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Biomedical subjects

M Yamazaki

Publications and source records attributed to M Yamazaki.

At least 325 records · Page 18Linked to original sources

Genomic structure of human cystatin A.

Cystatin A is a cysteine proteinase inhibitor with a molecular mass of 11 kDa, and is located mainly in the keratohyaline granules of the stratum granulosum and the cornified envelope of the stratum corneum in the epidermis. In this study, we demonstrated the genomic structure of this proteinase inhibitor in which there were three exons of 111 bp, 102 bp and 226 bp in length, while the lengths of the 1st and 2nd intron were approximately 14 Kbp and 4 Kbp, respectively. The conserved sequence of QVVAG was encoded in the 2nd exon and was not inserted by any introns. There were binding sites for SP-1 and AP-2 in the promoter region and an AP-1 binding site in the 1st intron. The successful amplification of each exon of cystatin A may possibly contribute to the detection of the genomic abnormality of some skin disorders e.g. keratinization disorder, chronic bacterial infection or photophobia.

Amino Acid Sequence↗

An electrocution death of an infant who had received an electric shock from an uncovered oval shaped lamp switch in his mouth while in a hospital.

A male infant aged one year and nine months was found dead on a bed after admission to hospital with suspected pneumonia. The patient apparently put an uncovered oval shaped lamp switch (pendant switch) into his mouth and died of electric shock after contacting the exposed wires of the switch (100 V, 60 Hz alternating current). There were extensive first- to fourth-degree burns on the inner surface of the both lips. Because the histological findings were consistent with electric burns and the burns showed vital reactions, electric shock was judged to be the cause of death. The pendant switch is normally a very convenient piece of bedside equipment for inpatients. However, when the patient is an infant who naturally puts all the objects into the mouth, such a switch should be placed out of reach, and it should be certain that the cap is not loose.

Burns, Electric↗

Growth-inhibitory and apoptosis-inducing activities of calprotectin derived from inflammatory exudate cells on normal fibroblasts: regulation by metal ions.

We have shown previously that a calcium-binding protein complex, calprotectin, derived from polymorphonuclear leukocytes exerts a cytostatic and cytolytic effect against a very broad range of tumor cell lines. We also described that calprotectin is an apoptosis-inducing factor for certain tumor cells and that zinc ion attenuates the calprotectin activities. The titers of the factor in body fluids are known to increase greatly in various types of inflammation. In this study, to learn the role of calprotectin in inflammation, the growth-inhibitory and the apoptosis-inducing activities of the factor against normal fibroblasts were examined because fibroblasts are a cell type constituting a local inflammatory site. Rat calprotectin inhibited the growth of murine embryonic as well as human dermal fibroblasts. Although calprotectin induced apoptotic morphology in both fibroblasts, the reaction was slower and less efficient than cases using tumor cells as targets. The activities were significantly abrogated by 10-50 microM Zn2+, Cu2+, Mn2+, or Fe2+, respectively, whereas the trivalent cations Al3+ and Fe3+ had no effect. The dose-response curves of the calprotectin effects were shifted to about 10-fold lower concentration ranges in the divalent metal ion-depleted medium. These results suggest that calprotectin extracellularly affects the inflammatory processes by modulating the growth and survival states of normal fibroblasts, and that the effects are physiologically controlled by several metal ions.

Animals↗

[An autopsy case of pulmonary thromboembolism: a delayed complication of a victim by traffic accident].

A 35-year-old male had fallen down from his motor bike caused a fracture of the medial condyle of the right tibia and the acromion of the left scapula. He had received screw fixed operation for his right tibia and had been in the hospital for one month. He died suddenly in the hospital and was autopsied to find out the cause of death. On external examination, it was found that affected leg was bruised and swollened. Partially organized thrombosis in the posterior tibial vein was revealed and bilateral pulmonary arteries were packed with reddish massive thromboemboli. The causes of the posterior tibial vein thrombosis were intimal damage and decreased venous flow, attributable to bed rest for long days and external fixation of the lower extremity. We presumed that direct cause of death was a large thromboemboi which were migrated from posterior tibial vein and lodged at the bifurcation of the pulmonary artery causing obstruction of pulmonary blood flow. Finally we opened the direct cause of death was pulmonary thromboembolism due to leg injury. Clinical instability may hinder the diagnostic elevation and delay therapeutic intervention, it is the most often happened in sudden death cases within the hospital. The importance of early diagnosis and early prevention is underscoped, because the symptoms of pulmonary thromboembolism are not always produced. To prevent fatal pulmonary thromboembolism in trauma, prophylactic use of low-dose heparin therapy and/or the use of oral anticoaglant (warfarin) have been effective and recommended in USA and Western Europe. The routine use of these therapy has not yet been spread in Japan, because the incidence is still apparently lower than in USA and Western Europe as well as the risk of hemorrhage. If the victims of road traffic accident receive the prophylactic use of low-dose heparin and/or oral anticoaglant (warfarin), it might be an effective way to reduce mortality.

Accidents, Traffic↗

[A case of Guillain-Barré syndrome after the travel in southeast Asia--isolation of Campylobacter jejuni PEN 5 serotype].

A 57-year-old man, while on travel in Malaysia, suffered from diarrhea after he ate fruits. He developed limbs weakness without sensory disturbance after his return to Japan. Serum from the patient had high IgG anti-GM1 antibody titer. Campylobacter jejuni was isolated from his stool. The serotype belonged to PEN 5. The patient received double-filtration plasmapheresis 7 times during from days 6 to 17. Muscle strength began to recover gradually on day 10, and returned to normal 5 months after the onset of neurologic symptoms. Repeated neurophysiologic studies indicated that the axonal degeneration of motor nerves was predominant process. This case suggests that Guillain-Barré syndrome is a complication of traveler's diarrhea.

Campylobacter Infections↗

[A suicidal case of electrocution with hypnotic drug poisoning: an autopsy report].

A 28-year-old male was found dead on a bed in a hotel. He had two electric wires, the ends of which were fastened to each coin (50 and 100 yen); the coins were attached to a left hypochondrial region and a left side of the chest. The other ends of the wires were connected to a time switch, which had been connected to a plug top (100 V, 60 Hz alternating current). An empty box of a commercially available hypnotic (bromvalerylurea), a suicide note and a manual book for suicide were found at the spot. As autopsy findings, both burns on the left hypochondrial region and on the left side of the chest were carbonized at their central parts and erythemas were also noted around them. Histological findings were consistent with electric marks and the burns showed vital reactions. Copper stain was slightly positive; iron stain was negative. Bromvalerylurea concentrations in blood, urine, brain, liver and kidney samples were 14.5, 37.7, 5.8, 5.2 and 6.2 micrograms/ml or g, respectively. The blood level showed that he had been moderately intoxicated by the drug, but not fatal. The cause of death was thus judged to be suicidal electrocution. It seems that suicide was influenced by a "Manual Book of Suicide", which was found in his bag.

Adult↗

Sudden death due to diabetic coma in insulin-department diabetes mellitus: an autopsy report.

Sudden death caused by the acute onset of diabetic coma is reported. A 15-year-old female had been suffering from insulin-dependent diabetes mellitus for the prior 8 years and had a fever and vomiting for the past few days. On the 4th day, after the onset of fever and vomiting, she died suddenly, and was autopsied to clarify the cause of death. Macroscopic examination revealed that the pancreas was atrophic (40 g) whereas the liver was markedly enlarged (2,740 g). Histological findings were: 1) The islets of Langerhans were decreased in size and number. They were not positive for aldehyde-fuchsin staining, 2) There were severe fatty changes in the liver cells. The retained blood in the left ventricle was analyzed: glucose, 1,016 mg/dl; acetone, 345 mg/l; acetoacetate, 5.91 mmol/l: D-3-hydroxybutyrate, 4.17 mmol/l; hemoglobin A1c, 10.2%; fructosamine, 416 mumol/l; total serum cholesterol, 220 mg/dl; triglycerides, 205 mg/dl; free fatty acid, 8.0 mEq/l; urea nitrogen, 40 mg/dl. Although the biochemical estimation of the glucose and ketone levels in post-mortem body fluids was recognized as being unreliable, many of these values were far elevated in comparison with those of normal individuals. Thus, we concluded that the cause of death was diabetic ketoacidosis. We also discuss the diagnostic problems of postmortem blood chemistry.

Adolescent↗

[Antineoplastic glycoproteins in marine invertebrates].

We searched marine invertebrates for new host defence molecules. We found several new cytolytic factors in Arthropoda and Mollusca. Especially, sea hares were revealed to have strong antitumor glycoproteins. These novel glycoproteins were purified to apparent homogeneity from Aplysia kurodai and Dolabella auricularia, and designated aplysianins and dolabellanins, respectively. The isolated glycoproteins lysed all the tumor cells tested, including TNF-resistant cells, but did not lyse normal white and red blood cells. The glycoproteins completely inhibited the synthesis of DNA and RNA by tumor cells within 2 hours and caused tumor lysis within 18 hours. Cytolysis was inhibited by the presence of N-acetylneuraminic acid, suggesting that the recognition of the sugar moiety is a key step in the tumor lysis by these antineoplastic glycoproteins from sea hares. These antitumor factors, except dolabellanins C and P, also showed anti-microbial activities. The sequence of the N-terminal part of dolabellanin A was similar to aplysianin A and achacin.

Animals↗

Biliary excretion of pravastatin in rats: contribution of the excretion pathway mediated by canalicular multispecific organic anion transporter.

The biliary excretion of pravastatin in normal rats and Eisai hyperbiliruminemic rats (EHBRs) was examined in vivo and in vitro using bile canalicular membrane vesicles (CMVs). In vivo, the total body clearances at steady-state (CLtot) for both rat strains decreased as the infusion rate increased. At the lowest infusion rate, CLtot for normal rats was 1.6 times higher than that for EHBRs. Under this set of conditions, the biliary excretion clearance (CLbile), defined as the biliary excretion rate at steady-state divided by the concentration in the liver (Cliver), for normal rats was 3-fold higher than that for EHBRs. The CLbile fell markedly with increasing Cliver for normal rats and the Michaelis constant (KM) for Cliver was 180 microM; in contrast, the degree of saturation was slight if any in EHBRs. In vitro, the uptake of pravastatin by CMVs prepared from normal rats exhibited clear ATP-dependence, whereas only a minimal effect of ATP was observed on the uptake by CMVs from EHBRs. Transport kinetic studies were performed over a wide range of pravastatin concentration (0.2-10,000 microM) with a tracer tritium-labeled pravastatin. Saturation was observed both in the ATP-dependent (KM: 220 microM) and ATP-independent (KM: 480 microM) uptake by CMVs prepared from normal rats. ATP-dependent uptake of 2, 4-dinitrophenyl glutathione, a typical substrate for the canalicular multispecific organic anion transporter (cMOAT), was inhibited by pravastatin in a concentration-dependent manner and the resultant inhibitory constant of pravastatin (170 microM) was comparable with the KM value of ATP-dependent pravastatin uptake itself. In conclusion, biliary excretion of pravastatin is mediated mainly by cMOAT in normal rats. This can explain the decrease in the biliary excretion of pravastatin in EHBRs.

Animals↗

[A case of liver metastases from leiomyosarcoma in the chest wall which was made resectable by chemoembolization].

We here report a recently experienced case in which TAE and intra-arterial infusion chemotherapy for treatment of liver metastases of leiomyosarcoma in the chest wall caused a shrinking of the metastasized focus, thus facilitating liver resection. Patient; a 38-year-old man Present History and Courses; Resection of leiomyosarcoma in his chest wall was done in May, 1994. However, a local recurrence was noted in September, 1995, and the tumor was removed. Then, he received systemic chemotherapy with CDDP (100 mg) and ADM (45 mg). Abdominal CT and ultrasonic examinations made in February, 1996 revealed liver metastases at S2,5,8. Angiography detected densely stained images of tumors at a number of sites along with S2,5,8. Since these were thought unresectable, TAE therapy with EPIR (30 mg) and lipiodol (4 ml) was attempted 3 times. Then, a reservoir for intra-hepatic arterial infusion was implanted in April, 1996 and EPIR at a dose of 30 mg (150 mg in total) was given through arterial infusion, resulting in tumor disappearance at S5,8 but further growth of the tumor metastasizes at S2. Therefore, a resection of the left lateral segment of liver was done August 23. Though he was discharged in October, metastasis was found in the thoracic spine in December. Thus, he underwent resection of the vertebral arch including the tumor.

Adult↗

[Evaluation of CTA for arterial infusion chemotherapy for liver metastasis from colorectal cancer].

To compare between the arterial blood supply of metastatic liver tumor and effects of intrahepatic arterial infusion chemotherapy (IHAC), we examined 8 patients with 27 liver metastasis from colorectal cancer. They were treated with ADM/lipiodol/5-FU/LV (19 nodules) or 5-FU/LV (8 nodules). To evaluate the arterial blood supply, CT arteriography (CTA) was performed, which classified tumors into 3 grades. Grade (Gr) 0; almost no enhancement, Gr1: less than one-third of tumor, Gr 2; less than two-thirds; Gr 3 over two-thirds (no case). As a result, 3 of NCs and 3 of PDs were Gr 0, 7 of MRs, 3 of NCs and 2 of PDs were Gr 1, and CR, PR and 7 of MRs were Gr 2. These results suggest that the arterial blood supply is necessary for a better response of IHAC and CTA is effective to forecast the response to IHAC.

Antineoplastic Combined Chemotherapy Protocols↗

[A case of unresectable advanced cancer of the gall bladder successfully treated by arterial infusion therapy with cisplatin].

A 70-year-old male was admitted for obstructive jaundice. He was diagnosed as an unresectable advanced cancer of the gall bladder that was stage IV associated with direct extension of the liver (Hinf3) and the bile duct (Binf3), and with enlargement of paraaortic lymph node (N4(+)) by image analyses. Intraarterial infusion therapy with cisplatin (CDDP, 50 mg) was started through the common hepatic artery. Since the primary tumor and the enlarged paraaortic lymph node shrank markedly and the bile duct was completely obstructed, additional arterial infusion with CDDP (50 mg) was made. CT examination thereafter revealed that the paraaortic lymph node enlargement disappeared although thickening of the gall bladder wall still remained. Therefore this case was considered as a complete response (CR). Then, a reservoir for hepatic arterial infusion was implanted and CDDP (a total of 230 mg) was repeatedly infused 5 times. CT scanning images taken 7 months after the start of the treatment showed neither primary tumor nor enlargement of paraaortic lymph node. An extensive cholecystectomy was performed. Histopathological examination revealed signet-ring cell carcinoma located in all layers of the gall bladder. Factors indicating clinicopathological stage were se, hinf1, vs0, bw1, hw0 and ew2 (according to the General Rules for Surgical and Pathological Studies on Cancer of Bile duct).

Aged↗

[An autopsy case of carbon dioxide intoxication].

A 44-year-old male, engaged in the transportation of dry ice, was found dead on the floor of the freezer of his refrigerator car which was parked in front of the place where he was scheduled to make a delivery. Autopsy was performed to investigate the cause of death. Apart from the signs of acute death, no other significant findings were obtained, either macro or microscopically; carbon dioxide poisoning was thus strongly suspected. We created a simulation experiment by using the refrigerator car to reproduce the events of the accident. The oxygen concentration in the freezer was 21.0% as indicated by oxygen sensors, but decreased to 17.1-17.4% when the engine was stopped. This decrease in oxygen concentration supposedly results from the production of carbon dioxide by the vaporization of dry ice. Carbon dioxide concentration in the air could be calculated from the change in the oxygen concentration in the closed space of the freezer. The concentration was assessed at 17.1-18.6%. An oxygen concentration of 17.1-17.4% does not of itself cause serious hypoxia, but a carbon dioxide concentration of 17.1-18.6% probably causes serious intoxication, because this value is beyond that of intoxication levels published in references. Therefore, we concluded that the cause of death in this case was carbon dioxide intoxication.

Adult↗

Occult Breast Cancer: A Case Report and Review of the Literature.

We report a case of a 44-yar-old woman with occult breast cancer presenting as an axillary mass in whom sonography was able to detecct an involved internal mammary node also, thus helping to establish a diagnosis of breast cancer. The patient underwent extended radical mastectomy, including internal mammary lymphadenectomy. Microscopy of the removed specimen failed to find a primary breast cancer lesion. Metastatic cancer was seen in the palpable axillary node, another resected axillary node and a removed internal mammary node. The estrogen and progesterone receptor analysis of the axillary node were negative. Since occult breast cancer was found highly potential for metastasizing to the infraclavicular or internal mammary nodes, it is reasonable to treat such patients in the same way as those with palpable breast cancer, with adjuvant chemotherapy.

Journal Article↗

Possible stimulation of retinal rod recovery to dark state by cGMP release from a cGMP phosphodiesterase noncatalytic site.

Cyclic GMP phosphodiesterase, a key enzyme for phototransduction, contains alpha, beta (Palphabeta), and two gamma (Pgamma) subunits. In addition to catalytic sites, Palphabeta has two classes of noncatalytic cGMP binding sites with different affinities (Kd values <100 nM and >1 microM). Pgamma regulates Palphabeta as an inhibitor of cGMP hydrolysis and as a stimulator of cGMP binding to the high affinity noncatalytic sites. Pgamma release from Palphabeta by the GTP-bound alpha subunit of transducin (GTP.Talpha) interrupts these two functions. Here we describe a novel regulation of the Pgamma release by [cGMP] and its physiological implication. We isolated Pgamma mutants that exhibit abnormally one of these two functions, indicating the distinct domains in Pgamma are involved to express these functions. When [cGMP] was high ( approximately 5 microM), Pgamma responsible for the inhibition of cGMP hydrolysis was preferentially released, and cGMP hydrolysis activity of Palphabeta was increased about 10 times. When [cGMP] was low (less than approximately 0.5 microM), Pgamma responsible for the stimulation of cGMP binding to the high affinity sites was released. The Pgamma release resulted in the decrease of relative affinity of cGMP for the high affinity sites to at least (null)/1;10, followed by the rapid release of cGMP from one of the high affinity sites (apparent t1/2 = 3.8 s). cGMP ( approximately 5 microM) inhibited the extraction of Palphabeta from rod membranes by a Mg2+-free hypotonic buffer. The inhibition of Palphabeta extraction was not affected by Pgamma, suggesting that Palphabeta detects on the order of micromolar [cGMP] using low affinity noncatalytic sites on Palphabeta. Because [cGMP] is approximately 5 microM in darkness and lowered by photoexcitation and phosphodiesterase concentration is approximately 30 microM in rod photoreceptors, it is possible that cGMP phosphodiesterase functions to increase cytoplasamic [cGMP] after [cGMP] is reduced to the illuminated level.

3',5'-Cyclic-GMP Phosphodiesterases↗

Organic solvents induce interdigitated gel structures in multilamellar vesicles of dipalmitoylphosphatidylcholine.

We have investigated the effects of several water-soluble organic solvents which also have a high solubility for alkanes, on the structure and phase behavior of multilamellar vesicles of dipalmitoylphosphatidylcholine (DPPC-MLV). Of these solvents, we selected five organic solvents; such as, acetonitrile, acetone, propionaldehyde, ethanol, and tetrahydrofuran. The main transition temperature of DPPC-MLV decreased with an increase in acetonitrile concentration from 0% to 6.0%(v/v) acetonitrile, and increased above 6.0%(v/v). X-ray diffraction data indicated that a phase transition from L beta', to L beta I phase (interdigitated gel phase) in DPPC-MLV, occurred at 5.0%(v/v) and DPPC-MLV were completely in the L beta I phase above 6.0%(v/v) acetonitrile at 20 degrees C. Results of the excimer method (Yamazaki, M. et al. (1992) Biochim. Biophys. Acta 1106, 94-98) supported the above results; the ratio of excimer to monomer fluorescence intensity (E/M) of pyrene-PC in DPPC-MLV rapidly decreased at 5.1%(v/v) and E/M became very low above 6.0%(v/v) acetonitrile. By the excimer method, we have found that other organic solvents; such as, acetone, propionaldehyde, and tetrahydrofuran, induced a phase transition from L beta', to L beta I phase in DPPC-MLV. Threshold concentrations of acetone, ethanol, propionaldehyde, and tetrahydrofuran for this phase transition at 20 degrees C were 9.4%(v/v), 5.5%(w/v), 3.5%(w/v), and 3.7%(w/v), respectively. Substitution of H2O by D2O (deuterium oxide) increased the threshold concentrations of all the organic solvents. A mechanism of these phase transitions and the effect of the substitution of H2O by D2O is proposed and discussed; a concept of the chi parameter, which is an interaction energy parameter between the surface segments of DPPC-MLV and solvents, may explain these phenomena reasonably.

1,2-Dipalmitoylphosphatidylcholine↗

Quantitative determination of cardiac glycosides in Digitalis lanata leaves by reversed-phase thin-layer chromatography.

An analytical method for the determination of cardiac glycosides in Digitalis lanata leaves by reversed-phase thin-layer chromatography (RP-TLC) was developed. The procedure consisted of extraction of dry leaf powder with 50% methanol and clean-up by Sep-Pak cartridges prior to RP-TLC analysis. RP-TLC was performed on an octadecylsilyl bonded silica gel plate, using a developing solvent of acetonitrile-methanol-0.5 M NaCl (1:1:1) for primary glycosides and acetonitrile-methanol-0.5 M NaCl (12:7:9) for secondary glycosides. The plate was scanned with a reflectance densitometer at 225 nm. The quantitation was carried out by the internal standard method. The present method is reliable and relatively simple for the determination of cardiac glycosides in Digitalis lanata leaves.

Cardiac Glycosides↗

Brain somatostatin depletion by cysteamine attenuates the penile erection induced by serotonergic and dopaminergic, but not by cholinergic, activation in rats.

To clarify the role of brain somatostatin in the expression of penile erection, the effects of cysteamine, a somatostatin depletor, on the penile erection induced by serotonergic, cholinergic and dopaminergic stimulants were investigated in rats. Fenfluramine (0.1-10 mg/kg, i.p.), pilocarpine (0.032-3.2 mg/kg, i.p.) and apomorphine (0.01-1 mg/kg, i.p.) induced penile erection in rats, with bell-shaped dose-response curves. Pretreatment with cysteamine (200 mg/kg, s.c.) significantly attenuated the penile erection induced by fenfluramine and apomorphine, but scarcely affected that induced by pilocarpine. Neurochemical measures revealed that cysteamine pretreatment significantly reduced the somatostatin content in all brain regions examined. These results provide the first pharmacological evidence that the brain somatostatin may play an important role in drug-induced penile erection.

Animals↗