Search PubMed⌕ Search

Biomedical subjects

H Yoshida

Publications and source records attributed to H Yoshida.

At least 757 records · Page 42Linked to original sources
PubMed1998

Role of macrophages in acute murine cytomegalovirus infection.

It has been recognized that macrophages play an important role in controlling virus infection in experimental animal models. To evaluate the role of macrophages in acute murine cytomegalovirus infection, macrophages in the spleen and the liver were eliminated by an intravenous injection of liposomes containing a cytolytic agent, dichloromethylene diphosphonate. The depletion of macrophages led to a significant increase of virus titer in the spleen and lungs in both susceptible BALB/c and resistant C57BL/6 mice during the first three days after intravenous infection. In the spleen, the increase of virus titer in macrophage-depleted BALB/c mice was much greater than that in NK cell-depleted mice. These results suggest that macrophages contribute to protection mainly by the mechanisms which are independent of NK cells during the first three days after infection. The increase of virus titer in macrophage-depleted C57BL/6 mice was as great as that in NK cell-depleted mice because of the high contribution of NK cells to protection in C57BL/6 mice. In the liver in both strains of mice, the effects of macrophage depletion on virus titer were not as much as those in the spleen and lungs. Furthermore, the local depletion of peritoneal macrophages resulted in a great increase of virus titer in the spleen at three days after intraperitoneal infection. We conclude that macrophages greatly contribute to decreasing the virus load in some organs possibly through either or both intrinsic and extrinsic mechanisms in the early phase of primary infection with murine cytomegalovirus.

Acute Disease↗
PubMed1998

Estrogen receptor mutations and changes in estrogen receptor and progesterone receptor protein expression in metastatic or recurrent breast cancer.

To investigate the frequency of estrogen receptor (ER) gene mutation in metastatic or recurrent breast cancer, metastatic lymph nodes or recurrent breast cancer tissue from 35 patients with ER-positive primary tumors were screened for mutations in the hormone-binding domain of the ER gene by sequence analysis. Four missense mutations, Val316Ile, Gly344Val, Ala430Val and Gly494Val, were identified in these lesions. Second, to clarify whether there is any disparity in hormone receptor status between primary and metastatic or recurrent tumors, we immunohistochemically studied 117 specimens including the above 35 specimens obtained from metastatic or recurrent breast cancer patients using monoclonal anti-ER and progesterone receptor (PgR) antibodies. Although hormone receptor status, especially ER, was highly maintained through disease progression, negative change in PgR expression at relapse (33%) was identified more frequently than in metastatic lymph nodes (6.7%). Therefore, it was suggested that development of PgR-negative phenotype might correlate with disease progression in some breast cancer patients. These results suggest that ER mutations in metastatic or recurrent breast cancer may be more frequent than in primary lesions, irrespective of high maintenance of ER protein expression through disease progression.

Breast Neoplasms↗
PubMed1998

Expression of MRP and cMOAT in childhood neuroblastomas and malignant liver tumors and its relevance to clinical behavior.

Advanced neuroblastoma and malignant liver tumor are representative childhood cancers for which combined chemotherapy including cisplatin and doxorubicin is routinely performed. The prognosis of patients with tumors which develop multiple drug resistance (MDR) is unfavorable. To elucidate the role of multidrug resistance-associated protein (MRP) and canalicular multispecific organic anion transporter (cMOAT) in the clinical behavior of the tumors, we examined 42 neuroblastomas and 10 malignant liver tumors for the expressions of MRP and cMOAT by quantitative RNA-polymerase chain reaction (PCR). The amplification and expression of N-myc oncogene in the neuroblastomas were also investigated. We found a close association between MRP and N-myc expression in each neuroblastoma sample but no significant relationship between MRP expression and the patients' outcome. The forced expression of N-myc failed to enhance the expression of MRP in N-myc transfected neuroblastoma cell lines. cMOAT was rarely expressed in the neuroblastomas, but was frequently expressed in the malignant liver tumors. The expression of MRP and cMOAT in the childhood liver tumors was more common and higher, especially in advanced cases with a poor outcome, than that observed in normal liver or in 9 hepatocellular carcinomas from adult patients. The enhanced expression of these genes might be characteristic of childhood malignant liver tumors and related to their clinical chemoresistance.

ATP-Binding Cassette Transporters↗
PubMed1998

In vivo adenovirus-mediated prodrug gene therapy for carcinoembryonic antigen-producing pancreatic cancer.

In gene therapy for malignancy, the herpes simplex virus thymidine kinase (HSVtk)-ganciclovir (GCV) system has been widely used. For pancreatic cancer targeting, we estimated the therapeutic efficacy of gene transduction by an adenovirus-carrying HSVtk gene under the control of a carcinoembryonic antigen (CEA) promoter (AdCEAtk) followed by systemic administration of GCV. Four cell lines, CEA-producing Su.86.86. BxPC-3 (pancreatic cancer cells), MKN45 (gastric cancer cells) and CEA-nonproducing HeLa, were used for analysis of GCV sensitivity induced by adenoviral gene transduction. To evaluate the therapeutic efficacy of AdCEAtk and GCV administration in human CEA-positive pancreatic cancer in vivo, a subcutaneously implanted tumor-bearing nude mouse model was used. When the HSVtk gene was transduced with a ubiquitous promoter into these cells, increase of the GCV sensitivity was independent of CEA-production. In contrast, when the cells were transduced with a CEA promoter, the cell-killing effect of GCV was increased in only CEA-producing cells. For in vivo analysis, AdCEAtk was delivered into subcutaneously established tumors of Su.86.86 cells. Immunohistochemical staining of the tumor showed that HSVtk protein was expressed only in tumor cells, and tumor growth was markedly suppressed by administration of GCV. These results suggest that the adenovirus-mediated transfer of HSVtk gene with CEA promoter specifically increases the GCV sensitivity of CEA-producing pancreatic cancer cells in vitro and in vivo. This strategy may provide a useful tool for treating pancreatic cancer, especially CEA-producing tumor cells.

Adenoviridae↗
PubMed1998

Time course of changes in the intestinal permeability of food-sensitized rats after oral allergen challenge.

Rats were sensitized with ovalbumin (OVA) with a molecular weight of 45 kd, challenged with OVA orally, followed by orally administered beta-lactoglobulin (BLG) as an intestinal permeability marker. BLG is a macro-molecular protein with a molecular weight of 18 kd. Blood BLG concentrations were measured (by ELISA) serially over 4 hours following BLG administration, which in turn was given 1 hour after OVA challenges. The maximum BLG concentration was at 2 hours. BLG was then administered orally 1, 3, 6, 12 and 24 hours after oral OVA challenge, and the serum BLG concentration at 2 hours after BLG administration was compared among the five groups. BLG appeared in the circulation of the animals 1, 6 and 24 hours after allergen challenge, but not after 3 and 12 hours. The serum BLG concentration was not significantly different at 1, 6 and 24 hours. Histopathological examinations of the intestines showed mast cell infiltration of the intestinal mucosa at 1 hour, remarkable edema of villi at 3 hours, eosinophil infiltration at 6 hours, an increase of goblet cells at 12 hours and villous atrophy and lymphocyte infiltration at 24 hours. The appearance in the serum of three BLG peaks of comparable heights suggested that the intestinal absorption of BLG may be related to a late and delayed phase as well as the immediate IgE-dependent phase response.

Administration, Oral↗
PubMed1998

Effects of the timing of exercise on the night sleep.

The effects of physical exercises taken at different times in the day upon subjective sleep feeling were examined in five healthy university students (aged 20-22 years); morning exercise, evening exercise, and late evening exercise. The late evening exercise with the strength of 50-60% VO2max of 1 h has the effect of getting better subjective sleep feeling in the morning and the effect of the decreased daytime sleepiness.

Adult↗
PubMed1998

Histological and biological characteristics of microinvasion in mammary carcinomas < or = 2 cm in diameter.

Fifty-two mammary carcinomas, 2 cm or less in diameter, were examined in order to clarify the morphology and biology of microinvasion. The morphological characteristics of microinvasion of carcinomas include: (i) a loss of myoepithelial cells and a rupture with concomitant loss of collagen IV and laminin in the basement membrane of involved mammary glands; and (ii) budding of carcinomas from the rupture into the stroma. When microinvasion was defined as a rupture of < 200 microm in the basement membrane with invasion, the number of microinvasions per 1 mm of basement membrane was larger in the tumors in which the area of invasion was larger. The prevalence of microinvasion showed a significant correlation with lymph node metastasis and the rate of histological deviation, while no correlation of expression of either estrogen receptors or progesterone receptors and c-erbB-2 protein was found. The study clarified that the early invasion of mammary carcinomas could be detected by the immunohistochemical method using anti-smooth muscle actin, laminin and collagen IV antibodies. The study also suggested that microinvasion might be an indicator of lymph node metastasis in mammary carcinomas < or = 2 cm diameter.

Adenocarcinoma, Papillary↗
PubMed1998

The expression of thymidine phosphorylase/platelet-derived endothelial cell growth factor is correlated to angiogenesis in breast cancer.

It has been shown that human thymidine phosphorylase (TP) is identical to platelet-derived endothelial cell growth factor and has angiogenic activity. In the present study, the expression of TP was examined in 139 mammary carcinomas and 35 benign mammary disorders using biochemical and immunohistochemical methods. Moreover, in order to evaluate the significance of TP expression in mammary carcinomas, the relationship between vascular density and various clinicopathological factors, including age and menopausal status of patients with a mammary carcinoma, were compared with the size, nodal status, expression of estrogen receptor (ER), progesterone receptor (PgR), c-erbB-2, p53 and TP of a mammary carcinoma. Thymidine phosphorylase expression increased in both the nuclei and cytoplasm of mammary carcinoma cells in comparison to mammary benign disorder cells. The number of microvessels in mammary carcinomas was generally correlated to the number of tumor cells with TP expression in cytoplasm. The number of cells with TP expression in cytoplasm was significantly large in tumors that measured 3-4 cm in diameter, compared with tumors measuring 1-2 and 5-6 cm in diameter. In mammary tumors of 1-4 cm diameter, TP expression and vessel density were significantly high in tumors negative for ER or positive for c-erbB2 and in tumors positive for TP or c-erbB2, respectively; whereas tumors of 5-6 cm in diameter were not modified by any clinicopathological factors. The results indicated that TP plays an important angiogenetic role in mammary carcinomas, especially tumors with a certain progression.

Adult↗
PubMed1998

Immunohistochemical studies on expression of human vascular smooth muscle myosin heavy chain isoforms in normal mammary glands, benign mammary disorders and mammary carcinomas.

The expression of myosin in normal and diseased mammary glands of 199 Japanese women was evaluated immunohistochemically by the avidin-biotin peroxidase complex method using antibodies to three human smooth muscle myosin heavy chain isoforms derived from the vascular smooth muscle: myosin SM1 is expressed consistently from fetal stage to adulthood, myosin SM2 appears only in well-differentiated smooth muscle after birth, and myosin SMemb is more abundant in embryonic aortas. SM1 was expressed in myoepithelial cells of normal mammary glands and fibrocystic diseases and in myoepithelial-like tumor cells in the basal layer of fibroadenomas and phyllodes tumors. SM2 was expressed only in the myoepithelial cells of mammary glands in breastfeeding women. SMemb was expressed more intensely in the cytoplasm of luminal epithelial cells in larger fibroadenomas (P< 0.01), or in the cytoplasm of carcinoma cells in invasive ductal carcinomas with metastasized lymph nodes (P< 0.001) and in those of higher histological grade (P<0.0001). Multivariate logistic analysis showed a significant correlation only between the expression of SMemb and histological grade (P< 0.0001), which is a prognostic factor of mammary carcinomas. These findings suggested the possible prognostic value of SMemb.

Adolescent↗
PubMed1998

Long-term results of definitive treatment in elderly patients with localized prostate cancer.

BACKGROUND: The indication and effectiveness of definitive local treatment for prostate cancer in patients with a limited life expectancy remains to be established. This study is a retrospective analysis of the long-term clinical outcome of elderly patients with localized prostate cancer treated by radiotherapy or a radical prostatectomy. METHODS: From 1982 to 1992, 37 patients with localized prostate cancer, aged 70 years or older, were treated initially by a pelvic lymphadenectomy and then with either external radiotherapy (n = 1 7) or a radical retropubic prostatectomy (n = 20). Lymph node metastasis was negative in all the cases, and no patients received hormonal treatment after the lymphadenectomy. The outcome of all patients was evaluated in June 1997. RESULTS: The 10-year overall and relative survival rates for the radiotherapy group were 27% and 85%, which were not significantly different from the rates of patients in the prostatectomy group (38% and 74%, respectively). The 5-year progression free rates for the radiotherapy group and the prostatectomy group were 63% and 95%, respectively (P= 0.06). CONCLUSION: In elderly patients with localized prostate cancer, the superiority of a radical prostatectomy over radiotherapy was not demonstrated in terms of either overall or relative survival rates, although the progression rate tended to be higher in patients in the radiotherapy group. The indication of definitive treatment in elderly patients should be further studied incorporating a quality of life assessment.

Aged↗
PubMed1998

Mesangiolytic glomerulopathy in severe congestive heart failure.

To study the glomerular morphological abnormalities in congestive heart failure (CHF), we analyzed 27 autopsy cases without other causes of renal disease. Their mean age was 59 years, and they showed mild prerenal azotemia. They had generally been treated with digitalis and diuretics, and a few of them with captopril or nifedipine. The abnormal glomerular findings of enlargement, hyperemia, and mesangial thickening were observed at high frequencies (61%, 64%, and 57%, respectively). They characteristically showed mesangiolysis (ML) by the findings of microaneurysms (81%) and mesangial degeneration (70%) such as loose reticular matrix and poor matrix area. In addition, glomerular infiltration of mononuclear leukocytes including macrophages was noted in 70% of the cases. Glomerular enlargement was not correlated with the grade of hyperemia, but it was correlated with the grade of ML index of % glomeruli with microaneurysms (F = 7.22, p < 0.004). There was an inverse relationship between the grades of mesangial thickening and of the ML index (P < 0.005). The number of glomerular leukocytes was positively correlated with mean glomerular size (P < 0.002) and with the ML index (P < 0.03). Notably, the glomerular macrophage-positive cases showed a prominently higher mean ML index than the negative cases (P < 0.005). There was an inverse correlation between the mean glomerular size and the partial oxygen pressure in arterial blood (PaO2; P < 0.01), and a positive correlation between the mean glomerular size and hematocrit (Hct) levels (P < 0.02). The cases positive for mesangiolytic mesangial degeneration showed significantly lower PaO2 values than the cases negative for this lesion (P < 0.04). In the analysis of the various causes of CHF, the patients with congenital cardiac anomalies showed mean levels of the lowest PaO2 (P < 0.02) and the highest Hct (P < 0.03) and histologically the largest mean glomerular size (P < 0.04). There was no difference in the ML index and the glomerular leukocyte number among the subgroups classified by the causes. These results indicate that ML associated with glomerular enlargement is the major glomerular abnormality characteristic in patients with severe CHF and suggest that glomerular infiltration of leukocytes, especially of macrophages, should play an important role in the progression of both ML and glomerulomegaly. The contributions of persistent hypoxia and up-regulated angiotensin II as the causative factors of these glomerular abnormalities in congestive heart failure are discussed.

Adult↗
PubMed1998

Optimally weighted wavelet transform based on supervised training for detection of microcalcifications in digital mammograms.

We are developing a computer-aided diagnosis (CAD) scheme for detection of clustered microcalcifications in digital mammograms. The use of an empirically chosen wavelet and scale combination for detection of microcalcifications as an initial step of the CAD scheme has been reported by us previously. In this study, we developed a technique for optimizing the weights at individual scales in the wavelet transform to improve the performance of our CAD scheme based on the supervised learning method. In the learning process, an error function was formulated to represent the difference between a desired output and the reconstructed image obtained from weighted wavelet coefficients for a given mammogram. The error function was then minimized by modifying the weights for wavelet coefficients by means of a conjugate gradient algorithm. The Least Asymmetric Daubechies' wavelets were optimized with 297 regions of interest (ROIs) as a training set by a jackknife method. The performance of the optimally weighted wavelets was evaluated by means of receiver-operating characteristic (ROC) analysis by use of the above set of ROIs. The analysis yielded an average area under the ROC curve of 0.92, which outperforms the difference-image technique used in our existing CAD scheme, as well as the partial reconstruction method used in our previous study.

Biophysical Phenomena↗
PubMed1998

A genetic algorithm-based method for optimizing the performance of a computer-aided diagnosis scheme for detection of clustered microcalcifications in mammograms.

Computer-aided diagnosis (CAD) schemes have the potential of substantially increasing diagnostic accuracy in mammography by providing the advantages of having a second reader. Our laboratory has developed a CAD scheme for detecting clustered microcalcifications in digital mammograms that is being tested clinically at the University of Chicago Hospitals. Our CAD scheme contains a large number of parameters such as filter weights, threshold levels, and region of interest (ROI) sizes. The choice of these parameter values determines the overall performance of the system and thus must be carefully set. Unfortunately, when the number of parameters becomes large, it is very difficult to obtain the optimal performance, especially when the values of the parameters are correlated with each other. In this study, we address the problem of identifying the optimal overall performance by developing an automated method for the determination of the parameter values that maximize the performance of a mammographic CAD scheme. Our method utilizes a genetic algorithm to search through the possible parameter values, and provides the set of parameters that minimize a cost function which measures the performance of the scheme. Using a database of 89 digitized mammograms, our method demonstrated that the sensitivity of our CAD scheme can be increased from 80% to 87% at a false positive rate of 1.0 per image. We estimate the average performance of our CAD scheme on unknown cases by performing jackknife tests; this was previously not feasible when the parameters of the CAD scheme were determined in a nonautomated manner.

Algorithms↗
PubMed1998

Use of a gastric juice-based PCR assay to detect Helicobacter pylori infection in culture-negative patients.

A gastric juice-based PCR assay was compared with culture, microscopy, and a rapid urease test with specimens from 114 subjects. The PCR and conventional tests were positive for 76 and 62% of the subjects, respectively. The prevalence of gastroduodenal disease and seropositivity for anti-Helicobacter pylori immunoglobulin G were similarly high among conventional-test-positive and PCR-only-positive subjects compared to all-negative ones. The PCR assay is recommended to confirm the H. pylori status of culture-negative peptic-ulcer patients.

Adult↗
PubMed1998

Deletion polymorphism of the angiotensin converting enzyme gene predicts persistent proteinuria in Henoch-Schönlein purpura nephritis.

OBJECTIVE: To study the influence of deletion/insertion polymorphism in the 16th intron of the angiotensin converting enzyme (ACE) gene on clinical manifestations of Henoch-Schönlein purpura nephritis. STUDY DESIGN: Cross sectional study. ACE gene polymorphism was determined in patients (4-15 years old at onset) with Henoch-Schönlein purpura nephritis (n = 40) and compared with that in patients with IgA nephropathy (n = 79). MAIN OUTCOME MEASURES: ACE genotypes, systemic blood pressures, urine protein excretion rate, haematuria, creatinine clearance, serum ACE activities. RESULTS: The initial clinical manifestations of both Henoch-Schönlein purpura nephritis and IgA nephropathy were no different among homozygotes for insertion (II) and deletion (DD), and heterozygotes (ID) for the ACE gene. In patients with Henoch-Schönlein purpura nephritis, the incidence of moderate to heavy proteinuria at four and eight years after onset was more than five times higher in the DD genotype than in the II or ID genotypes. No such trend was seen in patients with IgA nephropathy. The number of patients with Henoch-Schönlein purpura nephritis in whom proteinuria resolved at four and eight years after onset was significantly lower in the DD genotype compared with the II genotype, whereas no differences were detected among the three different genotypes in patients with IgA nephropathy. Plasma ACE activities in patients with the DD genotype were significantly higher than in those with non-DD genotypes. CONCLUSIONS: The ACE DD genotype predicts persistent proteinuria in Henoch-Schönlein purpura nephritis. The proteinuria might be related to a defective angiotensin system which is genetically determined by the D/I polymorphism.

Adolescent↗
PubMed1998

Analysis of effects of stimulation in vitro of ovalbumin primed lymph node cells on adoptive transfer of experimental immune mediated blepharoconjunctivitis in Lewis rats.

AIM: To analyse the role of stimulation in vitro of lymphocytes on the augmentation of experimental immune mediated blepharoconjunctivitis (EC, formerly EAC) in Lewis rats induced by adoptive transfer. METHODS: Two weeks after immunisation with ovalbumin (OVA), rat draining lymph nodes were collected and 50 x 10(6) cells were injected into naive syngeneic recipients either directly or after culture in vitro with OVA, concanavalin A (Con A), or purified protein derivative (PPD) for 3 days. Four days after injection the rats were topically challenged with OVA. 24 hours later, they were sacrificed and eyes and spleens were harvested for histology and proliferation assay. In some experiments, naive recipient rats were irradiated with 7 Gy gamma ray before transfer. The expression of adhesion molecules and cytokine profile of OVA primed lymph node cells were also investigated. RESULTS: Both infiltrated cell number and splenocyte proliferation in the recipients of stimulated cells were higher than those of unstimulated cells. In vitro stimulation with OVA or Con A induced a severe cellular infiltration, while stimulation with PPD did not. Irradiation markedly diminished cellular infiltration. Stimulation in vitro upregulated the CD4/CD8 ratio by four times and augmented expression of CD25, I-A, ICAM-1 molecules on OVA primed lymph node cells by about five times. IFN-gamma was detected in OVA primed cells by stimulation in vitro, while IL-4 mRNA was extinguished by stimulation in vitro. CONCLUSIONS: Augmentation of EC by stimulation in vitro of transferred lymphocytes might depend on the upregulation of expression of cell surface molecules and cytokine shift as well as augmented antigen specificity.

Adoptive Transfer↗
PubMed1998

Major virulence factors, VacA and CagA, are commonly positive in Helicobacter pylori isolates in Japan.

BACKGROUND: VacA and CagA proteins have been reported to be major virulence factors of Helicobacter pylori. However, antibodies against these proteins are frequently found in the sera of Japanese patients regardless of their gastroduodenal status. AIM: To evaluate the expression of VacA and CagA proteins by H pylori strains isolated in Japan. METHODS: By using specific antibodies raised against recombinant VacA and CagA proteins, the expression of VacA and CagA was evaluated in 68 H pylori strains isolated from Japanese patients; a vacuolating assay and genotyping of the vacA gene were also used in the evaluation. The results in analysed in relation to the gastroduodenal diseases of the hosts. RESULTS: VacA and CagA proteins were expressed in 59/68 (87%) and in 61/68 (90%) isolates respectively. The vacuolating assay was positive in 57/68 (84%) isolates, indicating that most immunologically VacA positive strains produced active cytotoxin. The prevalence of infection with strains expressing CagA and positive for vacuolating activity (Type I) was very high, 54/68 (79%), irrespective of the gastroduodenal status of the host. CONCLUSION: Most H pylori isolates in Japan are positive for vacuolating cytotoxin and CagA, and thus these virulence factors cannot be used as markers to discern the risk of developing serious gastroduodenal pathologies in the hosts. However, the high prevalence of infection with strains positive for vacuolating cytotoxin and CagA may contribute to the characteristics of H pylori infection in Japan.

Adult↗