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Biomedical subjects

Y Mitsuhashi

Publications and source records attributed to Y Mitsuhashi.

At least 37 records · Page 2Linked to original sources

Effect of lactoferrin on lipopolysaccharide (LPS) induced preterm delivery in mice.

BACKGROUND: The present study attempted to confirm the preventive effect of lactoferrin on lipopolysaccharide (LPS) induced preterm delivery in mice. METHODS: Female C3H/HeNCrj mice were pair-mated with male Crj: B6D2F1 mice. On day 15 of gestation, a 50 micron/kg intraperitoneal injection of LPS (LPS group) was administered twice with a 3-hour interval between injections (at 2:00 and 5:00 PM). The mice were also given an intraperitoneal injection of lactoferrin (0.2 or 1 mg/200 microl/body) 1 hour prior to each LPS injection) (at 1:00 and 4:00 PM). To determine the effect of LF on plasma IL-6 level, mother mice were sacrificed and blood samples were obtained at 6 hours after the second treatment of LPS. RESULTS: Preterm delivery was induced by LPS in all mice on day 16 of gestation. Lactoferrin administration to LPS-treated mice significantly prolonged (p<0.001) gestation when compared with the LPS group. Plasma levels of IL-6 in the LPS group (1.628+/-115 pg/ml) were significantly higher (p<0.001) than in the untreated group (497+/-39 pg/ml). On the other hand, administration of lactoferrin (1 mg/body) to LPS-treated mice significantly suppressed (p<0.001) IL-6 levels (1.060+/-154 pg/ml). CONCLUSIONS: Lactoferrin exerts a preventive effect on the incidence of preterm delivery in mice via a suppression of plasma IL-6 augmentation by LPS.

Animals↗

Antitumor activity and novel DNA-self-strand-breaking mechanism of CNDAC (1-(2-C-cyano-2-deoxy-beta-D-arabino-pentofuranosyl) cytosine) and its N4-palmitoyl derivative (CS-682).

We have studied the antitumor activity and the novel DNA-self-strand-breaking mechanism of CNDAC (1-(2-Ccyano-2-deoxy-beta-D-arabino-pentofuranosyl)cytosine) and its N4-palmitoyl derivative (CS-682). In vitro, CS-682 showed strong cytotoxicity against human tumor cells comparable with that of CNDAC; both compounds displayed a similar broad spectrum. In vivo, however, orally administered CS-682 showed a more potent activity against human tumor xenografts than CNDAC, 5'-deoxy-5-fluorouridine, 5-fluorouracil and 2',2'-difluorodeoxycytidine. Moreover, CS-682 was effective against various human organ tumor xenografts at a wide dose range and with low toxicity, and was effective against P388 leukemic cells resistant to mitomycin-C, vincristine, 5-fluorouracil or cisplatin in syngeneic mice. CNDAC, an active metabolite of CS-682, had a prolonged plasma half-life after repeated oral administrations of CS-682 but not after oral administrations of CNDAC itself. This difference may partially explain the higher antitumor activity of CS-682 relative to CNDAC. In both CNDAC- and CS-682-treated carcinoma cells, CNDAC 5'-triphosphate (CNDACTP) was generated and incorporated into a DNA strand. High performance liquid chromatography (HPLC) and mass spectrometric analysis of the nucleosides prepared by digestion of the DNA from the CNDAC-treated cells detected ddCNC (2'-Ccyano-2',3 '-didehydro-2',3 '-dideoxycytidine), which was shown to be generated only when the self-strand-breakage of CNDACTP-incorporated DNA occurred. The cytotoxicity of CNDAC was completely abrogated by the addition of 2'-deoxycytidine and was low against cells with decreased deoxycytidine kinase. Our results suggest that CNDAC is converted to CNDACMP by deoxycytidine kinase and that the resulting CNDACTP incorporated into a DNA strand as CNDACMP may induce DNA-self-strand-breakage. This novel DNA-self-strand-breaking mechanism may contribute to the potent antitumor activity of CS-682.

Administration, Oral↗

Effects of red blood cells on the coagulation of blood in normal and preeclamptic pregnancies.

OBJECTIVE: The objective of this study was to determine the cellular effects of whole blood, especially of red blood cells, on the hypercoagulability of blood from patients with preeclampsia. STUDY DESIGN: The time elapsed between mixing and the onset of coagulation was measured by means of a highly sensitive rheometer for whole blood, platelet-rich plasma (in which red blood cells had been removed from whole blood), and platelet-free plasma from 3 groups of subjects: 25 nonpregnant women, 25 women with normal pregnancies, and 10 patients with preeclampsia. RESULTS: Time to coagulation for whole blood from patients with preeclampsia was significantly shorter than that for whole blood from women with normal pregnancies. However, there was no significant difference in time to coagulation for platelet-rich plasma between women with preeclampsia and those with normal pregnancies. CONCLUSION: Hypercoagulability of blood in preeclampsia appears to be strongly related to red blood cell alterations.

Adult↗

Collateral expression of proangiogenic and tumorigenic properties in intestinal epithelial cell variants selected for resistance to anoikis.

Although in vitro anchorage-independent growth is widely used as a marker of cell transformation, the biological implications of this trait are poorly understood. We previously demonstrated that enforced anchorage-independent growth of a nontumorigenic, immortalized epithelial cell line (IEC-18) in multicellular spheroid culture results in massive apoptotic cell death. This death process, termed anoikis, is prevented by expression of transforming oncogenes, which also confer tumorigenic competence. This study examines whether acquisition of an anoikis-resistant phenotype is causally related to the tumorigenic capacity of transformed epithelial cells. Parental IEC-18 cells were subjected to 10 cycles of selection for survival in speroid culture. Unlike parental cells, the resulting anoikis-resistant variants (AR1.10 and AR2.10) formed relatively large tumors in nude mice. Both anoikis-resistant sublines displayed upregulated expression of vascular endothelial growth factor (VEGF), a potent angiogenesis stimulator. VEGF121 overexpression alone did not induce tumorigenic conversion of parental IEC-18 cells, which remained highly susceptible to anoikis. We postulate that both anoikis-resistance and angiogenic-competence contribute to tumor formation. Development of anoikis-resistance can be then viewed as a precondition for expression of the tumorigenic phenotype. Our results suggest that even when angiogenesis is not a rate limiting factor (e.g. in vitro) the selective pressures of solid tumor-like, 3-dimensional growth conditions favoring anoikis resistance result in collateral induction of a proangiogenic phenotype.

Animals↗

The association of latent Epstein-Barr virus infection with hydroa vacciniforme.

Patients with hydroa vacciniforme (HV)-like eruptions and malignant potential have been reported from Asia and Mexico, and those patients frequently had an associated latent Epstein-Barr virus (EBV) infection. In order to elucidate the association of latent EBV infection with HV, we studied six children with typical manifestations of HV by detection of EBV genes and EBV-related RNAs in biopsy specimens from cutaneous lesions. Cutaneous lesions of all six children with typical HV contained EBV-encoded small nuclear RNA (EBER)+ cells in 3-10% of the dermal infiltrates, whereas no Bam HI-H, l-fragment (BHLF) mRNA, or transcripts encoding EA-D antigen, were detected. No EBER + cells were detected in other inflammatory or benign lymphoproliferative skin disorders tested. Polymerase chain reaction amplification confirmed the presence of EBV DNA sequences in five of six biopsy specimens from the patients. Latent EBV infection is associated with the development of cutaneous lesions of HV.

Burkitt Lymphoma↗

Netherton's syndrome in siblings.

We report the perinatal presentation and evolution of Netherton's syndrome in siblings. The first patient, a female infant, presented with asphyxia at birth due to aspiration of desquamated scale, non-bullous ichthyosiform erythroderma, and hypernatraemic dehydration which she had for several days. Subsequently, she failed to thrive, with recurrent bacterial infections until 5 months of age, and very high serum IgE levels (1200 U/mL). Trichorrhexis invaginata and pili torti were identified at 18 months. The second patient was the younger brother of the first. Hydramnios and hyperechoic material in the amniotic fluid were observed by ultrasound at 35 weeks gestation, and he was delivered by elective Caesarian section at 40 weeks. At birth, no hair abnormality was demonstrated but, like his sister, his body was covered with thick caseous material, and he was erythrodermic. He failed to thrive, but serum IgE levels were normal until 5 months of age. Typical trichorrhexis invaginata was not observed until 7 months of age. Thus, the hair abnormality and high serum IgE levels in Netherton's syndrome appear late relative to the ichthyosiform erythroderma.

Female↗

An immunohistochemical study of E-cadherin expression in human squamous cell carcinoma of the skin: relationship between decreased expression of E-cadherin in the primary lesion and regional lymph node metastasis.

E-cadherin is a Ca(2+)-dependent, intercellular adhesion molecule that is specifically expressed in epithelial tissues and is essential for maintaining intercellular connections. It has been reported that E-cadherin expression of tumor cells is often decreased in some types of metastasizing carcinomas as compared with those without metastasis. We immunohistochemically examined the expression of E-cadherin with anti-E-cadherin monoclonal antibody and compared primary lesions of human squamous cell carcinoma of the skin (SCC) with regional lymph node metastasis to those without regional lymph node metastasis. Tumor samples from fifty-five cases of SCC (32 cases of SCC without metastasis and 23 cases with metastasis) were formalin-fixed, paraffin-embedded, and examined. E-cadherin was reduced or absent in 39 (70.9%) out of 55 cases of SCC, and in 21 (91.3%) of 23 cases with regional lymph node metastasis. Our results suggest that the decreased expression of E-cadherin in the primary lesion is correlated with regional lymph node metastasis in SCC and that it is more frequently correlated with well-differentiated than with poorly differentiated SCC. E-cadherin may be useful as a marker for metastatic potential in well-differentiated SCC.

3,3'-Diaminobenzidine↗

Osteo-nevus of Nanta: a case report and review of the Japanese literature.

We reported a 58-year-old Japanese male with osteo-nevus of Nanta on his right cheek. Histological examination revealed nests of nevus cells throughout the entire dermis. Just beneath the nevus in the lower dermis, several basophilic oval-shaped membranous structures were positive with Kossa stain. No inflammatory infiltrate or foreign-body granuloma were seen. We reviewed 28 cases of osteo-nevus of Nanta reported in the Japanese literature and discussed the pathogenesis of ossification in the lesions of nevus cell nevi.

Humans↗

Acute generalized exanthematous pustulosis induced by salazosulfapyridine in a patient with ulcerative colitis.

We report a case of acute generalized exanthematous pustulosis (AGEP) induced by salazosulfapyridine in a patient with ulcerative colitis. A 26-year-old Japanese man, who had been receiving medical attention for ulcerative colitis for one year, presented with diffuse erythema and pustules on his face and trunk, malaise, and fever up to 39 degrees C one day after the administration of salazosulfapyridine. A skin biopsy specimen disclosed intracorneal pustule composed of neutrophils and lymphohistiocytic infiltrate in the dermis. A drug lymphocyte stimulation test for salazoslufapyridine was positive, but the patch test was negative. Immunological mechanisms are suggested in the pathogenesis of psoriasis and ulcerative colitis. We suspect that a similar immunological pathway played a role in the pathogenesis of AGEP appearing in psoriasis and ulcerative colitis.

Adult↗

Enzymic method for the determination of nitrite in meat and fish products.

A simple spectrophotometric method for the determination of nitrite is described. Nitrite is measured enzymically through its reaction with nitrite reductase coupled with NADH. The entire enzymic procedure required 15 min to complete. The calibration curve was linear in the range 0.1-10 micrograms cm-3 nitrite with a slope of 6.25. The relative standard deviation at 5 microgram g-1 was 1.7% (n = 5). The method greatly simplifies the procedure of nitrite determination and enables the routine inspection of a number of samples with very little laboratory equipment. A comparison study showed that the method was superior to the GC method for samples containing large amounts of reducing substances while good agreement was achieved between both methods for other foods.

Fish Products↗

Cutaneous disseminated actinomycosis in a patient with acute lymphocytic leukemia.

Actinomycosis is an uncommon infectious disease caused predominantly by Actinomyces israelii. The cutaneous disseminated form is usually caused by hematogenous dissemination from a primary extra-cutaneous lesion. We report here cutaneous disseminated actinomycosis without any detectable extra-cutaneous lesions in a 42-year-old Japanese woman with acute lymphocytic leukemia. Multiple soft nodules developed on her upper and lower extremities. Histopathological examination revealed "sulfur granules", which are a specific finding for actinomycosis. Cultures from biopsy specimens were not successful. There were no cervicofacial, thoracic, nor abdominal lesions. These findings suggest that cutaneous disseminated actinomycosis in our patient developed primarily in the skin. Although the patient was immunocompromised, antibiotic treatment with minocycline was effective.

Actinobacillus↗

Contact dermatitis due to sodium colistimethate.

Colistin methanesulfonate sodium (CLMS) is a widely-used antibiotic. To our best knowledge, only two cases of contact allergy to CLMS have been reported. We described a 4-year-old girl with contact dermatitis evoked by CLMS that had been applied as an ophthalmic solution. The dermatitis started after administration for 21 days. The diagnosis was confirmed by as is and constituent patch tests. We reviewed the literature in which contact allergy due to CLMS and colistin sulfate is described.

Anti-Bacterial Agents↗