Biomedical subjects

H Okada

Publications and source records attributed to H Okada.

At least 505 records · Page 28Linked to original sources

PubMed1995

Human nasal mucosal carboxypeptidase: activity, location, and release.

BACKGROUND: Carboxypeptidases (CPs), such as carboxypeptidase N (CPN) (kininase I, E.C.3.4.17.3), may regulate peptide-mediated vasodilation and vascular permeability in respiratory mucosa by degrading proinflammatory peptides such as bradykinin, anaphylatoxins, and neuropeptides during allergic and nonallergic inflammation. The sources of CP activity in human nasal secretions were investigated. METHODS: Well-characterized human nasal provocation and secretion analysis methods were used. Potential sources of CPN in human nasal mucosa were identified by immunohistochemistry. CP activity was defined as DL-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid inhibitable Bz-Gly-Lys degradation. CP activity was measured in nasal mucosal homogenates and nasal lavage fluids induced by methacholine, histamine, and allergen nasal provocation. RESULTS: CPN-immunoreactive material was localized to the glycocalyx of the epithelium, some vessels, and gland ducts near the epithelial basement membrane but not to submucosal gland cells. CP activity in human nasal lavage fluid after saline nasal provocation was 0.10 +/- 0.04 U/L. Histamine provoked secretion of significantly more CP activity (3.84 +/- 0.99 U/L; p < 0.01 vs saline). Methacholine did not significantly increase secretion (0.54 +/- 0.22 U/L). After nasal allergen challenge, CP activity was at a maximum between 11 and 20 minutes, and CP activity correlated with IgG concentration (r = 0.91, p < 0.01), a marker for proteins of plasma origin, suggesting that CP activity originated in plasma. CONCLUSIONS: These data suggest that plasma is the predominant source of CP activity secreted from human nasal mucosa and that plasma extravasation and interstitial fluid exudation across the epithelium are the primary processes regulating its appearance in nasal secretions.

Adult↗

PubMed1995

Antitumor effect of arterial administration of a medium-chain triglyceride solution of an angiogenesis inhibitor, TNP-470, in rabbits bearing VX-2 carcinoma.

Using rabbits bearing VX-2 carcinoma on the inner side of the leg, we examined the antitumor activity of a medium-chain triglyceride (MCT) solution of an angiogenesis inhibitor, TNP-470 (AGM-1470, 6-O-(N-chloroacetylcarbamoyl)-fumagillol), following administration into the femoral artery feeding the tumor. The MCT solution of TNP-470 (1 and 5 mg) strongly suppressed tumor growth following a single intra-arterial (i.a.) injection 2 or 3 weeks after tumor inoculation. Moreover, remarkable regression of well-developed tumors, those 4 weeks after inoculation, was obtained by i.a. injection of the MCT solution containing 20 mg of TNP-470 without any influence on body weight. The antitumor effects were potentiated by coadministration of doxorubicin or mitomycin C (MMC) in the solution or microspheres containing MMC. In a shell-less chorioallantoic membrane (CAM) assay, angiogenesis was inhibited when a droplet of the MCT solution containing 25 micrograms of TNP-470 was placed on the CAM for 2 days, suggesting that the prolonged antitumor effect resulted from the inhibition of tumor neovascularization by sustained drug release from the preparation. These results indicate that i.a. injection of the MCT solution of TNP-470 is promising for treating well-developed tumors.

Animals↗

PubMed1995

Role of a rat membrane inhibitor of complement in anti-basement membrane antibody-induced renal injury.

In the kidneys of anti-glomerular basement membrane (anti-GBM) antibody disease, binding of antibodies to tubular basement membrane (TBM) is often observed. The present work was performed to explore the mechanisms of binding of anti-GBM antibodies to TBM in vivo with special reference to 5I2Ag, a rat membrane inhibitor of complement which regulates complement activation at C3 convertase level. To suppress functions of renal 5I2Ag, F(ab')2 fragment of 5I2 (a neutralizing mAb against 5I2Ag) was perfused in the left kidney and then blood circulation was restored. Mild proteinuria ( < 10 mg/16 hr) was observed during first several days. Five days later, there were tubulointerstitial injuries defined by tubular vimentin staining and leukocyte infiltration. Significant deposition of C3 was observed in the capillaries and in TBM. In rats intravenously injected with rabbit anti-rat GBM antibodies five minutes after kidney perfusion with 5I2, strong binding of rabbit IgG to TBM was observed at one and five days after injection. Although these rats showed mild proteinuria comparable to those perfused with 5I2 and those injected with normal rabbit serum, tubulointerstitial injury was significantly enhanced at Day 5. In contrast, rats perfused with irrelevant mAb and injected with anti-GBM antibodies did not show any significant binding of antibodies to TBM nor tubulointerstitial injury. Furthermore, rats which were made proteinuric by puromycin aminonucleoside and injected with anti-GBM antibodies did not show any significant binding of rabbit IgG to TBM. These results indicate that 5I2Ag, a rat membrane inhibitor of complement at the C3 convertase level, regulates vascular permeability in the living kidney, and that dysfunction or decreased expression of this molecule leads to increased accessibility of anti-GBM antibodies to TBM.

Albuminuria↗

PubMed1995

The antisense homology box: a new motif within proteins that encodes biologically active peptides.

Amphiphilic peptides approximately fifteen amino acids in length and their corresponding antisense peptides exist within protein molecules. These regions (termed antisense homology boxes) are separated by approximately fifty amino acids. Because many sense-antisense peptide pairs have been reported to recognize and bind to each other, antisense homology boxes may be involved in folding, chaperoning and oligomer formation of proteins. The antisense homology box-derived peptide CALSVDRYRAVASW, a fragment of human endothelin A receptor, proved to be a specific inhibitor of endothelin peptide (ET-1) in a smooth muscle relaxation assay. The peptide was able to block endotoxin-induced shock in rats as well. Our finding of endothelin receptor inhibitor among antisense homology box-derived peptides indicates that searching proteins for this new motif may be useful in finding biologically active peptides.

Amino Acid Sequence↗

PubMed1995

Senile dementia-Alzheimer's type and estrogen.

Some reports have suggested the ameliorative effects of estrogens on clinical symptoms, such as short memory, in women suffering from senile dementia-Alzheimer's type, in vivo. The action mechanism of estrogen remains to be clarified, but 1) an anti-depressive effect, 2) improvement of cerebral blood flow, 3) direct stimulation of neuron, 4) development of gliacyte and 5) suppression of apolipoprotein E have been suggested. Some mechanisms may be combined, contributing to the beneficial effects on clinical symptoms.

Alzheimer Disease↗

PubMed1995

Identification and characterization of a fibroblast marker: FSP1.

We performed subtractive and differential hybridization for transcript comparison between murine fibroblasts and isogenic epithelium, and observed only a few novel intracellular genes which were relatively specific for fibroblasts. One such gene encodes a filament-associated, calcium-binding protein, fibroblast-specific protein 1 (FSP1). The promoter/enhancer region driving this gene is active in fibroblasts but not in epithelium, mesangial cells or embryonic endoderm. During development, FSP1 is first detected by in situ hybridization after day 8.5 as a postgastrulation event, and is associated with cells of mesenchymal origin or of fibroblastic phenotype. Polyclonal antiserum raised to recombinant FSP1 protein stained the cytoplasm of fibroblasts, but not epithelium. Only occasional cells stain with specific anti-FSP1 antibodies in normal parenchymal tissue. However, in kidneys fibrosing from persistent inflammation, many fibroblasts could be identified in interstitial sites of collagen deposition and also in tubular epithelium adjacent to the inflammatory process. This pattern of anti-FSP1 staining during tissue fibrosis suggests, as a hypothesis, that fibroblasts in some cases arise, as needed, from the local conversion of epithelium. Consistent with this notion that FSP1 may be involved in the transition from epithelium to fibroblasts are experiments in which the in vitro overexpression of FSP1 cDNA in tubular epithelium is accompanied by conversion to a mesenchymal phenotype, as characterized by a more stellate and elongated fibroblast-like appearance, a reduction in cytokeratin, and new expression of vimentin. Similarly, tubular epithelium submerged in type I collagen gels exhibited the conversion to a fibroblast phenotype which includes de novo expression of FSP1 and vimentin. Use of the FSP1 marker, therefore, should further facilitate both the in vivo studies of fibrogenesis and the mapping of cell fate among fibroblasts.

3T3 Cells↗

PubMed1995

Endometrial oestrogen and progesterone receptors and their relationship to sonographic endometrial appearance.

The present study was undertaken to evaluate a possible relationship between the endometrial concentrations of oestrogen receptor (ER) or progesterone receptor (PR), and the sonographic appearance of human endometrium. Sonographic assessments and aspirations of the endometrium at the time of or prior to ovulation were made in 48 cycles of 45 infertile women. Endometrial patterns were classified as A, triple line pattern, or B, not triple line, on the basis of echogenicity. We did not find a correlation between ER or PR and serum oestradiol or endometrial thickness. Furthermore, serum oestradiol concentrations were not correlated with endometrial pattern or thickness. The only significant correlations were found between the concentrations of ER and PR in the pattern A endometrium (r = 0.80, P < 0.01) and in the pattern B endometrium (r = 0.49, P < 0.05). There were no differences in the mean concentrations of ER and PR despite differences in endometrial pattern and thickness. However, PR was measured at > 800 fmol/mg protein in 12 out of 38 pattern A endometria, while PR was < 800 fmol/mg protein in all pattern B endometria. These data suggest that high PR expression in the pre-ovulatory period is related to an adequate endometrial growth and thereby increases the responsiveness of the endometrium to progesterone stimulation after ovulation.

Buserelin↗

PubMed1995

Effects of novel, nonpeptide vasopressin antagonists on progressive nephrosclerosis in rats.

Effects of novel, nonpeptide vasopressin V1 and V2 receptor antagonists on partially nephrectomized and salt-loaded spontaneously hypertensive rats (SHR), which develop severe hypertension and progressive nephrosclerosis, were investigated. SHR were 5/6-nephrectomized and fed a high salt diet. The rats were divided into four groups: group 1 was an untreated control, group 2 received the V1 antagonist OPC-21268, group 3 received the V2 antagonist OPC-31260, and group 4 received both the V1 and V2 antagonists. The V1 antagonist alone or combined with the V2 antagonist significantly decreased the increase in blood pressure (BP) of groups 2 and 4 rats, but the V2 antagonist alone did not reduce the increase in BP of the group 3 rats. The V2 antagonist alone or combined with the V1 antagonist induced a significant diuresis of rats in groups 3 and 4. The increase in urinary protein excretion and the progression of renal hyaline arteriolosclerosis were attenuated by the V1 antagonist with or without the V2 antagonist in rats in groups 2 and 4, but not by the V2 antagonist alone in rats in group 3. This implies that the progressive nephrosclerosis in SHR with partial renoablation and salt-loading was associated with V1 agonism.

Animals↗

PubMed1995

Renal responses to angiotensin receptor antagonist and angiotensin-converting enzyme inhibitor in partially nephrectomized spontaneously hypertensive rats.

To investigate the role of the renin-angiotensin system (RAS) on nephrosclerosis in salt-loaded, partially nephrectomized spontaneously hypertensive rats (SHR), we evaluated the effects of angiotensin II (ANGII) blockade on the progression of nephrosclerosis with an angiotensin type 1 receptor (AT1rec) antagonist [TCV-116 (TCV)] and an angiotensin-converting enzyme (ACE) inhibitor (enalapril) at the doses equivalent in reducing systemic blood pressure (BP). SHR were five/sixths nephrectomized and were fed a high-salt diet. In addition to being significantly preventive against an increase in systolic BP, both TCV and enalapril significantly attenuated the increases in proteinuria and the renal histopathological alterations. Transcription of AT1rec mRNA in the remnant kidney was enhanced with the progression of nephrosclerosis, but was inhibited by TCV as well as enalapril. In these aspects, there were no apparent differences between effects of TCV and enalapril. The RAS system plays an important role in nephrosclerosis in partially nephrectomized SHR despite a high-salt diet, and direct ANGII blockade certainly protected the kidney against hypertensive injury in this model.

Angiotensin Receptor Antagonists↗

PubMed1995

Primary Sjögren's syndrome and psoriasis vulgaris in a case of OKT4 epitope deficiency.

We report a 29-year-old female OKT4 epitope deficiency patient with primary Sjögren's syndrome and psoriasis vulgaris. Immunological investigations during the prolonged clinical course of her herpes zoster revealed that she has OKT4 epitope deficiency and primary Sjögren's syndrome. She had been treated for psoriasis vulgaris for 17 years without systemic immunosuppressive therapy. Flow cytometric study revealed that her OKT4 deficiency is heterogeneous and excluded interference with the OKT4 epitope by anti OKT4 autoantibodies. The rare coexistence of primary Sjögren's syndrome and psoriasis implicates an immune disturbance due to an unusual phenotype of CD4.

Acyclovir↗

PubMed1995

C-cell distribution in ovine thyroid gland.

The number and percentage of C-cells per unit area were investigated in 2-3-year-old sheep by an immunoperoxidase technique, using a digital-image analysis. C-cells were distributed throughout the thyroid lobes but were not present in either the isthmus or the superior and inferior poles of the thyroid. C-cells were more concentrated in the deep central region of the lobes and decreased gradually toward the periphery. There was a high correlation between the number and the percentage of C-cells per unit area of thyroid gland in sheep. Significant differences were not present between male and female sheep of 2-3 years of age.

Animals↗

PubMed1995

Alteration of the hypothalamus-pituitary-testis axis in oligozoospermic men with normal gonadotropin levels.

BACKGROUND: Serum basal hormone levels such as lutenizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone, which is important to regulate testicular function, do not necessarily indicate the normal integrity of the hypothalamic-pituitary-testicular axis and the static measurement is not enough to detect the endocrine disorder. The dynamic measurement of gonadal hormone by GnRH test is considered to be more helpful to understanding the endocrine regulation of spermatogenesis. In this study, we performed GnRH test in oligozoospermic patients with normal levels of LH and FSH to examine the subtle alteration of hypothalamic-pituitary-testis axis. METHODS: GnRH test was performed in 41 patients with oligozoospermia and normal gonadal hormone levels. RESULTS: The responses of LH and/or FSH were excessive in most patients in spite of their normal gonadotropin levels. The patients with sperm concentration < 10 x 10(6)/ml had significantly higher peak levels of both LH and FSH than did those with sperm concentration > 10 x 10(6)/ml. In the patients with normal peak levels of both LH and FSH, sperm concentration was significantly higher than those with exceeded peak levels of FSH and/or LH after GnRH test. No significant differences were observed in estradiol, testosterone, free testosterone, or prolactin (PRL) levels between patients with normal responses and abnormal responses of LH and/or FSH. CONCLUSIONS: The feedback control of gonadotropin release from testis was worse in more severely oligozoospermic patients, although the precise mechanism of feed back still remains unknown.

Adult↗

PubMed1995

Suppression of natural killer cell activity by monocytes following immunotherapy for recurrent spontaneous aborters.

PROBLEM: Natural killer (NK) cell activity has previously been shown to decrease in normal pregnancy as compared with the nonpregnancy state. The purpose of this study was to determine NK cell activity in recurrent aborters and to investigate the kinetics of NK cell activity following immunotherapy. METHODS: Recurrent aborters (N = 17) were immunized with husbands' mononuclear cells (1 x 10(8)) twice during the early stage of current pregnancy. NK cell activity of recurrent aborters as well as that of normal pregnant (N = 12) and nonpregnant (N = 6) women (controls) was determined by 51Cr release assay. Monocytes were depleted from the mononuclear cell fraction and its effect on the NK cell activity was determined as well. RESULTS: At around 5 wk of gestation, NK cell activity in recurrent aborters before treatment was significantly higher (28.0 +/- 5.1%) than that in normal pregnancy (18.9 +/- 4.3%) (P < 0.01). Following immunotherapy, NK cell activity of recurrent aborters (N = 13) who maintained their pregnancy decreased significantly (21.7 +/- 8.9%) (P < 0.05). In contrast, NK cell activity of recurrent aborters (N = 4) who aborted their current pregnancy did not decrease. Depletion of monocytes resulted in a significant increase in NK cell activity (P < 0.05). CONCLUSIONS: This study suggests that the immunotherapy induces suppression of NK cell activity which may contribute for the maintenance of pregnancy. Moreover, monocytes may be involved in this suppression.

Abortion, Habitual↗

PubMed1995

[Clinical utility of DNA fingerprinting by arbitrarily-primed polymerase chain reaction (AP-PCR) in nosocomial infection caused by methicillin-resistant Staphylococcus aureus].

Recently, nosocomial outbreaks of MRSA have become an serious social problem in Japan. To examine the routes of transmission of MRSA, the establishment of an accurate MRSA typing system is essential. Previously, we reported that the DNA fingerprinting by AP-PCR might be a useful method to differentiate MRSA strains. In this study, we tried to investigate the clinical usefulness of DNA fingerprinting by AP-PCR using clinically-isolated MRSA strains. Twenty-four MRSA strains (12 with coagulase type IV, and 12 with coagulase type II) isolated from patients in our department were used. Other typing methods (the sensitivity of antibiotics, pulsed-field gel electrophoresis, and plasmid analysis) were also performed. As a result, the typing pattern by AP-PCR correlated well with other typing methods. MRSA strains with coagulase type IV showed almost the same pattern, suggesting that these strains were nosocomially transmitted. On the other hand, MRSA strains with coagulase type II showed various patterns, suggesting these strains were not nosocomially transmitted. In conclusion, the typing by AP-PCR seemed to be a useful tool evaluate a nosocomial MRSA transmission.

Cross Infection↗

PubMed1995

[DNA fingerprinting by arbitrarily primed polymerase chain reaction (AP-PCR) for methicillin-resistant Staphylococcus aureus].

Recently, nosocomial outbreaks of MRSA have become an important social problem in Japan. To examine the routes of transmission of MRSA, the establishment of accurate MRSA typing system is essential. However, more recently, because MRSA strains with type II coagulase have been increasing, it is difficult to discriminate MRSA strains by the coagulase typing method. Under this background, our study was designed to evaluate the clinical significance of DNA fingerprinting by arbitrarily primed polymerase chain reaction (AP-PCR). Several MRSA strains isolated from patients in our department were used in this study. To optimize the condition of AP-PCR, the differences of amplified products by AP-PCR were evaluated according to the following conditions: extracting methods of DNA from MRSA strains, buffer conditions, the temperature of AP-PCR, cycles of AP-PCR, and several primers. As a result, the optimal conditions of AP-PCR were as follows: extracted DNA using the InstaGene kit, amplified DNA by two-step AP-PCR using a M13 reverse primer with a buffer condition of 3.5 mM of magnesium chloride, and a pH of 8.5. The results of AP-PCR correlated well with the results of pulsed-field gel electrophoresis. In conclusion, DNA fingerprinting by AP-PCR seems to be useful in examining the nosocomial MRSA outbreak.

Bacterial Typing Techniques↗

PubMed1995

[Effect of erythromycin on macrophage functions].

Recently, it has been suggested that macrolide antibiotics act as immunomodulators. In this study, we evaluated the effect of EM on macrophage function. We used the mouse macrophage cell line, J774.1. The following direct effects of EM on macrophage function were evaluated: chemotaxis to EM, chemokinetic effect by EM, and the effect of EM on macrophage growth. In order to examine the indirect effects of EM on macrophage functions, we preincubated macrophages with several concentrations of EM and then removed the EM. Thereafter, the phagocytosis of beads, cytocidal activity against Candida albicans, and chemotaxis to lipopolysaccharide were evaluated. EM (at the concentration between 0.04 and 0.2 microgram/ml) directly stimulated macrophage chemotaxis and chemokinesis. In addition, EM dose-dependently stimulated the growth of macrophages. EM pretreatment (for 4 hours at the contractions between 0.04 and 0.2 microgram/ml) stimulated macrophage phagocytosis, cytocidal activity against Candida albicans, and chemotaxis to lipopolysaccharide. These results suggest that EM has direct and indirect effects on macrophage functions.

Animals↗

PubMed1995

[Effect of clarithromycin on macrophage functions].

Recently, it has been suggested that macrolide antibiotics act as immunomodulators. In this study, we evaluated the effect of clarithromycin (CAM) on macrophage function. We used the mouse macrophage cell line, J774.1. The following direct effects of CAM on macrophage function were evaluated: chemotaxis to CAM, chemokinetic effect of CAM, and the effect of CAM on macrophage growth. In order to examine the indirect effects of CAM on macrophage functions, we preincubated macrophages with several concentrations of CAM and then removed the CAM. Thereafter, the phagocytosis of beads, cytocidal activity against Candida albicans, and chemotaxis to lipopolysaccharide were evaluated. In addition, the indirect effects of CAM on endoxan (4 mg/ml) treated macrophage phagocytosis, cytocidal activity, and chemotaxis were evaluated. CAM (at the concentration between 0.04 and 0.2 microgram/ml) directly stimulated macrophage chemotaxis and chemokinesis. In addition, CAM dose-dependently stimulated the growth of macrophages. CAM pretreatment (for 4 hours at the concentrations between 0.04 and 0.2 microgram/ml) stimulated macrophage phagocytosis, cytocidal activity against Candida albicans, and chemotaxis to lipopolysaccharide. In addition, CAM recovered macrophage phagocytosis, cytocidal activity, and chemotaxis which were decreased after endoxan exposure. These results suggest that CAM has direct and indirect effects on macrophage functions.

Animals↗

PubMed1995

Endemic occurrence of glomerulonephritis associated with streptococcal impetigo.

We report here a case of type 1 mesangiocapillary glomerulonephritis as well as a case of mesangial proliferative glomerulonephritis associated with streptococcal skin infection superimposed on atopic dermatitis. Both were endemic occurrences of postinfectious glomerulonephritis developed after repeated dirty-skin treatments for atopic dermatitis performed by unauthorized individuals under unsanitary conditions. Of 20 patients who were similarly treated and subsequently admitted to our hospital because of skin infection and fever, 8 (40%) showed urinary abnormalities. Four patients had renal dysfunction with acute nephritic onset. Almost all showed a decrease in CH50 values and an increase in levels of antistreptolysin O and IgE. In the 2 cases presented here, the disease eventually regressed in association with improvement of the skin infection. Although the occurrence of postinfectious glomerulonephritis has recently become uncommon, we must take care to note urinary abnormalities as early as possible in order to prevent the progression of glomerulonephritis.

Adolescent↗