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S Kasai

Publications and source records attributed to S Kasai.

At least 37 records · Page 2Linked to original sources
PubMed2001

Chromosome 13 locus, Pbd2, regulates bone density in mice.

Bone density is inherited as a complex polygenic trait. Previously, we identified two quantitative trait loci (QTLs) specifying the peak relative bone mass (bone mass corrected by bone size) on chromosomes (Chrs) 11 and 13 by interval mapping in two mouse strains: SAMP2 and SAMP6. The latter strain is an established murine model of senile osteoporosis and exhibits a significantly lower peak relative bone mass than SAMP2 mice. In this study, we report the effects of the Chr 13 QTL on peak bone density (Pbd2). First, we constructed a congenic strain P6.P2-Pbd2b, which carried a single genomic interval from the Chr 13 of SAMP2 on an SAMP6-derived osteoporotic background, to dissect this polygenic trait into single gene factors. This congenic strain had a higher bone density than the background strain using three measurement methods with different principles for bone density. Next, we measured the peak relative bone mass of the AKR/J strain and the 13 senescence-accelerated mouse (SAM) strains, which are considered to be a series of recombinant-like inbred (RI) strains derived from the AKR/J strain and other unspecified strains. We then determined the microsatellite marker haplotypes of these strains around the Pbd2 locus, in which three strains with a high relative bone mass shared the same haplotype over the 26-centimorgan (cM) region. In the Pbd2 locus, a high relative bone mass was associated with alleles of the unknown strain, whereas a low relative bone mass was associated with the alleles from the AKR/J strain. These results confirmed the existence of a Pbd2 locus regulating bone density in the SAM strains.

Alleles↗
PubMed2001

Prognostic significance of the labeling of Adnab-9 in pancreatic intraductal papillary mucinous neoplasms.

BACKGROUND: Pancreatic intraductal papillary mucinous neoplasms (IPMN), morphologically resembling colonic adenomas, often have an indefinable malignant potential. We used a monoclonal antibody (MAb) raised against colonic adenomas, Adnab-9, to identify patients with a better prognosis. METHODS: We assessed Adnab-9-labeled sections of these neoplasms from 50 patients, 13 pancreatic adenocarcinomas, and 32 colonic adenomas using standard immunohistochemical techniques. RESULTS: 26% of the IPMNs labeled with Adnab-9 as compared to 0% of pancreatic ductal cancers or surrounding benign tissues, (p < 0.001) and 53% of adenomas (p < 0.025). Labeling in IPMNs was usually seen in the noninvasive epithelium suggesting that Adnab-9 is a premalignant marker in these lesions. Labeling of invasive IPMN's identified a group of patients with a superior overall survival (p = 0.027). CONCLUSION: Adnab-9 labeling-characteristics appear similar for both IPMNs and adenomatous polyps, suggesting that they are analogous lesions. Adnab-9 labeling may also be a useful prognostic marker for invasive intraductal papillary mucinous neoplasms.

Adenocarcinoma, Mucinous↗
PubMed2001

[Health status and lifestyle issues of homeless people in Sapporo city, 2000].

OBJECTIVE: To clarify the health status and lifestyle issues of homeless people in Sapporo city, voluntary "health consultations and medical examinations" were carried out near an emergency kitchen. METHODS: The voluntary activities were held in a park near the shelter tents of homeless people seven times from December 1999 to December 2000. The homeless people who consulted us, medical doctors, were asked detailed questions about past history, present illness, subjective symptoms, lifestyles and so on, and were examined for their blood pressure and urinary parameter. RESULTS: A total of 60 homeless people, including 59 men and 1 woman, were consulted and examined, Fifty-seven percent of them were 50 years old of older, and 30% had been homeless for less than half a year. Forty percent had some dental problems, 28% suffered neck stiffness, and 27% back pain. The medical examination found 53% of them to be hypertensive and 26% to be diabetic. Twenty-five percent had meals only once a day, 55% had meat or fish in their diet not more than twice a week and 57% had vegetables in their diet not more than twice a week. Forty-two percent slept not more than 5 hours a day, 13% often drank alcohol in the daytime, and 83% were smokers. CONCLUSION: The present results suggest that lifestyle-related chronic diseases are more significant problems among homeless people in Sapporo city than common infectious diseases such as tuberculosis or dysentery, probably because it is colder and therefore there are fewer homeless people in Sapporo city than in other major cities in Japan such as Tokyo and Osaka. Further studies of the homeless people living in such a cold environment are warranted to develop better health policies for them in the context of their social and economical determinants. In addition, it is important to establish a more reliable registration system for these people in order to plan and provide a comprehensive social and health support network as needed.

Adult↗
PubMed2000

Immunoassay of the MRSA-related toxic protein, leukocidin, with scanning electrochemical microscopy.

Scanning electrochemical microscopy (SECM) was applied to the immunoassay of leukocidin, which is a toxic protein produced by methicillin-resistant Staphylococcus aureus (MRSA), with the intention of developing and early diagnostic for MRSA infection. An antibody-chip for leukocidin was prepared by self-assembling of anti-leukocidin on a protein A-coated glass substrate. A sample solution containing leukocidin was spotted onto the antibody-chip, followed by labeling with horseradish peroxidase (HRP) via a sandwich method. The reduction current of the oxidized form of ferrocenylmethanol generated by the HRP reaction was monitored to view SECM images of the spot of captured leukocidin. The amplitude of reduction current depended on the concentrations of sample solutions used for making spots. This SECM-based immunoassay detects as low as 5.25 pg mL(-1) leukocidin.

Electrochemistry↗
PubMed2000

Combined effects of tirapazamine and mild hyperthermia on anti-angiogenic agent (TNP-470) treated tumors-reference to the effect on intratumor quiescent cells.

PURPOSE: To evaluate the efficacy of the use of tirapazamine (TPZ), especially combined with mild hyperthermia (40 degrees C, 60 min), in the treatment of solid tumors following an anti-angiogenic treatment with TNP-470. In addition, we assessed the effect of TPZ and/or mild hyperthermia (MHT) combined with conventional radiotherapy or chemotherapy on TNP-470 treated tumors. MATERIALS AND METHODS: C3H/He mice bearing SCC VII tumors subcutaneously received TNP-470 at two doses of 100 mg/kg after tumor cell inoculation. At the same time, the tumor-bearing mice received 5-bromo-2'-deoxyuridine (BrdU) continuously for 5 days via implanted mini-osmotic pumps to label all proliferating (P) cells. The mice then received TPZ administration combined with or without MHT, gamma-ray irradiation combined with or without TPZ and/or MHT, or cisplatin injection with or without TPZ and/or MHT. Another group of mice received a series of test doses of gamma-rays while alive or after being killed to obtain hypoxic fractions (HFs) in the tumors at various time points after the above-mentioned cytotoxic treatment point. After each treatment, the tumors were excised, minced, and trypsinized. The tumor cell suspensions thus obtained were incubated with cytochalasin-B (a cytokinesis blocker), and the micronucleus (MN) frequency in cells without BrdU labeling (or quiescent [Q] cells) was determined using immunofluorescence staining for BrdU. The MN frequency in the total (P + Q) tumor cells was determined from the tumors that were not pretreated with BrdU. For the measurement of the HFs, the MN frequency of BrdU-unlabeled cells was then used to calculate the surviving fraction of the unlabeled cells from the regression line for the relationship between the MN frequency and the surviving fraction of total tumor cells. RESULTS: TPZ administration combined with TNP-470 treatment and MHT increased the MN frequency more markedly than treatment with TPZ alone, and this tendency was more remarkable in Q cells than total cells. In both total and Q cells, combined treatment with TPZ and MHT produced significant increases in MN frequencies whether gamma-rays were delivered to TNP-470 treated tumors or cisplatin was injected into the TNP-470 administered mice. Although not significantly, the HFs of total and Q cell populations within solid tumors increased after TNP-470 treatment. CONCLUSION: Combined treatment with TPZ and MHT, whether other cytotoxic treatments such as gamma-ray irradiation or chemotherapy using cisplatin were combined or not, was useful for sensitizing tumor cells in vivo including Q cells even after TNP-470 treatment.

Angiogenesis Inhibitors↗
PubMed2000

Molecular cloning, nucleotide sequence and gene expression of a cytochrome P450 (CYP6F1) from the pyrethroid-resistant mosquito, Culex quinquefasciatus Say.

To analyze cytochrome P450s in the southern house mosquito, Culex quinquefasciatus, we quantified the content of P450s and b5 in larval microsomes of guts and carcasses. Results indicated that content was 30 times higher in guts than in carcasses. A conserved region in the alignment of insect P450 family 6 (CYP6) proteins served as a guide for the synthesis of degenerate oligonucleotide primers to clone P450 cDNAs. Primers were used in the reverse transcription-polymerase chain reaction (RT-PCR) of gut mRNA from 4th-instar larvae of the permethrin-susceptible or resistant C. quinquefasciatus. PCR products of ca. 250 base pairs (bp) were cloned, and nucleotide sequences of 35 clones from susceptible and 28 from resistant strains determined. Alignment of the deduced amino acid sequences from these clones showed them to be classifiable into six isoforms. We next screened a cDNA clone (CYP6F1) from a gut cDNA library and determined the nucleotide sequence. Northern blot analysis showed that the CYP6PF1 gene in the permethrin-resistant strain appeared to be expressed more strongly than in the susceptible strain. The deduced amino acid of CYP6F1 showed that it has conserved domains of a membrane-anchoring signal, reductase binding sites, a heme-binding site, ETLR motif and substrate recognition sites in P450s. Phylogenetic analysis showed that CYP6F1 is strongly related to CYP6D1 involved in pyrethroid detoxification.

Amino Acid Sequence↗
PubMed2000

The cytoprotective role of lipopolysaccharide-induced nitric oxide against liver damage during early phase of endotoxemia in rats.

Lipopolysaccharide (LPS)-induced endotoxemia produces nitric oxide (NO); however, the role of the NO during endotoxemia is still controversial. The aim of this study was to investigate a role of LPS-induced NO during the early phase of endotoxemia. Wistar rats were intraperitoneally injected with saline or LPS at various doses (0.001, 0.01, or 5 mg/kg), and intra-abdominal NO concentration was determined by chemiluminescence before and after LPS administration at indicated times (1, 2, 6, 10, and 18 h). Serum aspartate aminotransferase and alanine aminotransferase levels were determined and histological examination was performed 10 h after LPS administration to assess liver damage. N(G)-nitro-L-arginine-methyl ester (L-NAME), a nonselective inhibitor of NO synthase, was used to investigate the possible roles of NO during LPS-induced endotoxemia. The intra-abdominal NO concentration was elevated within 2 h and reached a maximal level at 10 h after low doses of LPS injection (0.001 and 0.01 mg/kg) while liver damage was not observed. After high-dose LPS (5 mg/kg) administration, liver damage was observed and intra-abdominal NO was elevated continuously until 18 h. A time course study revealed very similar patterns of intra-abdominal NO increase after the three different dose of LPS at each times points during the first 10 h. Pretreatment of L-NAME inhibited the intra-abdominal NO release and aggravated the liver damage caused by low doses (0.001 and 0.01 mg/kg) of LPS as well as high dose (5 mg/kg) of LPS. Therefore, NO, released during the first 10 h after LPS injection, may play a cytoprotective role in the liver.

Alanine Transaminase↗
PubMed2000

A case of allergic urticaria caused by erythritol.

A case of allergic urticaria due to erythritol is herein reported. A 24-year-old female presented with severe wheals over her whole body. The urticaria occurred after she had drunk a glass of canned milk-tea. When the cause of her skin reaction was examined, it was found that the drink contained erythritol; this was determined to have caused her urticaria. Erythritol has recently been used as an artificial sweetener in many kinds of foods and drinks because it contains no calories. Food and drink additives should thus be included in the differential diagnosis of allergic urticaria.

Acute Disease↗
PubMed2000

Usefulness of tirapazamine as a combined agent in chemoradiation and thermo-chemoradiation therapy at mild temperatures: reference to the effect on intratumor quiescent cells.

C3H / He mice bearing SCC VII tumors received 5-bromo-2'-deoxyuridine (BrdU) continuously for 5 days via implanted mini-osmotic pumps to label all proliferating (P) cells. The mice then received one of six different DNA-damaging agents with or without mild temperature hyperthermia (40 degrees C, 30 min, MTH). These agents were adriamycin (ADM), mitomycin C (MMC), cyclophosphamide (CPA), bleomycin (BLM), cisplatin (CDDP), and tirapazamine (TPZ). After the drug treatment, the tumor-bearing mice were irradiated with a series of doses of gamma-rays. Immediately after irradiation, the tumors were excised, minced and trypsinized. The tumor cell suspensions thus obtained were incubated with cytochalasin-B (a cytokinesis blocker), and the micronucleus (MN) frequency in cells without BrdU labeling ( = quiescent (Q) cells) was determined using immunofluorescence staining for BrdU. The MN frequency in the total (P + Q) tumor cells was determined from the tumors that had not been pretreated with BrdU. MTH significantly increased the MN frequency of total cells in tumors irradiated with gamma-rays combined with CPA, BLM, CDDP or TPZ, and that of Q cells in tumors irradiated with gamma-rays combined with BLM or TPZ. The sensitivity difference in the MN frequency between total and Q tumor cells was significantly decreased by the combination with TPZ. TPZ combined with radiotherapy and TPZ combined with thermo-radiotherapy at mild temperatures appear to be promising modalities for sensitizing tumor cells in vivo, including Q tumor cells.

Animals↗
PubMed2000

Changes in the sensitivity of intratumor cells during fractionated tirapazamine administration.

Mice bearing solid tumors received 10 intraperitoneal administrations of 5-bromo-2'-deoxyuridine (BrdU) to label the proliferating (P) tumor cells. Then, as a priming treatment, tirapazamine (TPZ) was intraperitoneally administered. Further, 0 through 48 h later, the tumor-bearing mice received TPZ again at various doses. The tumor cells were isolated and incubated with a cytokinesis blocker. The micronucleus (MN) frequencies in cells with and without BrdU labeling, which were regarded as P and quiescent (Q) cells at the priming treatment, respectively, were determined using immunofluorescence staining for BrdU. The MN frequency in the total (P + Q) tumor cells was determined from the tumors that were not pretreated with BrdU. In addition, P cell ratios in the tumors at the second treatment were determined using immunofluorescence staining for P cell nuclear antigen. In each cell fraction, the longer the interval between the two treatments, the higher was the sensitivity to TPZ, except 1 h after the priming treatment. More than 24 h later, total and P cells, especially P cells, showed significantly higher sensitivity to TPZ than in the case of a single TPZ treatment. The longer the period between the two TPZ treatments, the lower was the P cell ratio at the second treatment. These findings were thought to indicate that the use of TPZ in the treatment of solid tumors causes a shift from the P to the Q state in vivo.

Animals↗
PubMed2000

Change in oxygenation status in intratumour total and quiescent cells following gamma-ray irradiation, tirapazamine administration, cisplatin injection and bleomycin treatment.

C3H/He mice bearing SCC VII tumours received 5-bromo-2'-deoxyuridine (BrdU) continuously for 5 days via implanted mini-osmotic pumps to label all proliferating (P) cells. The mice then received gamma-ray irradiation, or administration of tirapazamine (TPZ), cisplatin or bleomycin. At various time points after each treatment, tumour-bearing mice were irradiated with a series of test doses of gamma-rays, while alive or after being killed, to obtain hypoxic fractions (HFs) in the tumours. Immediately after gamma-ray test irradiation, the tumours were excised, minced and trypsinized. Tumour cell suspensions obtained were incubated with cytochalasin-B, a cytokinesis blocker, and the micronucleus (MN) frequency in cells without BrdU labelling (i.e. quiescent (Q) cells) was determined using immunofluorescence staining for BrdU. MN frequency in the total (P + Q) tumour cells was determined from the tumours that were not pre-treated with BrdU. MN frequency of BrdU-unlabelled cells was then used to calculate the surviving fraction of the unlabelled cells from the regression line for the relationship between the MN frequency and the surviving fraction of total tumour cells. TPZ and cisplatin reduced the HF after treatment, especially in Q cells, and this tendency was particularly marked with TPZ. In contrast, bleomycin increased the HF after treatment. Both reoxygenation following gamma-ray irradiation or bleomycin treatment and a subsequent return to pre-treatment levels of HF following TPZ or cisplatin treatment (rehypoxiation) occurred more rapidly in total (P + Q) cells than in Q cells. Based on our previous report that total (P + Q) and Q cells within this tumour have large acutely and chronically HFs, respectively, we conclude that acute hypoxic cells play a major role in reoxygenation and rehypoxiation in SCC VII tumours.

Animals↗
PubMed2000

Compactin suppresses bone resorption by inhibiting the fusion of prefusion osteoclasts and disrupting the actin ring in osteoclasts.

Compactin (mevastatin), which inhibits 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, and thus biosynthesis of cholesterol and the prenylation of proteins, inhibits osteoclastic bone resorption. Although it has been suggested that compactin inhibits bone resorption by inducing apoptosis of osteoclasts, the pathway by which compactin inhibits resorption has not been established. We investigated the effect of compactin on the differentiation of osteoclasts and the relationship between the morphological changes elicited by compactin and its inhibitory effect on bone resorption. Compactin inhibited the differentiation of osteoclasts, interfering with the fusion process by which prefusion osteoclasts (pOCs) develop into multinucleated osteoclast-like cells (OCLs), and also disrupted the actin ring of OCLs. The potency of compactin to inhibit fusion of pOCs and to disrupt the actin ring of OCLs corresponded to that of compactin to inhibit bone resorption. The effects of compactin were prevented by the addition of MVA lactone or its downstream products farnesylpyrophosphate (FPP) and geranylgeranyl-pyrophosphate (GGPP) but not by squalene. Apoptosis of OCLs was not induced by the concentration of compactin that inhibited fusion of pOCs and disrupted the actin ring. The normal process of pOC fusion and the integrity of the actin ring were restored by the withdrawal of compactin from the cultures after they had been treated with compactin for 24 h, but they were not restored by the addition of zVAD-fmk, a caspase inhibitor. Compactin also reversibly inhibited interleukin-1beta (IL-1beta)-, 1alpha,25-dihydroxyvitamin D3 (1 alpha,25(OH)2D3)-, and parathyroid hormone (PTH)-stimulated 45Ca release in bone organ cultures. Our results indicate that the inhibitory effects of compactin on bone resorption result from the inhibition of fusion of pOCs into OCLs and disruption of actin ring in OCLs and that apoptosis of OCLs is not necessary for these inhibitory effects of compactin. These effects of compactin are likely to be a consequence of the inhibition of prenylation of proteins that play an important role in the fusion of pOCs and in maintaining actin ring integrity in OCLs.

Actins↗
PubMed1999

Influence of non-ionic surfactants, pH and propylene glycol on percutaneous absorption of piroxicam from cataplasm.

The influence of pH in the formulation, ethylene oxide chain length of polyoxyethylene (POE) non-ionic surfactants and addition of propylene glycol (PG) on percutaneous absorption of piroxicam (Px) from cataplasm was investigated in guinea-pig in vivo. The area under the plasma concentration of Px curve until 8 h after the application (AUC(0-8)) increased with increasing the cataplasm base pH up to 6.5 and then plateaued from pH 6.5 to 7.2. Px solubility in water increased markedly with increasing pH from pH 6 as Px is a weak acid and its pK(a) is 5.3. The ionic form of Px in the cataplasm was suspected to contribute to the percutaneous absorption of Px. The percutaneous absorption of Px from the cataplasms containing 5% of POE non-ionic surfactants with various POE lengths were examined. The parabolic relation between the Px absorption and the POE length was observed. POE length from 5 to 15 enhanced percutaneous absorption to a greater extent. An attempt was also made to examine the influence of the addition of PG to the formulation containing POE (9) lauryl ether. The addition of 20% PG to the formulation significantly increased the Px concentration in plasma, compared to 0, 5, 10 and 15% PG. Skin and cutaneous muscle concentrations significantly increased by addition of 20% PG, compared to those by 0% PG but not in deeper muscle.

Administration, Topical↗
PubMed1999

House-fly cytochrome P450 CYP6D1: 5' flanking sequences and comparison of alleles.

CYP6D1 is a cytochrome P450 found in the house fly, Musca domestica. Expression is greater in pyrethroid-resistant vs. -susceptible strains and can be induced by phenobarbital in adult susceptible flies. CYP6D1 is expressed only in adult flies. To gain information about possible regulatory elements involved in CYP6D1 expression, and to confirm the gene sequence that was previously determined by polymerase chain reaction (PCR), we screened a house-fly library prepared with genomic DNA from the pyrethroid-resistant LPR strain. A CYP6D1v1 clone was isolated and sequenced. This clone contained 887 nucleotides 5' to the open reading frame and a previously unknown 2.4-kb intron. Using polymerase chain reaction with primers based on the CYP6D1v1 allele, the sequences 5' to the ORF were obtained from five pyrethroid susceptible strains. The transcription initiation site (TIS) was identified at the same position in LPR and two susceptible strains (86 nucleotides upstream from the translation start site). A comparison of the 5' flanking sequences revealed a high degree of similarity for most regions, although differences in the sequences were identified. The possible roles of these sequence differences in regulation of CYP6D1 expression are discussed.

Alleles↗
PubMed1999

Adenosquamous carcinoma of the rectum showing endocrine-cell differentiation: report of a case.

PURPOSE: Previous records of adenosquamous carcinomas with endocrinologic features rarely have been reported. Although the disease behaves in an extremely aggressive manner, chemotherapy after surgery has never been proposed. We used regional chemotherapy for treatment of unresectable liver metastases. METHODS: Hartmann colostomy was performed and 5-fluorouracil was infused into the hepatic artery for 15 weeks after the operation. RESULTS: Multiple liver metastases were present at the initial operation. Three months after the start of the chemotherapy, computed tomography showed that metastatic tumors in the liver had disappeared. The patient survived 18 months after the initial operation. CONCLUSION: This case report describes the first successful treatment with adjuvant regional chemotherapy of a patient who had an adenosquamous carcinoma with endocrine-cell differentiation in the rectum and liver metastases.

Aged↗
PubMed1999

Metastatic seeding of bile duct carcinoma in the transhepatic catheter tract: report of a case.

We describe herein the case of a 51-year-old woman in whom metastatic tumor seeding of the percutanenous transhepatic biliary drainage tract occurred following a pancreatoduodenectomy for carcinoma of the distal common bile duct. An abdominal computed tomography scan done 6 months after the initial operation detected a hepatic lesion located at the site of the previous percutaneous transhepatic biliary drainage tract. Implantation of bile duct carcinoma in the drainage tract was diagnosed, and the recurrent tumor was successfully resected by performing a subsegmentectomy of segment 3 and removal of the adjacent abdominal wall. At present, 5 years and 4 months after the second resection, the patient is in good health without any signs of recurrence. This case report demonstrates that an aggressive surgical approach should be performed for tumor seeding of a transhepatic biliary catheter tract.

Carcinoma, Squamous Cell↗