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Biomedical subjects

M Funayama

Publications and source records attributed to M Funayama.

At least 37 records · Page 2Linked to original sources
PubMed1998

Intracellular Ca2+ store-operated influx of Ca2+ through TRP-R, a rat homolog of TRP, expressed in Xenopus oocytes.

To elucidate whether rat transient receptor potential (TRP-R), a rat TRP4 homolog, functions as a store-operated Ca2+ channel (SOC), we have measured the Ca2+ entry after thapsigargin treatment in Xenopus oocytes injected with mRNA for TRP-R. While non-injected oocytes elicited an SOC response, significantly larger responses were observed in the oocytes expressing TRP-R. The oocyte-native SOC response was inhibited by injection of antisense oligodeoxyribonucleotide for mammalian TRP1. When Ca2+ concentration-SOC response curve was examined, the EC50 value was much smaller in oocytes expressing TRP-R than that of non-injected oocytes. These results suggest that TRP-R functions as SOC having higher sensitivity to external Ca2+ than amphibian TRP1 channel.

Animals↗
PubMed1998

Child death related to insulin omission by mother.

A 4-year-old child was found dead in her house. She had been suffering from insulin-dependent diabetes mellitus (IDDM) for 3 years. She had been admitted to hospital three times, and attended the hospital once a month. Her glycaemic control remained poor. Autopsy findings revealed a remarkably fatty liver and lack of beta cells in the pancreatic islets of Langerhans. The laboratory reported ketoacidosis, ketonuria, glycosuria, and high levels of vitreous glucose and ketones. Her father had been absent for the 3 days before her death, and the mother should have fed her. Her mother was found drunk on the floor. No detailed history was available because of the mother's death, but the probability of the mother's omission of the insulin injection was suggested. Poor control of IDDM might have also been closely connected to general neglect by the mother. This case was considered child abuse.

Journal Article↗
PubMed1998

A new deleted allele in the human cytochrome P450 2A6 (CYP2A6) gene found in individuals showing poor metabolic capacity to coumarin and (+)-cis-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one hydrochloride (SM-12502).

The S-oxidation of (4)-cis-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one hydrochloride (SM-12502) and the 7-hydroxylation of coumarin are primarily catalyzed by cytochrome P450 2A6 (CYP2A6). The activities of SM-12502 S-oxidase and coumarin 7-hydroxylase were investigated with liver microsomes from 20 human individuals. Liver microsomes from individual H16 showed the lowest activities of both enzymes. The expression of CYP2A6 protein was not detectable in liver microsomes from individuals H4, H5, H7, H8, H12 and H16. CYP2A6 mRNA was hardly detectable in the liver of the individual H16. A new SacI-restriction fragment length polymorphism showing the lack of a 2.6 kb fragment was found in two of forty genomic DNA preparations from individuals H16 and No. 594, using CYP2A6 cDNA as a probe. This deletional 2.6 kb fragment was isolated from a genomic library prepared from one individuals showing normal coumarin 7-hydroxylase activity and was sequenced. This fragment contained a CYP2A6 gene region from 319 bp upstream of a putative exon 6 to a SacI site in exon 9, indicating that this region was deleted in the two individuals in this study. We also demonstrated by polymerase chain reaction analysis that the exon 8 of CYP2A6 gene was deleted in individuals H16 and No. 594. These results indicate that the reduced activity of SM-12502 S-oxidase and no activity of coumarin 7-hydroxylase are caused by the lack of CYP2A6 mRNA and CYP2A6 protein caused by the CYP2A6 gene deletion.

Aryl Hydrocarbon Hydroxylases↗
PubMed1998

Inhaled air trapping effect of Japanese bedding as a risk of sudden unexpected death in infancy.

We assessed some Japanese bedding on the assumption of the effects of air trapping using an infant mannequin. The change of CO2 concentration in the airway of a mannequin head placed on bedding was continuously monitored using a CO2 analyzer during simulated breathing. To compare the level of CO2 dispersal among different items of bedding, CO2 half time (t1/2) values were used. The t1/2 values were calculated by measuring the time required for the expired percent CO2 to reach 1/2 the initial percent end-tidal PCO2. We also measured softness and resistance to airflow (R) of the same items. As for the bedding, 4 types of futon and several types of bottom sheets/towels were combined. The t1/2 value in supine position was 9.8 seconds. When the model was placed prone on futon, the t1/2 values increased to 14.1 seconds (hard mattress type)--17.2 seconds (soft cotton-like futon). With respect to present Japanese baby futon (hard mattress type), there may be a relatively low potential for rebreathing to occur, compared with soft futon. In every case, the t1/2 value was prolonged by the use of a towel spread on the futon. CO2 dispersal may depend not only on the softness of the futon, but also on the combination of bottom sheet/towel and mattress. There was no relationship between R values and t1/2 values. The potential of rebreathing increased in face down position among all bedding, and supine position was the best CO2 dispersal position.

Bedding and Linens↗
PubMed1998

[Simple and rapid detection of HLA-DRB polymorphism from forensic samples].

Simple and rapid detection of HLA-DRB polymorphism has been performed using AMPLICOR HLA-DRB Typing Kit. We tried to apply this kit to various forensic samples. When DNA was extracted from the forensic samples using conventional phenol-chloroform method, addition of 7.5 mM MgCl2 was required to PCR amplification. HLA-DRB types were detected from DNA more than 0.1 ng by PCR amplification. Typing of unrelated 50 Japanese showed 38 different patterns, of which 30 patterns occurred once in the group. A total of 16 serotypes were deduced from the HLA-DRB DNA types. Out of them, high frequency serotypes were DR4 (24%), DR9 (18%) and DR15/16 (14%). This kit was very useful in forensic cases such as rape and in paternity cases. When we tried to detect HLA-DRB types from a single hair shaft of 3 cm in length, we were successful in detection from only one of five persons.

Alleles↗
PubMed1997

Changes in cerebral blood flow accompanied with reduction of blood pressure treatment in patients with hypertensive intracerebral hemorrhages.

Blood pressure usually is reduced in patients with hypertensive intracerebral hemorrhage for the prevention of the expansion of the hematoma and recurrent hemorrhage in acute stage. However, disturbed autoregulation of cerebral circulation is expected, and decreased cerebral blood flow (CBF) caused by excessive hypotension has been pointed out. There are different mechanisms of action in hypotensives, thereby the influence of hypotension on CBF in patients with the thalamic hemorrhage was investigated using nitroglycerin (TNG), diltiazem hydrochloride (DH) and trimethaphan camsilate (TC). Average CBF in a hemisphere on the hematoma side, the hemisphere without hematoma, and around the hematoma showed a slight decline after administration of TNG or DH. However, CBF declined more, after TC than DH. DH and TNG are preferable in descending order to control blood pressure of patients with intracerebral hemorrhage in the acute stages in view of a smaller decline in CBF.

Adult↗
PubMed1997

Problems on the diagnosis of sudden infant death syndrome.

Various autopsy cases of sudden unexpected death (SUD) in infancy were examined at the Tokyo Medical Examiner's Office between 1985 and 1994. More than half of the SUD were diagnosed as sudden infant death syndrome (SIDS), but a number of other causes, such as mechanical asphyxia, were also diagnosed. SIDS is diagnosed by autopsy, but there are no clear diagnostic criteria differentiating SIDS from other causes of SUD. SUD is diagnosed as SIDS when other causes are excluded, but it is difficult to distinguish between SIDS and mechanical asphyxia. There was not a large difference in autopsy findings, or in death scene or statistical data, between SIDS and non-SIDS cases. In their estimation of the diagnostic ratio of SIDS to other causes of death, medical examiners might be divided into three groups: 'SIDS tolerationist' examiners think that SUD should be positively diagnosed as SIDS, insofar as another cause of death is not proved clearly. A second group of examiners might be regarded as 'SIDS exclusionist': these consider microscopic findings or peculiar death scenes as important contributing factors leading to death. The third group represents a middle stance somewhere between these two. We thought that (forensic) pathologists as well as medical examiners in Japan might have differing stances on SIDS diagnosis. The statistical analysis of SIDS in certain research areas may be affected by the diagnostic 'preference' of pathologists belonging to a certain institute.

Asphyxia↗
PubMed1997

Spontaneous bilateral dissections of the intracranial vertebral arteries: a case report.

A 41-year-old woman died of subarachnoid hemorrhage. She had had severe headaches for 10 days, but no abnormalities were detected on the brain computer tomography (CT) taken about a half day prior to her death. At autopsy, bilateral dissecting aneurysms were found in the intracranial vertebral arteries. Headaches related to dissection are considered to be due to distension of the artery, and the dissection may have occurred 10 days before her death. In considering the brain CT and autopsy findings, subaracnoid hemorrhage may have occurred within several hours of death. Although multivessel dissections suggest the possibility of underlying angiopathy, the present case had no clear finding of angiopathy in any of the brain vessels. When one sees subarachnoid hemorrhage in the basal area of the brain and finds "black" or "bluish black" discoloration(s) in the circle of Willis, one should suspect a dissecting aneurysm(s).

Adult↗
PubMed1996

Cloning and expression localization of cDNA for rat homolog of TRP protein, a possible store-operated calcium (Ca2+) channel.

A 3.2 kbp cDNA clone encoding a possible candidate for the store-operated Ca2+ channel was isolated from a rat brain cDNA library. The deduced amino acid sequence was 51.8% identical to TRP encoded by a Drosophila trp (transient receptor potential) gene and contained ankyrin motifs, a coiled-coil structure and six transmembrane segments similar to the previously identified TRP family and named as TRP-R (rat TRP). By in situ hybridization histochemistry of rat body on embryonic day 15, no significant expression signal for TRP-R was detected. On embryonic day 20 and postnatal day 1, the expression signals were most evident in the septum, cerebral cortical plate and hippocampal neuronal layers. On postnatal day 7 and thereafter the expression in the cerebral cortex and the septum decreased progressively, and weak expression remained only in the CA1 and CA2 neuronal layers of the hippocampus in the brain on postnatal day 21 and 49. This limited spatiotemporal expression of this novel molecule. TRP-R, suggests that it is involved in some specific functions related to the neuronal differentiation.

Amino Acid Sequence↗
PubMed1996

(+)-cis-3,5-dimethyl-2-(3-pyridyl) thiazolidin-4-one hydrochloride (SM-12502) as a novel substrate for cytochrome P450 2A6 in human liver microsomes.

(+)-cis-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one hydrochloride (SM-12502) was oxidized by human liver microsomes to produce the S-oxide as a sole metabolite. Indirect evidence suggested that the S-oxidation was catalyzed by cytochrome P450 (CYP). Eadie-Hofstee plots showed biphasic pattern, suggesting that at least two enzymes were involved in the S-oxidation in human liver microsomes. Kinetic parameters of the S-oxidase with high-affinity showed Km and Vmax values of 20.9 +/- 4.4 microM and 0.111 +/- 0.051 nmol/min/mg microsomal protein, respectively. The S-oxidase activity was inhibited by coumarin and anti-CYP2A antibody. Among the contents of forms of CYP 20 samples of human liver microsomes, the content of CYP2A6 correlated with S-oxidase activity measured with 50 microM SM-12502 (r = .808, P < .0005). A close correlation (r = .908, P < .0001) was observed between activities of SM-12502 S-oxidase and coumarin 7-hydroxylase. Microsomes from genetically engineered human B-lymphoblastoid cells expressing CYP2A6 metabolized SM-12502 to the S-oxide efficiently. The results indicate that CYP2A6 isozyme is a major form of CYP responsible for the S-oxidation of SM-12502 in human liver microsomes. Thus, SM-12502 will be a useful tool in further research to analyze a human genetic polymorphism of CYP2A6.

Animals↗
PubMed1996

An autopsy case of abandoned infant body with severe destruction.

One case of infanticide and abandonment by the natural mother is presented. The body was extensively damaged, evidently by a fox. Fortunately, since the body showed less advanced putrefaction due to cold weather, it was possible to narrow down the cause of death and to detect the drug which had been forced down the victim's throat before the crime. However, our estimates of age and postmortem interval were erroneous. We comment as to why we were misled. Pathological problems associated with "aspiration of vomitus" are also discussed.

Age Determination by Teeth↗
PubMed1995

On an accident by liquid nitrogen--histological changes of skin in cold.

Two young researchers were found lying beside 3 Dewar flasks for liquid nitrogen in a cold experimental room of a university. They were sent to a hospital but died 1.5 h after cardiopulmonary resuscitation. One of the cadavers had dark red discoloration of the skin on the left arm at autopsy. By the histological investigation of the discolored region karyopyknosis and vacuolation of the keratinocytes were noticeably observed in the epidermis. In addition, hyperemia and edematous changes were seen. Hemoglobin (Hb) was not immunodetected in the skin tissue except intravascular erythrocytes. Therefore, these histological findings of the discolored skin can indicate that the skin damage was produced by cold due to liquid nitrogen before death. The cause of death was asphyxia due to oxygen deficiency. There were few autopsy findings which showed the participation of liquid nitrogen in the accident. But, the histological findings of the discolored region demonstrate that liquid nitrogen was involved in this accident.

Accidents, Occupational↗
PubMed1995

Dysautoregulation in patients with hypertensive intracerebral hemorrhage. A SPECT study.

In patients with hypertensive intracerebral hemorrhage, changes in regional cerebral blood flow (rCBF) following drug-induced blood pressure reduction were examined by SPECT. METHODS. The subjects were 68 patients with hypertensive intracerebral hemorrhage. The site of cerebral hemorrhage was the thalamus in 28 patients, and the putamen in 40 patients. RCBF was measured by SPECT using the 133Xe inhalation method. To reduce blood pressure, trimethaphan camsilate (an autonomic ganglion blocker) and diltiazem hydrochloride (a calcium antagonist) were used. RESULTS. 1. In the acute period, mean CBF declined as the mean arterial blood pressure declined by more than 20% in both the putaminal and the thalamic hemorrhage group (p < 0.01). 2. During the chronic period, a greater reduction in blood pressure was needed to induce mean CBF reduction. 3. Neither of the two drugs significantly reduced the mean arterial blood pressure, but the group receiving trimethaphan demonstrated a 7.9 approximately 7.5% decreased in CBF, group while the receiving diltiazem showed a 2.2 approximately 2.4% decrease (p < 0.05). CONCLUSIONS. In patients with hypertensive intracerebral hemorrhage, a 20% or more drug-induced decrease in blood pressure resulted in a decrease in mean CBF. During the acute period of intracerebral hemorrhage, blood pressure showed reduced by 20%. Clinically, diltiazem was more effective than trimethaphan.

Adult↗
PubMed1995

Effects of alpha- and beta-arbutin on activity of tyrosinases from mushroom and mouse melanoma.

The effects of alpha- and beta-arbutin on the activity of tyrosinases from mushroom and mouse melanoma were examined. alpha-Arbutin was synthesized from hydroquinone and starch using glucoside synthetase (GSase). beta-Arbutin inhibited both tyrosinase activities from mushroom and mouse melanoma. alpha-Arbutin inhibited only the tyrosinase from mouse melanoma, 10 times as strongly as beta-arbutin. The IC50 of alpha-arbutin was 0.48 mM and its inhibitory mechanism was speculated to be mixed type inhibition, while that of beta-arbutin was noncompetitive.

Animals↗
PubMed1994

Cloning and expression of a cytoskeleton-associated diacylglycerol kinase that is dominantly expressed in cerebellum.

A third species of diacylglycerol kinase (EC 2.7.1.107) cDNA was cloned from a rat brain cDNA library. The isolated cDNA encoded a 788-amino acid, 88-kDa polypeptide. This isozyme shared 58% identity with the previously isolated rat 80-kDa and 90-kDa diacylglycerol kinases. EF hand motifs, cysteine-rich zinc finger-like sequences, and putative ATP-binding site were all conserved among these isozymes. The 88-kDa diacylglycerol kinase was expressed specifically in brain and localized predominantly in cerebellar Purkinje cells. This isozyme was associated equally with particulate and supernatant fractions in cDNA-transfected COS-7 cells and dominantly with the particulate fraction in the brain. After Triton X-100 extraction, this isozyme remained in the detergent-insoluble cytoskeletal fraction of the brain and transfected COS-7 cells.

Adenosine Triphosphate↗
PubMed1994

Case report: repeated neonaticides in Hokkaido.

Five cases of repeated neonaticides were reported in Hokkaido, the northernmost island of Japan, during the 10 years from 1983 to 1992. Four or more neonates were involved in each case by each mother. All the suspected mothers were not mentally ill. Two of them were single and the rest were married. Each husband was not aware of the pregnancy of his wife, because he was away from home very often. The main motive of murder seemed to be economic and/or to save appearances. Sentences were 1 year penal servitude with a stay of 3 years for one case, but 30-42 months in prison for the other four cases. We rarely find reports of repeated infanticides committed by the same mother in European countries and the United States.

Adult↗