Biomedical subjects

Y Hirai

Publications and source records attributed to Y Hirai.

At least 109 records · Page 6Linked to original sources

PubMed1998

Structural significance of the benzoyl group at the C-3'-N position of paclitaxel for nitric oxide and tumor necrosis factor production by murine macrophages.

The antitumor agent paclitaxel (Taxol) mimics the actions of lipopolysaccharide (LPS) on murine macrophages (M phi). Recently, we have shown that the benzoyl group at the C-3' position of paclitaxel is the most important site to induce nitric oxide (NO) and tumor necrosis factor (TNF) production by C3H/HeN M phi (Biochem. Biophys. Res. Commun. 210, 678-686, 1996). In the present study, synthetic analogs of paclitaxel with replacement of the C-3'-N position were examined for their potencies to induce NO and TNF production by peritoneal M phi of LPS-responsive C3H/HeN mice and LPS-hyporesponsive C3H/HeJ mice, by human blood cells and human M phi. In this structure-activity relationship study, we found that (i) the p-substitution of the benzoyl group definitely affects the activity to activate C3H/HeN M phi, (ii) the analogs having a methyl or chloro group at the p-position exhibit stronger activity than that of paclitaxel, (iii) there is good correlation between NO and TNF production by the M phi in response to compounds, (iv) the compounds tested do not induce either NO or TNF production by C3H/HeJ M phi or TNF production by human cells, (v) a previous treatment of C3H/HeN M phi with the inactive compounds can hardly affect either paclitaxel- or LPS-induced TNF production by the M phi, (vi) paclitaxel and its analogs marginally affect LPS-induced TNF production by human blood cells, and (vii) there is no correlation between the NO/TNF inducibility to C3H/HeN M phi and growth inhibitory activity against M phi-like J774.1 and J7.DEF3 cells.

Animals↗

PubMed1998

Epimorphin functions as a key morphoregulator for mammary epithelial cells.

Hepatocyte growth factor (HGF) and EGF have been reported to promote branching morphogenesis of mammary epithelial cells. We now show that it is epimorphin that is primarily responsible for this phenomenon. In vivo, epimorphin was detected in the stromal compartment but not in lumenal epithelial cells of the mammary gland; in culture, however, a subpopulation of mammary epithelial cells produced significant amounts of epimorphin. When epimorphin-expressing epithelial cell clones were cultured in collagen gels they displayed branching morphogenesis in the presence of HGF, EGF, keratinocyte growth factor, or fibroblast growth factor, a process that was inhibited by anti-epimorphin but not anti-HGF antibodies. The branch length, however, was roughly proportional to the ability of the factors to induce growth. Accordingly, epimorphin-negative epithelial cells simply grew in a cluster in response to the growth factors and failed to branch. When recombinant epimorphin was added to these collagen gels, epimorphin-negative cells underwent branching morphogenesis. The mode of action of epimorphin on morphogenesis of the gland, however, was dependent on how it was presented to the mammary cells. If epimorphin was overexpressed in epimorphin-negative epithelial cells under regulation of an inducible promoter or was allowed to coat the surface of each epithelial cell in a nonpolar fashion, the cells formed globular, alveoli-like structures with a large central lumen instead of branching ducts. This process was enhanced also by addition of HGF, EGF, or other growth factors and was inhibited by epimorphin antibodies. These results suggest that epimorphin is the primary morphogen in the mammary gland but that growth factors are necessary to achieve the appropriate cell numbers for the resulting morphogenesis to be visualized.

Animals↗

PubMed1998

The value of squamous cell carcinoma antigen as a predictor of nodal metastasis in cervical cancer.

Preoperative serum squamous cell carcinoma antigen (SCC) levels were examined in 148 cases of stage Ib squamous cervical cancer undergoing radical hysterectomy. The effect of the pelvic lymph node status on the marker level was examined by comparing 113 cases with cancer limited to the uterus and 23 cases with cancer confined to the uterus and pelvic lymph nodes using two different multivariate analyses. Ninety-five percent of patients with cancer limited to the uterus showed SCC levels of 4 ng/ml or below. Nearly two-thirds (65%) of patients with serum levels above 4 ng/ml exhibited pelvic lymph node metastasis. The marker values exceeding 4 ng/ml increased the risk of nodal metastasis by eight times, compared with serum levels of 4 ng/ml or below. Multivariate analyses confirmed that the pelvic lymph node metastasis had a larger impact on the marker level than did tumor size or depth of stromal infiltration. SCC levels greater than 4 ng/ml can be considered a high-risk zone for nodal metastasis.

Adolescent↗

PubMed1998

Ovarian metastasis in endometrial carcinoma.

A retrospective study was conducted to investigate the clinical significance of ovarian metastasis in 439 patients with clinical stage I endometrial cancer surgically treated by performing total abdominal hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymphadenectomy. Histologic examination revealed that 22 patients (5%) had ovarian metastasis. The maximum diameter of the ovarian metastases ranged from 1 to 100 mm. In 18.2% (4/22) of patients with ovarian metastasis, the maximum diameter was less than 2 mm. Patients with metastasis limited to the ovarian surface showed 100% positive peritoneal cytology, 0% lymph node metastases, and 50% recurrence, while patients with metastasis inside the ovary showed 10% positive peritoneal cytology, 36% lymph node metastases, and 53% recurrence. The prognosis of patients with ovarian metastasis alone was situated midway between that of patients with cancer limited to the uterus and that of patients with lymph node metastasis alone. The lymph node status was of importance to determine the prognosis of patients with ovarian metastasis. The series also suggests that there may be two routes for ovarian metastasis; one is a route via the fallopian tube to the ovarian surface and the other is a route via the lymphatics to the inside of the ovary.

Analysis of Variance↗

PubMed1998

A clinicocytopathologic study of adenoma malignum of the uterine cervix.

OBJECTIVES: To investigate the nature and the clinical course of adenoma malignum (the so-called minimal deviation adenocarcinoma) of the uterine cervix by conducting a retrospective study of 6 cases consecutively treated in a single institute. METHODS: The pathologic classification of adenoma malignum was performed according to the WHO classification (1994). RESULTS: These tumors accounted for only 1.32% (6/453) of invasive cervical adenocarcinomas. All the cases showed either a watery discharge or atypical genital bleeding, or both, at the time of diagnosis. The preoperative cytologic diagnosis of adenoma malignum was made in 83.3% (5/6) of cases. The preoperative punch biopsy, on the other hand, failed to confirm the diagnosis of adenoma malignum in all cases, although the presence of the disease was suspected in 2 cases (33%). The 5-year survival rate and 5-year disease-free survival rate were 100 and 83.3%, respectively. CONCLUSIONS: This series demonstrates that cytologic examination is a potent screening method to detect this rare disease. When the presence of this disease is suspected by the cytologic examination, a deep biopsy is necessary to make an accurate diagnosis. An ordinary cervical biopsy is usually insufficient to detect deeply positioned tumor glands. The prognosis of the disease may be better than that for ordinary cervical adenocarcinoma.

Adenocarcinoma, Mucinous↗

PubMed1998

Prognostic validity of neoplastic cells with notable nuclear atypia in endometrial cancer.

OBJECTIVE: To investigate how the architectural grade of endometrial adenocarcinoma should be adjusted in the presence of neoplastic cells with notable nuclear atypia in order to assign the histologic grade. METHODS: Four hundred seventy-six patients with stage I endometrial cancer (endometrioid type) who were surgically treated in a single institute formed the study population. The architectural grade and the proportion of tumor cells with notable nuclear atypia were examined for each case. The effects of notable nuclear atypia on the disease-free survival of each architectural grade were analyzed. RESULTS: The disease-free survival of architectural grade 1 and grade 2 tumors was significantly affected and was worse than that of architectural grade 3 tumors when more than 25% of the tumor cells showed notable nuclear atypia. Tumors that had 26% to 50% of neoplastic cells with notable nuclear atypia showed a similar probability of recurrence as did tumors that had more than 50% of neoplastic cells with notable nuclear atypia. CONCLUSION: The series suggests that the upgrading of architectural grade 1 or 2 tumors, in which more than 25% of the neoplastic cells show notable nuclear atypia, into a grade 3 tumor may be more practical than upgrading by one architectural grade 1 or 2 tumors, in which the majority of neoplastic cells show notable nuclear atypia.

Adenocarcinoma↗

PubMed1998

Lifespan of human memory T-cells in the absence of T-cell receptor expression.

To evaluate the intrinsic lifespan of human memory T-cells in the absence of T-cell receptor signaling, we used radiation-induced mutant CD4+ T-cells lacking surface expression of TCR/CD3 complex as an in vivo cell marker. We analyzed the long-term kinetics of TCR/CD3 - mutant T-cells among CD4+ CD45RA+ naive and CD4+ CD45RA- memory T-cell fractions in peripheral blood of gynecological cancer patients receiving radiotherapy. Both the proportion and number of these mutant T-cells decayed exponentially with time following radiotherapy. The estimated half-life of mutant memory T-cells was 2 to 3 years and did not differ from that of mutant naive T-cells. These results indicate that the lifespan of mature CD4+ T-cells is limited regardless of their memory or naive phenotype in the absence of TCR/CD3 expression. This finding may suggest that continued T-cell receptor signaling is required for lifetime maintenance of human memory T-cells.

Adult↗

PubMed1998

Effect of ultrasound application on skin metabolism of prednisolone 21-acetate.

PURPOSE: The effect of ultrasound on skin penetration and metabolism of prednisolone (PN) and prednisolone 21-acetate (PNA) was investigated in the hairless mouse skin in vitro. METHODS: The abdominal skin excised freshly was pretreated under different ultrasound intensities (4.32, 2.88, and 1.50 W/cm2) for 10, 30, and 60 min. The penetration/metabolism rate of PNA and its metabolite (PN) was then measured using a side-by-side diffusion cell. RESULTS: The skin penetration of PN was enhanced by the ultrasound pretreatment. This enhancement was attributed to the decrease in the stratum corneum barrier capacity by ultrasound energy. The steady-state appearance rate of PN following the skin bioconversion of PNA decreased appreciably with increasing the product of the duration of pretreatment (Dp, min) and the intensity of ultrasound applied (Iu, W/cm2). When the product value was less than 40 W/cm2 . min, the steady-state appearance rate of the PN hardly increased in spite of the penetration enhancement of PNA. CONCLUSIONS: These findings indicated a possible deactivation of the skin enzymes by ultrasound energy.

Animals↗

PubMed1998

[Evaluation of a rapid enzyme immunoassay membrane test for diagnosis of influenza A virus infection].

A rapid enzyme immunoassay membrane test, Directigen Flu A (Becton Dickinson, USA), was evaluated by using virus isolates and clinical specimens. The reference laboratory diagnosis was based on the results of virus isolation. Directigen Flu A was reactive for all subtypes of human influenza A viruses, including reference strains of H1N1, H2N2 and H3N2. Moreover, H5N1 (Hongkong/156/97) was also detected by this kit. No cross reactivity was detected with other respiratory viruses. Directigen Flu A showed positive reaction with the solution containing influenza A virus of 2.4 x 10(3) pfu/assay. The rapid test demonstrated 77.9% sensitivity and 98.4% specificity for testing of throat swabs from children with respiratory symptoms. It showed higher sensitivity and specificity (92.1% and 100%) for testing of nasopharyngeal aspirates. Directigen Flu A should be useful for the rapid diagnosis of influenza A virus infection.

Antigens, Viral↗

PubMed1998

[Impact of influenza A virus infection as a cause of pediatric hospitalization and use of rapid antigen test of influenza A virus].

From the winter of 1997 to the spring of 1988, a severe epidemic caused by influenza A (H3N2) developed in Japan. During the epidemic (December 1997 to February 1998), 239 children were admitted to the pediatric ward of Nippon Kokan Hospital: as many as 76 (31.8%) were hospitalized with influenza A (H3N2) infection. Most were young healthy children (mean age, 3.7 years), suggesting the need of influenza immunization for this age group. 110 specimens of hospitalized children were examined by rapid antigen test of influenza A virus (Directigen Flu A, Becton Dickinson, USA). The rapid test showed about 90% sensitivity and specificity, as compared with isolation and serum hemagglutination inhibition test. Directigen Flu A proved to be a reliable, rapid screen for influenza A from symptomatic patients.

Adolescent↗

PubMed1998

Effect of rebamipide, a novel antiulcer agent, on Helicobacter pylori adhesion to gastric epithelial cells.

Helicobacter pylori is a major etiological agent in gastroduodenal disorders. The adhesion of H. pylori to human gastric epithelial cells is the initial step of H. pylori infection. Inhibition of H. pylori adhesion is thus a therapeutic target in the prevention of H. pylori infection. Experiments were performed to evaluate the effect of rebamipide, a novel antiulcer agent, on H. pylori adhesion to gastric epithelial cells. MKN-28 and MKN-45 cells, derived from human gastric carcinomas, were used as target cells. Ten H. pylori strains isolated from patients with chronic gastritis and gastric ulcer were used in the study. We evaluated the effect of rebamipide on H. pylori adhesion to MKN-28 and MKN-45 cells quantitatively using our previously established enzyme-linked immunosorbent assay. The adhesion of H. pylori to MKN-28 and MKN-45 cells was significantly inhibited by pretreatment of these cells with 100 microg of rebamipide per ml. However, the adhesion was not affected by the pretreatment of H. pylori with rebamipide. On the other hand, the viabilities of H. pylori, MKN-28 cells, and MKN-45 cells were not affected by rebamipide. Our studies suggest that rebamipide inhibits the adhesion of H. pylori to gastric epithelial cells.

Alanine↗

PubMed1998

Analysis of immunoglobulin A antibodies to Helicobacter pylori in serum and gastric juice in relation to mucosal inflammation.

Helicobacter pylori is a major etiologic agent in gastroduodenal disorders. In this study, immunoglobulin A (IgA) antibodies to H. pylori antigens were evaluated in serum and gastric juice specimens obtained from patients with gastritis or peptic ulcers by utilizing antibody capture enzyme-linked immunosorbent assays (ACELISAs). Urease alpha subunit (UA), urease beta subunit (UB), the 66-kDa heat shock protein (HSP), and the 25-kDa protein (25K) were used as antigens for the ACELISAs. The antibody titers of the ACELISAs reflect the ratio of H. pylori-specific IgA to total IgA. The ratio is stable, although the antibody concentration fluctuates in gastric juice. By using ACELISAs it was possible to evaluate quantitatively not only serum IgA antibodies but also gastric juice secretory IgA (S-IgA) antibodies. In both serum IgA and gastric juice S-IgA ACELISAs, the titers of antibody to HSP and 25K were remarkably correlated with the histologic grade of gastritis, whereas those to UA and UB were not strongly correlated with histologic grade. Thus, it is useful for estimating the histologic grade of gastritis to quantify serum IgA and gastric juice S-IgA antibodies to HSP and 25K.

Adolescent↗

PubMed1998

Detection of Helicobacter pylori associated antigen and heat shock protein 60 on follicular dendritic cells in the germinal centres of low grade B cell lymphoma of gastric mucosa associated lymphoid tissue (MALT).

AIMS: To investigate the localisation of Helicobacter pylori antigens and the expression of human heat shock proteins (HSP) in stomachs affected by MALT lymphoma. METHODS: Surgically resected stomachs from 24 patients with MALT lymphoma were immunostained with anti-H pylori rabbit antibodies (ORP-1 and ORP-2) and anti-human HSP60 mouse monoclonal antibodies (mAb) (LK-1 and LK-2). RESULTS: Follicular dendritic cells of germinal centres in the stomachs affected by MALT lymphoma were immunostained with anti-H pylori polyclonal antibodies and with anti-human HSP60 mAb, as were the epithelial cells. None of the lymph node samples reacted. CONCLUSIONS: Human HSP60, which cross reacts with anti-H pylori polyclonal antibodies, is often expressed on follicular dendritic cells in gastric MALT lymphoma tissues and may be aetiologically relevant to lymphomagenesis of MALT lymphoma.

Antigens, Bacterial↗

PubMed1998

Antibody and cytokine responses in Helicobacter pylori-infected various mouse strains.

Helicobacter pylori (H. pylori) infection in the stomach is etiologically closely associated with chronic active gastritis, peptic ulcer, gastric cancer and gastric mucosa-associated lymphoid tissue lymphoma. In this study, we examined the antibody responses and cytokine profiles of three strains of mice (BALB/c, C3H/He, and C57BL/6) infected with H. pylori. Following this, correlations between host-immune reactions and intensity of inflammation were analyzed. H. pylori (ATCC43504) was intragastrically administered once a week to the mice from 4 weeks of age, and they were sacrificed at the ages of 4 and 7 months. In these mice, we examined the histology of the stomach, antibody titers against H. pylori, and serum levels of cytokines (IL-4, IL-10, TNF-alpha, IL-2 and Interferon-gamma). In BALB/c mice, inflammation of the stomach was minimal. Inflammation was observed in 63.6% of C57BL/6 mice and 33.3% of C3h/He mice. In C57BL/6 and C3H/He mice, all the cytokines tended to increase. In contrast, BALB/c mice were inactive in cytokine production except for IL-2. Two C3H/He mice developed severe inflammation with lymph follicles; one showed a response largely typical of Th-1, and the other showed a response largely typical of Th-2. Although a definite correlation was not shown between Th-1/Th-2 response evaluated by cytokine production and intensity of inflammation, it appears that in H. pylori-induced inflammation both cell-mediated (Th-1) and humoral (Th-2) immunity play a role in pathogenesis.

Animals↗

PubMed1998

[Evaluation on the clinical background on early death in patients with pulmonary tuberculosis during the past five years].

We evaluated the clinical background of early death (within 3 months after admission to our hospital) in patients with active pulmonary tuberculosis during the past five years (1992-1996). Among 65 active pulmonary tuberculosis patients who died during the past five years, 32 (49%) died directly of tuberculosis. Thirteen (41%) of those 32 patients died of acute respiratory failure and 9 patients (28%) died in emacitation state. Twenty two patients (69%) died within 3 months after admission to our hospital (the early death group) and 10 patients (31%) died after 3 months (the late death group). Thirteen patients (59%) in the early death group died of acute respiratory failure. On the other hand, none in the late death group died of acute respiratory failure but 4 patients died of chronic heart and/or respiratory failure and 4 patients died in emarciation state. Compared to the patients in the late death group, more patients in the early death group had long total delays (patient's and doctor's delays), had coexisiting diseases, had fallen into acute respiratory failure, and were under malnutrition. We evaluated the nutritional condition of patients using the Onodera's PNI (Prognostic Nutritional Index; 10 x serum almumin concentration + 0.005 x peripheral lymphocyte count) and the PNI value was lower among the patients in the early death group than among those in the late death group. To prevent death due to tuberculosis, we emphasize that it is important to start anti-tuberculosis therapy before patients fall into acute respiratory failure and/or malnutrition.

Acute Disease↗

PubMed1998

The effectiveness of the "Clean-Area-System" for infection control in the dental clinic.

The use of effective infection control procedures and universal precautions in dental clinics, prevents cross contamination that could extend to dental health care workers and patients. The present study was initiated to investigate airborne environmental contamination in the dental clinic by viable cell count of oral streptococci grown on Mitis-Salivarius and blood agar plates. The reduction of the contamination by the "Clean-Area-System" was evaluated. "Andersen-Microbe-Sampler-Apparatus" and "Laser-Particle-Counter-System" were used for sampling and counting the bacterial cells and airborne dust, respectively. Numbers of viable cells counted as total colony forming units (CFUs) in the dental clinic were found to be significantly higher than those in the waiting room and the research laboratory. We found that the "Clean-Area-System" significantly reduced the CFUs grown on blood agar plates (p < 0.05), and that using the "Clean-Area-System" combined with the "Extra-Oral-Vacuum-Aspirator" is desirable in dental procedures such as cavity preparation. The "Extra-Oral-Vacuum-Aspirator" reduced airborne environmental contamination during tooth cutting and ultrasonic scaling procedures. In non-grinding procedures, this system proved to be very useful for infection control in the operative area. The authors concluded that the combined use of "Clean-Area-System" (dust collection ablation) and "Extra-Oral-Vacuum-Aspirator" (absorb dust ablation) was effective to reduce airborne environmental contamination in the dental clinic. We also fully confirmed that oral streptococci were an adequate indicator in the assessment for infection control in dental institutions.

Air Conditioning↗

PubMed1998

Flow cytometry measurements of subsets of T, B and NK cells in peripheral blood lymphocytes of atomic bomb survivors.

Previous studies of blood cells from atomic bomb survivors have shown that frequencies of chromosome aberrations and somatic mutations are elevated in heavily exposed survivors and that T-cell functions and the number of mature T cells are decreased in the survivors who were exposed to radiation as adults. Current progress in flow cytometry allows a sophisticated analysis of various subsets of T, B and NK cells. In the present study, proportions of such subsets in peripheral blood lymphocytes from atomic bomb survivors (159 survivors estimated to be exposed to > or =1.5 Gy) and 252 controls were measured using multiple combinations of monoclonal antibodies to lymphocyte differentiation antigens to investigate whether the previous radiation exposure had altered the composition of the subsets. Among T-cell subsets, the proportion of CD4+ T-cell subsets was decreased significantly in the heavily exposed survivors; this tendency was apparent for the CD4+CD45RA+ naive T-cell subset. However, there were no significant differences in the proportions of CD8+ T-cell subsets between the exposed survivors and controls. As for the B-cell subsets, the proportion of both CD5+ and CD5 B cells as well as CD23+ and CD23- B cells increased in the heavily exposed survivors. Further, no effect of radiation was found in the proportion of NK-cell subsets. These results strongly suggest that previous radiation exposure altered the composition of T and B cells in the peripheral blood of atomic bomb survivors, and they raise the possibility that atomic bomb radiation may have affected the developmental processes of T and B cells.

Adult↗

PubMed1998

Modification of Helicobacter pylori adhesion to human gastric epithelial cells by antiadhesion agents.

Helicobacter pylori is a major etiological agent in gastroduodenal disorders. H. pylori adhesion to human gastric mucosa is the initial step of H. pylori colonization. Inhibition of H. pylori adhesion is thus a therapeutic target in preventing H. pylori infection. We have previously established a method using the enzyme-linked immunosorbent assay to analyze quantitatively H. pylori adhesion to gastric epithelial cells. This method is suitable for screening antiadhesion agents. Some mucoprotective agents are proved to have antiadhesion effects in vitro, and they may modify H. pylori adhesion. This evidence gives us a useful clue to analyze the molecular mechanism of H. pylori adhesion to mucosa. Furthermore, in clinical trials, these mucoprotective agents enhanced the eradication rate when administered with antibiotics. In conclusion, the antiadhesion agents may have potential as therapeutic regimens against H. pylori infection.

Bacterial Adhesion↗