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Biomedical subjects

K Takeda

Publications and source records attributed to K Takeda.

At least 541 records · Page 30Linked to original sources
PubMed1997

Crossover trial of simvastatin versus pravastatin in patients with primary hypercholesterolemia.

The effects of simvastatin and pravastatin administered alone at initial doses of 5 and 10 mg/day, respectively, on normalization of abnormal lipid metabolism in patients with hypercholesterolemia were evaluated by a crossover method. Patients whose serum levels of total cholesterol (TC) were > or = 220 mg/dl were randomly divided into two groups, and one of the groups (group S-P: 17 patients) was treated with simvastatin first and then with pravastatin whereas the other group (group P-S: 19 patients) was treated with pravastatin first and then with simvastatin. Simvastatin or pravastatin was replaced with the other drug after 8-week administration in each group. These drugs were administered for 8 weeks each. Simvastatin and pravastatin significantly reduced the following serum lipids as compared with the levels in the observation period: TC by 23.2 +/- 8.1% and 18.1 +/- 10.9%, triglyceride (TG) by 13.0 +/- 24.7% and 5.8 +/- 47.1%, and low-density lipoprotein cholesterol (LDL-C) by 31.3 +/- 10.1% and 23.1 +/- 14.3%, respectively. TC and LDL-C levels were significantly (p < 0.001) lower and decreased to significantly (p < 0.001) greater degrees after simvastatin treatment than after pravastatin treatment. TC was normalized in 77.8% of the patients (28 of 36) after simvastatin treatment and in 68.9% of the patients (23 of 36) after pravastatin treatment. LDL-C was normalized in 63.9% of the patients (23 of 36) after simvastatin treatment and in 44.4% of the patients (16 of 36) after pravastatin treatment. The percentage of patients whose LDL-C was normalized by simvastatin was significantly (p < 0.05) higher as compared with pravastatin. Results of this trial, which was conducted by a crossover method, show that the initial dose of simvastatin reduces serum cholesterol and LDL-C more potently than the initial dose of pravastatin in patients with hypercholesterolemia.

Adult↗
PubMed1997

Renal transplant biopsy: what does it tell?

The value of the renal allograft biopsy has been significantly enhanced by several developments in 1997 including the following: the first convincing demonstration that molecular biology techniques can be applied to renal allograft tissue to obtain a diagnosis of acute rejection with high sensitivity and specificity; the development of an improved, internationally agreed classification of kidney transplantation pathology ('Banff 1997'); and significant new insights into the specific pathology of chronic rejection, involving splitting and lamination of peritubular capillary basement membranes and the presence of increased apoptotic cell death. Although it is predictable that long-term technology might eliminate the need for renal allograft biopsies altogether, in the short term these new breakthroughs will greatly increase the value of this procedure in the management of renal transplant patients.

Biopsy↗
PubMed1997

Antigenic analysis of human herpesvirus 7 (HHV-7) and HHV-6 using immune sera and monoclonal antibodies against HHV-7.

Using polyclonal and monoclonal (MAbs) antibodies to human herpesvirus 7 (HHV-7), we have studied HHV-7-specific polypeptides. Human sera were obtained during the convalescent phase from patients with exanthem subitum due to HHV-7, and at least 16 HHV-7-specific polypeptides with apparent molecular masses of 26-210 kDa were immuno-precipitated. Sera prepared in mice also precipitated at least 17 HHV-7-specific polypeptides with molecular masses of 26-210 kDa. Among them, the most commonly observed antigenic protein had an apparent molecular mass of 52 kDa. Forty-two clones secreting MAbs against HHV-7-specific proteins, as determined by immunofluorescence assays, were established from BALB/c mice immunized with HHV-7-infected cell extracts. Seven MAbs which immunoprecipitated HHV-7-specific polypeptides were further characterized. Two of these, MAbs 5E12 and 5F12, reacted predominantly with glyco-proteins of 78 kDa and 85 kDa, respectively, and possessed neutralizing activity. This suggests that there are at least two neutralization-inducing proteins in HHV-7. MAb 16B4 reacted with the major immunogenic protein of 52 kDa. Five of the 42 MAbs also reacted in immunofluorescence assays with HHV-6 antigens to the same degree as to HHV-7. Two other MAbs, 7C10 and 10F1, recognized an HHV-7 protein of 40 kDa, and only 7C10 cross-reacted with an HHV-6 protein of 45 kDa.

Animals↗
PubMed1997

Identification of a variant B-specific neutralizing epitope on glycoprotein H of human herpesvirus-6.

We have identified the human herpesvirus-6 variant B (HHV-6B)-specific neutralizing epitope on glycoprotein H (gH) which is recognized by monoclonal antibody (MAb) OHV3, with complement-independent neutralizing activity. HHV-6 gHs from HHV-6A (strain U1102) and HHV-6B (strain HST) were expressed in a T7-vaccinia virus transient expression system. OHV3 reacted with HST gH, but not with U1102 gH, in an immunoprecipitation assay and an indirect immunofluorescence assay. In addition, OHV3 reacted with chimeric gHs, formed between U1102 gH and HST gH, containing amino acids 272 to 422 of HST gH. Sequence comparison between U1102 and HST showed seven amino acid differences in this region. Site-specific mutations were introduced into these positions and then reactivity against OHV3 was investigated. The arginine at position 389 of HST gH was shown to be a determinant of the HHV-6B-specific reactivity of OHV3.

Antibodies, Monoclonal↗
PubMed1997

IgA nephropathy-specific expression of the IgA Fc receptors (CD89) on blood phagocytic cells.

We analysed the biochemical features of receptors for the Fc-region of IgA (Fc alphaR, CD89) on blood monocytes and granulocytes of patients with IgA nephropathy (IgAN). Fc alphaR on monocytes of IgAN were found to have a higher Mr (60-80 kD) than those of control monocytes (50-75 kD) and granulocytes (55-75 kD) in both IgAN and controls as shown by immunoprecipitation analysis. Removal of N-linked carbohydrates from Fc alphaR on monocytes of IgAN revealed a 32-36 kD protein core, the Mr of which was still higher than that of controls (28-32 kD). When Fc alphaR transcripts were analysed by reverse-transcription-PCR, only one prominent band was visualized in PCR products from IgAN monocytes. Since the results thus far show that IgAN monocytes express Fc alphaR protein and mRNA differently from granulocytes and control monocytes, PCR products were then cloned and sequenced. The predominant band in PCR products from IgAN monocytes was identical to that of the Fc alphaR a.1 transcript, and an additional 10 transcripts containing five novel transcripts were obtained from granulocytes and control monocytes. In three transcripts, we found an insertion sequence between the S2 and EC1 domains, suggesting the existence of a new exon. These results suggest a predominant usage of Fc alphaR a.1 among various transcripts of Fc alphaR in IgAN monocytes.

Adolescent↗
PubMed1997

Inhibition of [Ca2+]i transients in rat adrenal chromaffin cells by neuropeptide Y: role for a cGMP-dependent protein kinase-activated K+ conductance.

The effects of neuropeptide Y on the intracellular level of Ca2+ ([Ca2+]i) were studied in cultured rat adrenal chromaffin cells loaded with fura-2. A proportion (16%) of cells exhibited spontaneous rhythmic [Ca2+]i oscillations. In silent cells, oscillations could be induced by forskolin and 1,9-dideoxyforskolin. This action of forskolin was not modified by H-89, an inhibitor of protein kinase A. Spontaneous [Ca2+]i fluctuations and [Ca2+]i fluctuations induced by forskolin- and 1,9-dideoxyforskolin were inhibited by neuropeptide Y. Increases in [Ca2+]i induced by 10 and 20 mM KCI but not by 50 mM KCI were diminished by neuropeptide Y. However, neuropeptide Y had no effect on [Ca2+]i increases evoked by (-)BAY K8644 and the inhibitory effect of neuropeptide Y on responses induced by 20 mM KCI was not modified by omega-conotoxin GVIA, consistent with neither L- nor N-type voltage-sensitive Ca2+ channels being affected by neuropeptide Y. Rises in [Ca2+]i provoked by 10 mM tetraethylammonium were not decreased by neuropeptide Y, suggesting that K+ channel blockade reduces the effect of neuropeptide Y. However, [Ca2+]i transients induced by 1 mM tetraethylammonium and charybdotoxin were still inhibited by neuropeptide Y, as were those to 20 mM KCI in the presence of apamin. The actions of neuropeptide Y on [Ca2+]i transients provoked by 20 and 50 mM KCI, 1 mM tetraethylammonium, (-)BAY K8644 and charybdotoxin were mimicked by 8-bromo-cGMP. In contrast, 8-bromo-cAMP did not modify responses to 20 mM KCI or 1 mM tetraethylammonium. The inhibitory effects of neuropeptide Y and 8-bromo-cGMP on increases in [Ca2+]i induced by 1 mM tetraethylammonium were abolished by the Rp-8-pCPT-cGMPS, an inhibitor of protein kinase G, but not by H-89. A rapid, transient increase in cGMP level was found in rat adrenal medullary tissues stimulated with 1 microM neuropeptide Y. Rises in [Ca2+]i produced by DMPP, a nicotinic agonist, but not by muscarine, were decreased by neuropeptide Y. Our data suggest that neuropeptide Y activates a K+ conductance via a protein kinase G-dependent pathway, thereby opposing the depolarizing action of K+ channel blocking agents and the associated rise in [Ca2+]i.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1997

Emergence of rifampin-resistant Rhodococcus equi in an infected foal.

To investigate the emergence of rifampin resistance in Rhodococcus equi strains isolated from foals and their environment in Japan, we compared the in vitro antimicrobial susceptibilities to rifampin of 640 isolates from 64 infected foals and 98 soil isolates from their horse-breeding farms. As a control, 39 human isolates from patients with and without AIDS were also tested for susceptibility to rifampin. All of the isolates showed rifampin sensitivity, except isolates from one infected foal and two patients with AIDS that showed rifampin resistance. To investigate the emergence of rifampin-resistant R. equi in the infected foal, which had received rifampin monotherapy for a month before euthanasia, 99 isolates of R. equi from the lesions and 20 isolates from the intestinal contents of the one foal with rifampin-resistant organisms were analyzed for rifampin susceptibilities, pathogenicities, and ribotypes. Of the 99 isolates from the lesions, all of which were virulent R. equi strains containing a virulence plasmid with a size of 85 or 90 kb, 90 (91%) isolates were rifampin resistant (MIC, > or = 12.5 microg/ml). On the other hand, of the 20 isolates from the intestinal contents, 11 (55%) isolates showed rifampin resistance (MIC, > or = 25 microg/ml), and 5 of them were avirulent R. equi strains. Among these 101 rifampin-resistant R. equi isolates with and without virulence plasmids characterized by ribotyping, 58 were type I, 20 were type II, 11 were type III, and 12 were type IV. These results demonstrated that at least eight different rifampin-resistant R. equi strains emerged concurrently and respectively from the different lesions and intestinal contents of the infected foal.

Actinomycetales Infections↗
PubMed1997

Uterine neoplasms: magnetization transfer analysis of MR images.

PURPOSE: To determine whether the magnetization transfer effects seen at fast spin-echo (SE) magnetic resonance (MR) imaging provide additional information in the diagnosis of uterine neoplasms. MATERIALS AND METHODS: MR images were obtained in 58 subjects with a normal uterus, 27 patients with cervical carcinoma (17 before therapy; 10 after irradiation), 10 with endometrial carcinoma, and five with endometrial hyperplasia. The magnetization transfer ratios (MTRs) were calculated by measuring the signal intensity on the central section of multisection fast SE images (15 sections) and that on a single-section fast SE image (5,000/136 [repetition time msec/echo time msec]). The additional imaging time required for MTR measurement was 4 minutes. RESULTS: Conspicuity of lesions and normal zonal anatomy was improved with single-section fast SE. The mean MTR in untreated cervical carcinoma (37.6% +/- 4.2 [standard deviation]) showed a statistically significant increase relative to that in irradiated cervical carcinoma (24.5% +/- 5.1, P < .01), normal cervical stroma (23.8% +/- 6.7, P < .01), or normal endocervix (24.2% +/- 7.3, P < .01). The mean MTR in endometrial carcinoma (34.5% +/- 3.6) was significantly higher than that in endometrial hyperplasia (25.5% +/- 1.5, P < .01) or normal endometrium (24.3% +/- 3.6, P < .01). CONCLUSION: Single-section fast SE imaging provides better lesion contrast than multisection fast SE imaging and enables quantification of the MTRs in uterine neoplasms.

Adolescent↗
PubMed1997

Pre-operatively determined prognostic factors in metastatic renal cell carcinoma.

OBJECTIVES: The aim of this study was to clarify the pre-operatively determined factors affecting the prognosis in patients with metastatic renal cell carcinoma (RCC). METHODS: We analyzed 69 patients with metastatic RCC who received nephrectomy. Multivariate analysis by Cox's proportional hazards model and survival studies were applied. RESULTS: Tumor thrombus in a renal vein or vena cava was the most significant poor-prognostic factor, followed by multiple-organ metastases and three or more abnormal findings of factors related to acute-phase proteins, in this order. Seven patients having these three risk factors died of cancer within 7 months after nephrectomy. On the other hand, half of the patients without risk factors survived for more than 2 years. CONCLUSIONS: Risk status should be used for selection of metastatic-RCC patients for treatment of the primary site.

Acute-Phase Proteins↗
PubMed1997

Pulsatile compression of the rostral ventrolateral medulla in hypertension.

The rostral ventrolateral medulla (RVLM) has been known to be a major regulating center of sympathetic and cardiovascular activities. An association between essential hypertension and neurovascular compression of the RVLM has been reported in clinical observations, including magnetic resonance imaging (MRI) studies. To reconfirm this relationship, we performed MRI using a high-resolution 512 x 512 matrix in patients with essential and secondary hypertension and in normotensive subjects. The duration of hypertension and the degree of organ damage by hypertension were not significantly different between the two hypertension groups. Neurovascular compression of the RVLM was observed in 74% of the essential hypertension group, and the incidence of compression was significantly higher than in the secondary hypertension group (11%) or in the normotensive group (13%) (P < .01). These results from the clinical studies suggest that neurovascular compression of the RVLM is, at least in part, causally related to essential hypertension. Although blood pressure elevation by pulsatile compression of the RVLM in an experimental baboon model has already been reported, its underlying mechanism is not well known. Accordingly, we performed experiments to investigate whether pulsatile compression of the RVLM would increase arterial pressure and to elucidate the mechanism of the pressor response in rats. Sympathetic nerve activity, arterial pressure, heart rate, and plasma levels of epinephrine and norepinephrine were increased by pulsatile compression of the RVLM. The pressor response was abolished by intravenous treatment with hexamethonium or RVLM injection of kainic acid. In summary, the results from the MRI studies suggest that neurovascular compression of the RVLM is, at least in part, causally related to essential hypertension. This was supported by the results from experimental studies using rats indicating that pulsatile compression of the RVLM increases arterial pressure by enhancing sympathetic outflow.

Animals↗
PubMed1997

Neurovascular compression of the rostral ventrolateral medulla related to essential hypertension.

The rostral ventrolateral medulla (RVLM) is thought to serve as a final common pathway for the integration of central cardiovascular information and to be important for the mediation of central pressor responses. An association between essential hypertension and neurovascular compression of the RVLM has been reported. To confirm this relationship and to quantitatively measure the distances between the RVLM and the neighboring arteries, we performed magnetic resonance imaging using a high-resolution 512x512 matrix and magnetic resonance angiography in 49 subjects (21 patients with essential hypertension, 10 patients with secondary hypertension, and 18 normotensive subjects). One patient with essential hypertension was excluded from the evaluations because of inadequate assessment due to poor images. Neurovascular compression of the RVLM was observed in 15 of 20 (75%) patients with essential hypertension. In contrast, neurovascular compression was observed in only 1 of 10 (10%) patients with secondary hypertension and only 2 of 18 (11%) normotensive subjects. The rate of observed neurovascular compression in the essential hypertension group was significantly higher than that in the secondary hypertension group and the normotensive group (P<.01 for both). The distances between the RVLM and the nearest arteries in the essential hypertension group were significantly shorter than those in the other groups (P<.05 for all). On the other hand, the distances between the surface of the medulla oblongata and the nearest arteries did not differ among these three groups. These results suggest that neurovascular compression of the RVLM, but not of the other regions of the medulla oblongata, is particularly related to essential hypertension.

Adult↗
PubMed1997

Noninvasive measurement of airway responsiveness in allergic mice using barometric plethysmography.

To study the mechanisms and kinetics underlying the development of increased airway responsiveness (AR) after allergic sensitization, animal models have been invaluable. Using barometric whole-body plethysmography and increases in enhanced pause (Penh) as an index of airway obstruction, we measured responses to inhaled methacholine in conscious, unrestrained mice after sensitization and airway challenge with ovalbumin (OVA). Sensitized and challenged animals had significantly increased AR to aerosolized methacholine compared with control animals. AR measured as Penh was associated with increased IgE production and eosinophil lung infiltration. In a separate approach we confirmed the involvement of the lower airways in the response to aerosolized methacholine using tracheotomized mice. Increases in Penh values after methacholine challenge were also correlated with increased intrapleural pressure, measured via an esophageal tube. Lastly, mice demonstrating AR using a noninvasive technique also demonstrated increased pulmonary resistance responses to aerosolized methacholine when measured using an invasive technique the following day in the same animals. The increases in Penh values were inhibited by pretreatment of the mice with a beta 2-agonist. These data indicate that measurement of AR to inhaled methacholine by barometric whole-body plethysmography is a valid indicator of airway hyperresponsiveness after allergic sensitization in mice. The measurement of AR in unrestrained, conscious animals provides new opportunities to evaluate the mechanisms and kinetics underlying the development and maintenance of airway hyperresponsiveness and to assess various therapeutic interventions.

Airway Resistance↗
PubMed1997

Evidence for linkage between asthma/atopy in childhood and chromosome 5q31-q33 in a Japanese population.

Susceptibility to the development of asthma and other atopic diseases is known to be associated with genetic components, and several candidate genes have been reported to be linked to atopy in Caucasian populations. We conducted a study of linkage between asthma and markers on chromosomes 5q31-q33 and 11q13 in 68 Japanese families (306 members) by affected sib-pair analysis. Families for the linkage study were ascertained through asthmatic children visiting the allergy clinic. The results provide supportive evidence for linkage between asthma and gene markers in or near the interleukin-4 (IL-4) gene, the IL-9 gene, and D5S393 on chromosome 5q31-q33 (p = 0.0013, p = 0.018, and p = 0.0077, respectively). Linkage between atopic phenotype and these genetic markers was also suggested (p = 0.006, p = 0.01, and p < 0.0001 for atopy, respectively). However, we failed to find evidence for linkage of asthma or atopy to the IgE high-affinity receptor gene on 11q13 (p > 0.1). These findings indicate that beyond ethnicity, there are specific loci that contribute to susceptibility to atopy on chromosome 5q31-q33. In addition, our findings suggest that loci on chromosome 5q31-q33 are linked to the development of asthma in childhood.

Adolescent↗
PubMed1997

CD23 deficient mice develop allergic airway hyperresponsiveness following sensitization with ovalbumin.

The low affinity receptor for IgE (CD23) is reported to regulate immune and inflammatory events and as a result, it may have a role in the development of allergic airway inflammation and hyperresponsiveness (AHR). To test this hypothesis CD23-deficient mice were studied following different modes of allergic sensitization. Mice were actively sensitized either intraperitoneally with ovalbumin (OA)/alum or via the airways (10 days exposure to OA aerosol with no adjuvant). Passive sensitization was performed by intravenous injections of OA-specific IgE. Airway responsiveness, serum IgE and IgG levels were assessed together with airway inflammation. Passive sensitization followed by airway challenges resulted in increased OA-specific lgG and IgE in the serum of wild-type mice only, while both the CD23+/+ and CD23-/- groups developed tracheal smooth muscle hyperresponsiveness to electrical field stimulation, indicating that IgE/CD23-mediated immune functions may not be necessary for the development of allergic changes. Active sensitization of both CD23-/- and CD23+/+ mice resulted in increased serum levels of OA-specific IgE and lgG, airway eosinophilia and significant AHR when compared with nonsensitized mice. The genetic deficiency of CD23-/- mice not only failed to prevent but was associated with a significant increase of these responses. These results indicate that CD23 may not be essential for the development of allergen-induced AHR and further, that its presence may have some inhibitory effects on the allergic response.

Allergens↗