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Biomedical subjects

T Shirai

Publications and source records attributed to T Shirai.

At least 379 records · Page 21Linked to original sources

Inhibitory effect of chlorophyllin on PhIP-induced mammary carcinogenesis in female F344 rats.

Chlorophyll and chlorophyllin, a water-soluble salt of chlorophyll, have been reported to inhibit carcinogen-DNA binding and exert antimutagenic activity for some carcinogenic heterocyclic amines and aflatoxins. In the present experiment, the possible inhibitory effects of chlorophyllin on 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP) carcinogenicity were investigated. Female F344 rats were administered both PhIP, 0.02% in the diet, and chlorophyllin, 1%, in the diet (group 1), or either PhIP (group 2) or chlorophyllin (group 3) alone for 54 weeks. The incidence of mammary adenocarcinomas induced by PhIP was reduced by chlorophyllin co-administration from 40% (8/20 rats) to 15% (3/20). While the difference was not statistically significant, the multiplicity of adenocarcinomas was significantly (P < 0.05) reduced by chlorophyllin co-administration from 0.50 per animal to 0.15. On the other hand, incidence of colon adenomas was slightly, but not significantly, increased from 10% to 20%. Neither mammary nor colon adenocarcinomas were observed in group 3. Thus, chlorophyllin reduced PhIP mammary carcinogenesis, suggesting that chlorophyllin is an effective chemopreventor when ingested simultaneously with the carcinogen.

Animals↗

Prevention of autoimmune symptoms in autoimmune-prone mice by elimination of B-1 cells.

Our recent studies on an autoantibody-transgenic mouse line demonstrated that peritoneal B-1 cells are responsible for autoimmune symptoms. However, whether B-1 cells in the peritoneum are generally involved in the pathogenesis of autoimmune disease remains controversial. To test the possible involvement of peritoneal B-1 cells in autoimmune symptoms of autoimmune-prone NZB mice, we eliminated the peritoneal cells by hypotonic shock with repeated i.p. injection of distilled water every 7 days into neonatal or 8-week-old NZB mice. By this treatment, B-1 cells, which self-renew within the peritoneal cavity, are expected to be preferentially eliminated, while other peritoneal cells can be easily supplied from bone marrows after this treatment. Indeed, in distilled water-treated old NZB mice, the number of B-1 cells decreased in spleen as well as in lamina propria of the gut but the numbers of conventional B cells and T cells did not change. Moreover, the production of autoantibodies against erythrocytes significantly decreased and the occurrence of autoimmune hemolytic anemia was reduced in 12-month-old treated NZB mice. Similarly, the elimination of peritoneal cells of NZB/NZW (NZB/W) F1 mice by water injection decreased anti-DNA IgG antibodies in the sera and reduced the pathological changes of the kidney. These results suggest that peritoneal B-1 cells may be a source of autoantibody-producing cells in autoimmune diseases of NZB and NZB/W F1 mice.

Anemia, Hemolytic, Autoimmune↗

Food restriction inhibits an autoimmune disease resembling systemic lupus erythematosus in (NZB x NZW) F1 mice.

To investigate the beneficial effects of food restriction on systemic lupus erythematosus in NZB x NZW F1 mice, we separated the mice into three groups. One was fed a diet in which total food intake was reduced to 60% of normal from age 2 mo onward, while the animals were still healthy (group 2R). A second group was selected at age 7 mo based on a positive lupus nephritis (proteinuria) and fed the 40% restricted diet thereafter (group 7R); a third group was allowed to consume food ad libitum (control). All control mice died of renal disease by age 14 mo, whereas all mice in group 2R and 80% of those in group 7R were living at that age. Measurements of anti-double stranded DNA antibody concentrations in sera and in supernatants of in vitro spleen cell cultures revealed that the production of the immunoglobulin G, but not immunoglobulin M, class of antibodies was markedly and significantly reduced in food-restricted mice. Age-associated changes in lymphocyte subsets seen in control mice, i.e., increases in B:T and CD4:CD8 T cell ratios, decreases in NTA260+ T cell subsets, and increases in aberrant activated NTA204+CD4+ T cells and cycling cells, were all significantly lessened in underfed mice. Food restriction did not suppress the secondary acquired antibody responses to a foreign antigen. Thus, the beneficial effects of food restriction in these mice may be related to the lessening of the age-related onset of T cell subset abnormalities, including activation of autoreactive T cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Eradication of Helicobacter pylori with lansoprazole, amoxicillin, and plaunotol in duodenal ulcer patients.

Helicobacter pylori eradication therapy combining amoxicillin (AMPC), plaunotol (PL), and a proton pump inhibitor (PPI) was examined as an alternative to triple therapy, which has a high rate of side effects and low patient compliance. Thirty-two H. pylori-positive patients (24 men, 8 women) with duodenal ulcers were examined. The diagnosis of H. pylori infection was made by the urease test on specimens biopsied from two sites in the stomach. Simultaneously, the IgG antibody against H. pylori was measured by the EIA method. The therapeutic regimen was lansoprazole (LPZ) 30 mg q.d. (6 weeks) and AMPC 1,500 mg t.i.d. (2 weeks) plus PL320 mg b.i.d. (6 weeks). The rate of ulcer healing was judged endoscopically after 6 weeks. Cases that become urease-negative after the cessation of the therapy were defined as having achieved clearance, and those negative after 1 month as eradication. Within 6 weeks, 31 of 32 patients had healed ulcers. All patients were H. pylori antibody-positive before therapy. The clearance rate was 71.9% (23/32) and the eradication rate was 45.8% (11/24). Adverse effects were observed only in one case. We conclude that combination therapy with LPZ, AMPC, and PL has a high therapeutic effect on ulcer healing and moderate effectiveness for eradication of H. pylori.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Usefulness of hard palate mucosa graft as nasal lining in alar reconstruction.

A hard palate mucosa graft was used as nasal lining for alar reconstruction in six patients. In five of the six patients, the "take" of the graft was complete. The nasal cavity was reconstructed satisfactorily, and no nasal obstruction was observed and no collapse of the nasal cavity was found in breathing because of the stiffness and thinness of the grafted mucosa. None of the patients suffered from erosion or irritation of the graft during the postoperative period. The palate donor site healed in 3 to 5 weeks, and no irritation or ulceration was seen after the healing. The hard palate mucosa can be considered as a lining material in alar reconstruction.

Aged↗

Localized cutaneous amyloidosis simulating lichen simplex chronicus.

We report a case of localized cutaneous amyloidosis in a 42-year-old Japanese woman. Skin lesions were confined to the nuchal area, and the clinical appearance resembled that of lichen simplex chronicus. Our experience with this case indicates that, in cases presenting with persistent skin lesions simulating lichen simplex chronicus, amyloid should be specifically looked for in biopsy material.

Adult↗

Induction of the 72-kD heat shock protein in human skin melanoma and squamous cell carcinoma cell lines.

Heat shock proteins (HSPs) or stress proteins comprise a characteristic group of proteins synthesized in cells exposed to heat or other environmental stimuli. Of the many HSPs, the 72-kD heat shock protein (HSP72) is the most stress-inducible one. In the present study, we examined the effects of heat, chemicals (azetidine and sodium arsenite), ultraviolet (UV) light, and gamma-ray irradiation on the induction of HSP72 in cultured human skin melanoma cell lines (P-39 and G-361), a human skin squamous cell carcinoma cell line (HSC-1), and an SV40-transformed human lung fibroblast cell line (WI38VA13) as a control. In these cell lines, heat treatment induced HSP72 more rapidly and intensely than did chemical exposure. Compared with the SCC cell line, the two melanoma cell lines produced less HSP72 with heat treatment. UVC irradiation (20 J/m2) induced HSP72 only in the WI38VA13 cells. After gamma-ray irradiation, no HSP72 induction was detected in any of the cell lines examined. These observations suggest that, in cultured cells, inducibility of HSP72 depends not only on the inducer but also on the origin of each cell line.

Arsenites↗

Site-specific effects of testosterone propionate on the prostate of rat pretreated with 3,2'-dimethyl-4-aminobiphenyl: dose-dependent induction of invasive carcinomas.

It has been shown that testosterone propionate (TP) strongly promotes induction of invasive carcinomas in previously initiated accessory sex organs. In this study, in order to clarify the dose-dependence of this promotion, TP was given at 3 different levels (high, medium or low doses) using different sizes (2, 1 and 0.5 cm long) of Silastic tube for 40 weeks after administration of 3,2'-dimethyl-4-aminobiphenyl to male F344 rats. The data showed development of invasive carcinomas in the dorso-lateral and anterior prostate and in the seminal vesicle to be dose-dependent with the high dose of TP being most effective for tumor induction. Average levels of serum testosterone were approximately 800, 600, 300 and 150 ng/dl in rats given the high to low doses and in control rats, respectively. Development of neoplastic lesions in the ventral prostate demonstrated an inverse dependence on the dose of TP. These findings, together with previous data, suggest that the tumor-promoting potential of TP on rat prostate is unlikely to be simply due to its androgenic action and other factors should also be considered.

Aminobiphenyl Compounds↗

Hepatocyte growth factor enhancement of preneoplastic hepatic foci development in rats treated with diethylnitrosamine and N-ethyl-N-hydroxyethylnitrosamine.

Effects of hepatocyte growth factor were investigated in a two-stage rat liver carcinogenesis protocol. Male F344 rats were first treated with diethylnitrosamine (200 mg/kg, i.p.) and then, starting two weeks later, with N-ethyl-N-hydroxyethylnitrosamine (EHEN) for 6 weeks at a dose of 0.01% in drinking water. Hepatocyte growth factor, which was injected i.v. at a dose of 200 micrograms/kg body weight one (at week 3) or two times (at weeks 3 and 4) during EHEN administration, significantly increased the development of preneoplastic glutathione S-transferase placental form-positive foci. Although the observed effects of hepatocyte growth factor were weaker than that of the two-thirds partial hepatectomy (PH) performed at week 3, the present results suggest that the enhancing effects of PH performed during the promotion stage may be largely mediated through induction of hepatocyte growth factor.

Animals↗

Modification by analgesics of lesion development in the urinary tract and various other organs of rats pretreated with dihydroxy-di-N-propylnitrosamine and uracil.

Effects of the analgesics phenacetin, acetaminophen and antipyrine on lesion development in the urinary tract and other organs in male F344 rats were investigated. Animals were concurrently administered with 0.1% dihydroxy-di-N-propylnitrosamine (DHPN) in drinking water and 3.0% uracil in the diet for 4 weeks and then, starting 1 week after the cessation of this treatment, received basal diet or diet containing phenacetin, acetaminophen or antipyrine for 35 weeks. The occurrences of renal cell tumors were increased in the groups given phenacetin or antipyrine, as compared with the DHPN + uracil alone controls. Antipyrine, but not the two other compounds, also enhanced development of hyperplastic lesions in the renal pelvis and ureter. In the urinary bladder, phenacetin and antipyrine treatments were both associated with increased incidence of preneoplastic or neoplastic lesions. Furthermore, phenacetin alone, without the initiating agent pretreatments, induced simple hyperplasias of the urinary bladder at high incidence. Antipyrine enhanced induction of hyperplastic lesions in the ureter and was also found to increase the incidences of preneoplastic and neoplastic lesions in the liver. Although decreased incidences of tumor development of lung and thyroid were observed for the group given phenacetin, this might have been linked to the decreased weight gain. The results confirmed that combination treatment with DHPN + uracil is effective for wide-spectrum initiation of carcinogenesis in the urological tract and demonstrated significant modification potential for both phenacetin and antipyrine.

Acetaminophen↗

Anti-Ro/SSA-associated annular erythema in childhood.

We report four children with anti-Ro/SSA positive who presented with an annular erythema as a manifestation of Sjögren's syndrome. One patient had an aseptic meningoencephalitis as well as cutaneous lesions. Children with annular erythema should be carefully followed for features of Sjögren's syndrome, which is believed to be a rare condition in children.

Adolescent↗

Aberrant insulinoma of the duodenal bulb.

A rare insulin-immunoreactive neuroendocrine tumor of the duodenum in a 54 year old male is reported. The incidentally identified tumor was located on the anterior free wall of the duodenal bulb and measured approximately 6 mm in diameter. Uncomplicated endoscopic resection of the tumor was carried out. The lesion exhibited classic histologic features of insulinoma of the beta-islet cell type with stromal amyloid deposition. In addition to positive reactivities of chromogranin A, neuron-specific enolase, synaptophysin, Leu 7 (CD57), cystatin C, CA15-3 and cytokeratin, the non-argyrophilic tumor cells were strongly immunoreactive for insulin and C-peptide. The stromal amyloid was clearly labeled for amylin. A few cells were stained for somatostatin, whereas other hormones were negative. Interestingly, a few isolated insulin-positive cells were identified in the non-neoplastic duodenal mucosa in the proximity of the tumor. Immunoelectron microscopy using paraffin sections disclosed insulin-immunoreactive secretory granules in the cytoplasm. The patient exhibited no signs or symptoms of hypoglycemia. Serum insulin levels were not measured prior to resection. No tumors were demonstrated in the pancreas. Magnetic resonance imaging revealed a 1 cm asymptomatic pituitary mass, in association with moderately elevated serum prolactin levels. The patient is currently being followed up in the outpatient clinic.

Duodenal Neoplasms↗

The etiology of bladder cancer--are there any new clues or predictors of behavior?

It is well documented that the etiology of bladder cancer involves environmental factors. Most chemical carcinogens probably affect the urothelial cells via their presence in the urine. As an important cofactor, cell proliferative activity may be increased by urinary bladder infection, irritation by bladder stones or through the action of a variety of endogenously produced direct acting chemicals or agents. Among the known causative factors, avoidable major ones are occupational exposure to certain chemicals such as benzidine and 4-aminobiphenyl, cigarette smoking and bilharzial infection, which could be eradicated by a combination of praziquantel, antihelminth therapy, education and improvements in social welfare. An anticarcinogenic drug, cyclophosphamide, used as an immunosuppressive agent also seems to be associated with a high risk of idiopathic induction of bladder cancer and physicians should therefore pay particular attention to its diverse effects when considering its prescription. In contrast to the above, the consumption of coffee and tea including artificial sweeteners is now thought unlikely to be major risk. So far there is no good biochemical tool to predict individual exposure to bladder carcinogens/or relative risk of bladder cancer development. However, acetylation capacity can be applied to assess susceptibility to carcinogenic amines in people exposed in their working environment. Progress in molecular biological analysis will hopefully bring to light etiology-specific DNA damage in the bladder tumors and prove useful for prediction of tumor behavior in the near future.

Diet↗

Risk factors for stroke following coronary bypass surgery.

Improvements in surgical technique and advances in myocardial protection have resulted in low rates of morbidity and mortality despite a greater incidence of high-risk patients. Noncardiac morbidity prolongs hospital stays and increases the costs of cardiac surgery. This study examines the preoperative predictors of stroke following isolated coronary bypass surgery. The clinical records of 3910 consecutive patients who underwent isolated coronary bypass surgery at the University of Toronto were reviewed. Stepwise logistic regression identified six independent predictors of stroke following CABG (percent in parentheses) and calculated factor adjusted odds ratios (OR) for each risk factor. Triple vessel coronary artery disease was the most important predictor (1.9%, OR 5.71), followed by normothermic systemic perfusion (3.8%, OR 4.85), age > 70 years (3.2%, OR 3.88), a previous history of transient ischemic attacks or stroke prior to surgery (6.1%, OR 3.7), peripheral vascular disease (4.7%, OR 2.77), and diabetes mellitus (2.6%, OR 2.01). The mechanism of stroke is likely different between these high-risk groups and strategies to prevent postoperative stroke should focus on the mechanisms responsible in high-risk patients.

Aged↗