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Biomedical subjects

M Hata

Publications and source records attributed to M Hata.

At least 37 records · Page 2Linked to original sources

A typical Y1 receptor regulates feeding behaviors: effects of a potent and selective Y1 antagonist, J-115814.

Neuropeptide Y (NPY) is a potent feeding stimulant. The orexigenic effect of NPY might be caused in part by the action of Y1 receptors. However, the existence of multiple NPY receptors including a possible novel feeding receptor has made it difficult to determine the relative importance of the Y1 receptor in feeding regulation. Herein we certified that the Y1 receptor is a major feeding receptor of NPY by using the potent and selective Y1 antagonist (-)-2-[1-(3-chloro-5-isopropyloxycarbonylaminophenyl)ethylamino]-6-[2-(5-ethyl-4-methyl-1,3-thiazol-2-yl)ethyl]-4-morpholinopyridine (J-115814) and Y1 receptor-deficient (Y1-/-) mice. J-115814 displaced (125)I-peptide YY binding to cell membranes expressing cloned human, rat, and murine Y(1) receptors with K(i) values of 1.4, 1.8, and 1.9 nM, respectively, and inhibited NPY (10 nM)-induced increases in intracellular calcium levels via human Y1 receptors (IC(50) = 6.8 nM). In contrast, J-115814 showed low affinities for human Y2 (K(i) > 10 microM), Y4 (K(i) = 640 nM) and Y5 receptors (K(i) = 6000 nM). Intracerebroventricular (ICV) (10-100 microg) and intravenous (IV) (0.3-30 mg/kg) administration of J-115814 significantly and dose-dependently suppressed feeding induced by ICV NPY (5 microg) in satiated Sprague-Dawley rats. Intraperitoneal (IP) administration of J-115814 (3-30 mg/kg) significantly attenuated spontaneous feeding in db/db and C57BL6 mice. Feeding induced by ICV NPY (5 microg) was unaffected by IP-injected J-115814 (30 mg/kg) in Y1-/- mice and was suppressed in wild-type and Y5-/- mice. These findings clearly suggest that J-115814 inhibits feeding behaviors through the inhibition of the typical Y1 receptor. We conclude that the Y1 receptor plays a key role in regulating food intake.

Animals↗

Involvement of stringent factor RelA in expression of the alkaline protease gene aprE in Bacillus subtilis.

Expression of Bacillus subtilis aprE, encoding an extracellular alkaline protease, is positively regulated by phosphorylated DegU, the regulator of a two-component regulatory system, DegS-DegU. We found that the expression of an aprE'-'lacZ fusion was greatly reduced in a disruption mutant with a mutation of relA, which encodes the stringent factor RelA. The level of DegU in the relA mutant was similar to that in the wild-type cell. A relA degU double mutation did not result in a further decrease of the aprE'-'lacZ level found in a degU single mutant. The expression of the aprE'-'lacZ fusion in the relA mutant was stimulated by multicopy degR or the degU32(Hy) and degS200(Hy) mutations that cause the stabilization of phosphorylated DegU. Furthermore, the expression of sacB'-'lacZ, which is also dependent on phosphorylated DegU, was stimulated by the relA mutation, and this stimulation was not seen in the relA degU double mutant. These results show that RelA (or its product guanosine-3',5'-bisdiphosphate [pp Gpp]) does not affect the phosphorylation of DegU and suggest that it participates in the expression of aprE and sacB through the regulation of DegU-dependent transcription.

Artificial Gene Fusion↗

Radiation therapy for life- or function-threatening infant hemangioma.

PURPOSE: To assess the effectiveness and long-term results of radiation therapy in infants with life- or function-threatening hemangiomas. MATERIALS AND METHODS: Thirteen patients with life- or function-threatening hemangiomas (eight male, five female; age range, 0-8 months; median age, 2 months) were treated with radiation therapy. Life-threatening hemangiomas were treated with five fractions of radiation per week, and function-threatening hemangiomas were treated with two fractions per week. A median dose of 10 Gy was delivered to each hemangioma. The presence of residual hemangiomas, skin changes, functional problems, and growth delay was evaluated. RESULTS: All patients with Kasabach-Merritt syndrome (KMS) showed regression of the hemangioma and an increase in platelet counts to greater than 100,000 per cubic millimeter (1.0 x 10(11) per liter) within 40 days after radiation therapy. The treatment field was inadequate in two patients who required reirradiation or a change of treatment portal. With the exception of the patients with KMS, all but one patient experienced relief from symptoms in 40 days. Severe long-term radiation-related morbidity was noted in one patient who required reirradiation for a relapsed hemangioma. CONCLUSION: Radiation therapy (in doses of < or = 10 Gy in 2-Gy fractions) is indicated for life-threatening hemangiomas and for some function-threatening hemangiomas.

Adolescent↗

Transorbital penetrating injury by a chopstick--case report.

A one-year-old boy presented with orbitocranial penetrating injury by a chopstick. Neurological examination did not reveal abnormal findings. Skull radiography did not reveal any sign of fracture and there were no abnormal findings. Initially, computed tomography (CT) of the head did not reveal any intracranial lesions. However, bone window CT showed a well-defined low-density abnormality measuring 2.5 cm in length in the right orbit and parasellar region. Magnetic resonance imaging clearly revealed a low-intensity structure extending from the orbit to the prepontine area. Surgical exploration was emergently performed and the wooden fragment was removed. The postoperative course was uneventful. Transorbital penetrating injury by a wooden foreign body is relatively rare. The wound may be superficial and trivial. Major neurological deficit does not usually manifest immediately, so the penetrating injury may be overlooked. If the foreign body is retained in the orbit and cranium, severe infectious complications may occur later.

Brain Injuries↗

Characterization of a processed pseudogene of human psiHSP40 on chromosome 2q32.

A pseudogene for the human Hsp40 gene has been characterized (psiHSP40). The pseudogene sequence shows 90% similarity to the human Hsp40 mRNA at the nucleotide level. No introns were found in the region corresponding to the human Hsp40 cDNA, and two direct repeats flank this same region. Because of these features, the pseudogene can be classified as a processed pseudogene. PsiHSP40 was assigned to chromosome 2q32 by in situ hybridization. This is the first report of a pseudogene for a member of the DnaJ (Hsp40) family protein gene.

Base Sequence↗

[Clinical efficacy of leuprolide acetate and combined treatment with estramustine for advanced prostate cancer].

BACKGROUND/PURPOSE: Twenty-two institutes have organized Keio University Prostate Cancer Study Group to study clinical efficacy and safety of Leuprolide acetate (Leuplin) for the treatment of advanced prostate cancer (clinical stage D1 and D2). Cotreatment of Leuplin and Estramustine phosphate disodium (Estracyt) has been performed to investigate its clinical efficacy. MATERIALS AND METHODS: One hundred and two cases of advanced prostate cancer were treated either with Leuplin alone (group I), Leuplin and Estracyt (group II) or Estracyt alone (group III). After 12 weeks treatment, clinical effects against subjective symptoms (pain, voiding difficulty, performance status and body weight), serum testosterone level, tumor size and serum PSA level were examined to investigate short-term effect of each treatment. The treatment had been continued for 24 months and the treatment effects including progression free survival and overall survival were analyzed. RESULTS: Clinical efficacy after 12 weeks treatment were examined among 97 cases (group I; 35 cases, group II; 36 cases, group III; 26 cases). The background of those patients in each group was statistically equal. Treatment effects against subjective symptoms and serum testosterone level statistically revealed no significant difference among 3 groups. Treatment effects against primary tumor, bone metastatic lesion, lymphnode metastatic lesion and serum PSA level were investigated and anti-tumor effect was characterized by total efficacy rate (complete remission rate plus partial remission rate) of each treatment group. Treatment efficacy rates for each lesion and PSA demonstrated no statistical difference among 3 treatment groups. Total efficacy rate of group I, II and III were 88.2%, 84.0% and 78.3%, respectively, which statistically revealed no significant difference. Total efficacy rate of each group after completing 24 months treatment was; group I 80.0%, group II 55.6% and group III 83.3%, which statistically showed no significant difference among 3 treatment groups. The median day for progression free survival of group I, II and III were 661, 731 and 517, respectively. The overall survival rate of group I, II and III after completing 24 months treatment were 77.5%, 83.0% and 72.4%, respectively. Both progression free survival rates and overall survival rates revealed no significant difference among 3 groups. Side effects during 24 months treatment were seen in 8.6% of group I, 47.2% of group II and 26.9% of group III, and these occurrence rates were significantly different among the groups (p = 0.0013). CONCLUSION: Although number of the cases had not been able to continue the treatment for their side effects, the statistical characterization demonstrated that cotreatment of Leuplin and Estracyt had no greater treatment effect than monotreatment of each drug.

Aged↗

[Early outcome with the Alfieri mitral valve repair].

OBJECTIVES: Mitral regurgitation in cases of prolapse of the anterior leaflet, posterior leaflet with calcified annulus, or prolapse of both leaflets is thought to be difficult to repair. The Alfieri repair has been developed to address these conditions. METHODS: Seven patients (four men and three women, mean age 71 +/- 9 years) underwent the Alfieri repair for mitral regurgitation at Austin and Repatriation Medical Centre between January 1999 and December 1999. The mechanism of mitral regurgitation was prolapse of the posterior leaflet with calcified annulus in one patient, prolapse of the anterior leaflet in two, and prolapse of both leaflets in four. Mitral regurgitation before operation was severe in all patients. The Cosgrove ring was used in all patients. Four patients underwent combined operation, coronary artery bypass surgery in three and tricuspid annuloplasty in one. RESULTS: There was no hospital death. Two patients had postoperative complications, transient ischemic attack in one patient and rapid atrial fibrillation in one. The mean hospital stay was 11.3 +/- 8.7 days. Mitral regurgitation after operation was mild in five patients and trivial in two. Mean pressure gradient of the transmitral valve was 4.0 +/- 1.4 mmHg. CONCLUSIONS: The Alfieri mitral valve repair is a simple and satisfactory technique to repair mitral regurgitation in selected patients. Long-term follow-up is required to evaluate the durability of this technique.

Aged↗

Doppler echocardiographic evaluation of St. Jude Medical valves in the tricuspid position: criteria for normal and abnormal valve function.

BACKGROUND: Although this examination for mitral and aortic prosthetic valves has been frequently reported to be available for the early diagnosis of complications, there are few reports on examinations for tricuspid prosthetic valves, particularly the mechanical valve such as the St. Jude Medical (SJM) valve. Furthermore, the criteria for early diagnosis of complications are unknown. The purpose of this study is to evaluate the SJM valve in the tricuspid position by Doppler echocardiography and to analyze valve-related complications. METHODS: Between September 1978 and March 1997, 46 patients underwent tricuspid valve replacements with SJM valves; these cases were evaluated by Doppler echocardiography. We divided the cases into Normal and Complication groups. RESULTS: In the Normal group, peak pressure gradient was 4.2+/-1.5 mmHg and pressure half-time was 123.5+/-22.9 msec. In the Complication group, peak pressure gradient was 12.7+/-3.6 mmHg and pressure half-time was 271.8+/-76.4 msec. In the Complication group, the lowest peak pressure gradient case was 8.0 mmHg and the shortest pressure half-time was 160.0 msec. CONCLUSIONS: We concluded that when the peak pressure gradient is more than 8 mmHg or the pressure half-time is more than 160 msec, there is a possibility of complications. Despite the problems, the absence of any structural change after more than ten years suggests that the SJM valve can be used in the tricuspid position with careful follow-up.

Adult↗

The mid-term results of ventricular containment (ACORN WRAP) for end-stage ischemic cardiomyopathy.

The acorn cardiac support device (ACSD) is a device designed to treat heart failure by containing the heart to prevent further dilation. Six patients with symptomatic heart failure due to ischemic cardiomyopathy were treated surgically with ACSD. All patients simultaneously underwent coronary artery bypass grafting. Ventricular reconstruction was also performed in 5 of the 6 patients. We followed up the patients for 12 months postoperatively, monitoring the left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), mitral regurgitation, and NYHA classification. Both the LVEDD and LVESD were significantly improved one month postoperatively (from 63.2 to 50.6 mm, p=0.004, and from 51.6 to 39.5 mm, p=0.025, respectively). These dimensions did not change significantly over the next 11 months. NYHA functional class improved significantly from a mean of 3 to 1.4 at 12 months (p=0.012). Mitral regurgitation improved from a mean of 2.7 preoperatively to 1.4 at 12 months and the average LVEF also improved from 27% preoperatively to 35.9% at 12 months after surgery. However these latter two results were not statistically significant. There were no late deaths and no readmissions for heart failure. Repeat coronary angiography at 6 months revealed patent grafts in all patients. The mid-term results of ACSD for patients with symptomatic heart failure suggest that ventricular containment may be useful for preventing further cardiac dilation in patients with ischemic cardiomyopathy. Randomized, long-term studies are needed to assess the efficacy and possible role of ASCD in the future management of heart failure.

Aged↗

A strictly "pair"-selective synthesis of conjugated diynes via Pd-catalyzed cross coupling of 1,3-diynylzincs: a superior alternative to the Cadiot-Chodkiewicz reaction.

A strictly "pair"-selective synthesis of conjugated diynes via Pd-catalyzed cross coupling of 1,3-diynylzincs is described. This method, like the Cadiot-Chodkiewicz reaction, requires three steps for the synthesis of R(1)Ctbd1;CCtbd1;CR(2) from R(1)Ctbd1;CH, R(2)X, and HCtbd1;CH. However, the high "pair"-selectivity permitting high-yield production of the desired conjugated diynes without separation of symmetrical diynes promises to make the present protocol superior to the Cadiot-Chodkiewicz reaction in many cases.

Alkynes↗

Murine cDNA encoding a novel type I HSP40/DNAJ homolog, mmDjA4(1).

We have cloned a cDNA encoding a novel type I HSP40/DNAJ protein from the mouse EST database, and designated it mmDjA4 (Mus musculus type I DnaJ homolog 4). This cDNA encodes 397 amino acid residues whose sequence shows 67 and 51% identity with the previously identified murine Hsj2 and mDj3, respectively. The sequence of mmDjA4 contains the four repeats of CxxCxGxG motif which are characteristic of type I HSP40/DNAJ proteins, and a CaaX prenylation motif at the carboxy terminus. Northern blot analysis showed that mmDjA4 is specifically expressed in mouse testis and heart. This is the fourth member of the mammalian type I HSP40/DNAJ family to be identified.

Amino Acid Sequence↗

Effects of irradiation on the sensitivity of melatonin release to norepinephrine in cultured pineal bodies of rats.

We measured levels of basal and norepinephrine (NE) -induced melatonin release in cultured pineal bodies of rats just after and 2 days after irradiation (20 or 200 Gy) or sham-irradiation. On the day of irradiation, basal and NE-induced melatonin release were not affected by irradiation. Two days after irradiation, basal melatonin levels in both irradiated groups were significantly lower than those in control group, whereas NE-induced melatonin levels in the irradiated groups were higher than those in the control group. These results suggested that irradiation decreases basal melatonin synthesis in pineal glands but that melatonin response to NE is increased after irradiation.

Adrenergic alpha-Agonists↗

Chaperones Hsp70 and Hsp40 suppress aggregate formation and apoptosis in cultured neuronal cells expressing truncated androgen receptor protein with expanded polyglutamine tract.

Spinal and bulbar muscular atrophy (SBMA) is one of a group of human inherited neurodegenerative diseases caused by polyglutamine expansion. We have previously demonstrated that the SBMA gene product, the androgen receptor protein, is toxic and aggregates when truncated. Heat shock proteins function as molecular chaperones, which recognize and renaturate misfolded protein (aggregate). We thus assessed the effect of a variety of chaperones in a cultured neuronal cell model of SBMA. Overexpression of chaperones reduces aggregate formation and suppresses apoptosis in a cultured neuronal cell model of SBMA to differing degrees depending on the chaperones and their combinations. Combination of Hsp70 and Hsp40 was the most effective among the chaperones in reducing aggregate formation and providing cellular protection, reflecting that Hsp70 and Hsp40 act together in chaperoning mutant and disabled proteins. Although Hdj2/Hsdj chaperone has been previously reported to suppress expanded polyglutamine tract-formed aggregate, Hsdj/Hdj2 showed little effect in our system. These findings indicate that chaperones may be one of the key factors in the developing of CAG repeat disease and suggested that increasing expression level or enhancing the function of chaperones will provide an avenue for the treatment of CAG repeat disease.

Apoptosis↗

Genome-wide detection of unknown subtle mutations in bacteria by combination of MutS and RDA.

We propose a procedure for detecting unknown, subtle DNA changes throughout the entire bacterial genome by a combination of MutS and RDA. Current techniques detect subtle mutations after PCR amplification of the target regions, so the mutation detection is done between amplified PCR fragments. In this paper, genome-wide subtle mutation scanning in bacteria was performed by combining the MutS and RDA techniques. Our strategy for cloning a small mutation region is composed of two steps: an enrichment of fragments containing subtle mutations using MutS, followed by an RDA subtraction procedure for further enrichment. We successfully identified small mutations such as a four-base insertion, a two-base insertion, and transition mutations in bacteria.

Adenosine Triphosphatases↗

Pedicled pericardial flap for pulmonary artery in adult dogs.

OBJECTIVE: Stenosis of extracardiac conduit after reconstruction of right ventricle outflow tract is a serious problem, and the purpose of this study was to identify the suitability of broadly pedicled autologous pericardial flap for the reconstruction of pulmonary artery trunk in adult dogs. METHODS: Eight mongrel dogs had replacement of a pulmonary artery trunk with extracardiac conduit, in which prosthetic vascular graft formed the posterior wall and pedicled (group P, n = 5) or free (group F, n = 3) autologous pericardium created the anterior wall. Six months after the operation, pressure gradient across the conduit were measured and put to death for pathological examinations. RESULTS: Pressure gradient across the conduit in groups F and P was 16.0 +/- 16.8 mmHg and 1.4 +/- 1.7 mmHg respectively. In the microscopic examination, flaps of group P had neo-intimal cells in the innermost layer, abundant cellular component with elastic fiber was seen within the middle layer, and collagen tissue within the outer layer. Conversely, the presence of calcification was shown within collagen fiber layer of all patches in group F. Sparse cellular component and the absence of neo-intimal cells were also observed in group F. CONCLUSIONS: Broadly pedicled pericardial flap is more conceivable to prevent the development of conduit stenosis after right ventricle outflow tract reconstruction, if compared with free pericardial patches.

Animals↗

Low-dose continuous infusion of human atrial natriuretic peptide during and after cardiac surgery.

BACKGROUND: We evaluated the effects of human atrial natriuretic peptide (hANP) during cardiopulmonary bypass (CPB). METHODS: Forty patients undergoing coronary artery bypass grafting were investigated. A group of patients given hANP for 24 hours from the start of CPB (hANP group) was compared with a non-hANP group. Parameters examined were hemodynamics, urine volume, dosage of furosemide, respiratory index, pleural effusion, ANP, cyclic guanosine monophosphate, renin activity (renin), angiotensin-II, aldosterone, and glomerular filtration rate. RESULTS: Central venous pressure, systemic vascular resistance index, and pulmonary vascular resistance index were significantly lower in the hANP group than in the non-hANP group. The hANP group showed significantly higher levels of ANP, cyclic guanosine monophosphate, glomerular filtration rate, and respiratory index, and significantly lower levels of renin, angiotensin-II, aldosterone, and pleural effusion, as compared with the non-hANP group. The dosage of furosemide was significantly lower and the urine volume was significantly larger in the hANP group. CONCLUSIONS: hANP can satisfactorily compensate for the shortcomings of CPB by decreasing the peripheral vascular resistance, suppressing the renin-angiotensin-aldosterone system, and exerting a strong diuretic effect.

Atrial Natriuretic Factor↗

A study on the mechanism of the proton transport in bacteriorhodopsin: the importance of the water molecule.

The mechanism of proton transport around the Schiff base in bacteriorhodopsin was investigated by ab initio molecular orbital (MO) calculations. Computations were performed for the case where there is a water molecule between the Schiff base and the Asp residue and for the case where there is no water molecule. Changes in the atomic configuration and potential energy through the proton transport process were compared between two cases. In the absence of water, the protonated Schiff base was not stable, and a proton was spontaneously detached from the Schiff base. On the other hand, a stable structure of the protonated Schiff base was obtained in the presence of water. This suggests that the presence of a water molecule is required for stability in the formation of a protonated Schiff base.

Aspartic Acid↗

Clinical results of coronary artery bypass grafting with use of the internal thoracic artery under low free flow conditions.

OBJECTIVE: Even when left internal thoracic artery flow is very low, we have used the artery for grafting without any further maneuvers. In this study, we investigated the clinical results of coronary bypass surgery using the left internal thoracic artery with low free flow. METHODS: A total of 163 patients were divided into 2 groups: group L (n = 43) had free flow of 20 mL/min or less and group H (n = 120) had free flow of more than 20 mL/min. We performed a comparative study on the basis of coronary angiography and pulsed Doppler echocardiography. Furthermore, 12 months' postoperative graft angiography was carried out in 11 patients from group L. RESULTS: No patient had low output syndrome or perioperative myocardial infarction. One month after the operation, 3 cases of graft occlusion and 9 cases of the "string sign" were identified in group H. However, group L had no graft occlusion and only 1 case of the "string sign." The 1-month postoperative Doppler echocardiographic study showed no significant differences in the diastolic fraction of velocity time integrals and the diastolic/systolic peak velocity ratio of the grafts. In the 11 patients undergoing angiography after 1 year, graft patency was excellent. Moreover, the graft diameter was significantly larger than it was 1 month after the operation. CONCLUSION: These results suggest that the left internal thoracic artery can be used for coronary artery bypass grafting even when the flow is less than 20 mL/min.

Blood Flow Velocity↗