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Biomedical subjects

M Mochizuki

Publications and source records attributed to M Mochizuki.

At least 235 records · Page 13Linked to original sources

[Pathological characterization of atypical ductal hyperplasia of the breast].

To clarify the pathological features of atypical ductal hyperplasia (ADH) defined by Page's criteria, histological patterns and the extent of 17 lesions of ADH including clinging carcinoma were examined. The nuclear measurements (mean nuclear area and irregularity of nuclear shape) and the MIB-1 labeling index of ADH were compared with those of noncomedo DCIS with lower grade nuclei, and usual ductal hyperplasia (DH). All ADH were classified into cribriform or micropapillary/clinging types. The extent of ADH was always less than 2.5 mm in the cribriform type (1.4 mm in average), against 5 mm or greater in 6 of 8 lesions of the micropapillary/clinging type (7.1 mm in average). Nuclei of ADH tended to be smaller (< or = 8 microns) than DH and DCIS (p < 0.05), and less irregular in shape than DH (p < 0.01), although indistinguishable from lower grade nuclei of DCIS using these parameters. The MIB-1 labeling index of ADH was very low (0-2.3%) and was the best parameter to distinguish from DCIS (p < 0.01). It was also suggested that the lower level of proliferative activity is one of the most distinctive features of ADH.

Breast↗

[Expression of epidermal growth factor, transforming growth factor-alpha and epidermal growth factor receptor messenger RNA in human endometrium and endometrial carcinoma].

To study the regulation of c-erbB, EFG and TGF-alpha in endometrium, we examined the expression of their mRNA in 5 normal endometrial and 5 endometrial carcinoma tissues by Northern blot and reverse transcription-polymerase chain reaction (RT-PCR). By Northern blot with 10 micrograms of total RNA, c-erbB mRNA was not detected in the normal endometrium, but it was detected in 3 samples of endometrial carcinoma tissues. On the other hand RT-PCR identified c-erbB mRNA in all the normal endometrium and endometrial carcinoma tissues by amplifying cDNA derived from c-erbB mRNA. EGF mRNA was detected by RT-PCR in normal endometrium except in the early follicular phase. It was detected in all cases of endometrial carcinoma tissues. TGF-alpha mRNA was also detected in all the normal and endometrial carcinoma tissues by RT-PCR. Our study suggests that an autocrine/paracrine mechanism of EGF may regulate the endometrial cycle. Because some endometrial carcinoma tissues express the c-erbB mRNA much more than normal endometrium, disruption of the autocrine/paracrine mechanism may trigger subsequent endometrial carcinogenesis.

Adenocarcinoma↗

Polyclonal use of T-cell receptor alpha for human T-cell lymphotropic virus type 1-infected T cells.

PURPOSE: To understand better the immunopathology of HTLV-I uveitis by investigating the clonality of HTLV-I-infected T-cell clones. METHODS: Eleven T-cell clones were established from the aqueous humor (six clones) and the peripheral blood (five clones) of a patient with HTLV-I uveitis, and the clonality of the HTLV-I-infected T cells was investigated by sequencing the T-cell receptor (TCR) alpha gene after the amplification of TCR alpha cDNA using an adaptor-ligation method and reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: TCR alpha use was different for each of 11 T-cell clones, encompassing eight different HTLV-I-infected T-cell clones (four from the aqueous humor and four from peripheral blood) and three HTLV-I-negative T-cell clones. CONCLUSIONS: This study demonstrated polyclonal use of TCR alpha for HTLV-I-infected T cells in the ocular lesion and the peripheral blood. Results suggested that these T cells are not precursors of the leukemic cells associated with malignant transformation. Instead, they might be randomly infected with HTLV-I in the process of HTLV-I uveitis.

Amino Acid Sequence↗

Detection of c-ras gene mutation and expression of p21 protein in dysplasias and carcinomas complicating ulcerative colitis.

Point mutations of c-ras genes and the expression of p21 protein were analyzed in 13 patients with colorectal carcinoma complicating ulcerative colitis; in 12 of the 13, there were dysplastic lesions close to the carcinomas. Point mutations of c-ras genes were studied by polymerase chain reaction and dot blot hybridization with 32p-labeled oligonucleotide probes. Findings indicated mutations of c-Ki-ras at condons 12, 13, and 61 and c-Ha-ras and c-N-ras at condons 12 and 61. The expression of p21 protein was analyzed by immunohistochemical staining using a monoclonal antibody. Only 1 of the 13 patients with carcinoma showed a point mutation, this being from G to A transition at the second position of codon 12 of c-Ki-ras. No point mutations of c-Ki-ras, c-Ha-ras, or c-N-ras were found in other carcinomatous lesions and dysplasias. In the dysplastic or carcinomatous lesions of 11 patients, the increased expression of p21 protein was observed. These results suggest that point mutations of c-ras genes are rare in dysplasias and carcinomas complicating ulcerative colitis and that the increased expression of p21 protein is not always correlated with point mutations of c-ras genes.

Colitis, Ulcerative↗

[A phase II study of FK506 (tacrolimus) on refractory uveitis associated with Behçet's disease and allied conditions].

A multicenter open study was conducted to investigate optimum dose schedule of FK506 on refractory uveitis associated with Behçet's disease and allied conditions. Fifty-three patients (41 with Behçet's and 12 with allied conditions) were enrolled in this study. A daily oral dose of FK506 was initially 0.05, 0.1, 0.15 or 0.2 mg/kg, but adjusted in more than half patients during the study based on clinical conditions of patients and/or adverse effects of FK506. The improvement rate of initial daily dose as well as final improvement rate were evaluated in the study. The improvement rate of initial daily dose was increased dose-dependently; 37.5% with 0.05 mg/kg initial daily dose group, 60.0% with 0.1 mg/kg, 91.7% with 0.15 mg/kg and 78.6% with 0.2 mg/kg. The final improvement rate was 76.5%. In patients with Behçet's disease, ocular symptoms improved in 30 (75.0%) of 40 patients evaluable for efficacy and the frequency of ocular attacks was significantly reduced. In eight (66.7%) of 12 patients with Behçet's disease in whom cyclosporin treatment had been failed, their ocular symptoms improved by FK506. Main adverse reactions of FK506 were renal impairment (28.3%), neurologic symptoms (22.6%), gastrointestinal symptoms (20.8%), hypomagnesemia (28.3%), hyperkalemia (13.2%), and hyperglycemia (13.2%. Most of the adverse effects disappeared or ameliorated after FK506 dose reduction or withdrawal from FK506 therapy. It seems that the incidence of the adverse effects depends on the dosage of FK506. The lower dosage (0.05 and 0.1 mg/kg) caused a relatively small number of adverse effects, and the higher dosage (0.15 and 0.2 mg/kg) caused them more frequently. Through level is recommended to maintain between 15-25 ng/ml during early days of treatment based on the safety and efficacy. It is also recommended that a initial daily dose is 0.15 mg/kg on the basis of the efficacy and safety results, and then adjusted based on symptoms of patients and whole blood through level of FK506.

Administration, Oral↗

Insulin-like growth factor-I as a local regulator of proliferation and differentiated function of the human trophoblast in early pregnancy.

In order to elucidate the role of insulin-like growth factor-I (IGF-I) in human placental growth and function, the effects of IGF-I on the proliferation and differentiation of trophoblasts were investigated using an organ culture system of early placental tissues. Explants of trophoblastic tissues obtained from 4-5-week or 6-12-week placentae were, respectively, cultured with or without IGF-I, in a serum-free condition. The effect of IGF-I on the proliferative activity of trophoblasts was examined by immunocytochemical techniques with a monoclonal antibody to proliferating cell nuclear antigen (PCNA), while the effect of IGF-I on the differentiated function of trophoblasts was assessed by determining the ability to secrete human chorionic gonadotropin (hCG) and human placental lactogen (hPL). In 4-5-week placentae, IGF-I and IGF-I receptor were almost exclusively localized in cytotrophoblasts and IGF-I augmented the proliferative activity of cytotrophoblasts without affecting the ability to secrete hCG and hPL. By contrast, in 6-12-week placentae, IGF-I and IGF-I receptor were localized in both cytotrophoblasts and syncytiotrophoblasts and IGF-I stimulated the secretion of hCG and hPL following the enhancement of the proliferative activity of trophoblasts. In column chromatography of the serum-free medium obtained following 5-day culture of early placental tissues, an elution peak of immunoreactive IGF-I was found in the fractions similar to the elution region of [125I]IGF-I. These findings suggest that IGF-I acts as an autocrine/paracrine factor in regulating early placental growth and function.

Cell Differentiation↗

[Maternal nutritional states and serum insulin-like growth factor-I (IGF-I) concentrations in normal and abnormal pregnancy].

It is well known that serum IGF-I concentrations are regulated endocrinologically since IGF-I has a growth-promoting action as a mediator of growth hormone. However, recent reports suggest that nutritional states influence serum IGF-I concentration because IGF-I shows anabolic effects like insulin. The aim of this study was to clarify the influences of maternal nutritional states or metabolism on the IGF-I concentrations in normal and abnormal pregnancy. In normal pregnant women, a significant positive correlation was indicated between serum IGF-I concentrations and maternal weight gain during pregnancy or serum triglyceride levels, and a significant negative correlation was observed between serum IGF-I concentrations and serum total protein levels. In the cases complicated with hyperemesis or hyperthyroidism during early gestation, a marked reduction of maternal body weight was observed, and serum IGF-I concentration was extremely low compared with that in normal pregnant women, but serum IGF-I levels gradually increased as the maternal body weight recovered after treatment by intravenous hyperalimentation or an anti-thyroid drug. In cases of severe toxemia of pregnancy, maternal weight gain and serum triglyceride levels were markedly increased, but serum IGF-I levels were significantly lower compared with those in normal pregnant women in the same gestational age. In severe toxemia of pregnancy, there was no significant correlation between serum IGF-I levels and maternal weight gain or serum triglyceride levels, and these results may be influenced by such abnormalities as water retention, hemoconcentration, severe hypoproteinemia and severe negative nitrogen balance not found in normal pregnancy. In conclusion, it is considered that IGF-I concentration is regulated not only by endocrinological factors, but also by metabolic factors in maternal circulation during pregnancy, and the measurement of maternal IGF-I concentration seems to be a useful parameter to evaluate the maternal nutritional states.

Adult↗

[The relationship between the changes in insulin-like growth factor-1 (IGF-1) and the nutritional states evaluated by nitrogen balance in pregnant rats].

The effects of nutrition on serum insulin-like growth factor-1 (IGF-1) concentrations during pregnancy of rats were investigated by using rat cultured hepatocytes in vitro, and by the assessment of nitrogen balance in vivo. IGF-1 concentration was measured by radioimmunoassay, and nitrogen balance was calculated by Pregl-Dumas method. The results were as follows: (1) Cultured rat hepatocytes produced IGF-1 in medium and it was significantly stimulated by the addition of various concentrations of glucose (1.1-4.4 mM) and/or several amino acid concentrations in a dose-related manner. (2) Serum IGF-1 concentrations, which indicated 368.6 +/- 143.8 ng/ml in a non-pregnant fed state, markedly decreased in a fasted state, reaching the levels of 143.8 +/- 30.4 ng/ml after 72 hours fasting. Nitrogen balance in these fasted rats also decreased according to the fasted period. (3) In early pregnancy (Day 0-12), serum IGF-1 concentrations were indistinguishable from those of non-pregnant fed rats. It gradually declined after the 13th day of pregnancy and reached the minimum levels of 77.0 +/- 12.1 ng/ml on the 21st day. On the other hand, mean nitrogen balance which was calculated from the difference of nitrogen retention in the maternal body and that in the fetal body, also decreased after 13 days of pregnancy and reached the levels of 14.9 g/day on the 21st day of pregnancy. These results suggested that IGF-1 concentrations in rat serum and conditioned medium might be regulated by nutritional factors, i.e., glucose and/or several amino acids. The curious profiles of IGF-1 concentrations observed in pregnant rats might be due in part to the effects of nutritional changes between the maternal and fetal body, especially, the changes of protein metabolism represented by the nitrogen balance.

Animals↗

Fine antigen specificity of human gamma delta T cell lines (V gamma 9+) established by repetitive stimulation with a serotype (KTH-1) of a gram-positive bacterium, Streptococcus sanguis.

We have established human gamma delta T cell lines specific for Streptococcus sanguis (S. sanguis) KTH-1 present in normal oral cavity flora. The CD4-CD8-CD3+V gamma 9+V delta 1-CD45RO+ CD25+ T cell lines showed a proliferative response to the streptococcal antigen (Ag) in the presence of autologous antigen-presenting cells without apparent evidence of HLA restriction. The proliferative response of the gamma delta T cell lines was completely blocked by anti-TcR gamma delta monoclonal antibody (mAb) and anti-HLA class I mAb (W6/32), whereas anti-HLA classical class Ia mAb (B-H9; anti-HLA-A,B,C), anti-HLA class II mAb (anti-DR, anti-DQ, and anti-DP) and anti-CD4 mAb did not have any inhibitory effects. Surprisingly, the gamma delta T cell lines showed the proliferative response against the original bacterial Ag KTH-1 exclusively, and exhibited no cross-reactivity with nominal Ag such as purified protein derivative of tuberculin, tetanus toxoid and Mycobacterium tuberculosis, or the same species but different strain of S. sanguis, American Type Culture Collection (ATCC) standard strain (10556), or even with the same strain but different serotype of S. sanguis, KTH-3. Moreover, cytokine production of the gamma delta T cell lines was similar to the Th1 pattern [interferon-gamma, tumor necrosis factor (TNF)-alpha and TNF-beta]. They also produced interleukin-8 that functions as one of chemoattractants for polymorphonuclear cells. Using direct sequencing technique of the polymerase chain reaction products, we found that junctional diversity of the T cell receptor (TcR) used by the parental KTH-1 specific gamma delta T cell line and its subclones is rather limited. It is suggested that gamma delta T cells with canonical TcR could preferentially respond to KTH-1 Ag. Thus, in addition to a broad or cross-reactivity of gamma delta T cells against phylogenetically conserved stress/heat-shock protein, which is well characterized by others, some peripheral blood gamma delta T cells could recognize and kill exogenous agents with fine antigenic specificity to protect the body against them.

Antigens, Bacterial↗

Effects of bucillamine, a new anti-rheumatic drug, on the experimental autoimmune uveitis in rats.

The in vitro and in vivo effects of a new immunomodulating agent, bucillamine, on experimental autoimmune uveitis (EAU) was studied in the rat. The capacity of S-antigen-sensitized lymphocytes to proliferate in response to the antigen or to produce antigen-specific antibodies was significantly suppressed by bucillamine in culture in a dose-dependent manner. The inhibitory effect of bucillamine was significantly enhanced by adding cyclosporin A (CYA) in the culture. The in vivo effects of bucillamine alone or in combination with CYA were further examined in Lewis rats immunized with S-antigen. All untreated rats developed severe EAU 17 days after S-antigen immunization, while rats treated with either bucillamine (200 mg kg-1 day-1) or CYA (2 mg kg-1 day-1) demonstrated milder symptoms of EAU. A combination therapy with bucillamine (20 or 200 mg kg-1 day-1) and CYA (2 mg kg-1 day-1) exhibited much more significant suppression of EAU induction. Although the in vivo treatment with bucillamine or CYA had no effects on the T-cell populations of spleen cells, the combination therapy significantly decreased the CD4+ T-cell population. As for the immune responses to S-antigen in drug-treated rats, bucillamine suppressed the lymphocyte proliferation to S-antigen, which was further suppressed by combination therapy with CYA. The serum antibody levels specific to S-antigen were not affected by tested dose of bucillamine.

Animals↗

Murine experimental autoimmune uveoretinitis induced by interphotoreceptor retinoid-binding protein and Klebsiella pneumoniae 03 lipopolysaccharide (K03-LPS): a relation between H-2 haplotype and EAU induction.

The pathogenicity of interphotoreceptor retinoid-binding protein (IRBP) in the mouse and H-2 restriction of IRBP-induced experimental autoimmune uveoretinitis (EAU) was tested by repeated immunization using Klebsiella pneumoniae 03 lipopolysaccharide (K03-LPS) as an adjuvant. It was shown that IRBP had a greater capacity to induce EAU than S-antigen. Based on the incidence of EAU induction using B10 congenic mice and other strains, the susceptibility to EAU was, at least in part, controlled by the I-Ak haplotype of the H-2 subregion. The results also indicated that non-major histocompatibility complex (MHC) genes play some role in disease susceptibility.

Animals↗

Value of thallium-201 early reinjection for assessment of myocardial viability.

To assess the efficacy of early reinjection for predicting post intervention improvement in thallium-201 (T1) uptake and regional wall motion, we reinjected a small dose of T1 following post-stress imaging and obtained reinjection early images (10 min after early reinjection) and reinjection delayed images (3 hr afterwards) in 40 patients who were referred to us for revascularization (group I). Twenty-nine patients in group I also underwent conventional stress-redistribution T1 scintigraphy (group II). Conventional stress-redistribution T1 scintigraphy was repeated after intervention. Contrast left ventriculography was performed before and after intervention and changes in regional wall motion were assessed in 22 of 40 patients. In group I, the predictive value for improvement and no improvement (the accuracy) of reinjection early images in perfusion was 83%, while that of reinjection delayed images was 91%. Furthermore, the accuracy of reinjection early images in regional wall motion was 80%, while it was 91% for reinjection delayed images. In group II, the accuracy in perfusion was 78% and the value in regional wall motion was 70%. Both accuracy in perfusion and in regional wall motion obtained from reinjection delayed images were significantly higher than the values in group II (p < 0.05). These data suggest that early reinjection is useful for predicting postintervention thallium uptake and regional wall motion.

Aged↗

A clinical feature of myocardial stunning associated with acute myocardial infarction.

We report a case of myocardial stunning after acute myocardial infarction. In the hyperacute phase of myocardial infarction, the patient's coronary arteries showed normal features on coronary angiography during extensive ST-segment elevation observed on a standard 12-lead electrocardiogram and extensive akinesis observed on a left ventriculogram. Thallium-201 emission computed tomography revealed extensive perfusion abnormality. In the chronic phase, the perfusion abnormality was markedly improved. However, the electrocardiogram demonstrated poor R wave progression, and the left ventriculography revealed slight hypokinesis in the anterolateral wall. The acetylcholine provocation test disclosed coronary vasospasm of the left anterior descending coronary artery. About six months thereafter, left ventricular wall motion became completely normal and no poor R wave progression was observed on the electrocardiogram. The findings in this case indicate that myocardial stunning resulted from brief but sever ischemia due to vasospasm which led to cardiogenic shock, and that the recovery of findings for thallium-201 perfusion might be followed by those of electrocardiography and left ventriculography in the stunned myocardium.

Acetylcholine↗

Inhibitory effects of recombinant feline interferon on the replication of feline enteropathogenic viruses in vitro.

Antiviral activities of a recombinant feline interferon (rFeIFN) KT-80 were evaluated against feline enteropathogenic viruses in feline and canine cell lines. Sensitivity to antiviral activities of the rFeIFN varied with cell types; Felis catus whole fetus (fcwf-4) cells were more sensitive than Crandell feline kidney cells, but no sensitivity was found for Madin-Darby canine kidney cells when vesicular stomatitis virus was used as a challenge virus. Reductions were generally IFN dose-dependent and were more consistent when the cells were continuously treated with the rFeIFN than when they were pretreated only before viral challenge. Compared with each virus control culture of fcwf-4 cells, yields of rotavirus, feline panleukopenia virus (FPLV), feline calicivirus and feline infectious peritonitis coronavirus were reduced by ranges of 1.3 to < or = 3.1 log10, 0.6 to 1.6 log2, 0.8 to 3.7 log10 and 0.5 to 0.6 log10, respectively, in the cultures continuously treated with 10 to 10000 U of the rFeIFN. The yield reduction of FPLV was considered to be in part attributable to inhibition of cell growth by the rFeIFN supplemented in the medium.

Animals↗

Two G3 feline rotavirus strains lacking cross-neutralization reactions represent distinct subtypes of serotype G3.

Two feline rotavirus strains, FRV-1 and FRV64, that have been shown to lack cross-neutralization reactions despite the sharing of serotype G3 were examined by plaque-reduction neutralization assays in relation to other G3 strains originating from cats, dogs, humans and monkeys. While FRV-1 and human G3 strains constituted one subtype (G3A), FRV64, canine strains and simian strains constituted another subtype (G3B).

Animals↗

Subtype analysis of HTLV-1 in patients with HTLV-1 uveitis.

The hypothesis that HTLV-1 uveitis, a recently identified disease entity associated with human T-cell leukemia virus type I (HTLV-1), is caused by a specific subtype of the virus was tested. The nucleotide sequences of the long terminal repeat of HTLV-1 from five patients with HTLV-1 uveitis (HU) and four with adult T-cell leukemia were phylogenetically analyzed. Our results showed that both subtypes which had been identified in Japan were associated with HU, indicating that there was no difference in pathogenicity between these phylogenetic subtypes. One of the subtypes was more frequently isolated in Okinawa than in Kyushu, suggesting a bias in the prevalence of each subtype among the inhabitants of these two areas of Japan.

Adult↗

[A child with iritis due to Chlamydia pneumoniae infection].

A case of uncommon iritis due to Chlamydia pneumoniae (C. pneumoniae) is reported. The patient was a 9-year-old boy who had suffered from cough, pharyngeal pain, and low grade fever. The symptoms persisted for more than 1 month in spite of an oral cephem antibiotic. Ophthalmalgia, congestion around the iris and cough had lasted with alleviation and exacerbation. A diagnosis of C. pneumoniae infection was made by specific polymerase chain reaction (PCR) method and microimmunofluorescence test (MIF). The symptoms subsided with administration of clarithromycin (CAM: 300 mg/day) for 2 weeks. Because of the simultaneous alleviation of iritis, C. pneumoniae infection was considered to introduce the iritis. Much remains to be clarified about this pathogenesis of iritis and more detailed evaluations are required.

Child↗