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Biomedical subjects

S Shimada

Publications and source records attributed to S Shimada.

At least 199 records · Page 11Linked to original sources
PubMed1996

In vitro-in vivo correlation of pharmacodynamics of felodipine in essential hypertensive patients based on an ion-channel binding model.

The relationship between the plasma drug concentration and the antihypertensive effect of felodipine was analyzed by an ion-channel binding model which takes into consideration the slow association/dissociation process of a drug at the calcium channel. The in vitro dissociation constant (Kd) of felodipine to the calcium channel in the heart of rats was determined, and was compared to the in vivo dissociation constant (Kd,calc) estimated by the pharmacodynamic analysis of the concentration-effect data in Japanese essential hypertensive patients obtained from literature. The relative relationship between Kd and Kd,calc of felodipine was substantially identical with eight other calcium channel blocking agents reported previously. This results suggested the possibility that we can predict the pharmacodynamic behavior of newly developed calcium channel blocking agents from the in vitro Kd value and plasma concentration-time profile in human using the ion-channel binding model.

Animals↗
PubMed1996

Comparative pharmacodynamics of eight calcium channel blocking agents in Japanese essential hypertensive patients.

The relationships between plasma drug concentration and antihypertensive effect of eight calcium channel antagonists (nicardipine, nifedipine, nilvadipine, benidipine, manidipine, barnidipine, nitrendipine and efonidipine) in Japanese essential hypertensive patients were analyzed. Based on the effect compartment model, we could explain the long duration of the pharmacological effect, and there was significant correlation (r = 0.876, p < 0.05) between estimated EC50 values and the dissociation constants (Kd) obtained from in vitro binding studies. We also developed the ion-channel binding model to understand the pharmacodynamics of long acting calcium antagonists. The model was also well fitted to antihypertensive effect data. A significant correlation between the apparent in vivo dissociation constants and in vitro Kd values was observed with a slope of 1.45 (r = 0.913), suggesting that the mechanism of long-lasting antihypertensive effect of newer developed calcium antagonists is due to their high binding affinity at ion-channel sites.

Adult↗
PubMed1996

[Home mechanical ventilation for children in Japan].

Children who require prolonged respiratory support often have to spend their whole lives in the hospital. It is important, however, to have time with their families in their own homes. Home mechanical ventilation can make it possible. In Japan, at present, there are probably more than 100 cases in which home mechanical ventilation is being used for children. We have had experience with twelve cases of home mechanical ventilation. By using a transport respirator for these children, there have been excursions 96 times and home stays 123 times. Three of these children could be released for home stay completely. Before taking the patients out of hospital, the patients received training in nursing procedures and in skillful use of the ventilator and equipment. Home mechanical ventilation was, thereby, managed successfully by the family members. Our experience revealed that home mechanical ventilation accelerated social and emotional development of these children, especially patients with neuro-muscular diseases. However, there are also many difficulties such as limitations in regard to social services and support systems, financial and educational problems, etc. Problems related to finances and support systems are the major concerns for the families. It is important to find a way out of these difficulties from the perspective of more human medicine and of quality of life. These problems should be resolved through the government support and social services. In the near future, home mechanical ventilation for children will be probably an important part of pediatrics in Japan.

Child↗
PubMed1996

[Study of the usefulness of a kit containing imipenem/cilastatin powder with diluent for injection: accuracy of reconstitution].

The usefulness of a kit consisting of non-glass packaging was evaluated in terms of accuracy of reconstitution. The newly developed imipenem/cilastatin powder-and-diluent kit consists of a polyolefin bag with two chambers that contain impenem/cilastatin powder and diluent (0.9% saline, 100 ml), respectively. The accuracy of reconstitution was determined by nurse and pharmacists at the Kitasato University East Hospital by measuring the amount of materials remaining in vials after reconstitution using the syringe dilution method and the transfer-needle dilution method. The mean percent amounts of imipenem and cilastatin remaining after preparation by the syringe dilution method were 5.58 +/- 2.60% and 4.08 +/- 1.77%, respectively. The mean percent amounts of imipenem and cilastatin remaining after preparation by the transfer-needle dilution method were 3.99 +/- 2.28% and 3.71 +/- 2.09%, respectively. The amount of imipenem/cilastatin remaining in the newly developed kit should be negligible, because the kit serves as both a vial and a dosing package. Therefore, greater accuracy in terms of reconstitution is expected with the newly developed kit than with the traditional syringe dilution or transfer-needle dilution methods.

Cilastatin↗
PubMed1996

A case of generalized pustular psoriasis followed by bullous disease: an atypical case of bullous pemphigoid or a novel bullous disease?

We describe a 31-year-old Japanese woman with generalized pustular psoriasis treated with PUVA who subsequently developed a bullous disease. Throughout the disease course, there was no phase of psoriasis vulgaris. Although several reports describe coexistence of psoriasis vulgaris and bullous disease such as bullous periphigoid, coexistence of generalized pustular psoriasis without any phase of psoriasis vulgaris and bullous disease is rare. As for the bullous disease, direct immunofluorescence study showed IgG and C3 deposition along the basement membrane zone. Indirect immunofluorescence disclosed IgG antibasement membrane zone antibodies. Indirect immunofluorescence on 1 mol/l sodium chloride-split skin demonstrated linear IgG staining almost exclusively on the dermal side of the split. Western immunoblot analysis revealed that the antibody was directed to neither epidermolysis bullosa acquisita antigen nor bullous pemphigoid antigens. Considering the unusual clinical course, we suspect the possibility of a novel autoimmune blistering disease.

Adult↗
PubMed1996

[Epidemiological analysis of Epstein-Barr virus infection].

We analysed the characteristics of 372 Epstein-Barr virus (EBV) infected patients visiting our hospital from 1981 to 1995 classifying the phase I (from 1981 to 1988), the phase II (from 1989 to 1991) and the phase III (from 1992 to 1995). The incidence of infectious mononucleosis (IM) as EBV primary infection increased especially in the patients over 30 years old in the phase II and III. Immunological data on EBV specific antibodies showed twice positivity for anti EBV VCA-Igm antibody and the patients with anti-EBNA antibody decreased in the phase II and III. It is indicative of early diagnosis on primary EBV infection. EBV also causes atypical diseases, non-IM in this report, including hematological or neurological disorders. In hematological ones, one of 4 cases with virus associated hemophagocytic syndrome (VAHS) took fatal courses in the phase I, others had recovered by early diagnosis and adequate therapies (pulse therapy of steroids, exchange transfusion etc.). We indicated here the increased number and advanced age of patients with IM and improvement of the early diagnosis in recent 6 years compared with the previous 8 years.

Adolescent↗
PubMed1996

Visualization of ischemic insult in caudate putamen with beta-CIT.

UNLABELLED: Dopamine (DA) has been considered to play an important role in the development of ischemic neuronal injury in the caudate putamen (CPu). The goal of this study was to examine the change in the dopamine transporter (DAT) after ischemic insult in CPu. METHODS: Male Mongolian gerbils (n = 10) were exposed to 10-min forebrain ischemia. Animals were decapitated 24 hr (n = 5) and 96 hr (n = 5) after ischemia. The change in the amount of DAT binding sites in CPu was evaluated by in vitro autoradiography with [125I]-beta-CIT (3 beta-(4-iodophenyl)tropan-2 beta-carboxylic acid methyl ester). In addition, the expression of DAT mRNA in CPu and the substantia nigra pars compacta (SNC) was examined. RESULTS: Iodine-125-beta-CIT specific binding was significantly increased in dorsolateral CPu with ischemic damage both 24 hr and 96 hr after ischemia, with greater increase at 96 hr. DAT mRNA in SNC was also significantly increased 96 hr after ischemia, which corresponded with the increase of [125I] beta-CIT binding. However, DAT mRNA in SNC was decreased 24 hr after ischemia. In the ischemic lesion in CPu, no expression of DAT mRNA could be detected both 24 hr and 96 hr after ischemia. CONCLUSION: The change in DAT after ischemic insult is clarified with [125I] beta-CIT. This increase of [125I] beta-CIT binding does not come from de novo expression of DAT in glial cells in the damaged area in CPu. This increase of beta-CIT binding reflects increase of DAT synthesis in DA neurons in SNC (96 hr) or other factors such as the impairment of the degradation of DAT in the damaged area in CPu.

Animals↗
PubMed1995

Ultrastructural effects of pressure stress to the nucleus in Saccharomyces cerevisiae: a study by immunoelectron microscopy using frozen thin sections.

The effects of hydrostatic pressure on subcellular structures, particularly the nucleus, of Saccharomyces cerevisiae were investigated by immunoelectron microscopy. Cells were treated with hydrostatic pressure from 0.1 to 400 MPa for 10 min at room temperature. Frozen thin sections of the cells revealed that spindle pole bodies disappeared at 100 MPa. At 150 MPa, the deposition of gold particles for anti alpha-tubulin was noticed in the nucleus, although the filamentous structure of microtubules was lost. At 200 MPa, fewer gold particles were scattered in the nucleus and the nuclear membrane in several portions was also observed to be open at 300 MPa. These results show that elements of the nuclear division apparatus were susceptible to pressure stress, particularly spindle pole bodies and microtubules. The damage to spindle pole bodies, microtubules, and nuclear membrane caused by pressure stress was followed by the inhibition of nuclear division. After the release of pressure, the spindle pole bodies and microtubules of pressurized cells at below 200 MPa regained their normal appearance at 24 h.

Cell Division↗
PubMed1995

Induction of TCR-gamma delta+ cells from thymocytes stimulated by a fetal liver-derived hepatocyte clone.

We have previously reported that a fetal liver-derived hepatocyte clone, FHC-4D2, can support hematopoiesis in vitro. Here, we show that fetal thymocytes (FT) or adult thymocytes (AT) proliferate on the monolayer of FHC-4D2 cells in the presence of rIL-2. Fresh thymocytes contained few TCR-gamma delta+ cells (< 4% for FT and < 1% for AT); significant numbers of TCR-gamma delta+ cells were detected (2-11% for FT and 15-33% for AT) after the coculture with FHC-4D2 and rIL-2. Although FT-derived TCR-gamma delta+ cells predominantly used the V gamma 5 chain, the major population in AT-derived TCR-gamma delta+ cells used V gamma 1, V gamma 4, or V gamma 7 chains. Both FT- and AT-derived TCR-gamma delta+ cells killed FcR-bearing target cells when incubated with anti-TCR-gamma delta Ab. Half of FT-derived TCR-gamma delta+ cells were CD4-CD8 alpha+8 beta-; the rest were CD4-CD8 alpha-8 beta-. AT-derived TCR-gamma delta+ cells expressed neither CD4 nor CD8 molecules. Separation of thymocytes from FHC-4D2 cells with a membrane filter reduced the proliferative response by two- to threefold. Taken together, these results demonstrate that a fetal hepatocyte clone supports thymocytes to develop preferentially into TCR-gamma delta+ cells in cooperation with rIL-2 through cell-cell contact, that the repertoire and the phenotype of induced TCR-gamma delta+ cells are determined by the age of the mice, and that hepatocytes might thus play an active role in T lymphopoiesis in the fetal liver.

Age Factors↗
PubMed1995

Alterations of angiotensin II receptor contents in hypertrophied hearts.

Tsukuba hypertensive mice, which carry the human genes for renin and angiotensinogen, show cardiac hypertrophy as well as hypertension due to activation of the renin-angiotensin system (RAS). Here, we compared the cardiac angiotensin II (Ang II) receptor contents in these and normotensive control mice by means of ligand binding studies and competitive reverse transcription-polymerase chain reaction analyses. The content of the Ang II receptor type 1 (AT1) was significantly higher at both the protein (2.5-fold; p < 0.01) and mRNA (1.4-fold; p < 0.05) levels in the hypertensive mice than that in control mice. Almost identical levels of the Ang II receptor type 2 (AT2) expression were identified at the mRNA levels in the two types of mice, although the levels were less than 20% of those of AT1 mRNA in control mice. These results suggest that AT1 in the heart is upregulated in response to Ang II-induced hypertrophic change and that, in particular, the upregulation of AT1 in particular contributes to the development and/or maintenance of cardiac hypertrophy in conjunction with the increase in Ang II production, because AT1 is responsible for cardiac hypertrophy related to the RAS.

Animals↗
PubMed1995

Relationship between multidrug resistant gene expression and multidrug resistant-reversing effect of MS-209 in various tumor cells.

MS-209 is a novel quinoline compound which can overcome multidrug resistance (MDR) both in vitro and in vivo, while having a low level of side effects, and is now being evaluated in a clinical phase II study. Reverse transcription-polymerase chain reaction (RT-PCR) was used to quantitate the expression levels of MDR genes in various mouse and human tumor cell lines. The MDR gene and the beta actin gene, as the internal reference standard, were coamplified separately, and the relative expression of the MDR gene was represented by the MDR/beta actin ratio. The in vitro MDR-reversing effect of MS-209 was then compared with the MDR gene expression (MDR/beta actin ratio). We found a significant correlation between these two parameters. Moreover, a significant correlation was also observed between the level of expression of the MDR1 gene and that of P-glycoprotein in human cell lines. Therefore, the efficacy of MS-209 seems to specifically depend on the level of MDR gene expression (P-glycoprotein). From these observations, it is suggested that RT-PCR assays of MDR1 gene in tumor biopsy specimens might be an effective means to predict the response of tumor cells to combination therapy with MS-209.

Animals↗
PubMed1995

Ruptured aneurysm associated with arachnoid cyst: intracystic hematoma without subarachnoid hemorrhage.

BACKGROUND: It is well-known that arachnoid cysts of the middle fossa are associated often with chronic subdural hematomas and/or intracystic hemorrhages. However, reports of an arachnoid cyst associated with an aneurysm are rare. CASE DESCRIPTION: A 45-year-old man was admitted with headache due to intracystic hemorrhage in the sylvian fissure, associated with a saccular aneurysm at the bifurcation of the internal carotid artery. The aneurysm ruptured into the arachnoid cyst, without causing a subarachnoid hemorrhage. Subsequently, the neck of the aneurysm was clipped successfully. The patient's postoperative course was uneventful, and there was no vasospasm. CONCLUSIONS: This is the first reported case of an intracystic hematoma due to a ruptured aneurysm. We discuss the possible etiology of the association between the aneurysm and the arachnoid cyst, and the formation mechanism for the intracystic hematoma that did not result in a subarachnoid hemorrhage.

Arachnoid Cysts↗
PubMed1995

Cloning and expression of a bovine glutamate transporter.

We have isolated a 3845 base-pair cDNA (BNGLUAS) encoding a bovine glutamate transporter (bovine GLAST) by screening a bovine retina cDNA library with an oligonucleotide probe corresponding to conserved regions of known glutamate transporters. The cDNA sequence predicted a protein of 542 amino acids and displayed 96% and 97% amino acid identity with the rat GLAST/GluT-1 and human GLAST, respectively. Expression of the bovine GLAST in Xenopus oocytes revealed Na(+)-dependent [14C]L-glutamate uptake and electrogenic glutamate uptake.

ATP-Binding Cassette Transporters↗
PubMed1995

The rat intrinsic factor gene: its 5'-upstream region and chief cell-specific transcription.

A DNA segment containing the 5'-upstream region and amino terminal reading frame of the gastric intrinsic factor gene was cloned from rat and its nucleotide sequence was determined. S1 mapping demonstrated that the transcription initiation site is located downstream of the second TATA-box sequence. Similar sequence motifs to those in the pepsinogen genes transcribed in gastric chief cells were found in the deduced sequence, suggesting that the rat intrinsic factor gene is transcribed in these cells. The genes for the intrinsic factor and its homologous protein transcobalamin I were apparently derived from a common ancestoral gene, since the positions of their intron insertions as well as the amino acid residues are conserved. Northern blot hybridization showed that the gene for the intrinsic factor is transcribed in the stomach but not detectably in the intestine, kidney, testis, brain, heart, liver, lung, or spleen. In situ hybridization using radioactive complementary RNA clearly indicated that the major transcription site in gastric glands is chief cells. Different locations of expression of intrinsic factor proteins in various mammals were observed previously using antibodies: in rat parietal cells and chief cells, in mouse chief cells, and in human parietal cells. The present results clearly demonstrated the intrinsic factor mRNA mainly in chief cells of adult rats, as in mice, suggesting that transcriptional regulation of the intrinsic factor gene is essentially the same in rodents.

Animals↗
PubMed1995

Differential responsiveness of Langerhans cell subsets of varying phenotypic states in normal human epidermis.

Epidermal Langerhans cell heterogeneity is poorly understood with regard to phenotypic characteristics, such as the expression of human leukocyte antigen (HLA)-DR, integrin, and Fc receptor molecules, as well as functional characteristics, such as the ability to process and present antigens or produce cytokines during various phases of immigration and maturation. Technical limitations of Langerhans cell number have limited functional assays on putative Langerhans cell subsets in in vivo epidermis. Therefore, we used flow cytometry for simultaneous phenotypic and functional assessment at the single-cell level within the Langerhans cell population. Freshly isolated human epidermal cell suspensions were stained with a battery of monoclonal antibodies, including anti-HLA-DR, -CD1a, -CD1c, -CD11c, -Fc gamma RII, and -Fc epsilon RI. Two distinct Langerhans cell subsets were identified by their different levels of HLA-DR expression. The DRHi subset expressed higher amounts of CD11c and exhibited greater cytoplasmic complexity and higher baseline calcium than the DRLo subset (p < or = 0.03 for each). Some subjects also expressed high levels of Fc epsilon RI in the DRHi, CD11cHi subset. To determine whether these phenotypic subsets may exhibit differential signal-transduction functional properties, Langerhans cells were partially enriched over Ficoll-Hypaque and their cytosolic mobilization after the addition of ionomycin was analyzed using the calcium indicator, indo-1, in conjunction with quantitative analysis of HLA-DR expression. By this real-time flow cytometric analysis, a new subpopulation was revealed within the DRLo Langerhans cell subset. This subset increased its cytosolic calcium concentration much more than the other two subsets (change in indo-1 blue:violet emission ratio of 37.33 +/- 2.34 in the Hi Flux DRLo subset versus 13.23 +/- 0.29 in the Lo Flux DRLo subset, and versus 7.6 +/- 2.99 in the Lo Flux DRHi subset). These data indicate that functional, as well as phenotypic, subsets of Langerhans cells exist within normal human epidermis. Their responses to physiologic stimuli may relate to maturational stage or the level of in vivo activation.

Adult↗
PubMed1995

Effect of an angiotensin II receptor antagonist, TCV-116, on neointimal formation following balloon injury in the SHR carotid artery.

1. In the present study, we examined the effect of a novel angiotensin II type I receptor antagonist, TCV-116, on carotid neointimal formation after balloon injury in SHR and WKY rats. 2. Oral administration of TCV-116 at a dose of 10 mg/kg per day reduced not only systolic blood pressure but also neointimal formation after carotid balloon injury. TCV-116 also suppressed cardiac hypertrophy. An angiotensin-converting enzyme inhibitor, lisinopril (20 mg/kg per day), had a similar effect to that of TCV-116. 3. In the WKY experiment, both TCV-116 and lisinopril suppressed neointimal formation as well as systolic blood pressure, but did not suppress cardiac hypertrophy. 4. Although SHR showed markedly enhanced neointimal formation after balloon injury compared with age-matched WKY rat, both TCV-116 and lisinopril showed similar suppressive effects on neointimal formation in both SHR and WKY rats. 5. These results confirm the important role of angiotensin II in neointimal formation following balloon injury. Further studies are needed to clarify the mechanism of the difference between SHR and WKY rats in the response of vascular smooth muscle cells.

Angiotensin II↗