Biomedical subjects

A Sasaki

Publications and source records attributed to A Sasaki.

At least 145 records · Page 8Linked to original sources

PubMed1999

Pigmented squamous cell carcinoma with dendritic melanocyte colonization in the external auditory canal.

A case of pigmented squamous cell carcinoma (SCC) with dendritic melanocyte colonization in the external auditory canal is reported and the previous cases are reviewed. A 65-year-old Japanese female was referred with a 7-year history of otitis. The patient also had a darkly pigmented 9 x 8 mm nodule in the external auditory canal. Microscopically, the tumor was SCC, but in some areas melanin pigments were found in the cytoplasm of the tumor cells. The tumor was thus diagnosed as pigmented SCC. As well as the tumor cells, dendritic-shaped cells colonized the tumor parenchyma and were immunohistochemically defined as melanocytes. The authors believe this is the first case of pigmented SCC with dendritic melanocyte colonization in the external auditory canal.

Aged↗

PubMed1999

Familial gastric cancer: clinicopathological characteristics, RER phenotype and germline p53 and E-cadherin mutations.

Gastric cancer frequently occurs in family members with hereditary non-polyposis colorectal cancer (HNPCC) and Li-Fraumeni syndrome (LFS) and germline E-cadherin mutations were recently identified in a subset of familial gastric cancers. Thus, families with an aggregation of gastric cancers were recruited by reviewing the genealogical trees of 3632 patients with gastric cancer. The criteria for recruiting such families were the following: at least three relatives should have gastric cancer and one of them should be a first degree relative of the other two; at least two successive generations should be affected; in one of the relatives gastric cancer should be diagnosed before age 50. Thirty-one cases (0.9%) fitted all three of these criteria. There were only gastric cancer patients in 18 of the 31 families and there were no families that fitted clinical criteria of HNPCC or LFS. Paraffin-embedded tissues were available in 29 probands and DNA was successfully isolated for molecular analyses in 13 probands. RER phenotype was detected in three (23%) cases, whereas germline p53 mutations were detected in none of 13 cases. A germline E-cadherin mutation was detected in one of three diffuse types and none of 10 intestinal types, however, a mutation resulting in the replacement of Gly by Val was detected in the precursor sequence. Thus, although familial clustering of gastric cancer occurs in approximately 1% of gastric cancer patients, germline mutations of the DNA mismatch repair, p53 and E-cadherin genes do not significantly contribute to such a clustering.

Adolescent↗

PubMed1999

Partial purification and characterization of a novel endo-beta-mannosidase acting on N-linked sugar chains from Lilium longflorum thumb.

An enzyme catalyzing the hydrolysis of the Manbeta1-4GlcNAc linkage of N-linked sugar chains was partially purified and characterized. Endo-beta-mannosidase activity was detected using pyridylaminated (PA-) Manalpha1-6Manbeta1-4GlcNAcbeta1-4GlcNAc as the substrate in a homogenate of lily flowers (Lilium longflorum Thumb). The enzyme was partially purified by ammonium sulfate precipitation, and Q-Sepharose, Superdex 200, hydroxyapatite, Poros PE/M, Mono Q, and Superdex 200 column chromatographies. The optimum pH was 5.0 and the estimated molecular weight of the enzyme was 78,000, as determined by gel filtration. The Km value found for Manalpha1-6Manbeta1-4GlcNAcbeta1-4GlcNAc-PA was 1.4 mM. The enzymatic activity was not influenced by the addition of 10 mM EDTA or 2 mM Ca2+. Experiments on the hydrolysis of several PA-N-linked sugar chains revealed that the enzyme hydrolyzed MannManalpha1-6Manbeta1-4GlcNAcbeta1-4GlcNAc-PA (n = 0-2) into a mixture of MannManalpha1-6Man and GlcNAcbeta1-4GlcNAc-PA, indicating that it is an endoglycosidase in nature. However, the enzyme did not hydrolyze beta1-4mannohexaose or p-nitrophenyl beta-mannopyranoside.

Carbohydrate Metabolism↗

PubMed1999

Morules with biotin-containing optically clear nuclei in colonic tubular adenoma.

Morules have been reported in pulmonary endodermal tumors (PET) resembling fetal lung, in thyroid carcinoma, and in endometrial and colonic neoplasms. A morule has biotin-containing optically clear nuclei (OCN) in PET and thyroid carcinoma. Biotin-containing OCN have been also reported in endometrial tissue during pregnancy and in endometrioid carcinoma of the ovary, and it has been postulated that morules or OCN develop under the influence of female sex hormones. The authors report here the first case, to their knowledge, of morules with OCN in a colonic adenoma from a 68-year-old man. The colonic polyp consisted of ordinary tubular adenomatous tissue and morules. Many cells in the morules contained OCN. The OCN were immunopositive for biotin and reacted with streptavidin. The neoplastic cells in the morules were immunopositive for oncofetal antigens. Serum levels of female sex hormones were within the normal range, and no cells in the adenoma were immunopositive for receptors for progesterone and estrogen. The results indicate that OCN are rich in biotin and that morules may be embryologically immature elements that develop independently of influence by female sex hormones.

Adenoma↗

PubMed1999

Subpicosecond pulse laser absorption by an overdense plasma with variable ionization.

Transient ionization of an overdense plasma produced by a subpicosecond, p-polarized obliquely incident pulse laser of moderate intensity (10(16)-10(18) W/cm(2)) changes the plasma heat transfer via processes dominated by the return current and the absorption rate via ion acceleration. To explore the effect of variable ionization, a hybrid one-dimensional electro-magnetic particle-in-cell method that conforms to a direct solution of the Fokker-Planck-Landau equation is applied. A method that includes the Langevin equation to account for Coulomb collisions and the average ion model to calculate the nonlocal thermodynamic equilibrium ionization balance provides good agreement between the computed absorption and the measured results.

Journal Article↗

PubMed1999

Direct spectroscopic observation of multiple-charged-ion acceleration by an intense femtosecond-pulse laser.

We have observed evidence of the emission of energetic He-and H-like ions of fluorine more than 1 MeV produced via the optical field ionization (OFI) from a solid target irradiated by an intense I=(2-4)x10(18) W/cm(2) (60 fs, lambda=800 nm), obliquely incident p-polarized pulse laser. The measured blue wing of He(alpha), He(beta), and Ly(alpha) lines of fluorine shows a feature of the Doppler-shifted spectrum due to the self-similar ion expansion dominated by superthermal electrons with the temperature T(h) approximately 100 keV. Using a collisional particle-in-cell simulation, which incorporates the nonlocal-thermodynamic-equilibrium ionization including OFI, we have obtained the plasma temperature, line shape, and maximal energy of accelerated ions, which agree well with those determined from the experimental spectra. The red wing of ion spectra gives the temperature of bulk plasma electrons.

Journal Article↗

PubMed1999

Medical cost for disability: a longitudinal observation of national health insurance beneficiaries in Japan.

OBJECTIVES: To measure the impact of disability on the use of medical care and its costs. DESIGN: A 1-year prospective cohort study of National Health Insurance beneficiaries in a rural Japanese community. Their physical function was examined by the Medical Outcomes Study questionnaire at the end of 1994; medical care and its costs were then monitored for 1 year. SETTING AND PARTICIPANTS: Participants were the 49,364 subjects, aged 40 to 79 years, who were beneficiaries of National Health Insurance and lived in the catchment area of Ohsaki Public Health Center, Miyagi, Japan. The subjects were mainly farmers, self-employed persons, housewives, or pensioners. MEASUREMENTS: Medical care utilization (number of outpatient visits and days of inpatient care) and the costs for each subject were obtained from National Health Insurance Claim History files. These measurements were collected from January to December 1995, and the relationship between physical functioning levels and medical costs was analyzed. RESULTS: The medical costs per capita increased with poorer physical function. Medical costs among those with limitations in performing self-care increased by 4 times in men and 3 times in women compared with those with no functional limitation. In this cohort, the 4.3% of the subjects who were dependent in self-care used 15% of the total inpatient days and 10% of the total medical costs. CONCLUSION: Treatment of patients with disability requires a huge amount of medical resources. There is an urgent need for cost-effective intervention programs for disability prevention, which could be offset against the cost for treating the disabled.

Activities of Daily Living↗

PubMed1999

[Prevention of diabetes mellitus].

Diabetes mellitus is one of the most common chronic diseases in the developed countries and is a major cause of blindness, renal failure or amputations, all of which require expensive health-care resources. Diabetes is also associated with the increased risk of cardiovascular and cerebrovascular diseases and a substantial reduction in life expectancy. Therefore, prevention of diabetes is desirable. Recently, epidemiological studies have provided a basis of understanding the environmental determinants of diabetes and several prospective studies have shown that in the aggregate, intensive therapy improves health-care status by improving not only microvascular disease but also macrovascular disease in both type 1 and type 2 diabetes.

Diabetes Mellitus↗

PubMed1999

[A case of coronary artery bypass grafting in a patient who has a rosary-like coronary lesion with Buerger's disease].

We report a case of coronary artery bypass grafting using left intra thoracic artery (LITA) in a 63-year-old male with Buerger's disease. His coronary angiography showed a long lesion seemed rosary in the left anterior descending (LAD). At operation, the surface of the coronary artery was dark red with white speckles. The LAD was opened distal end of disease, the intima of the coronary artery made much soft thin fold. The disease was never atheromatous. His coronary angiography showed a very rarely finding that seemed rosary.

Coronary Artery Bypass↗

PubMed1999

[Intraperitoneal administration of a combined CDDP, 5-FU and MMC therapy for pseudomyxoma peritonei].

Pseudomyxoma peritonei, which is the seeding of the peritoneum by mucin-secreting metastatic deposits and the filling of the peritoneal cavity by these secretions, is a malignancy that even after excision of the metastatic areas has a poor prognosis, since no effective therapy has yet been established. Herein, we report five cases of pseudomyxoma peritonei that responded to a combined postsurgical therapy consisting of CDDP, 5-FU and MMC. A 59-year-old women had a complete response who underwent an appendectomy, a right ovariectomy, and an omentectomy due to pseudomyxoma peritonei, and was postoperatively given a 50 mg intraperitoneal administration of CDDP. Further, a subcutaneous implant-type reservoir was positioned intraperitoneally for postoperative chemotherapy. At 14 days after surgery, therapy was begun which consisted of CDDP (70 mg/m2/day 1), 5-FU (350 mg/m2/day 1) and MMC (6 mg/m2/day 1) administered intraperitoneally, and 5-FU (350 mg/m2/day 1-3) that was continuously infused by an intravenous drip. She received 4 courses of postoperative chemotherapy. As a result of this therapy, the serum CEA values, which had elevated postoperatively, fell to within their respective normal ranges, and at 44 months postoperatively, this patient remains alive. Given the results above, intraperitoneal administrations of this combined CDDP, 5-FU, MMC therapy may be effective for patients with pseudomyxoma peritonei.

Adult↗

PubMed1998

CIS3 and JAB have different regulatory roles in interleukin-6 mediated differentiation and STAT3 activation in M1 leukemia cells.

We have reported JAK-signaling modulators, CIS1 (cytokine-inducible SH2 protein-1), CIS3 and JAB (JAK2 binding protein), which are structurally related. In M1 myeloid leukemia cells, CIS3 was induced by neither interleukin 6 (IL6) nor interferon gamma (IFNgamma), while JAB was induced strongly by IFNgamma and slightly by IL6 and leukemia inhibitory factor (ILF). Forced expression of CIS3 and JAB in M1 cells prevented IL6- or LIF-induced growth arrest and differentiation, even when their expression levels were comparable to endogenous ones in several cell lines such as HEL, UT-7, IFNgamma-treated M1, and CTLL2 cells. Pretreatment of parental M1 cells with IFNgamma but not IFNbeta resulted in suppression of LIF-induced STAT3 activation and differentiation, further supporting that physiological level of JAB is sufficient to inhibit LIF-signaling. However, unlike JAB, CIS3 did not inhibit IFNgamma-induced growth arrest, suggesting a difference in cytokine specificity between CIS3 and JAB. CIS3 inhibited STAT3 activation with slower kinetics than JAB and allowed rapid c-fos induction and partial FcgammaRI expression in response to IL6. In 293 cells, CIS3 as well as JAB bound to JAK2 tyrosine kinase domain (JH1), and inhibited its kinase activity, however, the effect of CIS3 on tyrosine kinase activity was weaker than that of JAB, indicating that CIS3 possesses lower affinity to JAK kinases than JAB. These findings suggest that CIS3 is a weaker inhibitor than JAB against JAK signaling, and JAB and CIS3 possess different regulatory roles in cytokine signaling.

Carrier Proteins↗

PubMed1998

A Janus kinase inhibitor, JAB, is an interferon-gamma-inducible gene and confers resistance to interferons.

It has been shown that interferons (IFNs) exert their signals through receptor-associated Janus kinases (JAKs) and signal transducers and activators of transcription (STATs). However, molecular mechanism of regulation of IFN signaling has not been fully understood. We have reported novel cytokine-inducible SH2 protein (CIS) and JAK binding protein (JAB) family genes that can potentially modulate cytokine signaling. Here we report that JAB is strongly induced by IFN-gamma but not by IFN-beta in mouse myeloid leukemia M1 cells and NIH-3T3 fibroblasts. NIH-3T3 cells ectopically expressing JAB but not CIS3 lost responsiveness to the antiviral effect of IFN-beta and IFN-gamma. M1 leukemic cells stably expressing JAB were also resistant to IFN-gamma and IFN-beta-induced growth arrest. In both NIH-3T3 and M1 transformants expressing JAB, IFN-gamma did not induce tyrosine phosphorylation and DNA binding activity of STAT1. Moreover, IFN-gamma-induced activation of JAK1 and JAK2 and IFN-beta-induced JAK1 and Tyk2 activation were inhibited in NIH-3T3 JAB transformants. These results suggest that JAB inhibits IFN signaling by blocking JAK activity. We also found that IFN-resistant clones derived from LoVo cells and Daudi cells expressed high levels of JAB without stimulation. In IFN-resistant Daudi cells, IFN-induced STAT1 and JAK phosphorylation was partially reduced. Therefore, overexpression of JAB could be, at least in part, a mechanism of IFN resistance.

3T3 Cells↗

PubMed1998

Effect of a newly developed bisphosphonate, YH529, on osteolytic bone metastases in nude mice.

YH529, [1-hydroxy-2-(imidazo [1,2-a] pyridin-3-yl) ethylidene]-bisphosphonic acid monohydrate, is a newly developed third-generation bisphosphonate with a potent inhibitory activity toward osteoclastic bone resorption. The primary cellular mechanism of osteolysis associated with metastatic cancer is osteoclast-mediated. It is likely that bisphosphonates would be efficacious in this situation. In the present study, we examined the effect of YH529 in a nude mice bone metastasis model, in which the intracardiac injection of a human breast cancer cell line, MDA-MB-231 (MDA-231), leads to osteolytic bone metastases. To examine whether YH529 would prevent such bone metastasis, we administered YH529 s.c. to nude mice simultaneously with cancer cell inoculation through the entire experimental period (protocol 1) or performed short-term prophylactic administration before inoculation of the MDA-231 cells (protocol 2). In addition, to examine the possible therapeutic effects of the drug on established bone metastases, we injected YH529 after radiographically small but distinct osteolytic bone metastases had been detected (protocol 3). In all protocols, YH529 (2 microg/mouse/day) markedly inhibited bone metastases as well as the progression of established metastatic foci that were quantified on the radiographs. Histological examination and histomorphometrical analysis revealed that YH529 markedly reduced the number of osteoclasts and the size of the tumor at the metastatic bone sites. Our results suggest that YH529 may suppress metastasis formation and tumor growth in bone through inhibition of osteoclastic bone resorption.

Animals↗

PubMed1998

Cloning, mapping, expression, function, and mutation analyses of the human ortholog of the hamster putative tumor suppressor gene Doc-1.

doc-1 is a putative tumor suppressor gene isolated and identified from the hamster oral cancer model. Here, we report the molecular cloning and the functional characterization of the human ortholog of the hamster doc-1 gene. Human doc-1 cDNA is 1.6 kilobase pairs in length and encodes for a 115-amino acid polypeptide (12.4 kDa, pI 9. 53). Sequence analysis showed 98% identity between human and hamster doc-1 protein sequences. DOC-1 is expressed in all normal human tissues examined. In oral keratinocytes, expression of DOC-1 is restricted to normal oral keratinocytes. By immunostaining of normal human mucosa, DOC-1 is detected in both the cytoplasm and nuclei of basal oral keratinocytes; while in suprabasilar cells, it is primarily found in the nuclei. Human oral cancers in vivo did not exhibit immunostaining for DOC-1. Like murine DOC-1, human DOC-1 associates with DNA polymerase alpha/primase and mediates the phosphorylation of the large p180 catalytic subunit, suggesting it may be a potential regulator of DNA replication in the S phase of the cell cycle. Using a human doc-1 cosmid as a probe, human doc-1 is mapped to chromosome 12q24. We identified four exons in the entire human doc-1 gene and determined the intron-exon boundaries. By polymerase chain reaction and direct sequencing, we examined premalignant oral lesion and oral cancer cell lines and found no intragenic mutations.

Amino Acid Sequence↗

PubMed1998

Angiogenesis inhibitor TNP-470 inhibits human breast cancer osteolytic bone metastasis in nude mice through the reduction of bone resorption.

Angiogenesis inhibitor TNP-470, 6-O-(N-chloroacetyl-carbamoyl)-fumagillol, semisynthetic analogue of fumagillin, has strong inhibitory activities against in vivo tumor growth and metastasis in a wide variety of tumors. However, it is still unknown whether this agent inhibits bone metastasis. We examined the effects of TNP-470 in a bone metastasis model in nude mice in which intracardiac injection of the human breast cancer cell line MDA-MB-231 (MDA-231) produced osteolytic bone metastasis. After inoculation of MDA-231 cells into the left heart ventricle, TNP-470 (30 mg/kg, three times a week) or PBS was s.c. administrated for 4 weeks. After this period, the TNP-470 had reduced not only the number and area of osteolytic bone metastases (approximately 60 and 70%, respectively) but also their radiolucency. Histological examination of the femurs of the untreated group revealed that most of the cancellous bone had been replaced by the metastatic cancer. Numerous active osteoclasts were present along the trabecular bone surface surrounded by the metastatic MDA-231 cancer cells aggressively invading the bone marrow. In contrast, in the bone from TNP-470-treated mice, bone destruction was markedly inhibited, and there were much fewer osteoclasts. In a murine bone marrow culture under 1,25-dihydroxyvitamin D3 in which mature functional osteoclasts formed in vitro, TNP-470 significantly inhibited the formation of tartrate-resistant acid phosphatase-positive multinucleated osteoclast-like cells. And also, TNP-470 suppressed the in vivo bone resorption in calvaria treated with interleukin-1beta, an osteoclast stimulator. These data suggested that TNP-470 inhibited bone metastasis through not only antitumor action by its angiogenesis inhibition but also by the inhibition of osteoclastic bone resorption. Our results indicate that TNP-470 should be a potentially beneficial drug to be used in the treatment of osteolytic metastasis.

Animals↗

PubMed1998

Effects of troglitazone on hepatic and peripheral insulin resistance induced by growth hormone excess in rats.

It is well known that short-term growth hormone (GH) administration in humans and animals induces insulin resistance and glucose intolerance. The purpose of the present study was to clarify whether troglitazone, a new insulin-sensitizing drug of the thiazolidinedione class, counteracts the insulin antagonistic effects of recombinant human (rh) GH on glucose metabolism in rats. Male Wistar rats weighing 184 to 226 g were treated either with rhGH (n = 8) or rhGH plus troglitazone (n = 8). rhGH (20 IU/kg body weight/d) was given by subcutaneous injection twice daily for 2 days. Troglitazone was given at 100 mg/kg/d orally for 5 days before and 2 days during rhGH. Saline was injected to the control rats (n = 7). Euglycemic clamp studies with an insulin infusion rate of 8 mU/kg/min were performed in these rats after an overnight fast. Hepatic glucose output (HGO), glucose infusion rate (GIR), and glucose disappearance rate (GDR) were measured. Fasting levels of plasma glucose (6.6 +/- 0.1, 6.1 +/- 0.3, 6.5 +/- 0.2 mmol/L), insulin (187.5 +/- 24.1, 206.4 +/- 24.1, 182.3 +/- 31.0 pmol/L), and serum free fatty acid (FFA) (1.58 +/- 0.18, 1.43 +/- 0.16, 1.61 +/- 0.25 mEq/L) were comparable among rats treated with rhGH, rhGH plus troglitazone, and controls, respectively. Basal HGO was also comparable among the three treatment groups. HGO was suppressed significantly during the hyperinsulinemic glucose clamp in control rats, but not in rhGH rats. When troglitazone was coadministered with rhGH, suppressibility of HGO during the glucose clamp was comparable to that of controls. GIR (13.5 +/- 4.5 v 24.1 +/- 4.1 mg/kg/min) and GDR (18.1 +/- 5.8 v 30.3 +/- 5.2 mg/kg/min) were decreased by rhGH treatment compared with control values. They returned to normal levels in rats treated with both rhGH and troglitazone (GIR, 22.4 +/- 5.9; GDR, 24.7 +/- 7.1). From these results, it is evident that rhGH treatment impaired insulin's ability to suppress HGO and stimulate peripheral glucose utilization. Troglitazone could block the insulin antagonistic effects of GH on hepatic glucose output and peripheral glucose utilization.

Administration, Oral↗

PubMed1998

Three siblings of fatal infantile encephalopathy with olivopontocerebellar hypoplasia and microcephaly.

We report three male siblings born with fatal encephalopathy comprising microcephaly, myoclonus and muscle hypertonia. All three patients died during infancy. Postmortem examination on the brain revealed that all infants had neuronal loss in the cerebellar cortex, inferior olivary and pontine nuclei, which were more pronounced in the older subject than the younger ones. In addition, they were associated with polymicrogyria in the cerebral cortex of the insula, olivary and dentate nuclear dysplasia, and a hypoplastic corticospinal tract. The clinical and neuropathological findings in our cases were identical to those in fatal infantile encephalopathy with olivopontocerebellar hypoplasia and microencephaly [Albrecht et al., Acta Neuropathol 1993;85:394-399], but an association of malformations suggests a new genetic factor in pathogenesis of olivopontocerebellar hypoplasia.

Abnormalities, Multiple↗

PubMed1998

Structural comparison of 1 beta-methylcarbapenem, carbapenem and penem: NMR studies and theoretical calculations.

Structural comparisons of meropenem (1), desmethyl meropenem (2) and the penem analogue (3) which contain the same side chains at both C-2 and C-6 were performed using 1H NMR measurements together with 3-21G* level of ab initio MO and molecular mechanics calculations. The ab initio MO calculations reproduced the skeletons of these strained beta-lactam rings in good agreement with the crystallographic data. 1H NMR measurements in aqueous solution together with molecular modeling studies indicated that there were conformational differences of the C-2 and C-6 side chains in this series of compounds. These observations suggested that the conformational differences could affect their biological activities.

Anti-Bacterial Agents↗