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Biomedical subjects

K Honda

Publications and source records attributed to K Honda.

At least 307 records · Page 17Linked to original sources

Vitamin B12 amplifies circadian phase shifts induced by a light pulse in rats.

Vitamin B12 (VB12) is a putative modulator of the human circadian clock, improving entrainability to the 24 h light-dark cycle. The present study was intended to elucidate the mechanism of VB12 action in an animal model. In male rats free-running under constant dim illumination, a single light pulse of 50-1000 lux for 20 min given at circadian time (CT) 20 induced a 0.28 to 1.08 h phase advance and at CT 14 induced a 0.54 to 2.10 h phase delay. A 3 h intracerebroventricular (icv) infusion of 30 nmol VB12 starting 2 h prior to a 20 min 200 lux light pulse significantly amplified phase shifts in comparison with saline-treated or untreated controls. The mean phase advance (1.13 h) was 1.8-fold greater than that of saline-infused controls, whereas the mean phase delay (2.28 h) was 2.9-fold greater. These values were comparable to the maximal phase shifts caused by 1000 lux light pulses in untreated rats. Since the same VB12 treatment alone had failed to induce a phase shift in a previous experiment, these results indicate that VB12 strongly enhanced light pulse-induced phase shifts and thus augmented the entrainability of the circadian clock to light.

Animals↗

Identification of a region of Bacillus subtilis Ffh, a homologue of mammalian SRP54 protein, that is essential for binding to small cytoplasmic RNA.

Bacillus subtilis Ffh and scRNA are homologues of mammalian SRP54 and SRP RNA, respectively, which are components of the eukaryotic signal recognition particle (SRP). Ffh (446 amino acids) interacts with scRNA to form a stable complex in vivo. Here, we identified an RNA-binding domain of Ffh. The results obtained using a series of deletion mutants show that amino acid positions 364 to 432 in the C-terminal region of Ffh correlates with its ability to bind RNA. The amino acid sequence of this region is well conserved among members of the SRP54 protein family. This sequence contains two hydrophobic regions (h2, 364 to 391, and h3, 416 to 435), separated by the positively charged amino acid motif, 398RRKRIAKGSG407. Among the basic amino acid residues in this region, Arg-401 was essential for binding to scRNA, but Arg-399 and Lys-400 were not. The co-existence of Arg-398 and Lys-404 was necessary for the same affinity as wild type Ffh. The two glycine residues of the 405GSG407 were also essential. MH23 peptide (91 amino acids) encompassing from 356 to 446, consisting of h2-RRKRIAKGSG-h3, bound scRNA with the same affinity as wild type Ffh, whereas a 24-amino acid synthetic peptide 392DIINASRRKRIAKGSGTSVQEVNR415 did not. The region containing two hydrophobic segments separated by the positively charged motif is the minimal requirement of Ffh for RNA binding.

Amino Acid Sequence↗

Amplitudes and time courses of milk ejection bursts of oxytocin neurons in the midbrain-hemitransected lactating rat.

In the midbrain-hemitransected rats, 22 pairs of oxytocin neurons were recorded from 17 rats. Of the bursts on the lesioned side, the amplitude was smaller, the onset time was later and the burst span was shorter (P < 0.01). These results indicated that the amplitude and time course of the burst of oxytocin neurons mainly depend on suckling information from the nipples on their opposite side.

Animals↗

Detection and analysis of the human D4 dopamine receptor gene (DRD4) sequence variant in the Japanese and Mongolian population.

A PCR-based Sma I restriction fragment length polymorphism (RFLP) in the human D4 dopamine receptor (DRD4) gene was investigated in 200 subjects each of Japanese and Mongolian populations. When compared to allele frequencies for Caucasians previously reported by Petronis et al., Japanese and Mongolian populations showed a decreased frequency of the allele which could not be digested with Sma I. The difference in allele distributions between these two ethnically defined populations (Japanese and Mongolians, and Caucasians) was statistically significant (p<0.05). This RFLP was suggested to be a racial difference between Asian and European populations. However, since the frequency of the non-digested allele was extremely low (1%) in the Asian populations, we cannot exclude the possibility that this allele represents a mutation. Sma I PCR-RFLP typing would not only be one of genetic markers, but might also be a specific marker for searching some neuropsychiatric abnormalities.

Alleles↗

Changes in glucose transporter 2 and carbohydrate-metabolizing enzymes in the liver during cold preservation and warm ischemia.

In order to examine glucose metabolism in liver grafts during cold preservation (24 and 48 hr), warm ischemia (60 and 120 min), a combination of the two and reperfusion, the amount of protein and mRNA of glucose transporter 2 and the activities of enzymes in glycolysis (glucokinase, phosphofructokinase, pyruvatekinase), gluconeogenesis (glucose 6-phosphatase, fructose 1,6-bisphosphatase), and the pentose phosphate pathway (glucose 6-phosphate dehydrogenase) were measured. It appeared that glucose transport, the pentose phosphate pathway, and gluconeogenesis were maintained during cold preservation and warm ischemia. The activity of glucokinase significantly decreased from the control value of 1.33 +/- 0.23 IU/g protein to 0.70 +/- 0.17 (24 hr, P<0.05) and 0.57 +/- 0.12 (48 hr, P<0.01) only during cold preservation. However, the activity of phosphofructokinase significantly decreased from the control value of 4.37 +/- 0.06 IU/g protein to 2.67 +/- 0.15 (60 min, P<0.0001) and 1.53 +/- 0.06 (120 min, P<0.0001) only during warm ischemia. This indicates that glycolysis deteriorates during both cold preservation and warm ischemia and demonstrates further that the balance between glycolysis and gluconeogenesis shifts to gluconeogenesis. Even when cold preservation was combined with warm ischemia, the activity of glucokinase decreased only during cold preservation and the activity of phosphofructokinase decreased only during warm ischemia. Furthermore, these changes were time-dependent. It is suggested that they can be used as a clock to measure the durations of cold preservation and warm ischemia separately and that the magnitude of an ischemic injury to a liver and a liver graft's viability can be indirectly estimated before transplantation.

Animals↗

Characteristic changes in sleep patterns during pregnancy in rats.

The purpose of this study was to evaluate changes in sleep patterns during pregnancy to better understand sleep regulation during pregnancy. We uninterruptedly recorded electroencephalogram (EEG), electromyogram (EMG), and brain temperature (Tbr) throughout pregnancy in rats. The duration of non-rapid eye movement (non-REM) sleep decreased after day 5 of pregnancy associated with an inverse increase in the number of non-REM sleep episodes. Thus, the amount of total non-REM sleep time remained constant throughout pregnancy. The amount of total REM sleep time decreased on day 17 of pregnancy after which the reduced state was sustained. That was mainly due to a decrease in the number of REM sleep episodes. Brain temperature (Tbr) gradually decreased as pregnancy advanced, reaching its lowest value 3 days before delivery. These observations provide a better understanding of the sleep patterns during pregnancy, and useful information for investigation of mechanisms of sleep regulation during pregnancy.

Animals↗

Guidelines for donor selection and an overview of the donor operation in living related liver transplantation.

Guidelines for donor selection and an overview of the donor operation are reported on the basis of our experience with 120 cases of living related liver transplantation (LRLT) in pediatric patients. Once the parents had clearly expressed their desire to serve as donors, tests were performed to functionally and anatomically screen the donor livers to determine whether or not the parents' general physical condition allowed them to serve as donors. We then evaluated which of the two parental candidates was more suitable as a donor. The wishes of the family as to which parent should serve as donor was considered secondary and taken into account only in a few cases in which certain functional and/or anatomical abnormalities were uncovered that made the prime candidate less suitable. For the 120 LRLTs, 135 candidates were evaluated as potential donors, 15 (11.1%) of whom were rejected for various reasons. The mean volume of blood loss during the donor operation decreased significantly from 489 g in the first 60 LRLTs to 390 g in the latter 60 LRLTs; this was accompanied by a significant decrease in the mean volume of autologous blood transfused from 449 g to 390 g. Mean cold ischemia time of the graft increased significantly from 71.4 to 128.0 min, while mean operation time conversely decreased from 6.7 to 6.2 h. Bile leakage from the cut surface of the remnant liver, which was the only post-operative surgical complication encountered, was noted in five cases. We conclude that donor candidates should be strictly selected according to basic guidelines, taking into account both the results of preoperative screening and the wishes of the family. With this accumuled experience, we have been able to simplify our LRLT operative procedure, resulting in decreases in blood loss volume, blood transfused, and operation time.

ABO Blood-Group System↗

Involvement of protein kinase C in muscarinic agonist-induced contractions of guinea pig ileal longitudinal muscle.

1. Carbachol (10(-5) M) caused an initial transient contraction (phasic contraction) and a subsequent late contraction (tonic contraction) in the guinea pig ileum. The phasic contraction was markedly suppressed by calmodulin antagonist W-7, but not by protein kinase C inhibitor H-7. 2. The tonic contraction was suppressed by H-7, but not by W-7. 3. The carbachol-induced phasic contraction in the absence of extracellular Ca2+ was suppressed by both W-7 and H-7. 4. Carbachol (10(-5) M) stimulated the formation of inositol phosphates (IPs) in the guinea pig ileum. The carbachol-induced IPs formation was dependent on the extracellular Ca2+ concentration.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Successful engraftment of sibling cord-blood stem cell transplantation in a child with acute promyelocytic leukemia.

Cord blood stem cell transplantation (CBSCT) was performed on a patient with acute promyelocytic leukemia. The patient was a boy 3 years and 8 months old, who had shown complete remission following treatment with intensive chemotherapy. However, after the final course of consolidation chemotherapy, chromosome analysis of his bone marrow aspirates revealed 46XY, t(15,17)(q22;q21), and a PML-RAR alpha fusion gene was detected by the reverse transcriptase-polymerase chain reaction test. All-trans retinoic acid diminished the chromosomal abnormality, but the PML-RAR alpha fusion gene remained. The patient was then treated with CBSCT from an HLA-matched sibling donor. The number of nucleated cells in the cord blood was 2.2 x 10(7)/kg of body weight, and that of granulocyte-macrophage colony-forming units 0.6 x 10(4)/kg. Methotrexate was given, on days 3 and 6, as prophylaxis against graft-versus-host disease (GVHD). The neutrophil count rose to above 500/microliters on day 22. The platelet count exceeded 50,000/microliters on day 48. Platelet transfusions were given 12 times after CBSCT, the last one on day 36. Grade I acute GVHD was treated with steroids. The patient was well and discharged on day 103, without symptoms or laboratory data suggestive of relapse. Following this experience we instituted a project of the Kanagawa Cord Blood Bank, which is scheduled for expansion nationwide.

Adult↗

Evaluating the significance of HLA class II genotype matching in living-related liver transplantation.

To evaluate the clinical significance of HLA class II matching in living-related liver transplantation, the genotypes of HLA class II including DPB1 were determined by the PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) method and their matching was compared to the postoperative course. Conventional serotypes included 15.6% and 13.6% errors in DR and DQ, respectively. Among 42 consecutive cases that were followed up over 1 year after transplant, rejection occurred in seven cases. There was no correlation between the matching for each locus and the frequency of rejection episodes. In this study, rejection-free cases were investigated in terms of the potency of immunosuppressive therapy and graft function during 1 year after operation. The doses of tacrolimus in unmatched cases tended to be larger than those in matched cases for every locus except for DQA1. Its trough levels in matched cases were lower than those in unmatched cases, especially at 9-12 months after operation for DRB1 (p < 0.05). The termination of steroid administration tended to be postponed in unmatched cases for every locus. Serum levels of asparatan transaminase, alanine transaminase gamma-glutamyltranspeptidase (gamma-GTP) and total bilirubin were generally lower in matched cases than in unmatched ones for DRB1, DQB1 and DPB1, while in DQA1 the tendency was the opposite, especially total bilirubin and gamma-GTP, which were p < 0.02 and p < 0.05, respectively, at 6 months after operation. Investigation of subclinical immune responses other than rejection episodes showed that DRB1, DQB1 and DPB1 matching had a beneficial effect on graft function, while DQA1 matching seemed to have a varied effect.

Child↗

Cellular signaling and proliferative action of AVP in mesangium of SHR: effect of low density lipoprotein.

The present study was undertaken to determine whether low density lipoprotein (LDL) modulates the cellular action of arginine vasopressin (AVP) in cultured glomerular mesangial cells of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). The AVP-induced cellular signal transduction, including inositol 1,4,5-trisphosphate (IP3) production, fura-2 intracellular calcium measurements and cellular alkalinization, was significantly greater in cells of SHR than those of WKY. This is based on an increase in AVP V1 receptor number in cells of the SHR. Also, the AVP activation of mitogen-activated protein (MAP) kinase and [3H]thymidine incorporation was significantly exaggerated in cells of SHR compared with those of WKY. LDL at a concentration of 10 micrograms/ml augmented the cellular signaling and proliferative action of AVP in cells of WKY, but not in those of SHR. Since [3H]AVP receptor binding was not affected by the LDL pretreatment, LDL modulates the signal transduction between a location distal to the AVP receptors and proximal from the production of IP3 and diacylglycerol. These results indicate that an increase in AVP receptor capacity has a profound effect on the AVP-induced cellular signaling and proliferation, and that LDL has a slight alteration on the action of AVP in glomerular mesangial cells of SHR.

Animals↗

Milk ejection bursts of supraoptic oxytocin neurones during bilateral and unilateral suckling in the rat.

Extracellular recordings of the electrical activity of oxytocin neurones were made from the supraoptic nuclei (SON) of lactating rats, and the milk-ejection bursts and the background activity of oxytocin neurones were investigated during unilateral and bilateral suckling. When application of pups was limited to the nipples on either the same side (ipsilateral suckling) or the side opposite (contralateral suckling) to the oxytocin neurone recorded, the burst amplitude and background firing rate were significantly (P < 0.05) lower and the inter-burst interval was significantly (P < 0.05) longer than during bilateral suckling. Furthermore, the burst amplitude was significantly (P < 0.05) lower during ipsilateral suckling than during contralateral suckling. The majority of the oxytocin neurones showed a gradual increase in the burst amplitude during bilateral (88.9%) and contralateral (77.3%) suckling, but during ipsilateral suckling only 40% of the neurones did. The inter-burst interval became shorter with the progress of the milk ejection reflex during any mode of suckling. Three pairs of oxytocin neurones recorded simultaneously from both SON were successfully tested for the effect of bilateral and unilateral suckling on the electrical activity, and the results showed the same direction of change in the burst amplitude, background activity and burst interval as shown in single side recordings. These findings indicate that the burst amplitude mainly depends on the amount of afferent suckling signals arising from the nipples on the side opposite to the recording side, and that there may exist bilateral summation centres coordinating with the synchronization mechanism of milk-ejection bursts of oxytocin neurones.

Animals↗

Determination of ester-type local anesthetic drugs (procaine, tetracaine, and T-caine) in human serum by wide-bore capillary gas chromatography with nitrogen-phosphorus detection.

A sensitive method for simultaneous determination of ester-type local anesthetic drugs (procaine, tetracaine, and T-caine) has been developed using wide-bore capillary gas chromatography with nitrogen-phosphorus detection (GC-NPD). The extraction procedure, the experimental conditions for heptafluorobutyryl (HFB) derivative formation, and the percentage of the ester-type local anesthetic drugs from the human serum are described. The HFB derivatives of ester-type local anesthetic drugs showed sensitivity of approximately 2-3 fold higher than that without derivatization. The detection limits of HFB derivatives of the ester-type local anesthetic drugs were approximately 60-70 pg on column. Recoveries from the human serum were 85-94%. This method could be used to determine concentrations as low as 24-28 ng/mliters of the ester-type local anesthetic drugs.

4-Aminobenzoic Acid↗

Median preoptic neurones projecting to the supraoptic nucleus are sensitive to haemodynamic changes as well as to rise in plasma osmolality in rats.

Extracellular single unit activity was recorded from 73 neurones in the median preoptic nucleus (MnPO), identified by antidromic activation as projecting to the supraoptic nucleus (SON) area in urethane-anaesthetized male rats. Thirteen of 73 identified MnPO neurones were silent, and 44 of 60 spontaneously active MnPO neurones were tested for their responses to electrical stimulation of the nucleus tractus solitarius (NTS). The cells were divided into 4 groups according to their responses; those which were excited orthodromically (OD+; n = 15), those which were unresponsive (UN; n = 21), those which were inhibited orthodromically (OD-; n = 4), those which showed initial inhibition followed by excitation (OD-+ n = 4). Some of these neurones were further tested for their responses to haemorrhage and/or produced by intraperitoneal injection of 1.5 M NaCl. Six out of 10 OD+ cells were excited by haemorrhage, 6 out of 11 OD+ cells were inhibited by phenylephrine, and 5 out of 9 OD+ cells were excited by hypertonic saline. On the other hand the UN cells tended to be unresponsive to each type of stimulus. Three out of 7 OD+ cells were excited by both haemorrhage and hypertonic saline, and 3 out of 8 OD+ cells were inhibited by phenylephrine and excited by hypertonic saline. The results may suggest that MnPO neurones which receive afferent input from the NTS may be sensitive not only to haemodynamic change but also to change in plasma osmotic pressure and that such population of MnPO neurones may integrate a part of the haemodynamic and osmotic information and contribute to the control of neurohypophysial hormone release.

Animals↗

Oxytocin receptors expressed and coupled to Ca2+ signalling in a human vascular smooth muscle cell line.

1. In a human vascular smooth muscle cell line (HVSMC), binding experiments with [3H]-arginine8-vasopressin (AVP) have shown the existence of a homogeneous population of binding sites with affinity (Kd value) of 0.65 nM and a maximum number of binding sites (Bmax) of 122 fmol mg-1 protein. 2. Nonlabelled compounds compete for [3H]-AVP binding in the HVSMC membrane with an order of potency of oxytocin > lyspressin > or = AVP > Thr4, Gly7-oxytocin > (beta-mercapto-beta-beta-cyclopentamethylenepropionyl-O-Me Tyr2, Arg8) vasopressin > desmopressin > OPC21268 > OPC31260. This order was markedly different from that observed in rat vascular smooth muscle cells (A10), a well-established V1A receptor system. 3. In HVSMC both oxytocin and AVP increased inositol 1,4,5-trisphosphate (IP3) production and [Ca2+]i response, but the efficacy of the responses was greater for oxytocin than AVP. 4. Reverse transcription-polymerase chain reaction (RT-PCR) assay detected only oxytocin receptor but not V1A or V2 receptors in HVSMC, whereas only V1A receptors were found in A10 cells. 5. In conclusion, in HVSMC only oxytocin receptors are expressed among the vasopressin receptor family, and they coupled to phosphatidyl inositol (PI) turnover/Ca2+ signalling. This unexpected observation should provide new insight into the functional role of the oxytocin receptor in a human vascular smooth muscle cell line.

Animals↗

Acoustic characteristics of the human paranasal sinuses derived from transmission characteristic measurement and morphological observation.

This paper reports on the acoustic characteristics of the paranasal sinuses as determined from transmission characteristic measurements and morphological examinations. A new experimental approach was developed to explore the correspondence between antiresonance frequencies and the causal resonators [J. Dang and K. Honda, J. Acoust. Soc. Jpn. (E) 17, 93-99 (1996)], and it was adopted to determine the antiresonance frequency of each sinus cavity. In this study, the antiresonance frequencies and the locations of the sinus openings were estimated from transmission characteristics of the nasal tract for three subjects, and then MRI-based morphological data for the subjects were used to relate each antiresonance frequency to its causal sinus cavity. The results indicate that each of the three major sinuses, i.e., the sphenoidal, maxillary, and frontal sinuses, contributes its own antiresonances to the transmission characteristics of the nasal tract. The estimated antiresonance frequencies were compared with computed natural frequencies of Helmholtz resonators, and the differences were within 10% for the sinuses. On the basis of the frequency distribution of the sinus antiresonance, the acoustic characteristics of the paranasal sinuses were modeled by four Helmholtz resonators. The simulation with the four-zero model showed that the paranasal sinuses not only introduce antiresonances in the transfer function, but also change the spectral shape of the nasal formants.

Glottis↗

Morphological changes in the peritoneal vasculature of patients on CAPD with ultrafiltration failure.

Vascular changes in the peritoneum were histochemically assessed in patients on continuous ambulatory peritoneal dialysis (CAPD) with ultrafiltration failure. Light microscopy showed extensive interstitial fibrosis, mesothelial denudation and vascular changes. Morphological changes in the vasculature were observed at different levels. The specific changes in the vasculature in these patients were characterized by severe fibrosis and hyalinization of the media of venules. Immunofluorescence microscopy revealed extensive deposition of such extracellular matrices as type IV collagen and laminin in the vascular wall. Electron microscopy revealed a significant increase in collagenous fibers and degeneration of smooth muscle cells in the media. However, the endothelial cells at the levels of vasculature affected were relatively well preserved. These pathological alterations in the vasculature in CAPD patients with ultrafiltration failure suggest that certain toxic factors, such as a high osmolar dialysate or low pH of dialysate, had affected the peritoneal vasculature from the adventitial side rather than the endothelial side. These vascular changes in the peritoneum are thought to be irreversible, associated with deterioration of peritoneal function, and to cause ultrafiltration failure in the patients on long-term CAPD therapy.

Adult↗