Search PubMed⌕ Search

Biomedical subjects

S Ikeda

Publications and source records attributed to S Ikeda.

At least 379 records · Page 21Linked to original sources
PubMed1997

Acute acalculous cholecystitis with a decrease in CD4/CD8 ratio.

Acute acalculous cholecystitis (AAC) usually occurs in the elderly and in those with severe pre-existing pathological conditions. However, there have recently been reports of AAC in relatively young immunosuppressed patients, such as those with acquired immunodeficiency syndrome (AIDS). We report here a 27-year-old woman with AAC who received an emergent cholecystectomy. Although anti-human immunodeficiency virus antibody (anti-HIV) was not detected, a decrease in the CD4/CD8 ratio in sera was found. This rare case of AAC in a patient with decreased CD4/CD8 ratio who showed no other related diseases suggests that surgeons should keep in mind the possible presence of immunosuppression in this condition.

Acute Disease↗
PubMed1997

Management of giant common bile duct stones in high-risk patients using a combined transhepatic and endoscopic approach.

BACKGROUND: Endoscopic sphincterotomy (EST) for removing common bile duct stones is regarded as the safest and most successful method, particularly in patients with a high surgical risk. However, giant immobile stones still continue to present a therapeutic problem. METHODS: In our 12 patients, when endoscopic sphincterotomy and lithotomy proved to be unsuccessful a transhepatic choledochoscopic lithotomy was attempted. RESULTS: The stones were fragmented using choledochoscopic electrohydraulic lithotripsy and then were completely removed through both the transhepatic route and an EST opening in all 12 patients. The number of sessions required for these choledochoscopic procedures combined with EST was fewer than that required for only a transhepatic approach (2.5 +/- 1.3 versus 3.2 +/- 1.2), which thus resulted in a shorter hospital stay. Minor complications occurred in three patients with bleeding (two from the bile duct, one from the EST opening) and in two with postprocedure chills and fever. CONCLUSIONS: A combined lithotomy through duodenoscopic and choledochoscopic approaches is considered to be an efficient method for removing giant biliary calculi in patients who are not successfully treated by an ordinary duodenoscopic lithotomy.

Aged↗
PubMed1997

Blood supply to the retina in the laboratory shrew (Suncus murinus).

The blood supply to both retinae was studied light microscopically and by scanning electron microscopy in 48 adult laboratory shrews (Suncus murinus) of both sexes. Thirty-eight of the animals were injected into the left ventricle with Neoprene latex (Du Pont. 601A) or with Mercox (Dai Nippon Ink Ltd., CL-2R) to elucidate the blood supply to the retina from the ophthalmic artery. The remaining animals were kept for histological study of the retina. The central retinal artery, originating from the ophthalmic artery in the muscular part of the orbit, enters the optic nerve, passes through the optic disk together with the central retinal vein and penetrates the vitreous space (cavity of the eye) between the lens and the inner limiting membrane of the retina, where it divides into the dorsal, ventral, and caudal branches. Each branch, moreover, bifurcates into nasal and temporal arterioles and is distributed throughout the retina on the inner limiting membrane as far as the ciliary body and the lens. On the way they obliquely send small vessels through the inner limiting membrane into the outer plexiform layer of the retina. Their vascularization appears to correspond to the membrana vasculosa retinae found in teleosts, amphibia and reptiles.

Animals↗
PubMed1997

Synthesis and biological evaluation of orally active matrix metalloproteinase inhibitors.

The synthesis and biological evaluation of orally active inhibitors of matrix metalloproteinase are reported. Modifications of the P2' position and the alpha-substituent of hydroxamic acid derivatives were carried out, and revealed that the P2' substituent influenced the MMP inhibitory activities in vitro and in plasma after oral administration. The hydroxamates with phenylglycine at the P2' position were absorbed well orally. Compound 15e, which exhibited the longest duration of inhibitory activity in plasma after oral administration among the phenylglycine derivatives (5a-5d, 15a, 15c, 15e), was evaluated in a rat adjuvant arthritis model. A reduction in hind foot pad swelling and improvements of some inflammatory parameters were demonstrated when the compound was administered orally. These results indicate the potential of MMP inhibitors for rheumatoid arthritis.

Absorption↗
PubMed1997

The paradox of decreasing prices and increasing costs for diagnostic tests, imaging, and drugs in Japan.

Analysis of the 1987-91 national outpatient claims data shows that the percentage of patients under going sophisticated diagnostic tests tended to increase and was greater if the hospital was larger, in the public sector, or affiliated with an university. For imaging, the percentage that had CAT scans performed increased, while the percentage undergoing x-rays using contrast medium and other tomography decreased. However, for drugs, newer and more expensive ones tended to be preferred irrespective of the providers' characteristics. Although costs arising from the shift to more expensive and sophisticated technologies have been largely contained by reducing their prices in the fee schedule, this cost-containment strategy faces structural problems. We advocate the establishment of an infra-structure that offers incentives for providers to conduct technology assessment and to use the results.

Clinical Laboratory Techniques↗
PubMed1997

Inhibitory effects of TAK-044 on endothelin induced vasoconstriction in various canine arteries and porcine coronary arteries: a comparison with selective ETA and ETB receptor antagonists.

1. The inhibitory effects of the endothelin (ET) receptor antagonist, TAK-044, on ET-induced vasoconstriction in various canine arteries and porcine coronary arteries were studied and were compared to those of selective ETA and ETB receptor antagonists. 2. ET-1 (0.1 nM-0.3 microM) caused vasoconstriction in canine coronary, femoral, renal, mesenteric and basilar arteries, and the strongest responses were obtained in coronary and basilar arteries. TAK-044 (10 nM, 100 nM) inhibited this ET-1-induced vasoconstriction except in the case of mesenteric arteries. The strongest inhibitory effects were obtained in coronary arteries; an EC50 value for ET-1 was 5.2 +/- 0.77 nM (n = 12) in the control and 24 +/- 3.8 nM (n = 4) in the presence of TAK-044 at 10 nM. BQ-123 (1 microM) inhibited the vasoconstriction in coronary and femoral arteries but did not in renal, mesenteric or basilar arteries. 3. TAK-044 (10-100 nM) inhibited the ET-1-induced vasoconstriction in porcine coronary arteries to a degree similar to that in canine coronary arteries. In contrast, BQ-123 (10 microM) did not inhibit the contraction completely, and a BQ-123-insensitive component was identified. Although BQ-788 (1 microM) did not modify the concentration-response curve at all, it abolished the BQ-123-insensitive component when applied together with BQ-123 (10 microM). 4. Sarafotoxin S6c (10 pM-30 nM) caused vasoconstriction in porcine coronary arteries with the maximum amplitude of the contraction being 39% of that with ET-1. Both TAK-044 (10 nM, 100 nM) and BQ-788 (1 microM) inhibited this vasoconstriction, while BQ-123 (3 microM, 10 microM) did not. 5. Vasoconstriction induced by ET-3 (0.1 nM-0.3 microM) in porcine coronary arteries showed a concentration-response curve with two distinct phases in contrast to that seen with sarafotoxin S6c. TAK-044 (0.3 nM-10 nM) inhibited both phases in a concentration-dependent manner. BQ-123 (1 microM, 3 microM) inhibited only the second phase, while BQ-788 (1 microM) inhibited the first phase. 6. We concluded that the inhibitory effects of TAK-044 on ET-1-induced vasoconstriction were the strongest in coronary arteries among the canine arteries examined. In addition, we showed that both ETA and ETB receptors mediate vasoconstriction in porcine coronary arteries and TAK-044 inhibits the vasoconstriction mediated by both of these receptors.

Animals↗
PubMed1997

Vasodilator effects of adrenomedullin on small pulmonary arteries and veins in anaesthetized cats.

1. This study was conducted to determine adrenomedullin (AM) action sites in the pulmonary vascular bed and the relation between its vasodilator effects and vascular tone. Moreover, an examination was made into whether calcitonin gene-related peptide (CGRP) receptors mediate pulmonary vasodilatations induced by AM. To this end, we directly measured internal diameter (i.d.) changes in small pulmonary arteries and veins (100-1100 microns i.d.) by use of an X-ray television system on the in vivo cat lung. 2. Under control (resting vascular tone) conditions, AM injections into the left main pulmonary artery caused dose-related i.d. increases in both small arteries and veins. The mean i.d. increase of the 100-1100 microns arteries (4 +/- 1, 11 +/- 2, and 17 +/- 2% with 0.01, 0.1, and 1 nmol kg-1 AM, respectively) was significantly larger than that for the veins (1 +/- 1, 5 +/- 2, and 7 +/- 2% with 0.01, 0.1 and 1 nmol kg-1 AM, respectively) whatever the injected dose of AM. 3. When unilobar hypoxia (5% O2) had decreased the i.d. of the 100-1100 microns arteries and veins by 16 +/- 3 and 6 +/- 3%, respectively, AM (0.1 nmol kg-1) was able to induce significantly larger i.d. increases in the arteries (28 +/- 3%) and veins (11 +/- 3%) than those under control conditions. 4. The AM-induced i.d. response pattern in the serially connected pulmonary arteries was quite different from that induced by CGRP; AM caused a greater increase in smaller vessels (100-500 microns) than in larger vessels (500-1100 microns). In the case of CGRP, a greater increase was observed in the larger vessels. 5. CGRP8-37 (100 nmol kg-1, i.v., followed by a continuous infusion of 0.2 nmol kg-1 min-1) had no significant effect on the i.d. increase induced by AM (0.1 nmol kg-1) in any serial segments of the arteries and veins. 6. The results indicate that, in the cat, AM induces greater vasodilatation in small pulmonary arteries and lesser vasodilatation in small veins, the maximum dilatation being in the more peripheral arterial segment (100-500 microns). The vasodilator effect of AM was enhanced when vascular tone was elevated. The data suggest that the AM-induced pulmonary vasodilatation is not mediated by CGRP receptors but by its own specific receptor.

Adrenomedullin↗
PubMed1997

Immunohistochemical analysis of heme oxygenase-I in rat liver after ischemia.

Total hepatic ischemia was induced by clamping the hepatic artery, portal vein, and bile duct. After 15 min hepatic ischemia, we examined a time course of the changes in the steady-state levels of heme oxygenase-1 (HO-1) mRNA and protein in the livers. The levels of HO-1 mRNA was transiently induced and peaked at 4 h after the start of reperfusion. In addition, a pattern of the time course of HO-1 protein levels was similar to that of HO-1 mRNA levels. Immunohistochemical analysis clearly showed that the localization of HO-1 protein induced by hepatic ischemia was restricted to the hepatocytes in the pericentral vein.

Animals↗
PubMed1997

Ascorbic acid deficiency decreases the renal level of kidney fatty acid-binding protein by lowering the alpha2u-globulin gene expression in liver in scurvy-prone ODS rats.

The evidence for the role of ascorbic acid in gene expression or protein synthesis in vivo is limited. To investigate this role of ascorbic acid, we surveyed proteins whose tissue levels are changed by ascorbic acid deficiency by using ODS rats with a hereditary defect in ascorbic acid biosynthesis. Male ODS rats (7 wk old, body weight approximately 130 g) were fed a basal diet containing ascorbic acid (300 mg/kg diet) or an ascorbic acid-free diet for 14 d. Ascorbic acid deficiency decreased a renal protein with an apparent molecular mass of 17 kDa. The amino-terminal amino acid sequence of 16 residues of this 17-kDa protein was identical to a kidney fatty acid-binding protein known to be generated by proteolytic degradation of alpha2u-globulin, a major urinary protein of adult male rats. alpha2u-Globulin is synthesized in liver, secreted into blood and excreted into urine, but partially reabsorbed by renal proximal tubules. It exists in kidney in a proteolytically modified form. Ascorbic acid deficiency lowered the renal level of kidney fatty acid-binding protein to 53% (P < 0.05) and lowered the serum level of alpha2u-globulin to 52% (P < 0.05) of the level of the control group, but did not affect the amount of alpha2u-globulin excreted into urine. The hepatic level of alpha2u-globulin mRNA of the ascorbic acid-deficient rats was significantly lower (30%) than that of the control rats. These results suggest that in male ODS rats, ascorbic acid deficiency decreases the renal level of kidney fatty acid-binding protein by lowering alpha2u-globulin gene expression in liver.

Alpha-Globulins↗
PubMed1997

Alterations in expression of sarcoplasmic reticulum gene in Dahl rats during the transition from compensatory myocardial hypertrophy to heart failure.

OBJECTIVES: To clarify whether the functional changes during the transition from compensatory myocardial hypertrophy to failure are associated with changes in sarcoplasmic reticulum gene expression. METHODS: We examined the gene expression of sarcoplasmic reticulum proteins [sarcoplasmic reticulum Ca2+-ATPase (SERCA), phospholamban, calsequestrin and ryanodine receptor] in Dahl salt-sensitive (Dahl-S) rats fed a high-salt (8%) diet from the age of 6 weeks. In-vivo contractile functioning was evaluated using echocardiography, and gene expression of sarcoplasmic reticulum proteins in the left ventricle was analyzed by Northern blotting for each stage of left ventricular hypertrophy. RESULTS: SERCA messenger RNA (mRNA) levels in Dahl-S rats with compensatory hypertrophy did not change significantly, whereas phospholamban mRNA levels were increased by 61% (P < 0.01), and calsequestrin mRNA levels were increased by 130% (P < 0.01) compared with those in Dahl salt-resistant (Dahl-R) rats. SERCA mRNA levels in Dahl-S rats with decompensated dilatation were decreased by 32% (P< 0.05), whereas levels of phospholamban and calsequestrin mRNA remained unchanged. Ryanodine receptor mRNA levels did not change either with compensatory hypertrophy or with decompensated dilatation. CONCLUSIONS: Alterations in expression of sarcoplasmic reticulum gene may be related to changes in systolic and diastolic properties in compensatory hypertrophy and heart failure.

Animals↗
PubMed1997

Spindle cell carcinoma of the breast: a case report and an immunohistochemical study including p53 and Ki-67 expression.

A rare case of spindle cell carcinoma (SpCC) of the breast occurring in a 51-year-old Japanese woman is reported. A firm and well-circumscribed tumor, measuring 9 x 8.5 x 8.5 cm, was located on the upper lateral region of the right breast. Microscopically, the tumor consisted of sheets of both malignant spindle cells and poorly differentiated ductal carcinoma containing squamoid islands with gradual transition to the spindle cell component. The immunocytochemical expression of epithelial markers was recognized in the spindle cells, as well as in the carcinomatous cells. Moreover, the spindle cell component expressed vimentin, alpha-smooth muscle actin and S-100 protein. Ultrastructurally, in addition to the features of adenocarcinoma, squamous or myoepithelial differentiation was confirmed in the spindle cell component. These findings thus suggest an epithelial origin with squamous differentiation and myoepithelial participation in the genesis of SpCC. In a comparative study, the expression of p53 protein and Ki-67 as a proliferation marker in each component of this tumor was also investigated. The mean p53 labeling index (LI) in both the carcinomatous and spindle cell area was similar, however the mean MIB-1 LI in the spindle cell area was significantly higher than that in the carcinomatous area. The results indicate that p53 overexpression is involved in the tumorigenesis of both components in the SpCC, and the spindle cell component shows a higher degree of proliferative activity than the carcinomatous component.

Biomarkers↗
PubMed1997

Gastric carcinosarcoma (sarcomatoid carcinoma) with rhabdomyoblastic and osteoblastic differentiation.

A rare case of carcinosarcoma (sarcomatoid carcinoma) with rhabdomyoblastic and osteoblastic differentiation occurring in the gastric remnant is reported. A 69-year-old Japanese man who had undergone a partial gastrectomy for a duodenal ulcer 30 years earlier, presented with anemia, epigastralgia, and an abdominal mass. The diagnosis of gastric carcinosarcoma was made based on the findings of endoscopic biopsies. The patient was thus scheduled to undergo a surgical operation, but he died of respiratory failure. At autopsy, a huge polypoid tumor measuring 20 x 18 x 8 cm was located on the greater curvature of the gastric remnant. Microscopically, the tumor consisted of intimately mixed tubular adenocarcinoma and heterologous mesenchymal elements containing rhabdomyosarcoma and osteosarcoma. Between these components, a morphological transition from the adenocarcinoma element to the sarcomatous element was observed. Ultrastructually, rhabdomyoblastic differentiation was confirmed in the sarcomatous areas. Immunocytochemical expressions of epithelial markers including epithelial membrane antigen and cytokeratins (35bH11 and 34bE12) were recognized not only in the carcinomatous cells but also in the sarcomatous cells. These findings suggest that carcinomatous cells appear to transform into cells with sarcomatous features.

Aged↗
PubMed1997

Systemic reactive amyloidosis associated with Castleman's disease: serial changes of the concentrations of acute phase serum amyloid A and interleukin 6 in serum.

A case is reported of a 21 year old woman who suffered from Castleman's disease and systemic reactive amyloidosis. The serum concentrations of serum amyloid A (SAA) and interleukin 6 (IL-6) were extremely high and amyloid protein was immunohistochemically identified as AA. After surgical excision of a large retroperitoneal lymph node with the pathological findings of plasma cell type of Castleman's disease, both serum SAA and IL-6 declined, showing a similar pattern of reduction curves. All clinical symptoms and laboratory abnormalities greatly improved. The biochemical feature of Castleman's disease is abnormal production of IL-6 and this cytokine continuously may stimulate the synthesis of an amyloid precursor, SAA, causing systemic reactive (AA) amyloidosis. This pathogenetic theory is strongly supported by the present study.

Adult↗
PubMed1997

Deletions of p15 and/or p16 genes as a poor-prognosis factor in adult T-cell leukemia.

PURPOSE: To determine the frequency of the deletions of p15/p16 genes in adult T-cell leukemia (ATL) cells and to evaluate their value in the diagnosis of clinical subtypes of ATL patients and the prediction of their clinical outcome. MATERIALS AND METHODS: Peripheral-blood samples from 114 patients with ATL were examined by Southern blot analysis. In five chronic-type patients who showed disease progression to acute type, serial samples also were examined. RESULTS: Among 114 patients, 28 (24.6%) showed the deletions of p15 and/or p16 genes. The results were well correlated with the clinical subtypes. Patients with deleted p15 and/or p16 genes had significantly shorter survival times than the patients in whom both genes were preserved (P < .0001). A similar decline in survival time was observed in the analyses within the same subtypes. In multivariate analysis using the Cox proportional hazard model, the deletions of p15 and/or p16 genes emerged as an independent prognostic indicator. Moreover, three of the five chronic-type patients who progressed to acute type lost the p16 gene alone or both the p15 and p16 genes at their exacerbation phase. CONCLUSION: The results suggest the following: (1) that the deletions of p15 and/or p16 genes play a key role in the progression of ATL; and (2) that these deletions are reliable prognostic factors that predict shortened survival times.

Adult↗
PubMed1997

Structural requirements for potential Na/H exchange inhibitors obtained from quantitative structure-activity relationships of monocyclic and bicyclic aroylguanidines.

The quantitative structure-activity relationship (QSAR) of N-(3-amino-6-chloro-5-ethylisopropylaminopyrazine-4-carbonyl) guanidine (EIPA) 1ac and its derivatives as Na/H exchange inhibitors was analyzed using th steric parameters and an indicator variable. The results indicated that bicyclic aroylguanidines might have Na/H exchange inhibitory activity. Therefore, various bicyclic aroylguanidines were synthesized and tested for Na/H exchange inhibitory activity. The QSAR study of the bicyclic aroylguanidines showed that hydrophobic bicyclic rings seemed to be preferable for potent activity. The hydrophobicity of the aroyl ring moiety was thought to be particularly important. Thus, the QSAR of EIPA and its derivatives was re-analyzed using hydrophobicity and steric parameters. The results indicated that high hydrophobicity of the pseudo-ring moiety and a substituent of appropriate length at the position corresponding to the 5-position of the naphthalene ring enhance the activity. As expected from the results, 5-bromo-2-naphthoylguanidine 3b and 5-methoxy-2-naphthoylguanidine 3c exhibited strong activity. These findings will be helpful to design new, potent Na/H exchange inhibitors.

Animals↗
PubMed1997

Design, synthesis and quantitative structure-activity relationship study of N-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazine-7-carbonyl)guanidine derivatives as potent Na/H exchange inhibitors.

Inhibition of the Na/H exchanger is a promising approach for treating ischemia-reperfusion injury, but no clinical agent is yet available. Recently, we established the structural requirements for potent inhibitors of the Na/H exchanger. In the present work, we designed N-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazine-7-carbonyl)guanidine 3a as a new lead compound for potent inhibitors with good water-solubility, based on the previous information. During the structural optimization, care was taken to keep the hydrophobicity (clogP) in the range of about 1.5-2.0, which is considered optimum for good bioavailability. Various derivatives of 3a were synthesized and the quantitative structure-activity relationship (QSAR) was studied. The QSAR result indicated that the lengths of the substituents at the 2- and the 4-positions of the 2H-benzo[1,4]oxazine ring are parabolically related to activity. The most potent compounds were (R) and/or (S)-N-(2-ethyl-4-isopropyl(or ethyl)-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazine-7-carbonyl)guanidines 3q-t with IC50 values of 0.036-0.073 microM. The water-solubility of the hydrochlorides and methanesulfonates is 3-5 mg/ml, which is sufficient for therapeutic use.

Animals↗
PubMed1997

Synthesis and biological activity of novel 2-(alpha-alkoxyimino)benzylpyridine derivatives as K+ channel openers.

The search for novel K+ channel openers with a non-benzopyran skeleton, unlike cromakalim, led to the discovery of a new series of (Z)-2-(alpha-alkoxyimino)benzylpryridine derivatives. Synthesis was achieved by using a (Z)-dominant condensation reaction of benzoylpyridines with O-alkylhydroxylamines, followed by m-chloroperbenzoic acid (m-CPBA) oxidation. The compounds were tested for their vasorelaxant activity in tetraethylammonium chloride (TEA) and BaCl2- and high KCl-induced contraction of rat aorta to identify potential K+ channel openers, and also for their effects on the coronary blood flow (CBF) after intracoronary injection in anesthetized dogs. A large number of the 2-(alpha-alkoxyimino)benzylpyridines strongly inhibited TEA and BaCl2-induced contraction, had no effect on 80 nM KCl-induced contraction, and increased the CBF to more than 200% of the basal flow at 10-30 micrograms/dog. In particular, (Z)-2-[5-bromo-alpha-(tert-butoxyimino)-4-fluoro-2-hydroxybenzyl]- 3- hydroxypyridine 1-oxide (7d) showed highly potent vasorelaxant activity (EC50 = 0.28 microM) comparable to that of levcromakalim (EC50 = 0.17 microM), and gave a significantly longer-lasting increase (T1/2 = 30 min) in the CBF compared to levcromakalim, nicorandil, nitroglycerin, or diltiazem (T1/2 = 5.2, 0.9, 0.4, and 2.2 min, respectively). It also exhibited a stable and long-lasting hypotensive effect (over 7 h) upon oral administration of 1 mg/kg in spontaneously hypertensive rats (SHRs).

Administration, Oral↗