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Biomedical subjects

K Aoki

Publications and source records attributed to K Aoki.

At least 145 records · Page 8Linked to original sources
PubMed2000

Role of tyrosine kinase in fibroblast compaction and cerebral vasospasm.

Hemolysate, a proposed causative agent for cerebral vasospasm following subarachnoid hemorrhage, produces contraction of cerebral arteries by activation of tyrosine kinases. In addition, hemolysate accelerates fibroblast collagen compaction that could play a role in cerebral vasospasm. We studied the effect of hemolysate on tyrosine phosphorylation and fibroblast collagen compaction in cultured dog cerebral and human dermal fibroblasts using tyrosine kinase inhibitors and tyrosine antibodies (Western blot). 1) Hemolysate was found to enhance tyrosine phosphorylation of two proteins approximately 64 and 120 kDa. The effect of hemolysate was time- and concentration-dependent. 2) Two main components in hemolysate, oxyhemoglobin and adenosine triphosphate (ATP), produced similar results to that of hemolysate. 3) Tyrosine kinase inhibitor genistein and tyrphostin A51 (30 microM) markedly reduced the effect of hemolysate on tyrosine phosphorylation. 4) In another study, hemolysate increased fibroblast collagen compaction and the effect of hemolysate was reduced by genistein and tyrphostin A51. We conclude that hemolysate activates tyrosine kinase that may lead to acceleration of fibroblast compaction. This effect of hemolysate may contribute to cerebral vasospasm.

Animals↗
PubMed2000

Taste preferences and feeding behaviour in children with phenylketonuria on a semisynthetic diet.

UNLABELLED: Low-phenylalanine formula for phenylketonuria (PKU) made from free amino acids as a protein source (AAM formula) has a poor taste and smell. We developed a more palatable formula using low-phenylalanine peptide (LPP) as a protein source. Palatability tests performed by 41 healthy adults confirmed that the palatability of LPP formula was significantly better than that of AAM formula. A group of 48 patients with PKU who had been administered AAM formula since the newborn period were assessed for their preference between the AAM and LPP formulae and their feeding behaviour was compared to that in healthy children. Of patients, 90.9% and 66.6% of healthy infants less than 18 months of age took both formulae without apparent preference, suggesting that sensitivity to taste and smell is more immature in infancy than in later life. Of patients with PKU aged between 18 months and 11 years, 29.1% liked AAM formula rather than the LPP formula, while 66.7% took both formulae without apparent preference. Most healthy children in the same age group who had never previously tasted therapeutic formulae disliked it, although they tended to prefer the LPP formula. Of patients aged between 11 and 17 years, 84.6% preferred the LPP formula while 15.4% preferred the AAM formula. In the controls of this age group, 33% disliked therapeutic formulae, but they tended to prefer the LPP formula. CONCLUSION: In some young children with phenylketonuria the characteristic taste of amino acid mixture formula encountered in early life is considered to be imprinted and remains as a preference for a long time. Since school children with phenylketonuria usually obtain about 50% of their energy intake from natural food containing small amounts of protein, these patients are considered to have come to have similar preferences as healthy people which result from a waning of the imprinted taste of amino acid mixture formula.

Adolescent↗
PubMed2000

Complete nucleotide sequence and functional analysis of the genes for 2-aminophenol metabolism from Pseudomonas sp. AP-3.

A 13.9-kb region, which contained the 2-aminophenol 1,6-dioxygenase genes (amnBA) reported before, was cloned from the 2-aminophenol-assimilating bacterium Pseudomonas sp. AP-3. The complete nucleotide sequence of this region was determined and six genes were found downstream of amnBA. The eight genes together were designated amnBACFEDHG. Each gene was similar to the corresponding gene operating in the meta-cleavage pathway, except for amnB, amnA, and amnD. The four 2-aminophenol-metabolizing enzymes, 2-aminomuconic 6-semialdehyde dehydrogenase, 2-aminomuconate deaminase, 4-oxalocrotonate decarboxylase, and 2-oxopent-4-enoate hydratase, were purified and characterized. NH2-terminal amino acid sequences of each purified enzyme agreed with those deduced from amnC, amnF, amnE, and amnD, respectively. These genes were therefore assigned as the genes encoding these respective proteins. The tight clustering of the amn genes, which were all transcribed in the same direction, raised the possibility that these genes formed a single operon. The organization of the amn genes was entirely different from that of the atd, dmp, and xyl genes reported in the meta-cleavage pathway, although these latter genes clustered similarly.

Aldehyde Oxidoreductases↗
PubMed2000

Genomic structure and chromosomal localization of the gene encoding TRAX, a Translin-associated factor X.

The TRAX gene encodes a Translin-associated 33-kDa protein partner, TRAX. The TRAX protein has extensive amino acid homology with Translin, and contains bipartite nuclear targeting sequences, suggesting a possible role in the selective nuclear transport of Translin lacking any nuclear targeting motifs. In the present study, genomic clones of the human TRAX gene were isolated to determine the complete genomic organization. The genomic structure of the human TRAX gene was similar to that of the human Translin gene, consisting of six exons and five introns, encompassing approximately 27kb in genomic DNA. Northern blot analysis revealed a predominant transcript of approximately 2.7kb, and its distribution in various tissues was like that of Translin. Chromosomal mapping by fluorescence in situ hybridization (FISH) analysis allowed localization of the TRAX gene to human chromosome lq41.

Carrier Proteins↗
PubMed2000

Embryonic karyotype of abortuses in relation to the number of previous miscarriages.

OBJECTIVE: To examine the frequency of chromosomal abnormalities in products of conception from patients with recurrent miscarriages in relation to the number of previous miscarriages. DESIGN: Retrospective analysis. SETTING: Nagoya City University Medical Hospital. PATIENT(S): A total of 1,309 women with a history of 2-20 consecutive first-trimester abortions. INTERVENTION(S): Chromosomal analysis performed on products of conception with use of a standard G-banding technique. MAIN OUTCOME MEASURE(S): The frequencies of abnormal and normal embryonic karyotypes for each number of previous abortions were studied. The subsequent pregnancy outcome of patients whose previous miscarriages were karyotyped were studied along with the predictive value of karyotyping of previous miscarriages for subsequent miscarriages. RESULT(S): The miscarriage rate increased with the number of previous spontaneous abortions. The frequency of abnormal embryonic karyotypes significantly decreased and that of normal embryonic karyotypes significantly increased with the number of previous abortions. Among 71 patients whose embryonic karyotypes were normal, 44 aborted subsequently, and 23 of 60 patients whose embryonic karyotypes were abnormal aborted subsequently. Patients with a previous normal embryonic karyotype aborted more frequently than those with an abnormal karyotype. CONCLUSION(S): The frequency of normal embryonic karyotypes significantly increases with the number of previous abortions, and a normal karyotype in a previous pregnancy is a predictor of subsequent miscarriage.

Abortion, Habitual↗
PubMed2000

Distal anterior choroidal artery aneurysm associated with an arteriovenous malformation. Intraoperative localization and treatment.

BACKGROUND: Distal anterior choroidal artery aneurysms are rare. The outcome of patients with distal anterior choroidal artery aneurysms has been poor, and the treatment of such aneurysms is surgically challenging. CASE DESCRIPTION: The authors describe the case of an 8-year-old girl with a ruptured distal anterior choroidal artery aneurysm associated with an arteriovenous malformation (AVM). The patient experienced sudden onset of headache and vomiting. Computed tomography revealed an intraventricular haemorrhage, and cerebral angiography demonstrated an aneurysm arising from the distal portion of the right anterior choroidal artery. The patient also had an AVM in the ipsilateral temporal lobe fed by the branches of the middle cerebral artery. A right frontotemporal craniotomy was performed with the aid of intraoperative angiography to eliminate both the AVM and the aneurysm. Intraoperative angiography was helpful in confirming the complete removal of the AVM and in accurate localization of the small and deeply placed distal anterior choroidal artery aneurysm. Both the AVM and the aneurysm were successfully treated and the patient was discharged without any neurological deficits. CONCLUSION: This case is the youngest reported patient with a distal anterior choroidal artery aneurysm. This report is also the first to describe an association of such an aneurysm with an AVM. The etiology of the aneurysm formation in this case and surgical strategy for deeply placed vascular lesions are discussed.

Aneurysm, Ruptured↗
PubMed2000

Prevention of vasospasm in penetrating arteries with MAPK inhibitors in dog double-hemorrhage model.

BACKGROUND: Vasospasm in the penetrating arteries contributes to ischemic neurological deficit. It may be as important as angiographic vasospasm because it would explain the discrepancies between angiographic vasospasm and clinical symptoms in some patients. It may also underlie the different effects of vasodilators. The present study examined this hypothesis by looking at the effect of the inhibitors of mitogen-activated protein kinase (MAPK) on vasospasm of the penetrating arteries. METHODS: Twenty-two adult mongrel dogs of either sex were used for the dog double-hemorrhage model. The dogs were randomly divided into four groups: control-hemorrhage, vehicle-treated, PD98059-treated, and U0126-treated groups. The drug injections were started on Day 3 after the first subarachnoid hemorrhage (SAH). The clinical status of the dogs was studied, based on their activity, appetite, and focal neurological symptoms. On Day 7, all the dogs were sacrificed, and the penetrating arteries from the brain stem were prepared for transmission electron microscopy. RESULTS: (1) Severe vasospasm developed in the basilar arteries in the SAH-without-treatment group (control), in the DMSO-treated group (DMSO), and in the U0126 treatment group with mean reduction of the basilar artery diameter of 46.57%, 49.3%, and 39.6%, respectively. In the PD98059-treatment group only a mild vasospasm was observed and the mean reduction of the basilar artery diameter was 18.9%. (2) All the dogs in the control SAH and vehicle-treated groups developed severe angiographic and clinical vasospasm. The penetrating arteries were contracted, and the endothelial and smooth muscle cells were dystrophic. (3) The dogs in the U0126-treated group developed severe angiographic, but not clinical, vasospasm. The penetrating arteries were not contracted, and the endothelial and smooth muscle cells were not dystrophic. (4) The dogs in the PD98059 group developed mild angiographic vasospasm. No dog developed clinical symptoms that could be attributed to vasospasm. In morphological studies, the penetrating arteries were slightly contracted, but the cells were not dystrophic. CONCLUSIONS: Vasospasm of the penetrating arteries, but not angiographic vasospasm, is consistent with the clinical symptoms and signs of vasospasm. MAPK may be important in maintaining vasospasm of both major and penetrating cerebral arteries. The correlation of the improvement in the clinical score with the reduction of vasospasm in the penetrating arteries demonstrated an important role of penetrating arteries in the morbidity and mortality caused by SAH.

Animals↗
PubMed2000

Morphological changes of cerebral penetrating arteries in a canine double hemorrhage model.

BACKGROUND: Morphological presentations of cerebral vasospasm, such as dystrophy and desquamation of endothelial cells, corrugation of the internal elastic layer, and necrotic changes in smooth muscle cells, are well defined in large cerebral arteries. This study was undertaken to examine pathological changes in cerebral penetrating arteries in a canine double hemorrhage model. METHODS: Eighteen mongrel dogs were subjected to an autologous arterial blood (0.4 mL/kg) injection into the cisterna magna on day 0 and day 2 after withdrawal of an equivalent amount of cerebrospinal fluid. Angiogram was performed on day 0 before the blood injection and on the day the dogs were sacrificed. The dogs were divided into four groups: control (day 0) (n = 4), hemorrhage and sacrificed on day 3 (n = 4), day 5 (n = 5), and day 7 (n = 5). The penetrating arteries were removed and found to be spastic on days 3, 5, and 7, but not in the control group. RESULTS: Endothelial dystrophy and partial desquamation were recorded in all dogs sacrificed on days 5 and 7. Condensation of chromatin, blebbing of the membrane, and condensation of cytoplasm were identified in many endothelial cells, features that are consistent with apoptosis. The morphological changes in the penetrating arteries were more pronounced on days 5 and 7. CONCLUSIONS: Vasospasm occurred in cerebral penetrating arteries in a canine double hemorrhage model. The morphological change in penetrating arteries, especially apoptosis in endothelial cells, is consistent with an early phase of vasospasm. Vasospasm in a penetrating artery may contribute to the cerebral ischemia that occurs during vasospasm.

Animals↗
PubMed2000

Unusual occipital condyle fracture with multiple nerve palsies and Wallenberg syndrome.

A 52-year-old male presented with an extremely rare fracture of the occipital condyle involving the jugular foramen with marked medial rostrad displacement of the fragments. He had ipsilateral VII through XII nerves palsies and Wallenberg syndrome. Conservative treatment did not improve the cranial nerve palsies. A high-resolution CT-scan is essential to visualize these fractures.

Accidents, Occupational↗
PubMed2000

Tyk2 plays a restricted role in IFN alpha signaling, although it is required for IL-12-mediated T cell function.

Janus kinases (Jaks) play an important role in signal transduction via cytokine receptors. Tyk2 is a Janus kinase, and we developed tyk2-deficient mice to study the requirement for tyk2 in vivo. Tyk2-deficient mice show no overt developmental abnormalities; however, they display a lack of responsiveness to a small amount of IFNalpha, although a high concentration of IFNalpha can fully transduce its signal even in the absence of tyk2. Furthermore, IL-12-induced T cell function is defective in these mice. In contrast, these mice respond normally to IL-6 and IL-10, both of which activate tyk2 in vitro. These observations demonstrate that tyk2 plays only a restricted role in mediating IFNalpha-dependent signaling while being required in mediating IL-12-dependent biological responses.

Animals↗
PubMed2000

Elevation of transforming growth factor-beta1 is associated with recurrent miscarriage.

To investigate the significance of transforming growth factor-beta1 (TGF-beta1) in reproduction we have compared plasma levels in normal pregnant women and patients suffering miscarriages. We examined 188 normal pregnant women and 12 pregnant women with miscarriages. Eight women with severe recurrent miscarriages (mean +/- SD of previous number of miscarriages; 10.4 +/- 2.4 times) were also examined before conception; 34 nonpregnant women served as controls. Plasma TGF-beta1 level increased with the gestational week and returned within the normal range 1 month after delivery. The levels among pregnant women with miscarriages (mean +/- SD; 2.44 +/- 0.83 ng/ml) were significantly higher than those of pregnant controls (1.74 +/- 0.95 ng/ml) of matched gestational weeks; levels among nonpregnant women with severe recurrent miscarriages were extremely elevated (4.1 +/- 3.04 ng/ml) compared to the control value (1.34 +/- 0.59 ng/ml). These data suggest that TGF-beta1 may be necessary to maintain pregnancy but also may be a risk factor for recurrent miscarriages.

Abortion, Habitual↗
PubMed2000

Neurological abnormalities in cognitively impaired but not demented elderly.

OBJECTIVE: We determined the prevalence and clinical characteristics of elderly people with cognitively impaired but not demented (CIND) in the community. MATERIAL AND METHODS: We examined 945 elderly residents (aged 65 years or more) in a cross-sectional study of a standardized clinical examination in 27 randomly selected communities in the town of Mifune, a standard farming town in Japan. RESULTS: The prevalence of CIND and dementia were 10.8% and 4.8%, respectively, with both rates increasing with age. The frequency of most neurological signs in CIND elderly was greater than that found in subjects with no cognitive impairment (NCI) and less than that in subjects with dementia. The mean ADL disability score in CIND subjects also lay between the mean values for those with NCI and those with dementia. There were no differences in lifestyles between the CIND group and the other groups. CONCLUSION: The results suggest that a majority of CIND elderly suffer from brain dysfunction due to chronic neurological disorders or aging itself.

Activities of Daily Living↗
PubMed2000

Overexpression of DeltaFosB transcription factor(s) increases bone formation and inhibits adipogenesis.

Members of the AP-1 family of transcription factors participate in the regulation of bone cell proliferation and differentiation. We report here a potent AP-1-related regulator of osteoblast function: DeltaFosB, a naturally occurring truncated form of FosB that arises from alternative splicing of the fosB transcript and is expressed in osteoblasts. Overexpression of DeltaFosB in transgenic mice leads to increased bone formation throughout the skeleton and a continuous post-developmental increase in bone mass, leading to osteosclerosis. In contrast, DeltaFosB inhibits adipogenesis both in vivo and in vitro, and downregulates the expression of early markers of adipocyte differentiation. Because osteoblasts and adipocytes are thought to share a common precursor, it is concluded that DeltaFosB transcriptionally regulates osteoblastogenesis, possibly at the expense of adipogenesis.

Adipocytes↗
PubMed2000

Paraplegia caused by painless acute aortic dissection.

OBJECTIVES: Painless acute aortic dissection in which paraplegia is the only presenting sign is rare, with limited reported cases. CASE REPORT: The authors report a patient with painless acute aortic dissection who presented with sudden onset paraplegia. Ischemic diseases of the spinal cord were suspected as the cause. MRI revealed extensive acute aortic dissection with an intramural hematoma. The patient was treated conservatively by strictly controlling his blood pressure. The treatment was successful, although the motor function of the lower extremities could not be rescued. Although 3% to 5% of patients with acute aortic dissection present with paraplegia as a result of spinal cord infarction, most of these patients experience severe pain prior to presentation. CONCLUSION: Painless acute aortic dissection in which paraplegia is the only presenting sign is very rare. However, aortic diseases, including acute aortic dissection, should always be considered as a differential diagnosis of patients with sudden onset, painless paraplegia.

Acute Disease↗