Biomedical subjects

M Aoki

Publications and source records attributed to M Aoki.

At least 325 records · Page 18Linked to original sources

PubMed1998

Conditioned medium from HepG2 cells transfected with human apolipoprotein(a) gene stimulates growth of human vascular smooth muscle cells: effects of overexpression of human apolipoprotein(a) gene.

Lipoprotein(a) [Lp(a)] is well known to stimulate growth of vascular smooth muscle cells (VSMCs), resulting in atherosclerosis. Its mechanism is postulated to be decreased in active transforming growth factor (TGF)-beta. However, the exact mechanisms and cellular processing from apolipoprotein(a) [apo(a)] to Lp(a) have not yet been clarified because no cultured cells producing apo(a) are available. Therefore, it is necessary to establish apo(a)-producing cells to study the role of apo(a). We evaluated the effects of overexpression of human apo(a) gene on human aortic VSMC growth. First, we tested whether transfection of apo(a) gene into human hepatoma cells, HepG2 cells, producing human apoB resulted in the formation of Lp(a). Transfection of apo(a) gene into HepG2 cells resulted in detectable levels of Lp(a) in the medium, as assessed by ELISA and Western blot, whereas no Lp(a) was detected in the medium of HepG2 cells transfected with control vector and untransfected HepG2 cells. Expression of apo(a) mRNA was also confirmed by reverse transcription-polymerase chain reaction. In contrast, Western blotting showed a single band detected by specific anti-apo(a) antibody, but not anti-apoB antibody, in the medium of apo(a)-transfected VSMCs. These results demonstrate that Lp(a) can be formed from apo(a) on HepG2 cells, whereas transfection of apo(a) gene into VSMCs resulted in the production of apo(a) alone but not Lp(a). Next, we examined the biological effects of overexpression of apo(a) gene on growth of VSMCs and endothelial cells. Incubation of cultured medium of HepG2 cells transfected with apo(a) gene with human VSMCs or endothelial cells resulted in a significant increase in cell number compared with the conditioned medium of HepG2 cells transfected with control vector. In contrast, transfection of apo(a) gene directly into VSMCs caused no significant effect on VSMC growth. Therefore, we measured TGF-beta concentration in the conditioned medium of VSMCs. However, using ELISA, only latent but not active TGF-beta was detected in the medium of VSMCs. Moreover, addition of neutralizing anti-TGF-beta antibody did not alter VSMC growth. These results suggest that Lp(a) could stimulate growth of VSMCs via the independent mechanisms from the inhibition of TGF-beta activation. Overall, these data demonstrate that overexpression of apo(a) gene in cells producing apoB results in formation of Lp(a), resulting in a mitogenic action on human endothelial cells and VSMCs. These results provide new information to understand the mechanisms of the mitogenic action of Lp(a) and suggest the role of Lp(a) in the pathogenesis of atherosclerosis.

Apolipoproteins↗

PubMed1998

Negative regulation of local hepatocyte growth factor expression by angiotensin II and transforming growth factor-beta in blood vessels: potential role of HGF in cardiovascular disease.

Because hepatocyte growth factor (HGF) is a member of the endothelium-specific growth factors, we hypothesized that HGF may play a role in cardiovascular disease. Therefore we first examined the role of local HGF production in endothelial cell (EC) growth. Addition of anti-HGF antibody to EC resulted in a significant decrease in EC number. Moreover, coculture of vascular smooth muscle cells (VSMC) with EC resulted in an increase in EC number that was completely inhibited by anti-HGF antibody, suggesting that HGF secreted from EC and VSMC regulates EC growth in an autocrine-paracrine manner. Interestingly, transforming growth factor (TGF)-ss significantly decreased HGF secretion from EC, whereas interleukin 6 stimulated immunoreactive HGF secretion. In human VSMC, TGF-ss and angiotensin II suppressed local HGF production in a dose-dependent manner. Interestingly, anti-TGF-beta antibody resulted in significant but not complete inhibition of the decrease in local HGF production. To further study the regulation of local HGF production, we used a coculture system. Coculture of VSMC with EC resulted in a significant decrease in local HGF secretion. The decrease in local HGF production by coculture was significantly attenuated by anti-TGF-beta antibody, suggesting that inhibition of local HGF production in the coculture system was due to TGF-beta activation. Moreover, a further decrease in local HGF production in the coculture system by angiotensin II was also observed. Finally, we studied the role of angiotensin II in the regulation of the local HGF system in vivo by using a balloon injury rat model. Of importance, local HGF production was significantly decreased in balloon-injured arteries compared with intact vessels, accompanied by a reduction of HGF mRNA. An angiotensin-converting enzyme inhibitor (cilazapril) or an angiotensin II type 1 receptor antagonist (E-4177) significantly stimulated local vascular HGF production associated with the inhibition of neointimal formation after balloon injury compared with vehicle. In contrast, hydralazine did not alter local HGF production or neointimal formation despite decreasing blood pressure to a similar level as that in rats treated with cilazapril or E-4177. Overall, local HGF secretion from vascular cells was negatively regulated by TGF-beta and angiotensin II. The present study also demonstrated that blockade of angiotensin II significantly inhibited neointimal formation, accompanied by a significant increase in local vascular HGF production in vivo in the balloon injury model. Given the strong mitogenic activity of HGF on endothelial cells, increased local HGF production by blockade of angiotensin II may enhance reendothelialization after balloon injury. Downregulation of the local vascular HGF system by TGF-beta and vascular angiotensin may play an important role in the pathogenesis of cardiovascular diseases.

Angiotensin II↗

PubMed1998

In vitro cytotoxicity of recombinant human-TNF-alpha and actinomycin D on canine normal and tumor cells.

The in vitro cytotoxicity of recombinant human tumor necrosis factor-alpha (rh-TNF-alpha) and actinomycin D (ACT-D) on canine normal and tumor cells was investigated. rh-TNF-alpha showed dose-dependent cytotoxic and cell-growth inhibitory effects on cultured canine kidney carcinoma cells (CKCa-1). rh-TNF-alpha alone produced little cytotoxic effect on canine normal cells. However, combined with ACT-D, it showed moderate cytotoxicity on normal canine cells from the kidney medulla, spleen, heart muscle and lung. When the effects on the spontaneous tumor cells were examined, the combination of rh-TNF-alpha and ACT-D produced substantial cytotoxic effect on 60% of the tumor cells. All mammary mixed tumors and perianal gland tumors tested were susceptible to this combination. The data indicated the combination of rh-TNF-alpha and ACT-D have in vitro cytotoxicity on certain canine tumor cells.

Animals↗

PubMed1998

Cytotoxicity induced by recombinant human tumor necrosis factor-alpha dependent on the types of its receptors on canine cells.

Based on the recent findings that show how recombinant human tumor necrosis factor (rh-TNF)-alpha has potent antitumor activity on human cancer patients when it locally administrated, we have tested the cytotoxicity of rh-TNF-alpha on 3 canine cultured cells: (1) canine kidney carcinoma (CKCa-1), (2) mastocytoma and (3) Mardin Darby canine kidney cells (MDCK). The cell surface expression of TNF-alpha receptors on these canine cells was also determined with anti-human TNF RI and RII polyclonal antibodies. Our data shows that on CKCa-1 which has TNF RI receptors rh-TNF-alpha induced cytotoxicity. By contrast, it exhibited no toxicity on canine mastocytoma which has mainly RII receptors. The data also suggest actinomycin D (ACT-D), an anticancer antibiotic, enhanced the cytotoxicity of rh-TNF-alpha. Combined with ACT-D, rh-TNF-alpha showed the cytotoxicity on MDCK which possessed both TNF RI and RII receptors. The results indicate that the cytotoxicity of rh-TNF-alpha depends on the presence of TNF RI receptors on canine tumor cells.

Animals↗

PubMed1998

[A case of systemic sclerosis complicated with pneumoperitoneum and pneumatosis cystoides intestinalis].

Here we report a case of systemic sclerosis (SSc) complicated with pneumoperitoneum and pneumatosis cystoides intestinalis (PCI). A 58-year-old woman who had been treated with oxygen therapy for chronic respiratory failure caused by interstitial pneumonia was admitted to Tokyo Metropolitan Ohtsuka Hospital because of abdominal fullness. On admission, laboratory data showed accelerated erythrocyte sedimentation rate, mild anemia, hypoalbuminemia, and elevated level of lactose dehydrogenase (LDH). Anti-nuclear antibodies, anti-RNP antibodies, anti-Topoisomerase I antibodies, anti-Ku antibodies, and rheumatoid factor were positive. Chest and abdominal roentgenograms showed free air under the diaphragm, dilatation of small intestine and colon, and multiple intestinal cysts. The diagnosis of pneumoperitoneum and PCI was made with laboratory findings and radiographic findings. Her symptoms did not respond to medications altering colonic motility and oxygen therapy. Finally, abdominal symptoms and radiographic findings caused by pneumoperitoneum and PCI disappeared three weeks after treatment with 1,500 mg/day of kanamycin sulfate. PCI is rarely associated with SSc. Possible pathogenic relationship between these diseases was discussed.

Female↗

PubMed1998

Contribution of a vascular modulator, hepatocyte growth factor (HGF), to the pathogenesis of cardiovascular disease.

HGF is a mesenchyme-derived pleiotropic factor which regulates cell growth, cell motility, and morphogenesis of various types of cells, and is thus considered a humoral mediator of epithelial-mesenchymal interactions responsible for morphogenic tissue interactions during embryonic development and organogenesis. Although HGF is originally identified as a most potent mitogen for hepatocytes, HGF is also belonged to a member of endothelium-specific growth factors. Since endothelial cells are known to secrete various anti-proliferative and vasodilating factors, an agent that promotes seeding or regeneration of endothelium may have potential therapeutic value against vascular smooth muscle cell proliferation. The mitogenic action of HGF on human endothelial cells was most potent among growth factors. Moreover, the presence of local HGF system (HGF and its specific receptor, c-met) was observed in vascular cells and cardiac myocytes in vitro as well as in vivo. Production of local HGF production in vascular cells was regulated by various cytokines including transforming growth factor (TGF)-beta and Ang II. Furthermore, HGF may be therapeutic growth factors for the treatment of restenosis after angioplasty and arteriosclerosis oblerance, etc., as gene therapy. On the other hand, serum HGF concentration was significantly correlated with blood pressure. These results suggest that HGF secretion might be elevated in response to high blood pressure as a counter-system against endothelial dysfunction, and may be considered as an index of severity of hypertension. In this review, we discussed the potential role of HGF in cardiovascular disease.

Cardiovascular Diseases↗

PubMed1998

[The first-three year report of the Tuberculosis Control Project, Lumbini, Rupandehi].

The Tuberculosis Control Project, Lumbini, Rupandehi (TCPLR) is a bilateral cooperative venture between two NGO's, the Nepal Anti-Tuberculosis Association (NATA) and the Japan Anti-Tuberculosis Association (JATA), which consists of planning and implementing pilot tuberculosis control activities in Lumbini, Rupandehi district in Nepal, aiming at achieving high cure rate of newly detected smear-positive pulmonary tuberculosis patients before introducing DOTS strategies. Between December 1993 and July 1996, 349 tuberculosis (TB) cases were enrolled in the TCPLR. The categories of cases were as follows: 138 cases (40%) of new smear-positive pulmonary TB [new Sm(+) PTB], and 54 cases (15%) of smear positive pulmonary TB other than new Sm(+) PTB [other Sm(+) PTB] including such cases as continued treatment and relapse, 106 cases (30%) of new smear-negative TB [new Sm(-) TB], and 51 cases (15%) of other smear-negative TB other than New Sm(-) PTB [other Sm(-) TB]. The number and proportion of new Sm(+) PTB cases enrolled in the project have been increasing [6 cases (23%) for the first year, 102 cases (54%) for the third year] although the proportion is still low (40% overall). The regimens of chemotherapy in the initial intensive and the continuation phases of treatment according to the categories of TB were as follows: New Sm(+) PTB; 2HRZE(S)/6HE, other Sm(+) PTB; 2HRZES/1HRZE/5HRE, and Sm(-) TB; 2HRZ/6HE. The proportion of cases treated by the appropriate regimen of chemotherapy has increased. The cohort analysis of the treatment outcome of the cases enrolled in the project showed the following. The proportion of cured cases plus smear-unconfirmed cases completing treatment among new Sm(+) PTB was 74% overall, however, the proportion of defaulters increased in the third year. The proportion of cured cases plus smear-unconfirmed cases completing treatment among other Sm(+) PTB cases was 66% overall, which is slightly lower than that of new Sm(+) PTB cases, however, the difference was not so marked. The proportion of treatment completed cases among smear-negative pulmonary TB cases was 77% overall, however, proportion of defaulters increased in the third year. The treatment outcome in this report was obtained before the adoption of DOTS strategies: However, it showed that cure and treatment completion rates were comparable to those obtained in the SEARO countries which adopt DOTS strategies. The treatment outcome could be improved after the introduction of DOTS strategies in 1997.

Adolescent↗

PubMed1998

[Changes in acetylcholine level and its related enzyme activities in rat brain following focal ischemia].

At 1 to 4 weeks following middle cerebral artery occlusion in Wistar rats, levels of acetylcholine, which is neuro-transmitter, were measured. In the hippocampus, which plays an important role in memory, levels of acetylcholine in the ischemic group could not be detected the significant difference compared with those in the sham-operated group. But in the anterior cortex and the caudate-putamen, levels of acetylcholine in the ischemic group were recognized the significant difference compared with those in the sham operated group. Moreover activities of choline acetyltransferase, which is the synthetic enzyme of acetylcholine, and activities of acetylcholinesterase, which is the degradative enzyme of acetylcholine, were measured in the anterior cortex which was recognized decrease of the acetylcholine level and the hippocampus which could not be detected the difference of the acetylcholine level. Activities of both enzymes in the hippocampus could not be recognized the significant difference between the ischemic group and the normal group. But in the anterior cortex activities of both enzymes in the ischemic group were significantly decreased compared with those in the normal group. These results suggest that these decreases in the ischemic group were due to damage of injection of cholinergic neuron from Meynert nucleus (basal nucleus of Meynert) to anterior cortex.

Acetylcholine↗

PubMed1998

[A case of solitary retroperitoneal neurofibroma].

A 70-year-old woman was admitted to our hospital complaining of epigastralgia. Computed tomography, ultrasonography and magnetic resonance imaging revealed a round tumor measuring 6 cm in diameter, which was located in the medial side of the right kidney. It was successfully removed without injury to the surrounding large vessels and organs. Histological diagnosis was benign neurofibroma. This is the 27th case of solitary retroperitoneal neurofibroma reported in Japan.

Aged↗

PubMed1998

[Japan Coma Scale as a grading scale of subarachnoid hemorrhage: a way to determine the scale].

BACKGROUND: The grading scale for subarachnoid hemorrhage (SAH) with inter-grade outcome differences is essential for evaluating the effectiveness of newly developed therapeutic modalities. Although Hunt's grade and WFNS scale have been widely used, these grading scales do not meet this requirement. We previously proposed a revised WFNS scale based solely on the Glasgow Coma Scale (GCS) that has intergrade outcome differences of high-level significance. The Japan Coma Scale (JCS) has been long and widely used in Japan. The purpose of this study is to show whether it is possible to determine a reasonable SAH grading scale based on the JCS and to show a way to determine an SAH grading scale. PATIENTS AND METHODS: We retrospectively analyzed 1398 consecutive cases of aneurysmal SAH operated on within Day 7 of the latest onset. The preoperative JCS and GCS were evaluated just before the surgery and the Glasgow Outcome Scale (GOS), analyzed with numerical transformation (1 = dead to 5 = good recovery), was estimated at 6 months after the onset. All 510 possible combinations of scores of JCS were statistically tested under the following 2 assumptions; (1) JCS = 0 and JCS = 100 fall into a single independent grade. (2) No other single JCS score should fall into a single grade. RESULTS: The outcome differences between JCS 0 and 1, and 100 and 200 are significant. The outcome difference between JCS 30 and 100 is relatively higher than any other set of 2 scores of JCS. Only 5 combinations are practical among the candidates to be analyzed. Out of 510 combinations, the following combination shows the highest inter-grade outcome differences; I (JCS = 0, n = 375, mean GOS = 4.78) II (JCS = 1, 2; n = 310; mean GOS = 4.47) III (JCS = 3-30; n = 476; mean GOS = 3.96) IV (JCS = 100; n = 96; mean GOS = 3.10) V (JCS = 200, 300; n = 141; mean GOS = 2.33). In JCS, the mean outcome of JCS = 3 is worse than those of JCS = 10, 20, and 30. The outcome difference between JCS 0 and 1 is only significant in patients over 60 years old. CONCLUSION: Taking all the 510 possible combinations of JCS into consideration, we obtained a reasonable combination containing 5 grades. Although this grading scale showed good inter-grade outcome differences, JCS is not preferable to GCS as a consciousness evaluation system in the acute phase of SAH. We emphasize the importance of this way to determine a grading scale with a combinatorial approach, which can be applicable for re-evaluating the grading scales in the future.

Age Factors↗

PubMed1998

Cellulitis of the eyelids associated with sinusitis and brain abscess.

Erythema in the orbital area can indicate systemic and life-threatening diseases. We experienced an unusual and serious case of orbital cellulitis that was difficult to distinguish from a case with good prognosis. A 21-year-old man developed an erythema around his eyes. He exhibited no symptoms that would suggest lesions in deep tissues, but his condition turned out to be cellulitis retrogradely metastasized from an odontogenic sinusitis traced to a dental treatment problem. Computed tomography revealed complication of a large abscess in the frontal lobe. Cellulitis of the orbital area requires particular clinical discretion.

Adult↗

PubMed1998

[A case of primary Sjögren's syndrome accompanied by transverse myelitis].

Here we report a case of Sjögren's syndrome (SS) accompanied by transverse myelitis. A 46-year-old woman with 7-year history of primary SS was admitted to Tokyo Metropolitan Ohtsuka Hospital in September 1997 because of muscular weakness in lower extremities. She had had a low grade fever, numbness, and pain in bilateral lower extremities since July 1992. Neurological examination revealed transverse myelopathy at the level of Th 4, and peripheral neuropathy in lower extremities. Cerebrospinal fluid analysis showed slight elevation of protein and the cell count. A diagnosis of transverse myelitis and peripheral neuropathy presenting as neurologic manifestations of SS was made. Treatment was initiated with 30 mg of prednisolone, followed by improvement of fever and neurological findings. Although central nervous system complications of SS have been presented in Western countries, little information is available about Japanese patients. To our knowledge, this is the second case report which describes the occurrence of transverse myelitis in Japanese patients with SS.

Anti-Inflammatory Agents↗

PubMed1998

[Analysis of Mycobacterium tuberculosis-derived substance which induces interleukin-12 production from macrophages].

Protection of hosts against tuberculosis depends on expression of cellular immunity. To express cellular immunity, interleukin 12 (IL-12) has been shown to play an important role. Although Mycobacterium tuberculosis is known to induce IL-12 from macrophages (M phi s), the mechanism for the induction is still unclear. To understand the mechanisms of IL-12 induction from M phi s by M. tuberculosis, the IL -12-inducing ability of substances derived from M. tuberculosis was investigated in vitro. Production of IL-12 in culture medium of M phi s was measured by ELISA system using specific antibodies. Live M. tuberculosis H37Rv induced slightly higher IL-12 production than live M. tuberculosis H37Ra upon stimulation of human or mouse alveolar macrophages (hAM phi s or mAM phi s). Heat-killed M. tuberculosis failed to induce IL-12 production of alveolar macrophages (AM phi). The responses of hAM phi s and mAM phi s to M. tuberculosis were remarkably different. mAM phi s produced five times larger amount of IL-12, compared with that from hAM phi s. Human peripheral blood mononuclear cells (PBMC) obtained by the density gradient centrifugation were also used for induction of IL-12 production. Although production levels of IL-12 from PBMC stimulated with M. tuberculosis were below the detectable level, addition of interferon-gamma (IFN-gamma) or neutralizing antibody against IL-10 augmented the production of IL-12 from PBMC, suggesting that IFN-gamma and IL-10 regulate the production of IL-12 from M phi positively and negatively, respectively. To characterize the physicochemical properties of IL-12-inducing molecules, M. tuberculosis H37Rv was disrupted by pressing with 1,000 bar and centrifuged and separated into cytosol and cell wall fraction. The culture filtrate was also examined on IL-12-inducing activity. Among the three subjects examined, cytosol was found to induce the highest production of IL-12 from mAM phi s 1 day after the stimulation. Addition of IFN-gamma to the cytosol fraction markedly increased the production of IL-12 from mAM phi s. The molecular weight of IL-12-inducing substance was shown to be more than 30kDa by fractionating with molecular filters. Treatment of 30kDa-fraction with IL-12-inducing activity by proteinase K completely abolished the activity. Furthermore, approximately 90% of IL-12-inducing activity of 30kDa-fraction was lost by proteinase K treatment even in the presence of IFN-gamma. These results indicate that the major component of IL-12-inducing activity is a protein. The identification of this IL-12-inducing active substance may provide a new therapeutic tool for tuberculosis.

Animals↗

PubMed1997

Identification of a human LMX1 (LMX1.1)-related gene, LMX1.2: tissue-specific expression and linkage mapping on chromosome 9.

LMX1 is a LIM-homeodomain (LIM-HD)-containing protein expressed selectively in insulin-producing beta-cell lines, and it it has been shown to activate insulin gene transcription. The human LMX1 gene was mapped by fluorescence in situ hybridization to chromosome region 1q22-q23, yet Church et al. (1994, Nat. Genet. 6: 98-105) identified two exon-trapping products from human chromosome 9 that were highly homologous to hamster LMX1. In the current study, we demonstrate tissue-specific expression of an LMX1 (now known as LMX1.1)-related gene, named LMX1.2. The chicken C-LMX1 gene, recently cloned using the hamster LMX1.1 sequence and shown to specify dorsal cell fate during vertebrate limb development (9), is actually more related to human LMX1.2 than LMX1.1. We have identified a unique simple sequence repeat polymorphic marker (hLMX1.2CA1) in a P1 genomic clone containing the human LMX1.2 gene and genetically mapped the marker on chromosome 9 between markers D9S1825 and D9S290 with odds of at least 1000:1. In addition, we localized the human LMX1.1 gene to three CEPH "B" yeast artificial chromosome clones (907A11, 935B12, and 947B2), along with two nearby polymorphic markers (D1S426 and D1S194)). Identification of this new LIM-HD-related gene may provide the opportunity to elucidate further the function of LIM class homeobox genes. Nearby polymorphic markers will be useful in testing the hypothesis that mutations in these LIM-HD genes result in genetic diseases such as non-insulin-dependent diabetes mellitus.

Amino Acid Sequence↗

PubMed1997

Differential effects of a benzodiazepine on synaptic transmissions in rat hippocampal neurons in vitro.

The effects of midazolam, one of the most popular benzodiazepines, on synaptic transmissions were compared with intracellular recordings between CA1 pyramidal cells (CA1-PCs) and dentate gyrus granule cells (DG-GCs) in rat hippocampal slices. First, we studied the effects of midazolam on orthodromically evoked spikes, membrane properties and synaptic potentials. Secondly, the effects of a GABA(A) receptor agonist, muscimol, were examined on membrane properties to determine whether or not the densities of GABA(A) receptors are different between CA1-PCs and DG-GCs. Midazolam (75 microM) markedly depressed orthodromically evoked spikes in CA1-PCs, compared with those in DG-GCs. A GABA(A) receptor antagonist, bicuculline (10 microM), almost completely antagonized the depressant effects of midazolam on spike generation in CA1-PCs, whereas it had little effect on midazolam in dentate gyrus granule cells. Midazolam produced either depolarizing or hyperpolarizing effects on resting membrane potentials (Vm) with an input resistance decrease in CA1-PCs, whereas it produced depolarized Vm in DG-GCs. Midazolam significantly increased the amplitude of monosynaptic inhibitory postsynaptic potentials in CA1-PCs, whereas midazolam slightly decreased these in DG-GCs. Midazolam significantly decreased the amplitude of excitatory postsynaptic potentials both in CA1-PCs and DG-GCs. Muscimol (100 microM) produced either depolarizing or hyperpolarizing effects on Vm with an input resistance decrease in CA1-PCs, and it depolarized Vm with an input resistance decrease in DG-GCs. These results demonstrate that midazolam has differential effects on excitatory and inhibitory synaptic transmissions in hippocampal neurons. The mechanism of this difference could be partly due to the different types of GABA(A) receptors between CA1-PCs and DG-GCs.

2-Amino-5-phosphonovalerate↗

PubMed1997

Analysis of the McLeod syndrome gene in three patients with neuroacanthocytosis.

McLeod syndrome is a rare X-linked disorder involving neurological defects and acanthocytosis. We examined the XK gene in three patients with neuroacanthocytosis, one of whom had cardiomyopathy, and his symptoms were very similar to those of McLeod syndrome. We found two new transversions (C to G at codon 204 and G to C at codon 205) in exon 3 in all those cases. However, the transversion at codon 205 was found in all 70 Japanese normal subjects and four non-Japanese (two Caucasian males, one Chinese female and one Micronesian female) and that at codon 204 was also detected in all 14 normal Japanese males and the four non-Japanese. These findings suggest that they are not the cause of McLeod syndrome, but normal polymorphisms which have not been reported. Moreover, there is a possibility that patients with neuroacanthocytosis similar to McLeod syndrome exist without the XK gene abnormalities.

Acanthocytes↗

PubMed1997

Transformation of chicken cells by the gene encoding the catalytic subunit of PI 3-kinase.

The avian sarcoma virus 16 (ASV 16) is a retrovirus that induces hemangiosarcomas in chickens. Analysis of the ASV 16 genome revealed that it encodes an oncogene that is derived from the cellular gene for the catalytic subunit of phosphoinositide 3-kinase (PI 3-kinase). The gene is referred to as v-p3k, and like its cellular counterpart c-p3k, it is a potent transforming gene in cultured chicken embryo fibroblasts (CEFs). The products of the viral and cellular p3k genes have PI 3-kinase activity. CEFs transformed with either gene showed elevated levels of phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate and activation of Akt kinase.

Amino Acid Sequence↗

PubMed1997

Regional differences in the depressant effects of midazolam on excitatory synaptic transmission in the rat hippocampus.

The effects of midazolam, one of the most popular benzodiazepines, was examined on excitatory synaptic transmission in the hippocampus. Both CA1 pyramidal cells (CA1-PCs) and dentate gyrus granule cells (DG-GCs) were studied in rat hippocampal slices with extracellular recordings. Midazolam depressed the amplitudes of orthodromic population spikes (O-PS) and excitatory postsynaptic potential (EPSP) slopes of CA1-PCs in a dose-dependent manner, but depressed those of DG-GCs to a lesser extent. On the other hand, midazolam had little effect on the amplitudes of antidromic population spikes of both CA1-PCs and DG-GCs. A GABAA receptor antagonist bicuculline strongly antagonized the depressant effects of 75 microM midazolam on the amplitudes of O-PS by 73% in CA1-PCs, whereas it did not antagonize the effects of midazolam in DG-GCs. These results suggest that the differential effects of midazolam could be due to the different types and/or density of GABAA receptors between CA1-PCs and DG-GCs.

Animals↗