESWL using a Siemens Lithostar and compared it with that obtained using a Dornier HM3. One hundred patients were treated during the period of April through October, 1986 using an HM3, and 100 other patients were treated using a Lithostar from April to August, 1988. More cases were treated with a Lithostar than with a HM3. Nearly 10% of all patients treated by ESWL required additional therapeutic approaches (excepted ureteral stent) either with HM3 or Lithostar. However, in the cases of ureteral stone, with the Lithostar more cases required adjuvant procedures (TUL) than HM3. Significantly more shock waves were needed with Lithostar than HM3 for complete fragmentation of the same size of renal and ureteral stones. The stone-free rate during a one month period after ESWL was nearly the same for HM3 and Lithostar (HM3: 84.3%, Lithostar: 83.5%). Lithostar is a multifunctional lithotriptor which has most of the advantages required by the lithotripter.

Evaluation Studies as Topic

Comparative histochemical investigation of the glutathione S-transferase placental form and gamma-glutamyltranspeptidase during N-nitrosobis(2-hydroxypropyl)amine-induced lung carcinogenesis in rats.

Immunohistochemical staining using anti-rat glutathione S-transferase placental form (GST-P) rabbit antibody and enzyme histochemical staining for gamma-glutamyltranspeptidase (gamma-GT) were investigated in lesions appearing during lung carcinogenesis induced by N-nitrosobis(2-hydroxypropyl)amine (BHP) in rats. Rats were given BHP at a concentration of 2000 p.p.m. in drinking water, and were killed after 12 weeks of BHP intake, after 12 weeks of BHP intake followed by 12 weeks of tap water intake or after 20 weeks of continuous BHP intake. It was found that bronchiolo-alveolar hyperplasias, adenomas, adenocarcinomas, squamous metaplasias and squamous cell carcinomas had been induced by BHP. All of the squamous metaplasias and squamous cell carcinomas were shown to stain with GST-P but not with gamma-GT. On the other hand, the hyperplasias, adenomas and adeno-carcinomas stained with gamma-GT to various degrees and in different areas, but did not stain with GST-P. The incidence of gamma-GT phenotype and the average percentage of gamma-GT-positive areas in hyperplasias and adenomas suggested that adenocarcinomas might develop from hyperplasias and adenomas. These results suggest that GST-P is a marker for squamous lesions while gamma-GT is a marker for adenomatous lesions in rat lung carcinogenesis. Furthermore, squamous metaplasias appear to be preneoplastic lesions of squamous cell carcinomas while gamma-GT-positive hyperplasias or adenomas are preneoplastic lesions of peripheral adenocarcinomas.

Adenocarcinoma

Transplantable osteosarcomas with high lung metastatic potential in Fischer 344 rats.

Both spontaneous (SOS) and 4-hydroxyaminoquinoline 1-oxide (4-HAQO)-induced osteosarcomas (COS) could be serially transplanted in the subcutaneous back space of syngeneic F344 rats, the success rate becoming 100% within 5 passage generations. Transplanted tumors demonstrated rapid growth and displayed high potential for metastasis to the lung in later generations. Thus, a 100% lung metastasis rate was observed for SOS after the 20th and for COS after the 14th generation. The histological features of the primary SOS and COS were retained during serial transfer. These model systems should be useful for investigation of the biology of this very important tumor type.

4-Hydroxyaminoquinoline-1-oxide

Preventive effect of 3-aminobenzamide on the reduction of NAD levels in rat liver following administration of diethylnitrosamine.

Nicotinamide adenine dinucleotide is utilized as the substrate of a chromatin-bound enzyme, poly(ADP-ribose) polymerase. The effects of diethylnitrosamine and/or 3-aminobenzamide, a potent inhibitor of poly(ADP-ribose) polymerase, on the cellular NAD levels in rat liver were investigated. 3-Aminobenzamide (600 mg/kg) administered intraperitoneally was not detectable in the liver within 12 hr after administration; the inhibitor had a calculated half life of 90 min. Diethylnitrosamine reduced the NAD levels in rat liver in a dose-dependent way. The NAD content reached a minimum level at 8 hr, returning to 78% of the control value after 48 hr. The reduction of the NAD levels caused by diethylnitrosamine was completely prevented when 3-aminobenzamide was administered either simultaneously with diethylnitrosamine or 4 hr after diethylnitrosamine treatment. Furthermore, an immunohistochemical study showed that nuclear poly(ADP-ribose) decreased 1 hr after the administration of 3-aminobenzamide. These results suggest that inhibition of poly(ADP-ribosyl)ation is involved in the initiation of liver carcinogenesis by diethylnitrosamine and 3-aminobenzamide.

Animals

Studies of carcinogenicity of sodium chlorite in B6C3F1 mice.

The carcinogenic activities of sodium chlorite in B6C3F1 mice were examined. Sodium chlorite was given at concentrations of 0 (control), 0.025% (low dose), or 0.05% (high dose) in the drinking water of 150 female and 150 male mice for 80 weeks, after which time the animals were returned to distilled water without sodium chlorite. All mice were sacrificed 85 weeks from the beginning of the experiment. The incidence of tumor-bearing animals was 32% (control), 34% (low dose), and 26% (high dose) in female mice, and 46% (control), 57% (low dose), and 53% (high dose) in male mice. The types and incidence of neoplasms that occurred frequently in each group of both sexes were similar to those observed spontaneously in B6C3F1 mice. The incidence of lymphomas/leukemias in the high dose group of females (2%), however, was lower than that in the control group (15%). Furthermore, the incidence of pulmonary adenomas in the high dose group of males (12%) was higher than that in the control group (0%), but neither dose-related increases in the adenoma incidences nor increased incidences of the adenocarcinomas were observed. These results indicated no clear evidence of a carcinogenic potential of sodium chlorite in B6C3F1 mice.

Animals