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Biomedical subjects

Y Higashi

Publications and source records attributed to Y Higashi.

At least 109 records · Page 6Linked to original sources
PubMed1998

Angiotensin-converting enzyme inhibition, but not calcium antagonism, improves a response of the renal vasculature to L-arginine in patients with essential hypertension.

Endothelial function has been shown to be impaired in patients with essential hypertension. The purpose of the present study was to determine whether antihypertensive drug therapy improves impaired endothelium-dependent renal vasorelaxation in essential hypertensive patients without atherosclerosis. We evaluated the effects of intravenous infusion of L-arginine (500 mg/kg given over 30 minutes) on systemic and renal hemodynamics in 27 patients with mild to moderate essential hypertension who were randomly assigned to treatment with either the angiotensin-converting enzyme inhibitor imidapril or the calcium antagonist amlodipine for 12 weeks in a double-blind fashion. After the 12 weeks, the decrease in blood pressure was similar in the imidapril (n=14) and amlodipine (n=13) groups. The increase in renal plasma flow was also similar in both groups. L-Arginine-induced renovascular relaxation was increased by imidapril (renal plasma flow, 9.6+/-5.1% to 14.4+/-7.4%; renal vascular resistance, -10.4+/-8.1% to -16.7+/-9.2%, P<0.05, respectively) but not by amlodipine. Urinary excretion of nitrite/nitrate in response to L-arginine was significantly increased by imidapril (90+/-29% to 134+/-63%, P<0.05) but remained unchanged by amlodipine. These findings suggest that angiotensin-converting enzyme inhibition improves the impaired endothelium-dependent renovascular relaxation in patients with essential hypertension due to the increase in nitric oxide production and that the reduction in blood pressure with a calcium antagonist does not play a major role in the potentiation of L-arginine/nitric oxide-mediated effects.

Adult↗
PubMed1998

DeltaEF1, a zinc finger and homeodomain transcription factor, is required for skeleton patterning in multiple lineages.

DeltaEF1 is a DNA binding protein containing a homeodomain and two zinc finger clusters, and is regarded as a vertebrate homologue of zfh-1 (zinc finger homeodomain-containing factor-1) in Drosophila. In the developing embryo, deltaEF1 is expressed in the notochord, somites, limb, neural crest derivatives and a few restricted sites of the brain and spinal cord. To elucidate the regulatory function of deltaEF1 in mouse embryogenesis, we generated deltaEF1 null mutant (deltaEF1null(lacZ)) mice. The deltaEF1null(lacZ) homozygotes developed to term, but never survived postnatally. In addition to severe T cell deficiency of the thymus, the deltaEF1null(lacZ) homozygotes exhibited skeletal defects of various lineages. (1) Craniofacial abnormalities of neural crest origin: cleft palate, hyperplasia of Meckel's cartilage, dysplasia of nasal septum and shortened mandible. (2) Limb defects: shortening and broadening of long bones, fusion of carpal/tarsal bone and fusion of joints. (3) Fusion of ribs. (4) Sternum defects: split and asymmetric ossification pattern of the sternebrae associated with irregular sternocostal junctions. (5) Hypoplasia of intervertebral discs. These results indicate that deltaEF1 has an essential role in regulating development of these skeletal structures. Since the skeletal defects were not observed in deltaEF1deltaC727 mice, deltaEF1 bears distinct regulatory activities which are dependent on different domains of the molecule.

Abnormalities, Multiple↗
PubMed1998

A histological study of the organic elements in the human enamel focusing on the extent of the odontoblast process.

Topographic and tomographic studies were conducted on the organic elements occluded in the enamel of premolars removed from young orthodontic patients by using light (transmitted) microscopy, confocal scanning laser microscopy (CLSM), scanning electron microscopy (SEM), transmission electron microscopy (TEM) on ultrathin sections and freeze-etching replicas, and energy dispersive spectroscopy (EDS) X-ray microscope (EDX) analysis. The present fine structure study aimed in particular to determine the fine structure of the enamel spindle and the extent of the odontoblast process. Organic elements in the ground-sectioned enamel corresponding to simple projections and enamel rods/spindles, enamel tufts and lamellae were identified by conventional light microscopy and subsequently examined by CLSM. Both light microscopy and CLSM indicated that a number of enamel spindles were measured about 50 microns in length, some 4-7 microns in thickness and were mostly confined to the cuspal summits and conformed to previous descriptions. SEM examination revealed some simple projections extending from the dentine into the enamel as well as clearly identifiable enamel spindles; the enamel spindles were structures intervening enamel prisms and showing morphological complexity by branching and convergence of the distal endings of the invading organic structure from dentinal tubules. EDX-analysis revealed that enamel tufts, lamellae, and spindles contained less phosphorus and calcium elements than enamel prisms. The enamel spindles had a higher content than tufts or lamellae, but this may be the result of contamination from surrounding enamel. Both conventional ultrathin-section and freeze-etching replica TEM evaluation of the dentino-enamel boundaries in particular suggested that simple projections and enamel rods/spindles were extensions of the odontoblast processes trapped in the enamel during early amelogenesis. In contrast, both SEM and TEM observations failed to identify dentinal tubule, peritubular (intratubular) dentine, membranous structures or lamina limitans surrounding the enamel spindles and simple projections occluded in the human enamel.

Adolescent↗
PubMed1998

Observations on early development of the murine fetal oral vestibule.

Morphological and immuno/histochemical studies were performed on the vestibular lamina (VL) of gestational day 13 murine fetuses, using light microscopy (LM), confocal laser scanning microscopy (CLSM) and transmission electron microscopy (TEM), in an effort to elucidate the early development of the oral vestibule. Histochemistry employing LM demonstrated some PAS-positive glycogen particles in embryonic cells of the VL, dental lamina (DL), the primary epithelial band connecting the VL and DL, and the related stomodaeal simple epithelium. On the other hand, Gomori's aldehyde fuchsine method stained certain cystine-containing intracellular granules and intercellular amorphous substances, particularly in the central VL. Intense immunoreactivity for CK-10 intermediate-sized filament proteins was demonstrated in suprabasal and superficial cells of the VL stratified keratinized epithelium. Conversely, reactions for CK-19 filaments were found diffusely in both VL and DL cells retaining the cytokeratin characteristic of the simple epithelium. TEM of the VL revealed an increment in keratinosomes, tonofilaments and desmosomes in the suprabasal layers shifting toward superficial flat parakeratinized cells. The TUNEL method using CLSM detected programmed cell death in the VL, while TEM provided no morphological evidence of necrosis or typical apoptotic features during VL development. The present results indicate that physiological (naturally occurring) cell death and exfoliation of the oral-gingival type multilayered keratinizing epithelium are essential for degeneration and separation of the VL, ultimately leading to formation of the oral vestibule.

Animals↗
PubMed1998

Early organogenesis and cell contacts in the proliferating hypophysis of the developing mouse.

The mouse foetal hypophysis which contains the diencephalic downgrowth (Dd) and Rathke's pouch (Rp) was examined using morphological and immunocyto/histo-chemical methods to study the cell-cell and cell-extracellular matrix (ECM) interactions that occur during early organogenesis. While many studies have described that the differentiation of ACTH cells precedes the proliferation of other endocrine cells in the Rp, light and conventional transmission electron microscopic (TEM) investigations have failed to differentiate between the various endocrine cell types in the proliferating distal lobe at the late mid-foetal stage. Conversely, TEM studies have shown that the occurrence of dense secretory vesicles in glandular cells of the presumptive pars intermedia in close apposition with the presumptive neural lobe by a basal lamina, is the earliest sign of endocrine activity in the foetal hypophysis. However, a confocal laser scanning microscopy (CLSM) and fine structure study did not observe direct cell-to-cell contacts between the Dd, Rp and their associated mesenchyme at the late mid-foetal stage. Using CLSM and TEM, we detected active cell turnover with programmed cell death in the proliferating Rp, Dd and their associated cephalic mesenchyme. Morphological findings indicated that apoptosis in the cephalic mesenchyme subsequently brings neurohypophyseal pituicytes and adenohypophyseal precursor stem cells into closer proximity, and alternations in the boundary cell surfaces might initiate signal transduction mediated via the intervening ECM at the proliferation stage.

Animals↗
PubMed1998

[Is tacrolimus effective for ongoing renal allograft rejection?].

Tacrolimus has already gained a high reputation as an induction-maintenance immunosuppressive therapy after kidney transplantation. Recently, it is being used as rescue therapy against rejection, and its effectiveness also appears to have been established to some extent. In this study, we evaluated the efficacy of Tacrolimus rescue therapy at 4 institutions in the Kinki District. The subjects were 19 patients treated with Tacrolimus against rejection observed during immunosuppressive therapy using cyclosporin. Evaluation was made by classifying the patients into 6 with acute rejection that occurred within 3 months after transplantation (AR), 4 with late onset acute rejection that developed more than 3 months after operation (LAR), and 9 patients with chronic rejection (CR). In the AR group, many patients received combination therapy at the introduction of Tacrolimus, and the long-term outcome was satisfactory. Tacrolimus was effective in 2 (50%) of the 4 patients in the LAR group. The trough levels of Tacrolimus at its introduction were 10-15 ng/ml in the AR and LAR groups. Deterioration of the transplanted kidney function was prevented in 3 (50%) out of 6 patients in the CR group observed for less than 1 year, but it deteriorated in all 3 patients observed for 1 year or longer. The trough levels of tacrolimus at its introduction were 5-10 ng/ml in many patients in the CR group. The rescue therapy using Tacrolimus was effective against acute rejection but further follow-up is considered to be needed to evaluate its efficacy against chronic rejection.

Graft Rejection↗
PubMed1998

A founder effect is proposed for factor XIII B subunit deficiency caused by the insertion of triplet AAC in exon III encoding the second Sushi domain.

We previously concluded that genetic defects in the B subunit of factor XIII were the basis for former Type I deficiency (i.e. factor XIII B subunit deficiency). When we examined an Italian patient with the disease at the DNA level, restriction digestion and sequencing analyses of amplified DNAs revealed that the proband and her family members possessed an AAC insertion within the codon for Tyr-80 in exon III in the gene for the B subunit. a nucleotide polymorphism (A-G) in its 3'-noncoding region in exon XII, and a short tandem repeat polymorphism of (TTTA9, in the 3'-flanking region. These mutations and 3'-polymorphisms were also identified in another Italian family reported in a previous study (10). suggesting that a founder effect is responsible for factor XIII B subunit deficiency in Italians.

DNA Transposable Elements↗
PubMed1998

[Intraoperative radiotherapy combined with external beam radiation for prostate cancer without metastasis].

Between 1989 and 1996, 35 patients with prostate cancer without metastasis received intraoperative radiotherapy combined with external beam radiation. 10 of 16 stage B patients and all of 19 stage C patients received additional endocrine therapy for the initial treatment. The radiation therapy included 25-30 Gy of intraoperative radiotherapy for prostate and 30 Gy of external beam radiotherapy for small pelvic region. One patient of stage C was dead for cancer and 4 patient were dead for other causes during 15-99 (mean: 41.6) months follow up period. The overall actuarial survival at 5 years by Kaplan-Meier method were 92.3% for stage B and 87.2% for stage C. Although cystitis, proctitis and anal bleeding were observed as the adverse effects of radiotherapy, both acute and chronic symptoms were not critical. In conclusion, intraoperative radiotherapy combined with external beam radiotherapy was revealed as an effective treatment for prostate cancer without metastasis.

Aged↗
PubMed1997

Biochemical and pharmacological characterization of FK706, a novel elastase inhibitor.

FK706, sodium 2-[4-[[(S)-1-[[(S)-2-[[(RS)-3, 3, 3-trifluoro-1-isopropyl-2-oxopropyl]aminocarbonyl]pyrrolidin -1-yl]carbonyl]-2-methylpropyl] aminocarbonyl] benzoylamino] acetate, C26H32F3N4NaO7, is a synthetic water-soluble inhibitor of human neutrophil elastase. This compound demonstrated a competitive and slow-binding inhibition of human neutrophil elastase with a Ki of 4.2 nM. In studies using synthetic substrates, FK706 inhibited human neutrophil elastase activity and porcine pancreatic elastase activity with respective IC50 values of 83 and 100 nM. FK706, however, inhibited more weakly, (IC50 values > 340 microM) other serine proteinases such as human pancreatic alpha-chymotrypsin, human pancreatic trypsin and human leukocyte cathepsin G. FK706 also effectively inhibited the hydrolysis of bovine neck ligament elastin (2 mg/ml final concentration) by human neutrophil elastase (4 microg/ml final concentration) with an IC50 value of 230 nM. FK706 protected animals against human neutrophil elastase (50 microg/animal)-induced lung hemorrhage with ED50 values of 2.4 microg/animal by intratracheal administration and 36.5 mg/kg by intravenous administration, respectively. Subcutaneous administration of FK706 significantly suppressed human neutrophil elastase (20 microg/paw)-induced paw edema in mice in a dose-dependent manner (47% inhibition at a dose of 100 mg/kg). These results suggest that FK706 would be a useful tool for investigating the role of human neutrophil elastase in inflammatory disorders associated with an excess of elastase, such as pulmonary emphysema, adult respiratory distress syndrome, septic shock, cystic fibrosis, chronic bronchitis and rheumatoid arthritis.

Animals↗
PubMed1997

Lack of effect of transmembrane gradient of magnesium and sodium on regulation of cytosolic free magnesium concentration in rat lymphocytes.

The regulation of the intracellular concentration of Mg2+ ([Mg2+]i) is not fully understood. The level of Mg in lymphocytes is a good predictor of total body Mg status. We measured [Mg2+]i and total Mg in rat lymphocytes by using, respectively, the fluorescent Mg2+ indicator mag-fura-2 and atomic absorption spectrophotometry. The basal [Mg2+]i in rat lymphocytes was 328 +/- 23 micromol/l. An elevation to 5 mmol/l or the removal of extracellular Mg2+ did not affect [Mg2+]i. A reduction in extracellular Na+ did not influence [Mg2+]i for 60 min. The total Mg concentration in lymphocytes also remained stable. Results suggest that the permeability of the plasma membrane to Mg2+ is very low, and that Na+/Mg2+ exchange is not involved in the regulation of [Mg2+]i in rat lymphocytes.

Animals↗
PubMed1997

Fibromatosis of the Breast: A Case Report.

Fibromatosis develops in many anatomic sites, but it rarely arises as a primary lesion in the breast. This lesion is locally invasive and frequently recurs after a local excision, but it has no potential for distant metastasis. In this report, we present a case of mammary fibromatosis which was closely similar to carcinoma in clinical, mammographic and ultrasonographic findings, thus leading us to breast conserving surgery. Despite being a rare disease, fibromatosis should be included in the differential diagnosis of younger patients (the age of the present case was 51, and the mean ages of patients with fibromatosis ranges from 37 to 49) with abnormal changes on physical examinations and imaging studies.

Journal Article↗
PubMed1997

Abnormal FHIT transcripts in human breast carcinomas: a clinicopathological and epidemiological analysis of 61 Japanese cases.

Deletions in the short arm of chromosome 3 have been found in various human cancers, including breast cancer. Recently, the FHIT (fragile histidine triad) gene was identified at 3p14.2 as a candidate tumor suppressor gene. We examined the abnormal transcripts of the FHIT gene in 61 Japanese primary breast cancer specimens and found that 23 (38%) of them exhibited abnormalities, about half of which were categorized into two types of aberrant transcripts. Sequence analysis of these aberrant transcripts revealed the absence of exons 5-7 (type I) and exons 5-8 (type II). Clinicopathological and epidemiological analysis of patients showed that the abnormal FHIT transcripts were not associated with age, tumor-node-metastasis classification, tumor size, estrogen receptor and progesterone receptor status, local metastasis, family history of breast cancer, or lifestyle factors of patients, including cigarette smoking and alcohol consumption. On the other hand, we found that the abnormal transcripts of type I and type II were associated with the incidence of bilateral breast cancer and that decreased frequency of childbirth was also associated with FHIT abnormalities.

Adult↗
PubMed1997

Impairment of T cell development in deltaEF1 mutant mice.

Using the method of gene targeting in mouse embryonic stem cells, regulatory function of deltaEF1, a zinc finger and homeodomain-containing transcription factor, was investigated in vivo by generating the deltaEF1 mutant mice. The mutated allele of deltaEF1 produced a truncated form of the deltaEF1 protein lacking a zinc finger cluster proximal to COOH terminus. The homozygous deltaEF1 mutant mice had poorly developed thymi with no distinction of cortex and medulla. Analysis of the mutant thymocyte showed reduction of the total cell number by two orders of magnitude accompanying the impaired thymocyte development. The early stage intrathymic c-kit+ T precursor cells were largely depleted. The following thymocyte development also seemed to be affected as assessed by the distorted composition of CD4- or CD8-expressing cells. The mutant thymocyte showed elevated alpha4 integrin expression, which might be related to the T cell defect in the mutant mice. In the peripheral lymph node tissue of the mutant mice, the CD4-CD8+ single positive cells were significantly reduced relative to CD4+CD8-single positive cells. In contrast to T cells, other hematopoietic lineages appeared to be normal. The data indicated that deltaEF1 is involved in regulation of T cell development at multiple stages.

Animals↗
PubMed1997

Two promoters in expression of estrogen receptor messenger RNA in human breast cancer.

The human estrogen receptor (ER) gene has recently been shown to transcribe two types of mRNA originating from two distinct promoters in mammary tumor cell lines, which encode the same protein. However, use of the two promoters has not been addressed in human breast cancer, which reveals a heterogeneity in terms of ER expression status and clinical characteristics. In this report, we investigated which promoter is responsible for the expression of ER in human mammary tumors by a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis for discriminatory detection of the two transcripts in mammary tissues obtained from patients with breast cancer. First, the use of distinct promoters was confirmed in several mammary tumor cell lines by the present RT-PCR method. Secondly, expression levels of total ER mRNA and two types of mRNAs from the different promoters were analysed in tumor, surrounding tissue and normal tissue obtained from 12 patients with breast cancer, which showed various levels of ER protein. In tumors, levels of total ER mRNA and the mRNA transcribed from a distal promoter showed remarkable correlation to the ER protein levels with correlation coefficients 0.946 (P < 0.001) and 0.746 (P < 0.005), respectively. In contrast, mRNA from a proximal promoter showed no correlation to the ER protein levels. Our results indicate that the enhancement of the ER mRNA expression from the distal promoter plays an essential role in the mechanisms of overexpressing ER protein in human mammary tumors, implying that a tumor-specific regulation of ER expression involved use of the distal promoter.

Adult↗
PubMed1997

[Evaluation of the assay technique for detection of anti-chlamydial IgA and IgG antibodies in PID patients].

The purpose of this study is to evaluate the usefulness and limitation of Rapizyme CHLAMYDIA, enzyme-linked immunosorbent assay (ELISA) for qualitative detection of anti-chlamydial IgG and IgA antibodies, in the serum of 92 PID patients and 73 pregnant women, compared with those of Sero IPALISA CHLAMYDIA. The result of Rapizyme analysis was obtained within 10 minutes with no special devices. Overall agreements of Rapizyme and Sero IPALISA were 90.9% (IgG) and 90.3% (IgA) in the total patients, 88.0% (IgG) and 85.9% (IgA) in PID patients, and 94.5% (IgG) and 95.9% (IgA) in pregnant women. The positive rate of Chlamydia in PID was 17.4% (16/92). Positive agreement of Rapizyme in Chlamydia positive PID and pregnant women was 100% in both IgG and IgA, and negative agreement was also 100%. Positive agreement in Chlamydia negative PID was 100% in both IgG and IgA, and negative agreement was 90.0% (IgG) and 83.3% (IgA). The results of Rapizyme were in close agreement with those of Sero IPALISA. COI (cut off index) of Sero IPALISA clearly decreased in 3 of 6 PID patients during a 3 to 6 months period after chemotherapy, but those changes were not observed in Rapizyme. These results suggest that Rapizyme CHLAMYDIA is a useful diagnostic kit for Chlamydial PID of outpatients.

Antibodies, Bacterial↗