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Biomedical subjects

H Shiga

Publications and source records attributed to H Shiga.

At least 55 records · Page 3Linked to original sources
PubMed1996

Comparison of the efficacy of pentoxifylline and albifyllin (HWA 138) on endotoxin-induced cytokine production, coagulation disturbances, and mortality.

We have evaluated two different xanthine derivatives, pentoxifylline (POF) and albifyllin (HWA), in rat endotoxemia for their ability to reduce 1) cytokine formation, 2) coagulation disturbances, and 3) mortality. The animals were injected with lipopolysaccharide (LPS) (15 mg/kg i.p.) and received HWA or POF (25, 50, or 100 mg/kg) or saline 30 min before LPS administration. The plasma tumor necrosis factor levels were significantly reduced and in a similar manner by pretreatment with HWA or POF in vivo as well as in vitro. Neither the coagulation disturbance nor the characteristic leukopenia that follow an LPS challenge were significantly influenced by the xanthine derivatives. At a dose of 100 mg/kg, the 6 day mortality was significantly reduced by HWA to 36% but only attenuated by POF to 55% as compared to 80% in the control group. The similar effect of both agents on cytokine formation and coagulation disturbances indicate that, at least to a substantial degree, other mechanisms may account for the significant protection of rats against endotoxin-induced mortality by HWA only. HWA 138 may, therefore, be a new powerful agent against endotoxin-related disorders and mortality.

Animals↗
PubMed1996

Intracranial aneurysms: diagnostic accuracy of MR angiography with evaluation of maximum intensity projection and source images.

PURPOSE: To determine whether evaluation of source images from magnetic resonance (MR) angiography in addition to maximum-intensity projection (MIP) images improves the detection of aneurysms. MATERIALS AND METHODS: Conventional and MR angiography were performed in 193 patients with various intracranial vascular lesions or normal findings. Images were evaluated in a blinded manner. Two readings were performed 6 weeks apart by evaluating MIP images with and without source images. Results were evaluated with receiver operating characteristic analysis. RESULTS: Sensitivity for the detection of aneurysms increased slightly when source images were included. The detection rate of internal carotid artery aneurysms was most improved with the addition of source images. No statistically significant differences in performance were found between the readings with MIP images alone and with source images. CONCLUSION: Sensitivity may improve with combined reading of nonselective MIP and source images.

Case-Control Studies↗
PubMed1996

Antianginal effect of RS-5773, a diltiazem congener, in the methacholine-induced anginal model in rats.

The antianginal effect of RS-5773 ((2S,3S)-3-acetoxy-8-benzyl-2,3-dihydro-5-[2-(dimethylamino)- ethyl]-2-(4-methoxyphenyl)-1,5-benzothiazepine-4-(5H)-one hydrochloride), a newly developed benzothiazepine derivative, was evaluated in an angina model rat. Close-coronary artery injections of methacholine in anesthetized rats evoked ischemic electrocardiographic (ECG) changes (S wave elevation of about 0.6 mV). The ECG changes produced by methacholine were reproducible for as long as 6 hr. Intravenous and intraduodenal administration of RS-5773, diltiazem or clentiazem produced dose-dependent suppressions of the ischemic ECG changes. RS-5773 exceeded the other two agents both in the maximum suppressive effect on S wave elevation and in the duration of action after intravenous administration. The antianginal potency expressed as AUC (area under the curve), i.e., the percent suppression of S wave elevation integrated over time, revealed that RS-5773 was 16 times and 7 times more potent than diltiazem and clentiazem, respectively. A similar order of potency difference was observed after intraduodenal administration, and RS-5773 sustained its effect for about 6 hr at 3 mg/kg. In addition, RS-5773 did not cause excessive hypotension or depression of atrioventricular conduction. These results suggest that RS-5773 has a preferable profile as an antianginal agent.

Angina Pectoris, Variant↗
PubMed1996

[Skull base metastasis from renal cell carcinoma presenting as abducens nerve paresis: report of two cases].

We report two cases of skull base metastasis from renal cell carcinoma. Case 1: A 55-year-old female presented with a skull base tumor located on the clivus. Partial removal of the tumor was performed via the transsphenoidal approach. Case 2: A 44-year-old male presented with a skull base tumor occupying the orbital, nasal, and paranasal cavities. The first operation, partial removal of the tumor, was performed via the transsphenoidal approach. Thereafter, the tumor regrowth and the patient's symptoms were progressive, so a second operation was performed via Le-Forte I craniotomy to prevent cranial nerve dysfunction and air way obstruction. The initial symptom of these two cases was abducens nerve paresis, which is caused by the tumor extending from the clivus to the cavernous sinus. The neuroradiological features were the destruction of skull base bone and angiographic tumor stain. Histopathological examination of the surgically resected specimens revealed clear cell carcinoma, and thereafter they were diagnosed as skull base metastasis from renal cell carcinoma. We emphasize the necessity of a thorough medical workup to enable speedy diagnosis of renal cell carcinoma in such cases.

Abducens Nerve↗
PubMed1996

Identification of multiple HIV-1 cytotoxic T-cell epitopes presented by human leukocyte antigen B35 molecules.

OBJECTIVE: To identify HIV-1 cytotoxic T lymphocyte (CTL) epitopes presented by human leukocyte antigen (HLA)-B35 molecules that are associated with the accelerated progression of AIDS using a reverse immunogenetic approach. METHODS: 8-mer to 11-mer sequences carrying two anchor residues at position 2 and the carboxy-terminus were selected from HIV-1SF2 strain. Sixty-four peptides matched to these sequences were synthesized and tested by a peptide binding assay using RMA-S-B*3501 cells. Peripheral blood lymphocytes (PBL) from two HIV-1-infected donors carrying HLA-B35 were stimulated once-weekly with each HLA-B*3501 binding peptide. The CTL activity of the cultured cells for the HLA-B35-positive target cells loaded with the corresponding peptides was examined after the second and fourth stimulation. Furthermore, the CTL activity of the cultured cells possessing HLA-B*3501-restricted HIV-1 peptide-specific CTL activity were examined for the HLA-B*3501-positive target cells infected with the recombinant vaccinia virus containing corresponding HIV-1 gene. RESULTS: HIV-1 peptide-specific HLA-B*3501-restricted CTL was induced in PBL of HIV-1 infected donors by in vitro stimulation with 11 out of 27 HLA-B*3501-binding HIV-1 peptides. The specific CTL induced with 10 peptides killed the cells infected with recombinant vaccinia virus expressing the corresponding HIV-1 proteins. Out of these HIV-1 peptide epitopes, two epitopes were also presented by HLA-B51 molecules. CONCLUSION: In addition to the four HLA-B35-restricted HIV-1 CTL epitopes that have been previously reported, nine HLA-B35-restricted HIV-1 CTL epitopes were identified in the present study. These multiple epitopes will be useful in studies for immunopathogenesis of AIDS.

Antigen Presentation↗
PubMed1996

[Prevention and treatment of postoperative septic MOF and DIC and efficacy of blood purification].

Pathophysiologic concept of SIRS has been proposed for the better management of postoperative severe infection and septic MOF, and the concept has been found to be very useful. It is very important to identify the high risk SIRS patients of the development of septic MOF and to treat those patients aggressively to prevent the development of septic MOF. In the prevention and treatment of septic MOF, the blood purification has been found to be very effective. Among the blood purifications, continuous blood purification, such as continuous hemodiafiltration (CHDF) should be chosen for this purpose. CHDF has been claimed to be very effective to removal of causative humoral mediators from the blood stream. The concept of DIC has been changed recently and the concept of DII (disseminated intravascular inflammation) should be applied instead of DIC, since the main feature of this pathologic condition is the damage of endothelial cells due to extensive systemic inflammation.

Disseminated Intravascular Coagulation↗
PubMed1995

Fine tuning of peptide binding to HLA-B*3501 molecules by nonanchor residues.

The prerequisites of peptide HLA-B*3501 interactions have been revisited by quantitative peptide binding assays with 190 chemically synthesized peptide possessing two anchor residues corresponding to the HLA-B*3501 peptide motif and a statistical residue-position analysis of binding and nonbinding peptides. According to the peptide motif of HLA-B*3501, aliphatic hydrophobic (Leu, Ile, and Met) or aromatic residues (Tyr and Phe) specify the main anchor at the C terminus, and position 2 renders an auxiliary anchor for proline. The importance of these residues was confirmed as a minimum requirement for peptide binding. Moreover, we demonstrated that high affinity peptide binding requires more than one favorable position of positions 3, 4, and 7. Aliphatic hydrophobic residues and residues that contain -OH or -SH side chains in position 3, 7, and 4 significantly enhance binding. Positions 1 and 5, or 7 may deteriorate peptide binding if these positions are held by proline and small residues (Ala and Gly) or basic residues carrying positively charged side chains (Arg and Lys), respectively. Positions 6 and 8 were statistically free of constrains. Yet, bulky aromatic residues and basic residues with a positively charged side chain at position 8 decreased the binding affinity. These findings were used to assess the predictability of binding and nonbinding peptides. Our binding predictions of 28 nonamers were verified by experimental data. Taking into account the importance of anchor and nonanchor positions in peptide binding and their practical value in peptide binding prediction, the search for peptide epitopes becomes more efficient.

Amino Acid Sequence↗
PubMed1995

[Prognosis and outcome of rheumatoid arthritis--10 to 16 years of anti-rheumatic therapy].

One hundred twenty-eight rheumatoid arthritis (RA) patients were followed up over a long period of time (mean, 13.3 years; range, 10-16 years) in order to determine the role of pharmacotherapy in RA. Patients were aged 48.2 years on the average (23-79 years) and the mean RA duration was 7.8 years (0-58 years) upon initial visit to this unit. Although pharmacotherapy was effective in improving Lansbury's activity index and ESR, articular bone and cartilage destruction and functional impairment progressed gradually, resulting in the need for total hip, knee or ankle arthroplasty in 46 (96 joints) of the 128 patients. This finding indicates that current pharmacotherapy for RA has limitations in that it cannot completely prevent joint destruction and resulting functional impairment. This suggests that new therapeutic modalities, including new drugs, are necessary. Efforts were also made to determine factors which affect the prognosis of RA. The prognosis seemed pessimistic in RA patients with high activity and rheumatoid factor (RAPA) levels, long duration of illness, high Larsen scores and advanced functional impairment at the time of initial active therapy. It appeared necessary to maintain Lansbury's activity index at 30% or below in order to obtain a good prognosis.

Adult↗
PubMed1994

Intracranial aneurysms: diagnostic accuracy of three-dimensional, Fourier transform, time-of-flight MR angiography.

PURPOSE: To assess the accuracy of three-dimensional, Fourier transform, time-of-flight magnetic resonance (MR) angiography in the identification of intracranial aneurysms. MATERIALS AND METHODS: MR angiograms of 126 patients (59 male and 67 female patients, aged 12-77 years) with various intracranial vascular lesions were evaluated. Seventy-eight aneurysms, including 60 less than 5 mm in diameter, in 61 patients were depicted at conventional angiography. Eight projection images, as well as one axial collapsed MR angiogram obtained with a maximum-intensity projection algorithm, were used for evaluation. RESULTS: Sensitivity for the five observers ranged from 58% to 68% (mean, 63%). Higher sensitivity was achieved for anterior communicating and middle cerebral artery aneurysms, while that for internal carotid artery aneurysms was poor. Sensitivities for small and medium aneurysms ranged from 50% to 60% (mean, 56%) and from 77% to 94% (mean, 86%), respectively. CONCLUSION: MR angiography can depict intracranial aneurysms 5 mm or larger with good accuracy but is less useful for the identification of smaller aneurysms.

Algorithms↗
PubMed1994

Intracranial vascular stenosis and occlusion: diagnostic accuracy of three-dimensional, Fourier transform, time-of-flight MR angiography.

PURPOSE: To assess the accuracy of three-dimensional, Fourier transform, time-of-flight magnetic resonance (MR) angiography in the detection of intracranial steno-occlusive diseases. MATERIALS AND METHODS: One hundred thirty-one patients (62 male and 69 female patients, aged 6-77 years [mean, 53 years 8 months]) underwent MR and conventional angiography for evaluation of possible intracranial vascular disease. A total of 502 arteries were assessed. Eight projections and a collapsed image postprocessed by means of a maximum-intensity projection algorithm were reviewed by five observers in a blinded manner, with conventional angiography as the standard. RESULTS: A total of 32 steno-occlusive lesions were available for review. Receiver operating characteristic analysis from the pooled data revealed overall sensitivities of 85% and 88% and specificities of 96% and 97% for the internal carotid artery and the middle cerebral artery, respectively. CONCLUSION: MR angiography is useful as the primary diagnostic tool for evaluating suspected intracranial steno-occlusive disease.

Algorithms↗
PubMed1993

[Role of opioid peptide in rheumatoid arthritis--detection of methionine-enkephalin and leucine-enkephalin in synovial tissue].

A relationship between rheumatoid arthritis (RA) and endocrinological abnormality has been suspected for many years. In the present study, we immunohistologically identified the presence of methionine-enkephalin (Met-enk) and leucine-enkephalin (Leu-enk), in synovial tissues collected from RA patients and determined the amount of these peptides and interleukin 1 beta (IL-1 beta) in the culture supernatant of tissue explants by RI and ELISA. Synovial membrane samples obtained by biopsy during artificial joint replacement and plasma samples simultaneously collected from 11 RA patients (11 joint) diagnosed as having classic or definite RA according to the diagnostic criteria of the American Rheumatism Association were used. All 11 patients were females and aged between 36 and 64 years (mean: 45.8 years). As a result of immunohistological standing (ABC method), Met-enk was detected in vascular endothelial cells and Leu-enk in superficial cells, vascular endothelial cells and interstitial cells. Leu-enk concentrations (42.3 +/- 15.8 pg/ml) were higher in the culture supernatant of the synovial membrane than in the plasma (20.7 +/- 13.3 pg/ml). Furthermore, in the culture supernatant the concentration of Leu-enk was positively correlated with that of IL-1 beta (r = 0.789). These findings suggest that Met-enk and Leu-enk are locally produced by synovial tissues and may exert an immunological and/or inflammatory role in RA synovitis.

Adult↗
PubMed1992

Synthesis and antihypertensive activity of 3-acetoxy-2,3-dihydro-5-[2- (dimethylamino)ethyl]-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one (diltiazem) derivatives having substituents at the 8 position.

In order to improve the potency and duration of biological actions of diltiazem, a number of 1,5-benzothiazepine derivatives having the substituents at the 8 position were prepared and evaluated for their antihypertensive activity in spontaneously hypertensive rats. The introduction of methyl, ethyl, isopropyl, benzyl, methoxy, ethoxy, phenoxy, and methylthio groups increased the antihypertensive activity and prolonged duration of action, whereas cyclohexyl, cyclopentoxy, tolyloxy, p-methoxyphenoxy and phenylthio derivatives were less active than diltiazem. Among them, the 8-benzyl and phenoxy derivatives showed the most potent and long-lasting antihypertensive action.

Animals↗
PubMed1992

[Amino acids metabolism and nutritional support in acute renal failure].

It has been claimed that conventional essential amino acid (EAA) solution may give rise to adverse effects such as hyperammonemia, in acute renal failure (ARF). On the other hand the majority the ARF treated recently have been complicated by multiple organ failure (MOF). These data indicate that a new regimen in nutritional support should be applied to those patients. A new amino acid solution for renal failure, containing not only EAA but also branched chain and non-essential amino acids, has been developed. We administered this solution as total parenteral nutrition (TPN) to ARF patients complicated by MOF. Continuous hemodiafiltration is simultaneously applied to remove excess water. The nutritional status and the deranged aminogram are improved by this treatment. We believe that an ARF patient complicated by MOF should be nutritionally supported with this new regimen.

Acute Kidney Injury↗
PubMed1992

[Role of opioid peptide in rheumatoid arthritis--detection of beta-endorphin in synovial tissue].

The presence of beta-endorphin (beta-end) was immunohistologically identified in synovial tissue samples biopsied from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). The amount of beta-end in culture supernatants of synovial tissue explants was also determined by RIA. beta-end was strongly detected in mainly superficial synovial cells, vascular endothelial cells and a few synovial interstitial cells in RA patients, but not in OA patients. In RA patients the beta-end concentration was significantly higher in the supernatants of tissue explants (26.4 +/- 8.3 pg/ml) than in the plasma of the same patients (15.3 +/- 2.5 pg/ml) (p < 0.01). Using isolated synovial cells, the beta-end concentration in the culture supernatants of non-adherent cells (19.4 pg/ml) was higher than that of adherent cells (4.0 pg/ml). It is suggested that beta-end is produced by non-adherent cells such as lymphocytes and neutrophils in addition to synovial lining cells and endothelial cells and may play some role in the pathology of RA synovial inflammation.

Adult↗
PubMed1992

[A case report of rheumatoid arthritis patient with thoracic myelopathy].

The authors report a 39-year-old woman with rheumatoid arthritis associated with myelopathy at the thoracic level. X-ray films of thoracic spine showed scoliosis which had its apex at T6. Myelography demonstrated incomplete block at the level of T6. Computerized tomogram revealed destruction of left pedicle of the sixth thoracic vertebra and dislocation of the sixth rib into the spinal canal which compressed cord at T6 level. Hemi-laminectomy at T5-T7 level and decompression were performed. Pathological investigations of soft tissue around the cord and dura mater showed infiltration of small round cells. We concluded that the synovitis of costo-transverse joint or costovertebral joint led to the destruction of the pedicle. As a result, dislocation of the rib, scoliotic deformity and thoracic myelopathy occurred.

Adult↗
PubMed1992

Pharmacological profile of a novel 1,5-benzothiazepine calcium antagonist.

The in vitro cardiovascular effects of a new 1,5-benzothiazepine derivative, RS-5773 ((2S,3S)-3-acetoxy-8-benzyl-2,3-dihydro-5-[2-(dimethylamino)ethyl]-2-(4- methoxy-phenyl)-1,5-benzothiazepine-4-(5H)-one hydrochloride, CAS 129173-57-5), were examined in isolated rat aorta and isolated guinea pig heart preparations. Like diltiazem or nifedipine, RS-5773 preferentially relaxed K(+)-contracted aorta rather than phenylephrine-contracted aorta, suggesting that the agent interfered with calcium channels. Vasorelaxant effects of RS-5773 on K(+)-contracted aorta was about 5 times more potent than those of diltiazem. The vasorelaxation with RS-5773 developed very slowly and was resistant to washout. The negative effects of the agent on contractile force of guinea pig papillary muscles and beating rate of guinea pig atria were not much different from those of diltiazem, although the actions of RS-5773 developed more slowly than those of diltiazem. These results indicate that RS-5773 is a diltiazem congener with vascular preference and long-lasting actions. In this respect, RS-5773 resembled clentiazem. But vascular and cardiac effects of RS-5773 developed more slowly than those of clentiazem and they were more resistant to washout.

Animals↗