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Biomedical subjects

Y Shirai

Publications and source records attributed to Y Shirai.

At least 181 records · Page 10Linked to original sources
PubMed1995

Positive correlation of plasma transforming growth factor-beta 1 levels with tumor vascularity in hepatocellular carcinoma.

Transforming growth factor-beta 1 (TGF-beta 1) has been implicated in tumor progression by promoting angiogenesis or suppressing immune system. We reported previously that transforming growth factor-beta 1 (TGF-beta 1) is overproduced by human hepatocellular carcinoma (HCC) tissues and that plasma TGF-beta 1 levels are elevated in patients with HCC. In the present study, we investigated the relationship between plasma TGF-beta 1 levels and tumor vascularity as assessed by conventional celiac angiography in 17 patients with HCC. The plasma TGF-beta 1 level did not correlate with tumor size or underlying liver disease. However, we found that plasma TGF-beta 1 levels correlated positively with the tumor vascularity. These results suggest that excessive TGF-beta 1 production may contribute to tumor angiogenesis in HCC.

Aged↗
PubMed1995

Blunt pancreatic trauma with main pancreatic duct disruption managed successfully with total parenteral nutrition: report of a case.

Although surgery is the usual treatment of choice for pancreatic trauma with disruption of the main pancreatic duct, we report herein the case of a patient in whom blunt pancreatic trauma with disruption of the proximal main pancreatic duct was successfully managed by conservative treatment. An 18-year-old women presented with abdominal pain 22 days after being involved in a car accident in which her upper abdomen was thrust against the steering wheel. Computed tomography revealed a pancreatic pseudocyst and a prevertebral pancreatic fracture, and endoscopic retrograde pancreatography showed complete disruption of the main pancreatic duct at the neck. Considering that the patient had been clinically stable since the accident, we elected to continue with conservative management and placed her on total parenteral nutrition. Rapid recovery followed and 6 years later, the patient remains well without any exocrine or endocrine insufficiency despite atrophy of the distal pancreas. This experience indicates that selected cases of main pancreatic duct disruption following blunt trauma may be amenable to conservative management.

Adolescent↗
PubMed1995

Conservative management of idiopathic pneumoperitoneum masquerading as peritonitis: report of a case.

Pneumoperitoneum is most commonly caused by the perforation of a hollow viscus, in which case an emergency laparotomy is indicated. We report herein the case of a patient who presented with the signs and symptoms of peritonitis, but who was found to have idiopathic pneumoperitoneum which was successfully managed by conservative treatment. A 70-year-old man presented with epigastric pain, nausea, and a severely distended and tympanitic abdomen. Abdominal examination revealed diffuse tenderness with guarding, but no rebound tenderness. He was febrile with leukocytosis and high C-reactive protein. Chest X-ray and abdominal computed tomography demonstrated a massive pneumoperitoneum without pneumothorax, pneumomediastinum, pneumoretroperitoneum, or subcutaneous emphysema, and subsequent examinations failed to demonstrate perforation of a hollow viscus. Thus, a diagnosis of idiopathic pneumoperitoneum was made, and the patient was managed conservatively, which resulted in a successful outcome. This experience and a review of the literature suggest that idiopathic pneumoperitoneum is amenable to conservative management, even when the signs and symptoms of peritonitis are present.

Aged↗
PubMed1995

[Macrophage colony-stimulating factor in patients with rheumatoid arthritis].

Macrophage colony-stimulating factor (M-CSF) is a cytokine involved in the development and proliferation of the monocyte/macrophage lineage cells. M-CSF has also been reported to participate in the induction of osteoclasts, and may be important in the destruction of bone and cartilage and the periarticular osteoporotic changes seen in patients with rheumatoid arthritis (RA). We developed a new ELISA technique to measure M-CSF levels in synovial fluid with high sensitivity and reproducibility. The mean M-CSF level in the synovial fluid of patients with RA was 1.38 +/- 0.56 ng/ml, and that of patients with osteoarthritis (OA) was 0.67 +/- 0.13 ng/ml. In contrast, serum levels of M-CSF in patients with RA and in normal controls were 1.32 +/- 0.50 ng/ml and 0.90 +/- 0.09 ng/ml, respectively. These differences were both statistically significant. Since serum M-CSF levels correlate with inflammatory signs obtained from examination of blood, they indicate the general condition of patients with RA. Synovial fluid M-CSF levels increase even in the early phase of RA and remain high despite drug therapy, which suggests that they reflect the condition of affected joints including joint spaces and inflamed synovia more directly than do the levels of serum M-CSF. Measurement of the M-CSF level in the synovial fluid may be useful in the diagnosis, clinical evaluation, and assessment of the effects of treatment in patients with RA.

Adult↗
PubMed1995

Effect of the potassium channel opener YM934 on the contractile response to electrical field stimulation in pig detrusor smooth muscle.

PURPOSE: The effect of a potassium channel opener, YM934, on the contractile response to excitatory neurotransmitters was investigated in isolated pig detrusor smooth muscle. MATERIALS AND METHODS: Electrical field stimulation (EFS; 5 second trains, 50 V, 0.8 msec. duration), alpha, beta-MeATP (3 x 10(-7) to 10(-5) M.) or carbachol (3 x 10(-8) to 10(-6) M.) produced a contractile response in isolated pig detrusor smooth muscle. The effect of YM934 on the contractile responses was evaluated in comparison with the antagonism of the putative cotransmitters, acetylcholine and ATP. RESULTS: A tetrodotoxin-sensitive, frequency-dependent contractile response to electrical field stimulation was obtained. Atropine (3 x 10(-8) M.) significantly inhibited the contractile response at high frequencies, whereas alpha, beta-MeATP (5 x 10(-6) M.) (desensitizer of P2X-purinoceptors) significantly inhibited the response at low frequencies. YM934 (10(-8) to 10(-7) M.) dose-dependently inhibited the nerve-mediated contractile responses to all frequencies but preferentially at low frequencies, by analogy with alpha, beta-MeATP. A combination of YM934 (3 x 10(-8) M.) and atropine (3 x 10(-8) M.) reduced the response at all frequencies to between 10 and 20% of control, an effect similar to that obtained with alpha, beta-MeATP (5 x 10(-6) M.) and atropine (3 x 10(-8) M.). In addition, YM934 (3 x 10(-8) M.) markedly inhibited the contractile response induced by exogenously applied alpha, beta-MeATP (3 x 10(-7) to 10(-5) M.) but only slightly inhibited the contractile response induced by exogenously applied carbachol (3 x 10(-8) to 10(-6) M.). CONCLUSION: These results suggest that YM934 may hyperpolarize the membrane of pig detrusor smooth muscle through the opening of ATP-sensitive potassium channels and, as a result, may functionally inhibit the contractile response to purinergic nerve stimulation that elicits the membrane depolarization.

Adenosine Triphosphate↗
PubMed1995

The origin of the antiseptic-resistance gene ebr in Staphylococcus aureus.

The antiseptic-resistance gene ebr was detected not only in resistant strains of Staphylococcus aureus but also in sensitive strains of S. aureus, in coagulase-negative staphylococcal strains and in enterococcal strains by means of the polymerase chain reaction. The nucleotide sequence of the amplified DNA fragment of the ebr gene from a sensitive strain and that of the previously reported ebr gene were identical. It seems likely that antiseptic-resistant cells result from an increase in the copy number of a gene whose normal function is to remove toxic substances from normal sensitive cells of staphylococci and enterococci.

Anti-Infective Agents, Local↗
PubMed1994

Cardiovascular effects of YM099, a novel K+ channel opener, in anesthetized and conscious dogs.

Cardiovascular effects of a newly synthesized benzoxadiazol derivative K+ channel opener, YM099, 2-(7,8-dihydro-6,6-dimethyl-6H-[1,4]oxazino[2,3- f][2,1,3]benzoxadiazol-8-yl) pyridine N-oxide, were evaluated in dogs. In pentobarbital-anesthetized dogs, YM099 (1-10 micrograms/kg i.v.), similarly to levcromakalim (1-10 micrograms/kg i.v.), dose dependently increased coronary artery blood flow, max.d p/dt and cardiac output, and decreased total peripheral resistance and mean blood pressure, with a small increase in heart rate. These vasodilator effects were antagonized by glibenclamide (3 mg/kg i.v.). Interestingly, YM099 selectively increased coronary artery blood flow, although it increased carotid, coronary, mesenteric and renal artery blood flows and cardiac output. In addition, YM099 (1-10 micrograms/kg i.v.) increased large conductive coronary artery vessel diameter as well as coronary artery blood flow. In conscious dogs, YM099 (100 micrograms/kg i.v.) also increased the diameter of large conductive and small resistive coronary arteries. In conclusion, YM099 is a potent vasodilator agent, with particularly pronounced effects on the coronary artery. These effects of YM099 may be mediated by the opening of ATP-sensitive K+ channels.

Adenosine Triphosphate↗
PubMed1994

Plasma transforming growth factor-beta 1 in patients with hepatocellular carcinoma. Comparison with chronic liver diseases.

BACKGROUND: Many kinds of human malignant tissue, including hepatocellular carcinoma (HCC), were reported to overexpress transforming growth factor-beta 1 (TGF-beta 1) gene. However, little work has been done on the circulating TGF-beta 1 in patients with malignant tumors. METHODS: Plasma TGF-beta 1 levels in patients with HCC (n = 26) were compared with those in patients with chronic hepatitis (CH) (n = 12) and cirrhosis (n = 11) and in normal subjects (n = 20) using an enzyme-linked immunosorbent assay system after acid/ethanol extraction. RESULTS: The patients with HCC had significantly higher plasma TGF-beta 1 levels (19.3 +/- 19.5 ng/ml; mean +/- standard deviation [SD]) than those in normal subjects (1.4 +/- 0.8 ng/ml) and in patients with CH (3.0 +/- 3.1 ng/ml) and cirrhosis (3.7 +/- 2.1 ng/ml) (P < 0.01). Plasma TGF-beta 1 concentrations in the patients with cirrhosis were also significantly higher than those in the normal subjects (P < 0.05). The extracted plasma TGF-beta 1 from the patients with HCC had biologic activity according to a growth inhibitory assay using mink lung epithelial cells. No significant correlation was found between the plasma TGF-beta 1 levels in the patients with HCC and serum alpha-fetoprotein levels. After successful treatment for HCC, the amount of plasma TGF-beta 1 significantly decreased from 22.6 plus or minus 16.7 ng/ml (mean +/- SD) to 10.2 plus or minus 6.5 ng/ml (P < 0.05). CONCLUSIONS: We demonstrated higher levels of plasma TGF-beta 1 in the patients with HCC than those in patients with chronic hepatitis and cirrhosis. Plasma TGF-beta 1 might be a candidate for a novel tumor marker for hepatocellular carcinoma.

Biomarkers, Tumor↗
PubMed1994

Involvement of FtsH in protein assembly into and through the membrane. II. Dominant mutations affecting FtsH functions.

FtsH is an Escherichia coli protein with its amino-terminal region anchored to the cytoplasmic membrane and with its cytoplasmic domain significantly homologous to the members of an ATPase family found in eukaryotic cells. We previously showed that the loss of ftsH function results in reduced cytoplasmic retention of the alkaline phosphatase moiety that was attached to cytoplasmic regions of membrane proteins (the Std phenotype) and also in translocation retardation of some exported proteins. We now report that expression of some FtsH variants from plasmids causes dominant Std and translocation phenotypes. Such variants include carboxyl-terminally truncated forms of FtsH and some missense mutations in the cytoplasmic domain, notably Lys to Asn changes at the two ATP binding consensus sequences. In contrast, amino-terminally truncated variants lacked the dominant phenotypes. It was suggested that the amino-terminal membrane region of FtsH interacts with other component(s), and that the two putative ATP binding sites are of vital importance for the FtsH functions.

ATP-Dependent Proteases↗
PubMed1994

Major hepatectomy and pancreatoduodenectomy for advanced carcinoma of the biliary tract.

Seven patients with advanced carcinoma of the extrahepatic biliary tract, including two with cancer of the gallbladder, underwent major hepatectomy with concomitant pancreatoduodenectomy. The mean hepatic volume resected was 64 (range 35-81) per cent. Postoperative complications occurred in all patients and accounted for two hospital deaths. Two patients with gallbladder carcinoma survived without recurrence for 22 and 58 months. Three of five patients with bile duct cancer survived operation, although all three subsequently died from recurrent disease at 8, 10 and 27 months. Combined major hepatectomy and pancreatoduodenectomy may be appropriate in selected patients with advanced cancer of the gallbladder. Further evaluation is necessary before this approach can be recommended for those with advanced bile duct carcinoma.

Aged↗
PubMed1994

The role of extracellular Ca2+ in carbachol-induced tonic contraction of the pig detrusor smooth muscle.

The role of extracellular Ca2+ in the tonic-contractile response to muscarinic receptor stimulation was investigated in isolated detrusor smooth muscle from the pig urinary bladder. Carbachol (10(-8)-10(-5) M) produced a concentration-dependent contractile response in isolated pig detrusor smooth muscle strips consisting of an initial phasic component followed by a tonic component. During the plateau of the tonic contractions induced by carbachol at the submaximal concentration of 10(-6) M, the inhibiting effects of atropine, EGTA, nifedipine (a voltage-dependent calcium channel antagonist), H-7 [a protein kinase C (PKC) inhibitor] and YM934 (a potassium channel opener) on the contractions were evaluated. Atropine (10(-10)-3 x 10(-8) M) concentration-dependently inhibited the tonic contractions induced by carbachol. In the same experimental conditions, EGTA (4 mM) and nifedipine (10(-9)-3 x 10(-7) M) depressed the tonic contractions in a concentration-dependent manner as did H-7 (10(-5)-3 x 10(-5) M) and YM934 (10(-8)-10(-6) M). However, H-7 (10(-5)-3 x 10(-5) M) and YM934 (10(-6) M) were very weak in inhibiting the contractions induced by KCl (50 mM) in isolated pig detrusor smooth muscle strips. These results suggest that the tonic-contractile response induced by carbachol in pig detrusor smooth muscle strips is dependent mainly on depolarization of the cell membranes and an influx of extracellular Ca2+, and also suggest that this depolarizing response may be due to inactivation of ATP-sensitive potassium channels through muscarinic activation of PKC.

Animals↗
PubMed1994

Change in growth kinetics of hybridoma cells entrapped in collagen gel affected by alkaline supply.

The growth yields for glucose and glutamine of murine hybridoma cells entrapped in collagen gel particles were examined during the growth phase. The immobilized hybridoma cells were cultivated in a fluidized bed fermenter where the medium was circulating to supply oxygen separately. Procedures to supply an alkaline solution for adjusting the pH level strongly affected the growth yields. A direct supply of the alkaline solution to the cultivation system reduced both the growth yields for glucose and glutamine, probably due to a local increase in pH level. On the other hand, when fresh medium in which the pH was adjusted to around 8.5 was added to the cultivation system, the growth yields were unchanged even at the same pH level as when direct alkaline supply was used. These results suggest that an indirect alkaline supply could be recommended to adjust the pH level when using medium-circulating-fermenters.

Animals↗
PubMed1994

Obstructive jaundice caused by a cholesterol polyp of the gallbladder: report of a case.

We present herein the case of a 34-year-old man in whom obstructive jaundice was found to be caused by an impacted detached cholesterol polyp. A cholecystectomy with exploration of the common bile duct was performed after ultrasonography showed cholesterol polyps and stones in the gallbladder. Intraoperative cholangioscopy demonstrated an impacted cholesterol polyp at the distal end of the common bile duct which appeared to be detached from the gallbladder. To our knowledge, this is the first report of an impacted detached cholesterol polyp causing obstructive jaundice.

Adult↗
PubMed1994

Role of low-substituted hydroxypropylcellulose in dissolution and bioavailability of novel fine granule system for masking bitter taste.

Coated fine granules with water-insoluble film composed primarily of ethylcellulose, containing 20% of sparfloxacin (SPFX) and various amounts of low-substituted hydroxypropylcellulose (L-HPC) (0-52%) in the cores and which masked the bitter taste of SPFX, were orally administered to fasting rats to determine the effect of L-HPC on bioavailability. The release of SPFX in water from four kinds of these coated fine granules containing 0, 25, 40 and 52% of L-HPC showed the pseudo first order kinetics, followed by the second phase, with refractive points between 0.25 and 0.5 h. The rate constant (K1) up to 0.25 h increased with an increase [corrected] of the amount of L-HPC in the core, and the rate constant (K2) in subsequent release (the second phase) was lower than K1 in each fine granule. Areas under plasma concentration-time curves (AUC) of SPFX and the peak plasma SPFX levels (Cmax) after oral administration of coated fine granules lacking L-HPC to fasting rats were suppressed to one-eighth and one-ninth, respectively, of those obtained from the core granules that rapidly released SPFX. However, AUC and Cmax from the coated fine granules increased linearly with an increase in the amount of L-HPC in the cores, and nearly equaled those from the core fine granules when the content of L-HPC was 52%. These results confirmed that the addition of L-HPC to the cores increases not only the dissolution rate but also the bioavailability of SPFX.

Animals↗
PubMed1994

Pharmacologic profiles of YM934, a novel potassium channel opener.

Pharmacologic profiles of YM934, a newly synthesized 1,4-benzoxazin derivative K channel opener were evaluated in in vitro and in vivo experiments. In isolated rat portal vein, YM934 and a benzopyran derivative K channel opener lemakalim inhibited the frequency of spontaneous rhythmic contractions concentration dependently, with IC50 values of 14 and 38 nM, respectively. These inhibitory effects were competitively antagonized by glibenclamide (an ATP-sensitive K channel blocker; 10(-7)-3 x 10(-6) M). In isolated rabbit aorta, YM934 (10(-8)-10(-6) M) and lemakalim (10(-8)-10(-6) M) relaxed the contractions induced by 20 mM KCl concentration dependently but were ineffective against the contractions induced by 50 mM KCl. YM934 (10(-8)-3 x 10(-6) M) and lemakalim (3 x 10(-8)-10(-5) M), but not the calcium antagonist nifedipine, relaxed the contractions induced by norepinephrine (NE 10(-6) M) or prostaglandin F2 alpha (PGF2 alpha 3 x 10(-6) M) in the aorta. In pentobarbital-anesthetized dogs, YM934 (1-10 micrograms/kg intravenously, i.v.) dose-dependently increased coronary artery blood flow (CBF), and decreased total peripheral resistance (TPR) and mean blood pressure (MBP). YM934 selectively increased CBF, but had little effect on vertebral, carotid, mesenteric, renal and femoral artery BF. These vasodilatory effects of YM934 were antagonized by glibenclamide. YM934 is a potent K channel opener and possesses potent vasodilatory effects, with particularly pronounced effects on the coronary artery. These effects of YM934 may, like lemakalim, be mediated by opening of ATP-sensitive K channels.

Anesthesia↗
PubMed1994

Alteration in growth regulation of hepatocytes in primary culture obtained from cirrhotic rat: poor response to transforming growth factor-beta 1 and interferons.

Cell growth appears to be controlled by positive and negative cell growth regulation. Little is known about the growth regulation of hepatocytes in the cirrhotic liver. Clarifying the responses of hepatocytes obtained from cirrhotic liver to various growth factors and growth inhibitory factors might aid understanding of alterations in growth regulation of the hepatocytes in the cirrhotic liver. We investigated the effects of hepatocyte growth factor, epidermal growth factor, heparin-binding epidermal growth factor-like growth factor, transforming growth factor-beta 1, interferon-alpha and interferon-gamma on the DNA synthesis of hepatocytes from cirrhotic and normal rats in primary culture. Cirrhosis was induced in male Sprague-Dawley rats by means of oral administration of 0.05% thioacetamide in drinking water for 4 mo. Hepatocytes were isolated by means of an in situ perfusion method, and DNA synthesis was assessed from the amount of DNA-incorporated [3H]thymidine. Stimulation of the DNA synthesis of hepatocytes by hepatocyte growth factor, epidermal growth factor and heparin-binding epidermal growth factor-like growth factor was not different between normal and cirrhotic rat liver. Transforming growth factor-beta 1 inhibited the DNA synthesis of hepatocytes in both. However, the concentration of transforming growth factor-beta 1 giving a 50% inhibition of DNA synthesis was about two times higher in cirrhotic hepatocytes (0.11 ng/ml) than in normal hepatocytes (0.06 ng/ml). In cirrhotic hepatocytes, the expression of transforming growth factor-beta type II receptor gene was about 50% of that in normal hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

The association between extrahepatic biliary carcinoma and the junction of the cystic duct and the biliary tree.

OBJECTIVE: To establish accurately the sites of primary extrahepatic biliary carcinomas, so that optimal treatment may be given. DESIGN: Retrospective study. SETTING: University department of surgery. SUBJECTS: 120 patients with 121 primary extrahepatic biliary carcinomas. MAIN OUTCOME MEASURES: Site of tumour (primary site being geometric centre of tumour) and distance from junction of cystic duct and the biliary tree on histological examination of the resected specimen. RESULTS: 64 of the tumours (53%) were within 5 mm of the junction; 14 were proximal to the junction, 32 distal, and 18 within the cystic duct itself. CONCLUSIONS: Over half the primary extrahepatic biliary tumours were within 5 mm of the junction of the cystic duct and the rest of the biliary tree. Further investigations are required to find out if any particular aetiological factor can be identified.

Adenocarcinoma↗