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Biomedical subjects

M Miyazaki

Publications and source records attributed to M Miyazaki.

At least 325 records · Page 18Linked to original sources
PubMed1998

Hyperactive cytokine response after partial hepatectomy in patients with biliary obstruction.

The relation of interleukin-6 (IL-6) levels in serum to the postoperative complications was assessed in 50 patients following an extensive hepatectomy. In addition, the postoperative levels of IL-6, tumor necrosis factor-a, and interleukin-1beta in peritoneal exudative fluid were determined in 22 patients. The patients with preoperative biliary obstruction showed a higher incidence of postoperative infection compared to those without (44 vs. 12%, p = 0.043). The postoperative serum IL-6 levels on day 1 were significantly higher in patients with postoperative infection than in those without (p<0.01). Biliary obstruction and intraoperative blood loss contributed to the increase in the serum IL-6 levels in a multiple regression analysis (p = 0.01 and p = 0.044, respectively). Further, the fluid levels of inflammatory cytokines were significantly higher in patients with biliary obstruction than in those without (p<0.05). These results suggest that in patients with biliary obstructions a hyperactive cytokine response occurs after an extensive hepatectomy and results in a high incidence of postoperative infection.

Adult↗
PubMed1998

Induction of apoptosis in ischemia-reperfusion model of mouse kidney: possible involvement of Fas.

Although ischemia-reperfusion of mouse kidney is known to cause severe renal failure due to tubular cell death, the exact cellular mechanism responsible for this phenomenon is not clear. To investigate the spatial and temporal development of renal cell death and the role of Fas/APO-1/CD95 (Fas) in this process, the left renal vessels were occluded in a group of mice for 30, 60, or 120 min followed by reperfusion for 24 h (n = 4 for each group). Analysis of the isolated DNA in agarose-gel electrophoresis revealed a typical ladder pattern of bands consisting of multiples of 180 to 200 bp, considered the hallmark of apoptosis. The intensity of the bands increased proportionately with the duration of ischemia. Histochemical analysis using terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling showed the presence of nuclei with DNA double-strand breaks specifically in distal renal tubules of the outer medulla. The presence of apoptosis was also confirmed by electron microscopy. Analysis of total RNA by Northern blotting revealed one appropriate-sized band for Fas mRNA in the normal kidney, which intensified in the ischemia-reperfused kidney. Moreover, nonradioactive in situ hybridization revealed that distal renal tubular epithelial cells were positive for Fas mRNA in the outer medulla. Fas antigen was also localized to the renal tubular epithelial cells of the outer medulla by immunohistochemistry. The number of apoptotic cells in the ischemia-reperfusion kidney of the lpr/lpr mouse was low. These findings strongly indicate that ischemia-reperfusion of the kidney induces apoptosis of a specific area of tubular epithelial cells in the outer medulla through the Fas system.

Animals↗
PubMed1998

Liddle's syndrome in an elderly woman.

A 78-year-old woman with hypertension was hospitalized with acute bronchitis. However, she was also found to have hypernatremia, hypokalemia, and metabolic alkalosis. Detailed examination showed a low plasma renin activity and plasma aldosterone concentration. A provisional diagnosis of Liddle's syndrome was established and the patient was successfully treated with triamterene. Although Liddle's syndrome is generally considered an inherited hypertensive disease found in young people, a review of the literature indicated that muscle weakness is an important clinical finding in elderly patients with this disease. Liddle's syndrome should be considered in the differential diagnosis of hypertension even in elderly individuals.

Aged↗
PubMed1998

Chymase: its pathophysiological roles and inhibitors.

Chymase is a chymotrypsin-type serine protease mainly localized in mast cells (MCs). Human, primate, and dog chymase generate angiotensin II (Ang II) from Ang I, while mouse and rat chymases degrade Ang II. It is suggested that chymase generating Ang II might be an alternative Ang II-forming enzyme to angiotensin-converting enzyme (ACE) in the renin-angiotensin system in tissues, but not in blood, and cause hypertrophy and remodeling of cardiovascular tissues. Chymase also degrades extracellular matrix, and processes procollagenase, inflammatory cytokines and other bioactive peptides. As a result, chymase plays important roles in inflammatory tissues through its proteolytic activities to cause tissue remodeling, that is, a chymase inhibitor may have the ability to prevent diseases caused by the above inflammatory reactions. The investigation of chymase inhibitors by pharmaceutical companies has yielded peptide and peptide mimetic inhibitors. We also found potent non-peptide low molecular inhibitors. However, the in vivo functions of chymase have not been verified so far by applying a chymase inhibitor to in vivo pathological models. In this article, we overview the pathophysiological roles of chymase and chymase inhibitors proposed to date, and discuss the structure-activity relationships of substituted 3-phenylsulfonyl-1-phenylimidazolidine-2,4-dione derivatives.

Angiotensin I↗
PubMed1998

Aggressive surgical approaches to hilar cholangiocarcinoma: hepatic or local resection?

BACKGROUND: It has been reported that surgical excision of hilar cholangiocarcinoma rather than palliative surgical therapy, chemotherapy, or radiotherapy caused prolonged survival in some patients, However, excision is associated with high operative morbidity and mortality rates, particularly when hepatic resection is also performed. The aim of this study was to evaluate the clinical implications of hepatic resection in hilar cholangiocarcinoma. METHODS: The study involved 76 patients with hilar cholangiocarcinoma who were undergoing surgical resections. Twenty-one patients (28%) underwent a combined resection, with reconstruction of the portal vein in 20 patients and reconstruction of the hepatic artery in 7 patients. Sixty-five patients undergoing seven different types of hepatic resection with extrahepatic bile duct resection (BDR) and 11 patients undergoing BDR only were retrospectively compared for background, operative morbidity and mortality, and survival. RESULTS: Curative resection was obtained in 5 of 11 (45%) patients undergoing local resection and in 49 of 65 (75%) patients undergoing hepatic resection (p < 0.05). The surgical morbidity rates were 34% and 27% for hepatic and local resection, respectively. The 30-day mortality and hospital mortality rates were 4.6% and 15% for hepatic resection and 0% and 0% for local resection, respectively. The 5-year survival rate was 26% for all resected patients (76 patients); it was 40% versus 0% for curative versus noncurative resections (p < 0.05). No significant difference in surgical resection rates was revealed between hepatic and local resection among resected and curative resected patients. CONCLUSIONS: Aggressive surgical approaches to obtain curative resections could bring about a better prognosis in hilar cholangiocarcinoma independently of whether hepatic resection or local resection is performed.

Adult↗
PubMed1998

Three-dimensional fast spin-echo MR of the inner ear: ultra-long echo train length and half-Fourier technique.

We compared the image quality of the newly developed ultra-long echo train length (ETL) 3-D fast spin-echo (FSE) and half-Fourier technique, which is performed in less than 3 minutes, with the conventional 3D-FSE imaging technique, which takes 15 minutes, in assessing MR examinations of the inner ear. The new method's images were almost comparable to the conventional 3D-FSE images in depicting anatomic details and pathologic findings. Implementation of the ultra-long ETL and half-Fourier 3D-FSE imaging technique enables acquisition of inner ear MR studies in a vastly reduced time and with high spatial resolution without significant penalty, opening the possibility for low-cost screening of acoustic tumors without contrast enhancement in less than 3 minutes.

Ear Neoplasms↗
PubMed1998

[Fulminant Mycoplasma pneumoniae pneumonia resulting in respiratory failure and a prolonged pulmonary lesion].

A previously healthy 26-year-old woman presented with a fever and coughing on October 1, 1995. Despite treatment with beta-lactam antibiotics at another hospital, she had a high fever, coughing, and dyspnea. A chest roentgenogram showed diffuse infiltrates in both lung fields. On October 9, she was transferred to our hospital. On admission, a chest X-ray film showed marked diffusely infiltrates in both lung fields and a effusion in the left lung. Arterial blood gas analysis after inhalation of 4 liters per minute of oxygen via a nasal cannula revealed a PaO2 of 39.0 torr. Despite treatment with various antibiotics, including minocyclin and gamma-globulin, her respiratory condition rapidly deteriorated. She was mechanically ventilated by with intermittent mandatory ventilation and positive end-experiatory pressure, and received antibiotics and methylprednisolone pulse therapy. He chest X-ray and arterial blood gase findings, gradually improved. The passive hemagglutination titer for Mycoplasma rose from 1:4 on October 9, to 1:2,560 on the 14th hospital day. Acute respiratory failure due to Mycoplasma pneumoniae pneumonia was diagnosed. A chest X-ray film obtained 2 months after admission showed linear-reticular shadows in both lung fields and pulmonary-function tests revealed abnormally low vital capacity and diffusing capacity. Examination of a specimen obtained by transbronchial lung biopsy revealed focal intraalveolar exudate with fibrin and macrophages. Very mild interstitial thickening was also noted. The lymphocyte stimulation responses to PPD, PHA, and Con A were low early in the illness and became normal after recovery. Several reports have said that an enhanced pulmonary cellular immune response may be responsible for the development of severe Mycoplasma pneumoniae, resulting in a temporary decrease in the cell-mediated immune response. This case supports that hypothesis. We believe that in severe cases, steroid therapy including pulse therapy should be started as soon as possible.

Acute Disease↗
PubMed1998

Transaxillary endoscopic partial mastectomy for comparatively early-stage breast cancer. An early experience.

For optimal cosmetic results in breast cancer surgery, we developed an alternative operation using endoscopy to remove tumors through a small single incision remote from the breast itself. The tumor is endoscopically resected with electrocautery and low constant suction through a short incision in the axilla, 5 cm long, after which axillary dissection is performed through the same wound in the usual manner, under visualization by the naked eye. Primary reconstruction of the breast is performed with the remaining mammary gland and a subcutaneous fat flap on the serratus muscle. Seven patients underwent this surgery. The postoperative shape of the breasts was judged to be cosmetically satisfactory, and the surgical wounds were not visible from the front in all cases. This operation has the same therapeutic oncological effect as a standard lumpectomy and, in addition, offers a greater cosmetic advantage in cases of early breast cancer.

Adult↗
PubMed1998

Involvement of angiotensin II receptor subtypes during testicular development in rats.

Expression of testicular angiotensin II (AT2) receptors in Sprague-Dawley rats at various stages of development (1 and 5 days, 2, 3, 4 and 7 weeks postnatal) were studied by in vitro autoradiography and Northern blot analysis. The receptors were labelled with 125I-[Sar1, Ile8]AT2 and differentiated into two subtypes according to their susceptibility to AT1 (losartan, 5 microM) or AT2 (PD123319, 5 microM) antagonist. Total AT2 receptor binding in the testis was highest at 1 day of age (8.12 +/- 0.35 fmol/mg protein, mean +/- secEM, n = 8) and decreased gradually thereafter (5 days: 6.9 +/- 0.41, 2 weeks: 2.85 +/- 0.10, 3 weeks: 1.64 +/- 0.19, 4 weeks: 0.76 +/- 0.09, 6 weeks: 0.77 +/- 0.09 fmol/mg protein, n = 8-11). AT2 receptor binding was strikingly abundant in 1-day-old rat testis (6.98 +/- 0.34 fmol/mg protein), while considerably less AT1 receptor binding (1.46 +/- 0.19 fmol/mg protein) was observed. The relative amounts of each subtype did not change for the first 3 weeks but the 4-week-old rat testis contained almost exclusively AT1 receptors (0.63 +/- 0.05 fmol/mg protein). Northern blot analysis showed that mRNA expression of both AT1 and AT2 types decreased with age. Microscopic emulsion autoradiography was undertaken to clarify the localization of binding. At 10 days of age, both AT1 and AT2 receptors were present in the interstitial area, whereas seminiferous tubules contained mainly AT2 receptors. At 7 weeks of age, no significant binding was observed in the seminiferous tubule and the interstitial area contained AT1 receptors exclusively. These results demonstrate expression of AT2 receptors in the rapidly growing testis and suggest that change in the levels of AT2 receptor subtypes may be relevant to development and/or growth of the testis.

Angiotensin II↗
PubMed1998

Dose-dependent biphasic effects of phenobarbital on growth and differentiation of primary culture rat hepatocytes.

The actions of phenobarbital, a liver tumour promoter, on growth and differentiation of primary culture normal rat hepatocytes change biphasically as a function of its concentration. At low concentrations of 0.5-2 mmol/L, phenobarbital enhances DNA synthesis of normal adult rat hepatocytes in the presence of epidermal growth factor (EGF) and/or dexamethasone. This is also true for normal suckling (1-2-week-old) rat hepatocytes, without added growth factor(s), in serum-free primary culture. Contrarily, phenobarbital at high concentrations (3-4 mmol/L) suppresses DNA synthesis of suckling rat hepatocytes. Furthermore, phenobarbital inhibits DNA synthesis of transforming growth factor-alpha-stimulated primary hepatocytes from normal adult rats in a dose-dependent manner within a concentration range of 3-6 mmol/L. When normal adult rat hepatocytes are led to undergo multiple proliferative cycles upon stimulation with hepatocyte growth factor (HGF) and EGF in the chemically defined hepatocyte growth medium (HGM), 3 mmol/L phenobarbital also remarkably suppresses DNA synthesis. Phenobarbital at 3 mmol/L effectively keeps these hepatocytes morphologically differentiated and accelerates restoration of the expression of markers characteristic of differentiated cells after the initial cellular growth phase. In addition, phenobarbital efficiently supports prolonged survival of the hepatocytes.

Animals↗
PubMed1998

Influence of thermal cycling on dentin bond strength of two-step bonding systems.

PURPOSE: To investigate the influence of thermal cycling on bond strength to dentin of 2-step bonding systems. MATERIALS AND METHODS: The systems used were self-etching primer systems; Fluoro Bond (FB), Liner Bond II (LB), and Mac Bond II (MB); and self-priming adhesive systems; One-Step (OS), OptiBond Solo (OB), Prime & Bond 2.0 (PB), and Single Bond (SB). Bovine mandibular incisors were mounted in self-curing resin and the facial surfaces were wet ground with #600 SiC paper. Enamel and dentin surfaces were treated following each manufacturers' instructions. Adhesives were applied and composites were condensed into a Teflon mold (4x2 mm) placed on the dentin surface and light activated. Bonded specimens were divided into four groups; (a) stored in 37 degrees C water for 24 hours, (b) stored in 37 degrees C water for 24 hours followed by subjecting to thermal cycling between 5 degrees C and 60 degrees C for 3,000 times, (c) 10,000 times, and (d) 30,000 times. Twelve samples per test group were shear tested at a crosshead speed of 1.0 mm/minute. One-way ANOVAs followed by Duncan's multiple range test (P < 0.05) were performed. RESULTS: For FB, LB, and MB, a small decrease in bond strength was observed and no significant differences were observed among the thermal cycling groups. For OS, OB, PB, and SB, a significant decrease in bond strength was observed for the 30,000 thermal cycling groups. The changes in bond strength after TC were different between the bonding systems.

Analysis of Variance↗
PubMed1998

[Vascular resection during surgical resection for advanced gallbladder carcinoma].

We evaluated the results of vascular resection during surgical resection for advanced gallbladder carcinoma. Twelve patients underwent vascular resection (portal vein in 11, hepatic artery in 2, inferior vena cava in 2) in 58 resected patients with advanced gallbladder carcinoma (stage III and IV). The surgical rate was higher in the nonvascular resection group (61%) than in the vascular resection group (25%) (p < 0.05). Surgical morbidity and mortality rates were not significantly different between the two groups. The survival rate was remarkably higher in the curative resection group (n = 29) (55.6% at 1 year, 30.3% at 3 years, 20.8% at 5 years) than in the noncurative resection group (n = 29) (26.3% at 1 year, 0% at 2 years) (p < 0.05). Survival rates of the nonvascular resection group (n = 46) were 45.3% at 1 year, 23.4% at 3 years, and 16.1% at 5 years. However, no patient in the vascular resection group (n = 12) survived longer than 2 years. In conclusion, vascular resection during surgical resection for advanced gallbladder carcinoma does not result in a more favorable prognosis, despite similar surgical risk as in nonvascular resection procedures.

Adult↗
PubMed1998

[Single dose intravenous toxicity studies of T-3762, a novel parenteral quinolone antimicrobial agent, in rats, dogs and monkeys].

Single dose intravenous toxicity studies of T-3762, a novel parenteral quinolone antimicrobial agent, were conducted in rats, dogs and monkeys. The following results were obtained. 1. In the rat study, all males and females given 260 mg/kg survived and all males and 3 of 5 females given 391 mg/kg died. Approximate lethal doses in male and female rats were between 260 and 391 mg/kg. In survived animals, decrease in locomotor activity and irregular respiration were observed. These clinical signs were recovered within 1 hour after dosing. In female rats given 260 mg/kg, no abnormalities were observed in general signs. In dead animals, decrease in locomotor activity, irregular respiration, staggering gait and tonic convulsion were observed and died within about 90 minutes after dosing. Macroscopic examinations in dead animals showed dark red discoloration in lung and had white foamy liquid in trachea. In histopathological examinations of dead animals, congestion, hemorrhage and edema were observed in lung. 2. In the dog study, 2 animals given 260 mg/kg survived and 2 animals given 521 mg/kg died. Approximate lethal dose in dogs was between 260 and 521 mg/kg. In the 260 and 521 mg/kg groups, decrease in locomotor activity, lateral position, vomiting, salivation and decrease in body temperature were observed. In the 521 mg/kg group, one animal died at 4 minutes and another 7 days after dosing. Histopathological examinations in 2 dead animals showed congestion or hemorrhage in heart, lung, liver, kidney, spleen and digestive tract. Erosion and necrosis at cartilage layer and cluster of chondrocyte were observed in scapular fossa and head of humerus in the 260 and 561 mg/kg groups. 3. In the monkey study, 2 animals given 260 mg/kg survived and 2 animals given 520 mg/kg died. Approximate lethal dose in monkeys was between 260 and 520 mg/kg. In the 260 mg/kg group, soft feces was observed. In the 520 mg/kg group, paleness mucosa of oral cavity, muscle weakness, mydriasis and dyspnea were observed and animals died within 4 minutes after dosing. Macroscopic and histopathological examinations in 2 dead animals showed congestion in lung, liver and kidney.

Alanine Transaminase↗
PubMed1997

Growth inhibition of human ovarian cancers by cytotoxic analogues of luteinizing hormone-releasing hormone.

BACKGROUND: Receptors for luteinizing hormone-releasing hormone (LH-RH) are found in nearly 80% of human ovarian cancers. The chemotherapeutic agent doxorubicin can be linked to [D-lysine6]LH-RH to form a cytotoxic analogue (AN-152) that may have greater specificity for tumor cells. This study was conducted to investigate the effects of AN-152 on the growth of LH-RH receptor-positive OV-1063 human epithelial ovarian cancers. METHODS: Nude mice bearing human ovarian tumors, OV-1063 or UCI-107 (LH-RH receptor negative), were injected intraperitoneally with saline (control) or with equimolar doses of AN-152 or doxorubicin; experiments involving mice with OV-1063 tumors also included groups that were administered [D-lysine6]LH-RH either alone or in combination with doxorubicin. Tumor volume, weight, doubling time, and burden (i.e., tumor weight/body weight) as well as tumor apoptotic and mitotic indices were determined. The levels of receptors for LH-RH and epidermal growth factor (EGF) and their messenger RNAs were measured by use of radioreceptor and reverse transcription-polymerase chain reaction assays, respectively. RESULTS: The growth of OV-1063 ovarian tumors in nude mice, as based on reduction in tumor volume, was inhibited significantly (all P<.05, two-sided) 4 weeks after treatment with AN-152, even at the lowest dose tested (413 nmol/20 g weight); the toxic effects of an equivalent dose of doxorubicin caused substantial mortality. High-affinity receptors for LH-RH and EGF were found on cell membranes of OV-1063 cancers; however, after in vivo treatment with AN-152, LH-RH receptor-binding sites were not detectable and EGF receptors were reduced in number. The growth of UCI-107 ovarian cancers was not inhibited by AN-152. CONCLUSIONS: In nude mice bearing LH-RH receptor positive OV-1063 epithelial ovarian cancers, systemic administration of AN-152 is less toxic and inhibits tumor growth better than equimolar doses of doxorubicin.

Animals↗
PubMed1997

Characterization of chymase from human vascular tissues.

A chymostatin-sensitive angiotensin II-generating enzyme was found in human gastroepiploic arteries. The enzyme was purified using heparin affinity and gel filtration columns. The molecular mass of the purified enzyme was 30 kDa, and the optimum pH was between 7.5 and 9.0. Enzyme activity was inhibited by soybean trypsin inhibitor, phenylmethylsulfonyl fluoride and chymostatin, but not by ethylenediaminetetraacetic acid, pepstatin and aprotinin. The enzyme rapidly converted angiotensin I to angiotensin II (K(m), 67 mumol/l; Vmax, 43 pmol/s, kcat, 65/s), but did not hydrolyse angiotensin II, substance P, bradykinin, vasoactive intestinal peptide, luteinizing hormone-releasing hormone, somatostatin and alpha-melanocyte-stimulating hormone. The N-terminal sequence was identical to the sequence for human skin/heart chymase. Thus, the chymostatin-sensitive angiotensin II-generating enzyme in human vascular tissues is identified as chymase.

Adult↗
PubMed1997

Induction of chymase that forms angiotensin II in the monkey atherosclerotic aorta.

Chymase shows a catalytic efficiency in the formation of angiotensin (Ang) II. In the present study, the characterization and primary structure of monkey chymase were determined, and the pathophysiological role of chymase was investigated on the atherosclerotic monkey aorta. Monkey chymase was purified from cheek pouch vascular tissue using heparin affinity and gel filtration columns. The enzyme rapidly converted Ang I to Ang II (Km = 98 microM, k(cat) = 6203/min) but did not degrade several peptide hormones such as Ang II, substance P, vasoactive intestinal peptide and bradykinin. The primary structure, which was deduced from monkey chymase cDNA, showed a high homology to that of human chymase (98%). The mRNA levels of the aorta chymase were significantly increased in the atherosclerotic aorta of monkeys fed a high-cholesterol diet. These results indicate that monkey chymase has a highly specific Ang II-forming activity and may be related to the pathogenesis of atherosclerosis.

Amino Acid Sequence↗