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Biomedical subjects

K Shibata

Publications and source records attributed to K Shibata.

At least 361 records · Page 20Linked to original sources

Transvaginal pulsed and color Doppler sonography for the evaluation of adenomyosis.

In an earlier paper, we reported our scoring system for the diagnosis of adenomyosis by gray scale transvaginal sonography. In this study we evaluated 44 benign uterine masses (adenomyosis and myomas) and seven uterine malignancies. We used transvaginal color and pulsed Doppler imaging to determine whether this technique is useful to differentiate adenomyosis from uterine malignancies. The peak systolic velocity and the resistive index of intratumoral vessels were studied. The differences in these parameters for adenomyosis and uterine malignancies were statistically significant. Our results suggest that this technique is useful to differentiate adenomyosis from uterine malignancies.

Adult↗

[Air pollution by sevoflurane in operating room and serum and urine inorganic fluoride of anesthetists].

Since lower blood-gas partition coefficient of sevoflurane provides rapid induction and emergence from anesthesia, sevoflurane has been used widely for inhalational anesthesia. However, because higher minimum alveolar concentration of sevoflurane requires a large dosage of anesthetic than other volatile anesthetics, air pollution with sevoflurane in the operating room might be of great concern. Anesthetists may keep inhaling the low concentration of anesthetics every day, even though scavenging system is equipped in the operating room. The purpose of this study is to evaluate the effects on anesthetists of the low concentration of anesthetics by measuring the inorganic fluoride concentration in the urine and serum of anesthetists and operating room nurses. Healthy 29 anesthesiologists and two operating room nurses were studied. Informed consent was obtained. Inorganic fluoride ions in the serum and urine were measured. Simultaneously sevoflurane concentration in operating room was measured in three operating rooms, at two places in the corridor and in the recovery room. Sevoflurane concentrations in three operating rooms were 1.22 ppm, 2.13 ppm and 6.05 ppm respectively. Concentration in the recovery room was 0.544 ppm. Serum and urine concentrations of inorganic fluoride were 1.1 +/- 0.1 mumol.l-1 and 36.2 +/- 17.1 mumol.l-1, respectively (mean +/- SD). Serum concentration of inorganic fluoride was within normal ranges. Although it is possible that fluoride concentration in urine is influenced by urine volume and a half of fluoride deposits in bone, no abnormal values in urine were found in this study. These results suggest that long term exposure to low concentration of sevoflurane and isoflurane causes no significant increase in their metabolites in operating room staffs.

Adult↗

KMD-3213, a novel, potent, alpha 1a-adrenoceptor-selective antagonist: characterization using recombinant human alpha 1-adrenoceptors and native tissues.

alpha 1-Adrenoceptors (ARs) comprise a heterogeneous family, and subtype-selective ligands are valuable for studying the functional role of each receptor subtype. We characterized a newly synthesized, alpha 1-AR antagonist, KMD-3213, by using Chinese hamster ovary cells stably expressing the three cloned human alpha 1-ARs (alpha 1a, alpha 1b, and alpha 1d), as well as native rat and human tissues. KMD-3213 potently inhibited 2-[2-(4-hydroxy-3-[125I]iodophenyl)ethylaminomethyl]-alpha-tetralone binding to the cloned human alpha 1a-AR, with a Ki value of 0.036 nM, but had 583- and 56-fold lower potency at the alpha 1b- and alpha 1d-ARs, respectively. KMD-3213 inhibited norepinephrine-induced increases in intracellular Ca2+ concentrations in alpha 1a-AR-expressing Chinese hamster ovary cells with an IC50 of 0.32 nM but had a much weaker inhibitory effect on the alpha 1b- and alpha 1d-ARs. Using pharmacologically well characterized native rat tissues [submaxillary gland (alpha 1A-AR-expressing tissue), liver (alpha 1B-AR-expressing tissue), and heart (mixed alpha 1A- and alpha 1B-AR-expressing tissue)], binding studies showed that inhibition curves for KMD-3213 in submaxillary gland and liver best fit a one-site model (with Ki values of 0.15 and 16 nM, respectively), whereas KMD-3213 had high and low affinity sites in heart membranes. Chloroethylclonidine treatment of rat heart membranes completely eliminated the low affinity sites for KMD-3213. Furthermore, in human liver and prostate KMD-3213 could identify high and low affinity sites, the Ki values of which corresponded well to those for the cloned human alpha 1a- and alpha 1b-ARs, respectively. Moreover, the affinity of KMD-3213 was found to be approximately 10-fold higher at the cloned human alpha 1a-AR than at the cloned rat alpha 1a-AR. KMD-3213 is a potent and highly selective antagonist for the human alpha 1a-AR and would be useful for studying the physiological roles of human alpha 1-AR subtypes.

Adrenergic alpha-1 Receptor Antagonists↗

[Evaluation of the residual functional reserve and the early regeneration after the hepatic resection using asialoglycoprotein receptor imaging agent].

99mTc-DTPA-galactosyl human serum albumin (99mTc-GSA) is a newly developed liver imaging ligand which specifically binds to asialoglycoprotein receptor on the hepatic cell surface. We investigated whether 99mTc-GSA scintigraphy was able to be used as indexes for the residual functional reserve and the early regeneration of the hepatocyte after the hepatic resection. Four patients with metastatic liver cancer, 3 patients with hepatocellular carcinoma, and 1 patient with cholangiocellular carcinoma were studied. Basically, each patient was examined 4 times (before, 3, 10, 20 days after the operation). Immediately after i.v. injection of 185 MBq (3 mg) of 99mTc-GSA, serial images and dynamic data were obtained. Serial changes of HH15, as an index of blood clearance of the tracer calculated from the uptake ratio of heart at 15 minutes to that at 3 minutes, and LHL15, as an index of hepatic accumulation calculated from the uptake ratio of liver to liver plus heart at 15 minutes after the injection were analyzed before and after hepatectomy. Three out of 4 lobectomy patients which showed increased HH15, and decreased LHL15 as compared with the preoperative data were considered to be decreased residual hepatic functional reserve. The remaining one lobectomy patient showed increased HH15, but increased LHL15 inversely. One patient of two partial resections of hepatocellular carcinoma with liver cirrhosis demonstrated transiently decreased HH15, and increased LHL15. Two patients with metastatic liver cancer (one partial resection, six partial resections) showed decreased HH15, and increased LHL15. Postoperatively increased hepatic accumulation was presumed to be increased functioning hepatocyte or transiently increased asialoglycoprotein receptor on the cell surface by up-regulation. 99mTc-GSA scintigraphy might be helpful for non-invasive method to detect the residual functional reserve and the early regeneration of the hepatocyte after the hepatic resection.

Aged↗

[A case of cerebral infarction in a young adult following an abuse of cocaine and other drugs].

We reported a case of cerebral infarction in a young adult following an abuse of cocaine and other drugs. A 27-year-old male was admitted to our hospital because of the abrupt onset of right hemiplegia and dysarthria. Brain CT and MRI examinations showed cerebral infarction in the region of the left caudate head and the left corona radiata. Cerebral angiography revealed total occlusion at the origin of the left middle cerebral artery, with neither vascular malformation nor atherosclerotic change. There were no obvious causes that might lead to cerebral infarction in young adults, including potential cardiac sources of embolism, abnormalities of blood coagulation, or collagen vascular diseases. From his history we learned he had started abusing cocaine and other drugs at the age of 16 years, and that he had been addicted to these drugs up to at least 2 months earlier than the onset of cerebral infarction, so we suggested his drug abuse might have affected the occurrence of cerebral infarction. We would like to emphasize that using 'drugs' should be taken into consideration as a possible cause of cerebral infarction in young adults.

Adult↗

Membrane proteins with molecular masses of 88, 90 and 150 kDa are responsible for binding of human immunoglobulin G Fc fragment to the native cells of Mycoplasma salivarium.

Mycoplasma salivarium cells bound the Fc fragment of human immunoglobulin G. The activity was remarkably enhanced by Mn2+, but not by Mg2+ and Ca2+; significantly inhibited by D-mannose; and reduced by pronase treatment of the cells. About 90% of the cells treated with pronase were not disrupted. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of proteins of the cells treated with pronase indicated that proteins with molecular masses of 88, 90 and 150 kDa (88 kp, 90 kp and 150 kp) were specifically digested. The results presented suggest that 88 kp, 90 kp and 150 kp, located in the outer surface of the cell membrane, are responsible for the activity of the M. salivarium cells and interact with a carbohydrate-containing moiety (D-mannose) of the Fc fragment in a Mn(2+)-dependent manner.

Bacterial Outer Membrane Proteins↗

DT-diaphorase as a determinant of sensitivity to adriamycin in non-small-cell lung-cancer cell lines.

We have reported the establishment of a mitomycin-C (MMC)-resistant non-small-cell lung-cancer cell line, PC-9/MC4. As determined by an MTT assay, this resistant cell line was found to be 4 times more sensitive to adriamycin (ADM) than was the parental PC-9. There were no significant differences in sensitivity to etoposide, mitoxantrone, daunomycin, epirubicin, pirarubicin, 9-aminoanthracycline or 3'-deamino-3'-morpholino-13-deoxo-10-hydroxy carminomycin. These data suggest that neither qualitative or quantitative changes in DNA topoisomerase II nor the enhanced repair of DNA can explain the differing sensitivity to ADM observed. No significant differences were found in the accumulation of ADM and glutathione (GSH) in these cell lines. Although total glutathione-S-transferase (GST) activity in PC-9/MC4 cells was lower than that observed in PC-9 cells and treatment with ethacrynic acid (EA) reduced sensitivity to ADM in both cell lines, relative resistance was unaffected. NADH-cytochrome b5 reductase (B5R) activity in PC-9/MC4 cells showed a 3-fold greater decrease than that in PC-9 cells, and DT-diaphorase (DTD) activity in PC-9/MC4 cells showed an approximately 200-fold greater decrease than that in PC-9 cells. Addition of dicumarol, an inhibitor of DTD, decreased the sensitivity of ADM of PC-9 but not of PC-9/MC4. DTD activity in the PC-9 cell line was inhibited by treatment with dicumarol while in PC-9/MC4 it remained unchanged. These data suggest that DT-diaphorase is a determinant of sensitivity to ADM in the 2 cell lines.

Adenocarcinoma↗

Cloning, functional expression and tissue distribution of human cDNA for the vascular-type vasopressin receptor.

We have cloned a human vasopressin receptor from human mesenteric artery using RACE (Rapid Amplification of cDNA Ends) methods. The deduced amino acid sequence of the clone (HV-RACE) encodes a protein of 418 amino acids that showed a strong sequence homology to the previously cloned rat V1A vasopressin receptor. The [3H] arginine vasopressin (AVP) binding to HV-RACE expressed in COS-7 cells was potently inhibited by AVP (Ki = 2.9 nM). Interestingly, a new non-peptide "V1-selective" antagonist OPC-21268 exhibited markedly higher affinity for rat V1A receptor (Ki = 57 nM) rather than for HV-RACE (Ki = 56 microM). With the reverse-transcription polymerase chain reaction assay, we observed a large amount of HV-RACE transcripts in the mesenteric artery, while a small amount in a variety of other tissues. The data show that the clone HV-RACE encodes a human vascular-type vasopressin receptor cDNA.

Amino Acid Sequence↗

Clinical importance of extraordinary integration patterns of human T-cell lymphotropic virus type I proviral DNA in adult T-cell leukemia/lymphoma.

The proviral DNA of human T-cell lymphotrophic virus type I (HTLV-I) is known to be integrated monoclonally in the malignant cells of adult T-cell leukemia/lymphoma (ATL), which is a peripheral T-cell malignancy caused by this virus. We studied the relationship between the integration patterns of HTLV-I and clinical characteristics in 89 patients with ATL. The proviral DNA of HTLV-I was examined by the standard Southern blot analysis using the endonucleases EcoRI and Pst I. One clear band of greater than 9 kb was detected in most of the patients (83 case) when cellular DNA was digested with EcoRI. On the other hand, extraordinary integration patterns of HTLV-I proviral DNA were detected in 6 patients; 3 of them showed two bands, while the other 3 showed one band smaller than 9 kb. When cellular DNA was digested with PstI, the band patterns of these patients were quite different from those of typical patients. The patients with the extraordinary integration patterns had clinical characteristics dissimilar to those of the other 83 patients with the ordinary integration pattern. The patients with two bands by EcoRI digestion always had severe hypoxemia with extremely high levels of serum lactate dehydrogenase at first presentation and showed peculiar organ infiltrations, such as retina and muscle, which were less frequent in the other ordinary 83 patients. They all died within 8 months after the onset. In contrast, the patients with one smaller band by EcoRI digestion always had small and mature T lymphocytes with bilobulated nuclei without lymphadenopathy and showed a favorable clinical course, which was uncommon in the ordinary cases. They were alive 20 to 38 months after diagnosis. Rearranged bands of the T-cell receptor gene were detected in all patients with unusual integration. These findings indicate that the integration patterns of HTLV-I proviral DNA have a clinical implication and may be one of the explanations for heterogeneity in the behavior of this disease.

DNA, Viral↗

Physicochemical characterization of PEG-PPG conjugated human urokinase.

Human urokinase (UK) was conjugated with polyethylene glycol-polypropylene glycol (PEG-PPG) and its physicochemical properties were examined. PEG-PPG modification decreased the activity for plasminogen activation, but increased the half-life of this protein when injected intravenously in rabbits. Kinetic analysis of PEG-PPG conjugated UK (PEG-PPG-UK) revealed that the kcat for plasminogen activation decreased 1/5-fold with the increase of Km in comparison with that of UK, although these parameters for cleavage of synthetic substrate (S-2444) did not change. However, the inhibitor constant of PEG-PPG-UK for plasminogen activator inhibitor 1 (PAI 1) was equal to that of UK. Peptide mapping analysis revealed that PEG-PPG binding sites were mainly determined to be Lys 35, 46, 61, 98, 120 and 135 in A-chain and Lys 211, 300, 318, 338, 348, 383 and 404 in B-chain. In addition, the modification rates of A and B-chain were 37.8% and 19.8% on average, respectively.

Animals↗

Increase of hepatic mRNAS of profilin, actin and extracellular matrix proteins after carbon tetrachloride treatment and partial hepatectomy in rats.

The synthesis of liver collagen increases during the fibrotic process after administration of carbon tetrachloride and during regeneration after partial hepatectomy in rats. In the present study, we investigated the behavior of profilin and actin mRNA under such conditions. Profilin and actin mRNA increased after acute and chronic treatments of carbon tetrachloride, which is associated with the increase of fibronectin, type-III and -IV collagen mRNA. Furthermore, a simultaneous expression of profilin, actin and extracellular matrix proteins was observed during the regeneration of rat liver, that is, all mRNAs of these proteins showed biphasic peaks around 6 h and 48 h after partial hepatectomy. These results suggest that possible coupling might occur between the changes of extracellular matrix and the reorganization of actin cytoskeleton in vivo.

Actins↗

Effects of herbimycin A and its derivatives on growth and differentiation of Ph1-positive acute lymphoid leukemia cell lines.

The molecular basis of the Philadelphia chromosome (Ph1) is a structurally altered c-abl (bcr/abl) gene which encodes an abnormally large protein with protein tyrosine kinase activity. Herbimycin A, an inhibitor of tyrosine kinase, preferentially inhibited the growth of Ph1-positive acute lymphoid leukemia (ALL) cell lines, as well as Ph1-positive chronic myeloid leukemia (CML) cell lines. Although noncytotoxic concentrations of herbimycin A induced erythroid differentiation of two CML-derived cell lines, K562 and KU812, in a previous study, the differentiation-inducing effect of herbimycin A on Ph1-positive ALL cell lines was less strong. Herbimycin A enhanced some differentiation-associated properties of one Ph1-positive ALL cell line, L2, but the effect of herbimycin A on the other Ph1-positive ALL cell lines was cytotoxic rather than cytostatic (differentiation-inducing). Several derivatives of herbimycin A were synthesized and their effects on the cell proliferation of Ph1-positive CML and ALL cell lines were examined. The sensitivities of the Ph1-positive cell lines to herbimycin A derivatives were different from the data on the rat kidney cell line infected with Rous sarcoma virus (v-src) derived from a previous study, suggesting bcr/abl kinase may differ in sensitivity from other tyrosine kinases. Moreover, the sensitivities of the ALL cell lines were not the same as those of the CML cell lines. These results suggest that a specific inhibitor of bcr/abl kinase could be an effective antileukemic agent against Ph1-positive CML or ALL.

Antibiotics, Antineoplastic↗

A case of Purtscher's retinopathy.

This article describes a case of Purtscher's retinopathy, a syndrome believed to be caused by microembolic infarction of the retina, in a 20-year-old man after remote extraocular trauma. The patient jumped from a 20-meter high building. He suffered multiple crush injuries, but a computed tomographic scan of the brain and orbit was normal. More than 1 month after injury, his visual acuity diminished to light perception in the right eye and counting fingers in the left. The ophthalmoscopic picture was characteristic of Purtscher's retinopathy with cotton-wool exudates and retinal hemorrhages localized to the posterior pole. His vision was improved only slightly 6 months later. Although rare, emergency physicians should be familiar with this entity as a cause of diminished vision associated with extraocular trauma.

Adult↗

Extensive chemical burns from toluene.

A 22-year-old man with heavy, generalized exposure to a toluene-based paint developed extensive chemical burns on approximately 71% of his total body surface area followed by acute renal failure and disseminated intravascular coagulation that led to death. Although the skin damage initially appeared mild, it was followed by blistering, extensive necrosis, and massive loss of fluid. Histological examination of the skin showed findings similar to those observed in second-degree thermal burns. Although the most common toxic effects of toluene are depression of central nervous system activity, irritation of mucous membranes, and hepatic or renal dysfunctions, emergency physicians should be aware of the risk of skin toxicity. Therefore, it is important to irrigate the exposed skin immediately and vigorously.

Acute Kidney Injury↗