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Biomedical subjects

Y Nakata

Publications and source records attributed to Y Nakata.

At least 55 records · Page 3Linked to original sources
PubMed2001

Strategy for modulation of central dopamine transmission based on the partial agonist concept in schizophrenia therapy.

The dopamine system is known to be closely involved in brain neuronal dysfunction and in diseases such as Parkinson's disease, Tourette's syndrome, attention deficit hyperactive disorder, generation of pituitary tumors and schizophrenia. According to the classical dopamine hypothesis on the pathology of schizophrenia, conventional antipsychotics has D2 dopamine receptor antagonistic profiles. However, the use of typical antipsychotics has several limitations; that is, some patients do not respond to them, they can even worsen negative symptoms, and they can provoke unacceptable extrapyramidal and endocrine side effects. To produce effective antipsychotics with reduced side effects, partial agonists to D2 dopamine receptors (D2 receptors) have been developed. Despite the effectiveness of partial agonists for pre- and postsynaptic D2 receptors, administration of such drugs results in inconsistent clinical effects to ameliorate the symptoms of schizophrenia. Thus, strategies for obtaining ideal effective antipsychotics with reduced side effects are considered in this short review with respect to the intrinsic efficacies and affinities of the partial agonists, based on the partial agonist concept.

Antipsychotic Agents↗
PubMed2001

Natural history of scoliosis in children with syringomyelia.

We performed a retrospective review of 27 scoliotic patients with syringomyelia using MRI. Their mean age at the first MRI examination was 10.9 years, and at the final review 15.8 years. The mean ratio of the diameter of the syrinx to the cord on the midsagittal MRI (S/C ratio) decreased from 0.49 to 0.24; 14 patients showed a decrease of 50% or more (reduction group). In this reduction group, the cerebellar tonsillar herniation decreased from a mean of 11.3 mm to 6.0 mm, and some improvement in dissociated sensory disturbance was seen in nine of 13 patients. The scoliosis improved by 5 degrees or more in six patients in the reduction group. Our results indicate that spontaneous shrinkage of syringomyelia in children is not unusual and is associated with improvement in the tonsillar herniation, the scoliosis and the neurological deficit.

Adolescent↗
PubMed2001

[Incidence and severity of coronary artery disease in patients with acute aortic dissection: comparison with abdominal aortic aneurysm and arteriosclerosis obliterans].

OBJECTIVES: The incidence and severity of coronary artery disease were studied in patients with acute aortic dissection (AAD), and compared with coronary artery disease in patients with abdominal aortic aneurysm (AAA) or arteriosclerosis obliterans (ASO). METHODS: A total of 71 patients(42 males, 29 females, mean age 61.4 +/- 10.0 years) with AAD, undergoing coronary angiography between 1988 and 1999, were studied including 38 patients with open communication type and 33 patients with thrombosed type. According to the Stanford classification, 18 patients were type A and 53 patients were type B. Patients with AAD following Marfan syndrome or chest trauma were excluded from the study. Selective coronary angiography was performed in age- and sex-matched patients with AAA(n = 57; 42 males, 15 females, mean age 63.9 +/- 4.6 years) or ASO (n = 95; 66 males, 29 females, mean age 62.4 +/- 9.4 years). Coronary artery disease was defined as > or = 75% stenosis (left main trunk lesion of > or = 50% stenosis) by multidirectional imaging. RESULTS: Significant coronary artery disease was demonstrated in 14 patients with AAD (19.7%), 25 patients with AAA (43.9%), and 49 patients with ASO (51.5%). The incidence of coronary artery disease was significantly lower in the AAD group than in the other two groups (p < 0.05). One-vessel disease was present in approximately 70% of the patients with AAD and coronary artery disease. In contrast, multivessel disease was observed in approximately 50% of patients with AAA and ASO. Classification of the patients with AAD according to the blood flow in the false lumen showed coronary artery disease was more highly associated with the thrombosed type [10 (30.3%) of 33 patients] than the open communication type [4 (10.5%) of 38 patients]. Multivariate logistic regression analysis of the patients with AAD showed coronary artery disease was associated with a high serum total cholesterol level (p = 0.025) and the thrombosed type (p = 0.043). CONCLUSIONS: The incidence of coronary artery disease was significantly lower among patients with AAD than among age- and sex-matched patients with AAA or ASO. Coronary artery disease developed in 30% of the patients with the thrombosed type of AAD, although the prognosis seemed to be good.

Acute Disease↗
PubMed2001

Novel compound heterozygous mutations for lipoprotein lipase deficiency. A G-to-T transversion at the first position of exon 5 causing G154V missense mutation and a 5' splice site mutation of intron 8.

We systematically investigated the molecular defects causing a primary LPL deficiency in a Japanese male infant (patient DI) with fasting hyperchylomicronemia (type I hyperlipoproteinemia) and in his parents. Patient DI had neither LPL activity nor immunoreactive LPL mass in the pre- and post-heparin plasma. The patient was a compound heterozygote for novel mutations consisting of a G-to-T transversion at the first nucleotide of exon 5 [+1 position of 3' acceptor splice site (3'-ass) of intron 4] and a T-to-C transition in the invariant GT at position +2 of the 5' donor splice site (5'-dss) of intron 8 (Int8/5'-dss/t(+2)c). The G-to-T transversion, although affecting the 11 nucleotide of the 3'-consensus acceptor splice site, resulted in a substitution of Gly(154) to Val (G154V; GG(716)C(-->)GTC). The mutant G154V LPL expressed in COS-1 cells was catalytically inactive and hardly released from the cells by heparin. The Int8/5'-dss/t(+2)c mutation inactivated the authentic 5' splice site of intron 8 and led to the utilization of a cryptic 5'-dss in exon 8 as an alternative splice site 133 basepairs upstream from the authentic splice site, thereby causing joining of a part of exon 8 to exon 9 with skipping of a 134-bp fragment of exon 8 and intron 8. These additional mutations in the consensus sequences of the 3' and 5' splice sites might be useful for better understanding the factors that are involved in splice site selection in vivo.

Adult↗
PubMed2000

The personal identification of many samples recovered from under the sea.

An automatic and rapid DNA typing system was employed for personal identification, using fragmentary tissue samples from victims in an airplane accident. Two victims were crushed into small pieces, and 33 samples suspected to belong to them were recovered from under the sea. From each sample, 10 mg was used for testing. The parents' bloods of two presumptive victims were also examined. DNA extraction from samples was performed by the NaI method, and the obtained DNA samples were analyzed with the ABI PRISM system. Among 33 samples, 31 samples were identified to be human tissues, possibly from two victims. The other two samples seemed to be parts of marine animals. ABO blood group, STR polymorphism, and mitochondrial DNA polymorphism typing were possible in every examined human sample. Two victims' fragmentary tissues were identified by determining ABO genotype, STR type and mitochondrial DNA type. The system we employed enabled an accurate typing of many fragmentary samples in a short time, thus contributing to the fast and secure identification of many victims in such cases as big air accidents.

ABO Blood-Group System↗
PubMed2000

Effect of probucol on repeat revascularization rate after percutaneous transluminal coronary angioplasty (from the Probucol Angioplasty Restenosis Trial [PART]).

To address the issue of whether probucol reduces clinical events after percutaneous transluminal coronary angioplasty (PTCA), we surveyed clinical status at 1 year after PTCA of 101 patients who had entered the Probucol Restenosis Angioplasty Trial. Repeat angioplasty at index lesions were required in 5 patients in the probucol group and in 12 in the control group, suggesting that probucol administered beginning 4 weeks before PTCA reduces repeat revascularization rates for 1 year.

Angioplasty, Balloon, Coronary↗
PubMed2000

Repeated haloperidol treatment decreases sigma(1) receptor binding but does not affect its mRNA levels in the guinea pig or rat brain.

The effects of chronic treatment with haloperidol on sigma (sigma) receptors were investigated across brain regions and species. The regional distribution of [3H](+)-pentazocine binding to sigma(1) receptor was similar between the guinea pig and rat brains. The highest level of binding was detected in the brain stem and lowest in the striatum and hippocampus. The regional distribution of [3H]1, 3-di (2-tolyl) guanidine ([3H]DTG) binding in the presence of 100 nM (+)-pentazocine to sigma(2) receptor was similar to that of the [3H](+)-pentazocine binding in the guinea pig brain, while in the rat brain high levels of [3H]DTG binding were detected in the cortex, frontal cortex and cerebellum. The intraperitoneal administration of 2 mg/kg of haloperidol to guinea pig and rats once a day for 21 days produced inhibition of [3H](+)-pentazocine binding but did not affect [3H]DTG binding to sigma(2) receptors in any brain region examined. The effects of haloperidol on [3H](+)-penazocine binding in the rat were much weaker than those in the guinea pig. The regional distribution of the level of sigma(1) receptor mRNA determined by the ribonuclease protection assay was similar to that of the [3H](+)-pentazocine binding activity, except in the cortex and cerebellum where the levels of sigma(1) receptor mRNA were low in guinea pig and rat. Treatment with haloperidol did not affect the levels of sigma(1) receptor mRNA in any brain region in either species. These findings suggested that the sigma receptors differentially distributed in brain regions are down regulated by treatment with haloperidol across sigma receptor subtypes and animal species without changing the transcriptional activity of the sigma(1) receptor. The mechanisms by which sigma receptors could be differently regulated in vivo by chronic treatment with haloperidol in different species may contribute to the therapeutic efficacy of haloperidol.

Animals↗
PubMed2000

Effects of sigma(1) receptor agonist SA4503 and neuroactive steroids on performance in a radial arm maze task in rats.

This study examined the effects of sigma(1) receptor agonist SA4503 and neuroactive steroids dehydroepiandrosterone sulfate (DHEAS), pregnenolone sulfate (PREGS) and progesterone (PROG) on spatial working and reference memory in a radial arm maze task in rats. The insertion of a 6-min delay between the 2nd and 3rd choices caused a specific decline in working memory, but had no effect on reference memory. This decline in working memory was improved by SA4503, but not by DHEAS, PREGS or PROG. A non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine significantly impaired both working and reference memory in the presence or absence of a delay. The dizocilpine-induced impairments in the presence of a 6-min delay were ameliorated by SA4503, DHEAS and PREGS, whereas PROG had no effect. The beneficial effects of SA4503, DHEAS and PREGS were antagonized by treatment with sigma(1) receptor antagonist N, N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy)phenyl)-ethylamine hydrochloride (NE-100). Furthermore, PROG attenuated the ameliorating effects of SA4503, DHEAS and PREGS on dizocilpine-induced memory deficits. These results suggest that sigma(1) receptors play a significant role in short-term working memory. Furthermore, it is suggested that DHEAS and PREGS ameliorate dizocilpine-induced memory impairments by acting as sigma(1) receptor agonists, while PROG antagonizes their effects by acting as a sigma(1) receptor antagonist.

Animals↗
PubMed2000

Tacrolimus and myocardial hypertrophy.

Tacrolimus has been used as an immunosuppressive agent in the transplantation of all solid organs. Tacrolimus-induced hypertrophic cardiomyopathy has been reported to be an unusual but serious complication. To elucidate the effects of tacrolimus on myocardial hypertrophy, we studied the relationship between the blood levels of tacrolimus and cardiac wall thickening. Our findings demonstrated that tacrolimus-induced myocardial hypertrophy correlated with tacrolimus blood levels, and that myocardial hypertrophy induced by tacrolimus was reversible. However, no patients developed clinically significant symptoms related to myocardial hypertrophy.

Adolescent↗
PubMed2000

Molecular determinants of binding of a wasp toxin (PMTXs) and its analogs in the Na+ channels proteins.

The structural specificity of alpha-PMTX, a novel peptide toxin derived from wasp venom has been studied on the neuromuscular synapse in the walking leg of the lobster. alpha-PMTX is known to induce repetitive action potentials in the presynaptic axon due to sodium channel inactivation. We synthesized 29 analogs of alpha-PMTX by substituting one or two amino acids and compared threshold concentrations of these mutant toxins for inducing repetitive action potentials. In 13 amino acid residues of alpha-PMTX, Arg-1, Lys-3 and Lys-12 regulate the toxic activity because substitution of these basic amino acid residues with other amino acid residues greatly changed the potency. Determining the structure-activity relationships of PMTXs will help clarifying the molecular mechanism of sodium channel inactivation.

Amino Acid Substitution↗
PubMed2000

Hemophagocytosis by leukemic blasts in 7 acute myeloid leukemia cases with t(16;21)(p11;q22): common morphologic characteristics for this type of leukemia.

BACKGROUND: In a previous study of a case of acute megakaryoblastic leukemia with t(16;21)(p11;q22), which displayed hemophagocytosis by leukemic blasts, the authors mentioned that the same type of morphology had been cited in the literature for 4 other cases of acute myeloid leukemia (AML) with the same translocation. This observation prompted the authors to examine more cases of AML with t(16;21)(p11;q22) for this morphology. METHODS: The authors reviewed bone marrow smears for the presence of hemophagocytosis in 7 patients with AML identified as having t(16;21)(p11;q22). RESULTS: The leukemias belonged to the FAB-M1/M7 (n = 5), M5b (n = 2), and contained phagocytic blasts in various percentages (< 0.2-36.7%). The blasts contained either single or multiple cytoplasmic vacuoles, in some of which the phagosomes were visible. The engulfed hemopoietic cells (red cells, erythroblasts, lymphocytes, and thrombocytes) were also noted in their cytoplasm. These observations confirmed that hemophagocytosis by leukemic blasts is a common and characteristic feature of this type of leukemia. CONCLUSIONS: The study of 12 cases (the 7 cases described here and the previous 5 cases) strongly supports the hypothesis that hemophagocytosis by leukemic blasts is common and characteristic in this type of leukemia, which may be related to the specific chromosome aberration of t(16;21)(p11;q22).

Adolescent↗
PubMed2000

Vertebral decancellation for severe scoliosis.

STUDY DESIGN: The results of staged surgery including vertebral decancellation were reviewed retrospectively for 21 patients with severe scoliosis. OBJECTIVES: To evaluate the benefits and limitations of vertebral decancellation as new anterior surgical procedure. SUMMARY OF BACKGROUND DATA: The curvatures of severe scoliosis are often very rigid, and surgical correction using the anterior or posterior approach may not achieve the desired correction. Some studies reported neurologic complications might appear due to the aggressive approach or excessive correction force. METHODS: Twenty-one patients (average age, 17.0 years) with severe scoliosis, in whom Cobb angle was over 80 degrees (average angle, 107 degrees), underwent staged anterior and posterior spinal reconstruction. Vertebral decancellation was performed as anterior procedure, and until posterior instrumentation, halo traction was carried out. The transition of curvatures in coronal and sagittal planes was assessed in this series. RESULTS: The average correction rate of lateral curvature at the final follow-up was 46%. The average loss of correction was 2.5 degrees. Kyphosis, measured between T5 and T12, changed from 41 degrees to 36 degrees. Lordosis, measured between L1 and S1, changed from 56 degrees to 45 degrees. Transient neurologic deficit was seen in one case after vertebral decancellation. CONCLUSIONS: Staged surgery including vertebral decancellation is an effective surgical method for patients with severe scoliosis, where an inflexible rigid curve or the risk of occurrence of neurologic complications due to temporary correction may exist.

Adolescent↗
PubMed2000

Laparoscopic hepatic surgery guided by hookwire localization.

Due to recent improvements in radiographic technique, computed tomography (CT) occasionally delineates small hepatocellular carcinomas (HCCs) that are invisible with sonography. However, surgery has not been a viable option for these lesions because of the absence of tumor localization. We describe a new technique of preoperative tumor localization using a hookwire to guide laparoscopic surgery for such HCCs. A 68-year-old man with HCC had tumor recurrence after chemoembolization. Two recurrent lesions, 10 mm or less in diameter, located in segment III were demonstrated; not by sonography but by Lipiodol CT. We successfully placed a hookwire into the tumor through a 21-gauge needle under the guidance of CT. The hookwire instrument provided the only clue of tumor location at laparoscopy. The liver around the hookwire was thoroughly coagulated. The postoperative course was uneventful, and the tumor was completely ablated. Preoperative CT-guided hookwire placement is useful to localize and to laparoscopically treat small hepatic lesions.

Aged↗
PubMed2000

Aortic wall damage in mice unable to synthesize ascorbic acid.

By inactivating the gene for L-gulono-gamma-lactone oxidase, a key enzyme in ascorbic acid synthesis, we have generated mice that, like humans, depend on dietary vitamin C. Regular chow, containing about 110 mg/kg of vitamin C, is unable to support the growth of the mutant mice, which require L-ascorbic acid supplemented in their drinking water (330 mg/liter). Upon withdrawal of supplementation, plasma and tissue ascorbic acid levels decreased to 10-15% of normal within 2 weeks, and after 5 weeks the mutants became anemic, began to lose weight, and die. Plasma total antioxidative capacities were approximately 37% normal in homozygotes after feeding the unsupplemented diet for 3-5 weeks. As plasma ascorbic acid decreased, small, but significant, increases in total cholesterol and decreases in high density lipoprotein cholesterol were observed. The most striking effects of the marginal dietary vitamin C were alterations in the wall of aorta, evidenced by the disruption of elastic laminae, smooth muscle cell proliferation, and focal endothelial desquamation of the luminal surface. Thus, marginal vitamin C deficiency affects the vascular integrity of mice unable to synthesize ascorbic acid, with potentially profound effects on the pathogenesis of vascular diseases. Breeding the vitamin C-dependent mice with mice carrying defined genetic mutations will provide numerous opportunities for systematic studies of the role of antioxidants in health and disease.

Animals↗
PubMed2000

Multiple hepatic adenomas caused by long-term administration of androgenic steroids for aplastic anemia in association with familial adenomatous polyposis.

We report a rare case of hepatic adenomas (HA), in a 20-year-old Japanese girl treated for 6 years with anabolic androgens for aplastic anemia. In a review of the world literature using computer MEDLINE search, we found only 17 cases of androgen-induced HA published between 1975 and 1998 in the English-language literature. The patient was referred to us because of liver lesions detected during a follow-up examination for familial adenomatous polyposis. After being diagnosed with aplastic anemia at 14 years of age, she had been treated with oxymetholone (30 mg/day) for 6 years. Laboratory evaluation revealed normal liver function. Ultrasonography (US) and computed tomography (CT) demonstrated multiple liver lesions. Histopathological examinations of biopsied specimens from the liver tumor showed HA. After the patient was diagnosed with HA, oxymetholone was tapered off. Patients taking androgenic-anabolic steroids should be carefully monitored with US and CT and tumor markers should be measured. This report may be helpful in identifying the population who is at risk of developing hepatic sex hormone-related tumors.

Adenoma↗
PubMed2000

Effect of heat stress on serotonin-2A receptor-mediated intracellular calcium mobilization in rat C6 glioma cells.

This study was conducted to investigate an effect of heat stress at 44 degrees C for 30 min on intracellular Ca2+ signaling system and on heat shock protein (HSP)-70 expression. 5-HT-induced Ca2+ mobilization was reduced 1, 3 and 6 hrs after heat stress, and recovered to the control level 12 and 24 hrs after heat stress. One hr after heat stress, Ca2+ rise was significantly decreased when the cells were stimulated by any concentration of 5-HT. Thrombin-induced Ca2+ increase was also markedly reduced 1 hr after heat stress. HSP-70 level was increased 6 and 9 hr after heat stress. In HSP synthesis inhibitor quercetin-treated cells, HSP-70 expression was not enhanced after heat stress, and Ca2+ rise in response to 5-HT did not return to the control level. However, the Ca2+ rise induced by 5-HT was not restored to the control level after stress in Ac-Asp-Glu-Val-Asp-H (DEVD)-exposed cells while DEVD had little effect on heat stress-induced synthesis of HSP-70. Dexamethasone did not alter the change in HSP-70 expression or Ca2+ response after heat stress. These results indicate that heat stress attenuated 5-HT-induced Ca2+ mobilization and that HSP-70 expression played an important role in recovery from Ca2+ impairment, possibly via protease activity in C6 cells.

Animals↗
PubMed2000

Structure and biological activities of eumenine mastoparan-AF (EMP-AF), a new mast cell degranulating peptide in the venom of the solitary wasp (Anterhynchium flavomarginatum micado).

A new mast cell degranulating peptide, eumenine mastoparan-AF (EMP-AF), was isolated from the venom of the solitary wasp Anterhynchium flavomarginatum micado, the most common eumenine wasp found in Japan. The structure was analyzed by FAB-MS/MS together with Edman degradation, which was corroborated by solid-phase synthesis. The sequence of EMP-AF, Ile-Asn-Leu-Leu-Lys-Ile-Ala-Lys-Gly-Ile-Ile-Lys-Ser-Leu-NH(2), was similar to that of mastoparan, a mast cell degranulating peptide from a hornet venom; tetradecapeptide with C-terminus amidated and rich in hydrophobic and basic amino acids. In fact, EMP-AF exhibited similar activity to mastoparan in stimulating degranulation from rat peritoneal mast cells and RBL-2H3 cells. It also showed significant hemolytic activity in human erythrocytes. Therefore, this is the first example that a mast cell degranulating peptide is found in the solitary wasp venom. Besides the degranulation and hemolytic activity, EMP-AF also affects on neuromuscular transmission in the lobster walking leg preparation. Three analogs EMP-AF-1 approximately 3 were snythesized and biologically tested together with EMP-AF, resulting in the importance of the C-terminal amide structure for biological activities.

Amino Acid Sequence↗