Search PubMed⌕ Search

Biomedical subjects

M Hayashi

Publications and source records attributed to M Hayashi.

At least 289 records · Page 16Linked to original sources

The cerebellar and thalamic degeneration in Fukuyama-type congenital muscular dystrophy.

We report a male autopsy case of Fukuyama-type congenital muscular dystrophy (FCMD), with unusual neuropathological findings. The patient was a Japanese man aged 26 years at the time of death. He had shown severe psychomotor retardation and muscular dystrophy since early infancy, and was diagnosed as having FCMD at the age of 5 years. He died of respiratory failure. The main neuropathological finding was extensive cerebral and cerebellar cortical dysplasia, characteristic of this disorder. In addition, degeneration of the cerebellar efferent pathway, including the dentate nucleus, superior cerebellar peduncle, and red nucleus, and that of the lateral thalamic nucleus were observed. These findings suggest the possibility that the long survival can clarify the latent neurodegeneration in the cerebellum and thalamus in FCMD, in addition to congenital malformations. The system degeneration should be carefully evaluated in the pathological examination of this disorder.

Adult↗

Development of full-length Trk B-immunoreactive structures in the prefrontal and visual cortices of the macaque monkey.

Distribution and morphological changes of cells containing the signal transducing neurotrophin receptor, full-length Trk B (fl-Trk B), were investigated in the prefrontal cortex (area FD) and the primary visual cortex (area OC) of the macaque monkey between embryonic day 140 and the adult stage. In area FD at the adult stage, fl-Trk B immunoreactivity was mainly observed in the pyramidal cells in layers II/III, V and VI. Small numbers of granule cells in layer IV were immunopositive. Bipolar and multipolar cells in layer II were rarely immunoreactive. At embryonic day 140, the number of fl-Trk B immunoreactive pyramidal cell was high, and gradually decreased until the adult stage. In layer IV, the number of fl-Trk B-ir cells was also high at embryonic day 140, and decreased remarkably from postnatal day 7 to the adult stage. On the other hand, in area OC at the adult stage, cells in layers II/III, IV, V and VI were fl-Trk B immunopositive. From embryonic day 140 until adulthood, the cells in layer IVc were fl-Trk B immunoreactive. The strongest fl-Trk B immunoreactivity in areas FD and OC occurred at postnatal month 6, coinciding with the time of the synapse overproduction. These findings suggest that ligands of fl-Trk B, such as BDNF and NT4/5 may be involved in the development and maintenance of the monkey cerebral cortices.

Animals↗

Small bowel transplantation using grafts from living-related donors. Two case reports.

A living-related small bowel transplantation (SBT) was performed in two pediatric patients with short bowel syndrome. In both cases, the donor was the patient's mother. The distal ileum (100 cm, 120 cm) was harvested and the ileocolic vessels, ileocecal valve, and terminal ileum were left intact. The two donors were discharged from the hospital on postoperative days 15 and 6, respectively. Recipient 1 was a 2 year 6 month-old boy with short bowel syndrome who underwent SBT due to loss of venous access. The graft vein was anastomosed to the recipient's infrarenal inferior vena cava. Despite triple immunosuppression (tacrolimus, steroid, and azathioprine), there were four episodes of rejection. The patient had been on total parenteral nutrition for almost his entire posttransplant course. He died from Pneumocystis carinii pneumonia 16 months after the transplantation. Recipient 2 was a 4 year 5 month-old girl with short bowel syndrome who underwent an isolated small bowel transplantation because of recurrent line sepsis. Her pretransplant bilirubin was 8.0 mg/dl and a biopsy showed severe fibrosis. The graft vein was anastomosed to the recipient's inferior mesenteric vein. After transplantation, her bilirubin level became normal within 10 days. Triple immunosuppression (tacrolimus, steroid, and cyclophosphamide) together with a 3-day course of OKT-3 made her post-transplant course feasible. After overcoming a single episode of rejection she left the hospital 4 months after SBT. The patient is currently (10 months after transplantation) hospitalized due to rejection, which is being successfully controlled, and she is off total parenteral nutrition. From our experience, harvesting of the distal ileum for use as a bowel graft can be safely performed. The advantages of living-related grafts, optimal graft length, and choice of vascular reconstruction in SBT are yet to be explored.

Adult↗

Hepatic grafts from live donors: donor morbidity for 470 cases of live donation.

Living donor-morbidity was evaluated in 470 consecutive cases of living donor liver transplantation carried out from June 1990 to May 1999 at Kyoto University. Grafting was categorized into 4 groups according to the resection lines; left lateral segmentectomy (S2 + 3, n = 282, R1), extended left lateral segmentectomy without middle hepatic vein (MHV) (S2 + 3 + part4, n = 45, R2), left lobectomy with MHV (S2 + 3 + 4, n = 99, R3) and right lobectomy without MHV (S5 + 6 + 7 + 8, n = 43, R4). Intraoperative blood loss and operation duration were less for left lateral segmentectomy, but no significant difference was observed between left lobectomy and right lobectomy. The length of postoperative hospital stays was comparable among all groups except for the group with right lobe grafting. The AST values at the peak and at POD 7 were significantly elevated for right lobectomy, but the AST value normalized within one month in the majority of the cases. The close follow-up of donors with more than 1,000 ml intraoperative bleeding, and of those donors who stayed in hospital for more than 30 days, the close follow-up, furthermore, of those donors with AST values higher than 100 IU/ L AST after one month, revealed complete recovery. Biliary leakage was the most common and annoying complication after donor operations, especially in for right lobe grafting, but all donors recovered completely with conservative or minimal invasive therapy. The two cases of re-operation due to adhesive mechanical ileus we encountered were resolved completely. Finally, no donor-operation related death was noted. In conclusion, the morbidity of living donors is low or minimal even for right lobectomy, the most extended procedure, and complete recovery can be expected in all cases.

Adult↗

Different subtypes of human lung adenocarcinoma caused by different etiological factors. Evidence from p53 mutational spectra.

Human lung adenocarcinomas are only relatively weakly associated with tobacco smoke, and other etiological factors need to be clarified. These may also vary with the histopathology. Because the p53 mutation status (frequency and spectrum) of a carcinoma can provide clues to causative agents, we subclassified 113 adenocarcinomas into five cell types: hobnail, columnar/cuboidal, mixed, polygonal, and goblet (54, 23, 18, 13, and 5, respectively) and investigated relationships with p53 mutations and smoking history. In the hobnail cell type, a low mutational frequency (37%) and a high proportion of transitions (65%), especially G:C to A:T transitions at CpG dinucleotides (45%) associated with spontaneous mutations, were found with a weak relation to tobacco smoke. In contrast, a high mutation frequency (70%) with a higher proportion of transversions (50%), especially G:C to T:A (44%) on the nontranscribed DNA strand, caused by exogenous carcinogenic agents like tobacco smoke, were observed for the columnar cell type, as with squamous cell carcinomas. These results indicate that two major subtypes of lung adenocarcinoma exist, one probably caused by tobacco smoke, and the other possibly due to spontaneous mutations. For the prevention of lung adenocarcinomas, in addition to stopping tobacco smoking, the elucidation of endogenous mechanisms is important.

Adenocarcinoma↗

Event-related potentials elicited by wrong terminal notes: effects of temporal disruption.

Wrong terminal notes of familiar musical phrases are known to elicit a large positive deflection of the event-related potential (ERP). The present study examined whether the effect of wrong terminal notes on ERP was modulated by the timing of their occurrence. Sixteen non-musicians were asked to rate the congruity of the endings of 50 well-known musical phrases. Four different types of endings were made for each phrase by manipulating the timing (well-timed vs. delayed for 750 ms) and pitch (correct vs. wrong) of the last note orthogonally. These ending patterns were presented equiprobably in an unpredictable order. Wrong notes elicited large late positive waves irrespective of the timing of occurrence. When the notes were delayed, however, the positive waves were reduced in amplitude to about 50% of those elicited by well-timed notes. These results suggest that the temporal (rhythmic) structure of musical phrases strongly influences the processing of melodic information.

Adult↗

Long-term medical, educational, and social prognoses of childhood-onset epilepsy: a population-based study in a rural district of Japan.

The long-term prognosis of childhood-onset epilepsy has rarely been studied in a general population. We examined the long-term medical, educational, and social outcomes in individuals with a history of childhood-onset epilepsy aged 20 years or older in a defined area of Japan. Furthermore, the patients' recognition of epilepsy as well as the parents' concerns about the prognosis of epilepsy were also surveyed. After a mean follow-up period of 18.9 years, we had sufficient data on 148 surviving patients aged 20-38 years (mean, 26. 0 years) and seven dead patients. The follow-up rate was 92.8%. In the overall group, the percentages of those who had had each of the following were as follows: (a) 5-year remission, 62.8%; (b) a relapse of seizures, 17.4%; (c) psychiatric complications, 2.7%; (d) mortality, 4.5%; (e) attendance at regular classes of an ordinary school during compulsory education, 71.6%; (f) entrance to high school, 65.5%; (g) employment, 67.4%; (h) marriage, 23.0%; and (i) acquisition of a driver's license, 54.7%. The educational and social variables of the control population were as follows: (e) 99.1, (f) 97.0, (g) 96.6, (h) 51.9, and (i) 94.8%. In the 99 patients of normal intelligence, the results of the same analysis were as follows: (a) 75.8, (b) 10.7, (c) 0, (d) 0.6, (e) 100, (f) 96.0, (g) 95.2, (h) 33.3, and (i) 77.8%, in contrast to the corresponding variables of the 49 patients with mental retardation, that is, (a) 36.7, (b) 44.4, (c) 8.2, (d) 12.2, (e) 14.3, (f) 6.1, (g) 20.4, (h) 2.0, and (i) 4.1%, respectively. The best predictors of seizure remission included an early response to therapy, a low frequency of seizures or an absence of status epilepticus prior to therapy, and normal mental development. As for the current awareness of epilepsy and its prognosis, nearly 40% of the patients did not know the true name of their illness, and the same proportion of parents were still anxious about the prognosis even if their children had been taken off medication. Our data show that the majority of patients with childhood-onset epilepsy have a favorable long-term medical prognosis in terms of seizure remission and psychiatric complications, whereas they have a higher mortality rate and lower levels of educational background as well as employment and marital status compared with the general population. However, except for the low marriage rate for the younger age group and the low rate of holding a driver's license, patients of normal intelligence appear to have more favorable long-term prognoses in terms of educational and social aspects as well. In Japan, individuals with epilepsy may not seek a driver's license because of the law.

Activities of Daily Living↗

Spironolactone inhibits the transcardiac extraction of aldosterone in patients with congestive heart failure.

OBJECTIVES: The study evaluated the transcardiac extraction or spillover of aldosterone (ALDO) in normal subjects and in patients with congestive heart failure (CHF). BACKGROUND: Aldosterone promotes collagen synthesis and structural remodeling of target organs such as the heart. Spironolactone, an ALDO receptor antagonist, has recently been reported to reduce the mortality of patients with CHF; however, the effects of spironolactone on the transcardiac gradient of ALDO have not been clarified. METHODS: We measured plasma ALDO in the aortic root (AO) and coronary sinus (CS) in normal subjects and 113 consecutive CHF patients and also measured plasma procollagen type III aminoterminal peptide (PIIINP) in CS, a biochemical marker of myocardial fibrosis. RESULTS: Plasma ALDO was significantly lower in the CS than in the AO in normal subjects (n = 15; 61.2 +/- 9.3 vs. 83.1 +/- 11.8 pg/ml, p < 0.0001). In 96 CHF patients who did not receive spironolactone, plasma ALDO was significantly lower in the CS than in the AO (59.3 +/- 3.9 vs. 73.8 +/- 4.9 pg/ml, p < 0.0001). In contrast to the difference in these 96 patients, there was no significant difference in ALDO between the AO and CS in 17 patients who received spironolactone (127.4 +/- 20 vs. 124.0 +/- 19 pg/ml, p = 0.50). Stepwise multivariate analyses showed that spironolactone therapy had an independent and significant negative relationship with the transcardiac gradient of plasma ALDO in patients with CHF. In addition, significant positive correlations were seen between the transcardiac gradient of plasma ALDO and PIIINP (r = 0.565, p < 0.0001) and the left ventricular end-diastolic volume index (r = 0.484, p < 0.0001). CONCLUSIONS: These results indicate that plasma ALDO is extracted through the heart in normal subjects and in CHF patients who do not receive spironolactone and that spironolactone inhibits the transcardiac extraction of ALDO in CHF patients, suggesting that spironolactone blocks the effects of ALDO on the failing heart in patients with CHF.

Adolescent↗

Effect of portal hypertension caused by chronic high venous pressure on small-intestinal sugar absorption.

The effect of portal hypertension and chronic high venous pressure on the absorption of the small intestine was examined by constricting the suprahepatic and subdiaphragmatic inferior vena cava in rats. A group of rats with the constricted suprahepatic and subdiaphragmatic inferior vena cava comprised group 1 (n = 9) and another group of rats with only laparotomy comprised group 2 (n = 9). Two months after the operation, sugar absorption and other parameters were measured. The blood pressures of the infrahepatic inferior vena cava and the portal vein 8 wk after the operation in group 1 were significantly higher than those in group 2. The results of D-xylose absorption tests showed that the amount of excreted D-xylose in urine in group 1 was significantly lower than that of group 2, but the D-xylose everted sac test showed no significant differences between the two groups. The glucose everted sac test showed that the amount of glucose absorption in group 1 was significantly lower than that in group 2. These findings suggest that chronic high venous pressure caused by constriction of suprahepatic inferior vena cava may lead to sugar malabsorption. We conclude that portal hypertension with high venous pressure below the diaphragm can lead to sugar malabsorption in the intestine.

Animals↗

Improvement of intestinal absorption of peptides: adsorption of B1-Phe monoglucosylated insulin to rat intestinal brush-border membrane vesicles.

In a previous study we glycosylated insulin to improve its intestinal absorption. When the glycosylated product, p-(succinylamido)-phenyl-alpha-D-glucopyranoside (SAPG)-substituted insulin (SAPG-INS), was administered intra-intestinally to rats, it showed a greater hypoglycemic effect than native bovine insulin. The enhanced hypoglycemic effect of SAPG-INS was considered to be due to an increase in membrane permeability as well as an increase in resistance to enzymatic degradation. In particular, membrane permeability may be related to an interaction with the Na(+)-dependent D-glucose transporter (SGLT-1) which is located in the brush-border membrane of epithelial cells. The insulin product used in the previous study, however, comprised a mixture of mono-, di- and tri-SAPG-substituted insulin. In this study SAPG-INS with a defined substitution number and position was synthesized to examine the interaction between the transporter and glycosylated insulin in more detail. The new product was mono-SAPG-substituted insulin substituted at the B1-phenylalanine position (B1-SAPG-INS) and was selectively synthesized after protection of the A1-glycine and varepsilonB29-lysine amino acids. The hypoglycemic effect of B1-SAPG-INS in rats after an intravenous dose of 71 microg/kg was almost the same as that of native bovine insulin at a dose of 1 U/kg and B1-SAPG-INS retained about 60% of the immunoreactivity of native bovine insulin. The interaction of B1-SAPG-INS with the intestinal transporter was examined by a rapid filtration technique using (125)I-labeled B1-SAPG-INS and brush-border membrane vesicles (BBMVs) which were prepared from rat small intestine by the Mg-precipitation method. The amount of B1-SAPG-INS adsorbed or absorbed by BBMVs in the presence of an inward Na(+)-gradient into BBMVs was greater than that of native bovine insulin. This adsorption/absorption was significantly inhibited by the presence of 1 mM phloridzin. A similar inhibition was observed when Na(+) was replaced with K(+) and when B1-SAPG-INS was incubated with BBMVs at 4 degrees C. From the effect of osmolarity on the extent of adsorption/absorption, it was considered that B1-SAPG-INS was not taken up into the intravesicular space but adsorbed onto the external membrane surface of BBMVs. These findings suggested that B1-SAPG-INS was adsorbed specifically onto the transporter. The hypoglycemic effect of insulin was enhanced by glycosylation at the B1 position in in situ experiments using normal and diabetic rats. Consequently, it is suggested that B1-SAPG-INS was adsorbed specifically onto the glucose transporter of intestinal BBM. This specific adsorption may be involved in the mechanism of the enhanced hypoglycemic effect of B1-SAPG-INS both in normal and diabetic rats.

Adsorption↗

Synthesis and biological evaluations of C-23-modified 26,26,26,27,27,27-F6-vitamin D3 analogues.

A convenient synthetic method which could allow flexible modification at C-23 of 26,26,26,27,27,27-hexafluoro-1alpha,25-dihydroxyvitamin D3 (3) has been developed. An effective construction of hexafluoroacetone (HFA) aldol part on the side chain of 10 was achieved by aldol reaction with HFA gas. This route is also attractive as an approach to diverse 26,27-modified vitamin D3 analogues. The preliminary biological activities of 23-modifed 26,27-F6 vitamin D3 analogues are evaluated. The potency of VDR affinities of the C-23-substituted analogues (keto group (4); OH group (5a,5b); fluorine atom (6a,6b); and oxetane ring (7a,7b)) was found to vary depending upon both the nature and stereochemistry of the substituents. In contrast, the HL-60 cell differentiation property was less varied than VDR affinity, and depended upon the nature rather than the stereochemistry of the substituents.

Acetone↗

Synthesis and biological activities of the marine bryozoan alkaloids convolutamines A, C and F, and lutamides A and C.

Synthesis of convolutamines and lutamides, new 2,4,6-tribromo-3-methoxyphenethylamine alkaloids isolated from Floridian marine bryozoan Amathia convoluta, was accomplished by a sequence of reactions starting from 3-hydroxyphenethylamines. Cytotoxities of the synthetic lutamides, convolutamines and their de-O-methyl derivatives were examined using drug-sensitive and -resistant P388 as well as KB cell lines. The bioassay suggests that the 2,4,6-tribromo-3-methoxyphenethylamine is an indispensable unit for detection of the activities. Additionally, a reversal of drug resistance by those alkaloids is recognized.

Alkaloids↗

Synthesis and biological evaluations of A-ring isomers of 26,26,26,27,27,27-hexafluoro-1,25-dihydroxyvitamin D3.

The activated vitamin D3 derivative 26,27-F6-1alpha,25(OH)2D3 (2a), its three A-ring diastereomers (2b, 2c, 2d), and 5,6-trans isomer (2e) were prepared. Two analogues (2b, 2c) of these isomers were synthesized by a palladium catalyzed coupling reaction using vinyl bromide 5 and enynes (6a, 6b), which were derived from readily commercially available 2S-(+)-glycidyl p-toluenesulfonate 7, as a common starting material. Competitive vitamin D receptor (VDR) binding affinities of these diastereomers of 2a were evaluated. Interestingly, the stereochemical effects at C-1,3 of 2a were considerably more moderate than those of 1alpha,25(OH)2D3 (1). In particular, isomerization at the 5,6-double bond of 2a only slightly reduced VDR affinity, whereas 5,6-trans-1alpha,25(OH)2D3 had a significantly lower binding affinity than 1.

Animals↗

Topographical characteristics of slow wave activities during the transition from wakefulness to sleep.

OBJECTIVES: This study examined the topographical characteristics of slow wave(delta and theta) activities during the transition from wakefulness to sleep, using topographic mapping of EEG power and coherence. METHODS: Sonography of nocturnal sleep was recorded on 10 male subjects. Each recording, from 'lights-off' to 5 min after the appearance of the first sleep spindles, was analyzed. Typical EEG patterns during the transition from wakefulness to sleep were classified into 9 stages (EEG stages). RESULTS AND CONCLUSIONS: Topographic maps of coherence in delta-and theta-band activities demonstrated that the synchronous component at the anterior-central areas of the scalp appeared corresponding with increasing power. The populations of high coherence pairs among total pairs were computed for each band and each EEG stage to examine the regional differences of EEG. The populations of the delta-band activity increased clearly from EEG stage 6 in the anterior-central areas. The populations of the theta-band activity increased clearly from EEG stage 7 in the anterior-central areas. These results suggest that the dominant synchronous component of slow wave activities during the transition from wakefulness to sleep increased as a function of EEG stages in the anterior-central areas and increased clearly after the appearance of vertex sharp waves.

Adult↗

Efficient transformation of Mesorhizobium huakuii subsp. rengei and Rhizobium species.

The transformation of Mesorhizobium huakuii subsp. rengei B3 with either pBBR122 or pKT230 was carried out. We determined the optimal conditions required for transformation by electroporation and obtained up to 10(5) CFU/microg pBBR122. Plasmids prepared from strain B3 yielded higher transformation efficiency than those from various dam or dcm mutant strains of Escherichia coli. This result suggests that a high transformation efficiency is not related to the methylation of plasmid DNA in E. coli. Using the optimal conditions for electroporation, we performed transformation of several species of Rhizobium, Mesorhizobium and Sinorhizobium. All tested strains of these species were transformed with pBBR122. Strains of M. huakuii and R. phaseoli AHU1133 were transformed at high efficiency, whereas transformation efficiencies of Rhizobium sp. NGR234 and S. meliloti strains were less than 2 x 10(3) CFU/microg plasmid DNA.

Journal Article↗

Development of an enzyme-linked immunosorbent assay for the fungicide imazalil in citrus fruits.

Imazalil has been widely used in citrus fruits such as lemons, oranges, and grapefruits. A competitive enzyme-linked immunosorbent assay (ELISA) was developed for the detection of residual imazalil in citrus fruits. A monoclonal antibody (MoAb) generated to the synthetic imazalil hapten (EIT-0073)-protein conjugate was used. This assay was applied to lemon, orange, and grapefruit matrices for an imazalil analysis. The acceptable residue level for lemons, oranges, and grapefruits in Japan is 5 ppm. The matrix interference was minimized by direct dilution of the sample homogenate. No further cleanup was needed. The detection limit for imazalil in these citrus fruits was 0.1 ng/mL. The recovery of each fortified citrus fruit sample was >81.0%. The imazalil recovery measured by the proposed ELISA was compared to the recovery determined by a conventional HPLC. A good correlation was observed between the proposed ELISA and the HPLC. This proposed ELISA would be useful for monitoring for residual imazalil.

Antibodies, Monoclonal↗