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Biomedical subjects

K Nakazawa

Publications and source records attributed to K Nakazawa.

At least 109 records · Page 6Linked to original sources
PubMed1999

The effects of long-term bed rest on H-reflex and motor evoked potential in the human soleus muscle during standing.

H-reflex and motor evoked potential (MEP) induced by transcranial magnetic stimulation (TMS) in soleus muscle of five normal subjects were investigated before and after 20 days 6 degree head-down bed rest (BR). Soleus H-reflex during standing following bed rest decreased in all five subjects. The size of the maximum H-reflex (Hmax), expressed as a percentage of the maximum M-response (Mmax), decreased from 63.3+/-23.3% before BR to 26.7+/-12.5% after BR. However, there were no significant differences between MEPs before and after bed rest. Moreover, MEP/Hmax after bed rest was larger than before bed rest in all subjects. These results indicate a strong inhibition of H-reflex and no adaptation of MEP in soleus muscle during standing following bed rest.

Electromyography↗
PubMed1999

Neighboring glycine residues are essential for P2X2 receptor/channel function.

The roles of a glycine-rich region in the cloned P2X2 receptor/channel were evaluated by site-directed mutagenesis. Responsiveness to ATP was lost when Gly247 was replaced by alanine. The sensitivity to ATP was reduced when Gly248 was replaced by alanine, and the responsiveness to ATP was lost when Gly248 was replaced by valine. The results suggest that the neighboring glycine residues are essential for P2X2 receptor/channel function.

Adenosine Triphosphate↗
PubMed1999

Solution structure of the transactivation domain of ATF-2 comprising a zinc finger-like subdomain and a flexible subdomain.

Activating transcription factor-2 (ATF-2) is a transcription factor that binds to cAMP response element (CRE). ATF-2 contains two functional domains, an N-terminal transactivation domain and a C-terminal DNA-binding domain. The DNA-binding domain contains the basic leucine zipper (bZip) motif. Here, the three-dimensional structure of the transactivation domain of ATF-2 has been determined by NMR. The transactivation domain consists of two subdomains: the structure of an N-terminal half (N-subdomain) is well determined, while a C-terminal half (C-subdomain) takes a highly flexible and disordered structure. The architecture of the N-subdomain is very similar to that of the well-known zinc finger motif found in DNA-binding domains, consisting of an antiparallel beta-sheet and an alpha-helix. The zinc atom is tetrahedrally coordinated to two cysteine residues and two histidine residues. Amino acids that form the hydrophobic core in all of the DNA-binding zinc fingers are well conserved in the N-subdomain of the transactivation domain, whereas some amino acids that are responsible for binding to the phosphate backbone of DNA in the DNA-binding zinc fingers are substituted with other amino acids. The flexible C-subdomain, which contains two threonine residues that the stress-activated protein kinases phosphorylate, is likely to undergo a conformational change by specific binding to a target protein.

Activating Transcription Factor 2↗
PubMed1999

Block and unblock by imipramine of cloned and mutated P2X2 receptor/channel expressed in Xenopus oocytes.

Effects of imipramine on the cloned P2X2 receptor/channel and its mutants expressed in Xenopus oocytes were examined. Imipramine (100 microM) partially blocked an ionic current mediated through the wild-type P2X2 receptor/channel. With a higher concentration (300 microM) of imipramine, the current block was attenuated, suggesting that the second, lower affinity, 'unblocking' binding-site for imipramine exists in addition to the 'blocking' binding-site. These profiles of the modulation by imipramine were influenced by the substitution of negatively charged or polarized amino acid residues near the outer mouth of the channel pore (Asp315, Thr330 and Asn333) with neutral amino acid residues (Val or Ile). With the neutralization of Asp315, the current 'block' by 100 microM imipramine was attenuated. With the neutralization of Thr330, the current 'block' by 100 microM imipramine was enhanced. With the neutralization of Asn333, the 'unblock' by 300 microM imipramine disappeared. The results suggest that imipramine modulates P2X2 receptor/channels by interacting these amino acid residues.

Animals↗
PubMed1999

Evaluation of a hybrid artificial liver using a polyurethane foam packed-Bed culture system in dogs.

BACKGROUND AND AIMS: We developed a polyurethane foam packed-bed culture system of hepatocyte spheroids as a hybrid artificial liver (PUF-HAL), which was effective for recovery from liver failure in rat experiments. In this report, the design of a scaled-up PUF-HAL for dogs is described and evaluated using a dog acute liver failure model. METHODS: Warm ischemic liver failure was induced with a portocaval shunt in each dog. The dogs were divided into two groups: (1) a control group (N = 4), in which each dog was attached to a PUF-HAL without hepatocytes for 9 h, and (2) a HAL group (N = 5), in which each dog was attached to a PUF-HAL with hepatocytes. Blood pressure, blood ammonia, blood glucose, serum creatinine, and other parameters related to liver function were compared between the two groups. RESULTS: In the HAL group, blood ammonia and serum creatinine levels were significantly lower, and blood pressure and blood glucose levels significantly higher, than those in the control group. CONCLUSIONS: The scaled-up PUF-HAL developed for large animals is useful as a liver support system in the dog acute liver failure model.

Ammonia↗
PubMed1999

Level of spinal cord lesion determines locomotor activity in spinal man.

Recent studies have demonstrated that coordinated stepping movements can be induced in patients with complete para-/tetraplegia, when they were standing on a moving treadmill with their body weight partially unloaded and external assistance. The aim of this study was to determine which part of the spinal cord generated the locomotor pattern. In patients with complete paraplegia due to lesions at different levels of the spinal cord, the locomotor pattern was compared with that of healthy subjects. Any similarities in electromyographic (EMG) activity of gastrocnemius and tibialis anterior muscles between the patients and healthy subjects were reflected by the analysis of the variation ratio and amplitudes of the EMG activity. It was found that the higher the level of spinal cord lesion the more "normal" was the locomotor pattern. This suggests that neuronal circuits underlying locomotor "pattern generation" in man are not restricted to any specific level(s) of the spinal cord, but that an intricate neuronal network contributing to bipedal locomotion extends from thoracolumbal to cervical levels.

Adult↗
PubMed1999

Effect of pilsicainide, a pure sodium channel blocker, on spiral waves during atrial fibrillation: theoretical analysis by numerical simulation.

This study investigated the effects of a particular type of sodium channel blocker, pilsicainide, on spiral waves, which are a possible mechanism of atrial fibrillation, by using numerical simulation. A meandering spiral wave was induced on a two-dimensional matrix corresponding to the isolated atrial myocardium. The model attempted to simulate the changes caused by pilsicainide. The conductivity was depressed and the refractory period was prolonged with little change in the action potential duration. The dynamic change in the refractory period depended on the preceding coupling interval. A blockline occurred and changed gradually because of the change in the refractory period. The spiral wave became a stable reentry rotating around the blockline, decreasing the excitation frequency in the matrix before rushing out of the matrix. The electrocardiogram showed a slow coarse wave, as well as a real electrocardiographic change by pilsicainide. This might, in part, explain how pilsicainide acts on atrial fibrillation. Key words: sodium channel blocker, pilsicainide, spiral wave, atrial fibrillation, computer simulation.

Anti-Arrhythmia Agents↗
PubMed1999

The dynamics of vortex-like reentry wave filaments in three-dimensional computer models.

Recent studies using computer simulation and biological studies in 2-dimensional excitable media have suggested that spiral wave reentrant activation and its core dynamics are important elements in the mechanism of functional reentrant tachyarrhythmias, such as atrial and ventricular fibrillation. However, vortex-like reentry has been observed in homogeneous 3-dimensional excitable media, and the dynamics of the related "filaments," which have 3-dimensionally connected "cores" in 2 dimensions, have not been clarified. In order to determine whether the filaments of vortex-like reentry waves can be observed in 3-dimensional media using a mathematical ionic current heart model and whether the abnormal ionic currents in myocardium affect the complexity of the filaments, we studied the qualitative features of vortex-like reentry dynamics using mathematical models in computer simulations. We employed the Luo-Rudy Phase I and the FitzHugh-Nagumo models for our heart media, which were cubic and ventricular shaped, and consisted of 8,000,000 and 5,636,654 myocardial units, respectively. Functional reentry, in the form of vortex waves, was induced in the media by the S1-S2 method. The vortex-like reentry waves and their filaments were displayed by computer graphics. Computations were performed on an NEC SX-4 supercomputer (NEC, Tokyo, Japan) using programs written in C language. Computer simulation studies have shown that the filament dynamics of vortex-like reentry in the original Luo-Rudy model is considerably more complex than that in the FitzHugh-Nagumo model. However, when we mathematically modified the L-type calcium current and shortened the action potential duration, just as occurs with sustained rapid ventricular pacing, the dynamics of the vortex-like reentrant wave fronts and the filaments were similar in both models. Our results suggested that the original character of myocardium causes drastic changes in filament shape and location, resulting in intricate functional reentrant waves, and that if the L-type calcium current is depressed, the complexity of the dynamics of the filaments are decreased to some degree.

Calcium↗
PubMed1999

Screening for inducers of apoptosis in apoptosis-resistant human carcinoma cells.

Many anticancer agents are known to induce apoptosis in cultured cells, but human solid tumor cells are often resistant to apoptosis induction. Human pancreatic adenocarcinoma AsPC-1 cells were found to be resistant to apoptosis. So, we screened microbial culture filtrates and synthetic chemicals for their ability to induce apoptosis in AsPC-1 cells. Polyoxypeptin A was isolated from a Streptomyces culture broth as a potent inducer of apoptosis. Its cyclic hexadepsipeptide structure contains a simple but hitherto unreported amino acid, (2S,3R)-3-hydroxy-3-methylproline. Polyoxypeptin A induced early cell death, apoptotic morphology, and internucleosomal DNA fragmentation in AsPC-1 cells at low concentrations. Polyoxypeptin A can induce caspase 3 activation in human T cell leukemia Jurkat cells but not in AsPC-1 cells. The mechanism of apoptosis in AsPC-1 cells has not been elucidated yet. Less toxic derivatives of polyoxypeptin A are being prepared. A macrocyclic lactam called BE-14106 was also isolated from Streptomyces as an inducer of apoptosis in AsPC-1 cells. Histidine-pyridine-histidine-3 (HPH-3) is an oxygen-activating ligand derived from the structure of bleomycin, and it also induced apoptosis in AsPC-1 cells. Induction of apoptosis by HPH-3 was inhibited by zinc and copper ions, indicating that chelation with ferrous ion is responsible for induction of apoptosis, as is chelation by bleomycin to cleave DNA. Bleomycin A2 and its portion having no DNA-binding region, glycopeptide-3(GP-3), did not induce apoptosis in AsPC-1 cells. Thus, among the actions of bleomycin-related compounds, the induction of apoptosis is a unique characteristic of HPH-3.

Anti-Bacterial Agents↗
PubMed1999

Complement dependence of histamine release in chronic urticaria.

BACKGROUND: IgG autoantibodies directed to the alpha-subunit of the IgE receptor have been identified in 30% to 45% of patients with chronic urticaria. However, the exact mechanism by which histamine secretion is initiated is uncertain. OBJECTIVE: Histamine release from cutaneous mast cells may occur by cross-linking the IgE receptor or by activation of complement. Our goal is to distinguish these 2 possibilities. METHODS: We incubated human cutaneous mast cells with patient sera, decomplemented sera, or purified patient IgG. The IgG was also added to pooled normal serum or to sera deficient in either C2 or C5, and its ability to activate mast cells was assessed. Mast cells were incubated with human IgE myeloma to saturate alpha-subunits to determine the effect on histamine release. RESULTS: Patient sera released histamine (18.26% +/- 4.39%), but purified IgG from patients (5.5% +/- 4.3%) did not. Addition of the patient IgG to normal sera rendered the sera positive for histamine-releasing activity (18.4% +/- 4.3%), whereas control IgG or patient IgG added to C2- or C5-deficient sera did not release histamine. Histamine release with decomplemented patient sera was also diminished (8.34% +/- 4.3%). Preincubation of mast cells with a C5-blocking peptide decreased histamine release but was not statistically significant; there was a significant decrease after preincubating mast cells with IgE myeloma. CONCLUSION: The degranulation of mast cells by IgG autoantibodies in patients with chronic urticaria requires binding to the IgE receptor and activation of the classical complement cascade. Saturation of the IgE receptor with IgE inhibits such degranulation, presumably by preventing binding of the requisite IgG.

Cell Degranulation↗
PubMed1999

Behaviors of bulbar respiratory interneurons during fictive swallowing and vomiting.

Behaviors of the same individual medullary respiratory interneurons were examined during both swallowing and vomiting. In 8 decerebrated and paralyzed cats, 18 neurons having either augmenting expiratory (E-AUG), decrementing expiratory (E-DEC), decrementing inspiratory (I-DEC), or constant inspiratory (I-CON) firing patterns were recorded near the most rostral part of the nucleus ambiguus. All neurons exhibited elementary reflexes to single-shock stimulation of the superior laryngeal nerve. During fictive swallowing elicited by superior laryngeal nerve stimulation, all neurons were basically inactive. During fictive vomiting induced by vagal stimulation and/or emetic drugs, all E-AUG and E-DEC neurons tested either were silent or fired weakly between successive retches, whereas I-DEC and I-CON neurons tested exhibited burst activity during the retching and early-expulsion phases. These results indicate that these bulbar respiratory neurons, which may be involved in respiratory rhythmogenesis, are multifunctional neurons that could also be involved in vomiting but not likely in swallowing.

Animals↗
PubMed1999

5-Hydroxytryptamine inhibits P2X2 receptor channel pore mutants.

1. 5-Hydroxytryptamine (10 microM) enhanced ionic current mediated through the wild-type P2X2 receptor/channel expressed in Xenopus oocytes. 2. 5-Hydroxytryptamine (10 microM) inhibited a current mediated through P2X2 receptor/channel mutants when Thr330 or Asn333 was replaced with Ile (T330I and N333I). 3. Our results suggest that neutralization of Thr330 or Asn333 exposes a high-affinity, inhibitory binding site for 5-hydroxytryptamine. This implies that 5-hydroxytryptamine interacts with the P2X2 receptor/channel at their channel pores.

Action Potentials↗
PubMed1999

Laryngeal mask airway insertion using propofol without muscle relaxants: a comparative study of pretreatment with midazolam or fentanyl.

We determined the effects of pretreatment with midazolam or fentanyl on the ease of laryngeal mask airway insertion using propofol without a muscle relaxant. One hundred and eighty ASA class I or II patients were randomly allocated to one of three groups, 60 patients per group, to receive either placebo (Group C), midazolam 0.05 mg kg-1 (Group M) or fentanyl 2 micrograms kg-1 (Group F), respectively. Following intravenous administration of these drugs, Group C received propofol 2.5 (Group C-2.5) or 3.0 mg kg-1 (Group C-3.0). Group M and Group F received propofol 2.0 or 2.5 mg kg-1 (Group M-2.0, M-2.5, F-2.0 and F-2.5, respectively). There was a smaller incidence of severe head and limb movements on LMA insertion in Group M-2.5, Group F-2.0 and Group F-2.5 than in Group C-2.5. Airway obstruction and inadequate jaw relaxation, which were occasionally recognized in Group C and Group F patients, were not observed in Group M-2.5. Overall the ease of LMA insertion was significantly better in Group M-2.0, Group M-2.5 and Group F-2.5 than in Group C-2.5, however, the blood pressure in Group F after LMA insertion was significantly lower than in Group M. We conclude that pretreatment with midazolam 0.05 mg combined with propofol 2.5 mg kg-1 provides safe and satisfactory conditions for LMA insertion.

Adult↗
PubMed1999

Immunohistochemical analysis of proteoglycan biosynthesis during early development of the chicken cornea.

Antibodies to core proteins of chicken corneal keratan sulfate proteoglycan and chondroitin sulfate proteoglycan were prepared and purified by use of an affinity column. Using these antibodies and monoclonal antibody 5-D-4 to keratan sulfate (commercial), the localization of proteoglycans in developing corneas (Days 5 to 17 of embryonic age and 2 days after hatching) was determined immunohistochemically. Keratan sulfate proteoglycan antigen was not detected in cornea on Day 5, but it was detected uniformly over the whole stroma on Day 6, ca. 12 h after invasion of the primary stroma by mesenchymal cells. The absence of the antigen in cornea of Day 5 was confirmed by Western blotting of the corneal extract. Immunohistochemistry with 5-D-4 antibody revealed that the keratan sulfate chain was undersulfated in corneas of Days 6 to 7, because the staining was much weaker than that in cornea of Day 8. In addition, keratan sulfate proteoglycan antigen was detected uniformly over the whole stroma on Days 7 to 17 and 2 days after hatching, but not in the epithelial layer on Day 13 and after: because the epithelial layer was clearly not observed on photomicrographs until Day 13, it is not known whether keratan sulfate proteoglycan was synthesized by the epithelium during Days 6 to 12. In contrast, chondroitin sulfate proteoglycan antigen was detected in cornea on Day 5 and also, like keratan sulfate proteoglycan, uniformly over the whole stroma on Day 6 through 2 days after hatching. Furthermore, the chondroitin sulfate proteoglycan was not detected in the epithelial layer on Day 13 and after. These results show that keratan sulfate proteoglycan is synthesized by the stromal cells which invade the primary stroma between Day 5.5 and 6, while chondroitin sulfate proteoglycan is synthesized by epithelial and/or endothelial cells before the invasion, and also by the stromal cells after the invasion.

Animals↗
PubMed1999

Preexisting membranous nephropathy in allograft kidney.

A case of membranous nephropathy, preexisting in a donor kidney, will be reported. A 41-year-old man underwent a cadaver renal transplantation. An allograft biopsy specimen obtained during the operation showed spike formation on periodic acid-silver methenamine staining and deposition of IgG along the glomerular capillary loop on immunoperoxidase staining. Immunofluorescence staining for IgG remained in the specimens obtained on day 11 and after 4 weeks, but markedly decreased in the specimen obtained 7 weeks after transplantation. Electron-dense deposits also decreased in amount, but irregular thickening of the glomerular basement membrane with spikes, electron-lucent washout lesions, and small amounts of electron-dense deposits remained 20 months after the transplantation. These findings suggest that membranous nephropathy, as well as IgA nephritis and diabetic nephropathy, resolve after renal transplantation and that deposition of IgG markedly decreases within a few months after transplantation, but that complete histological restoration of the basement membrane needs at least a few years.

Adult↗
PubMed1999

[Leiomyoma of the lung: a case report].

An asymptomatic 43-year-old female was admitted to the Hospital because of an abnormal nodule in the left lung field on screening chest X-ray. Chest CT showed a tumor shadow mass (4 x 3 cm) in the left lower lobe. Bronchofiberscopy revealed an endobronchial polypoid mass obstructing the lower lobe bronchus at the orifice of left B10. Lt lower lobectomy was performed. Histopathological examination of the specimen showed the tumor (4.5 x 3.6 x 3.6 cm) developing not only within the tracheal lumen, but also in the lung tissue. Because immunohistochemical staining for desmin and alpha-smooth muscle actin was positive, we diagnosed leiomyoma. As MRI revealed multiple uterine masses after operation, we discussed the diagnostic problems in the relation to metastasizing leiomyoma of the uterus.

Adult↗
PubMed1999

[Emergency stenting for iatrogenic occlusion of internal carotid artery during percutaneous transluminal angioplasty: a case report].

The authors report the case of a 68-year-old male who underwent emergency stenting for iatrogenic occlusion of the internal carotid artery while he was receiving percutaneous transluminal angioplasty. He presented with a 1-month history of transient ischemic attacks with right-sided hemiparesis. Carotid angiography revealed a 95% eccentric stenosis at the origin of the left internal carotid artery. As the stenotic lesion was higher than the level of the third cervical vertebral body, percutaneous transluminal angioplasty was performed instead of carotid endarterectomy. During the procedure, the left internal carotid artery was dissected, then obstructed completely with rapid deterioration of his neurological condition. The Palmaz-Schatz stent was successfully deployed over the site of dissection to restore normal patency through the dissected carotid artery. Following emergency stenting, his neurological signs quickly subsided. Since then, with oral administration of antiplatelet medication, he has suffered no recurrence of cerebral ischemic events. Echo-ultrasonography 4 months after stent implantation showed good patency of the stented segment. It has been reported that angioplasty is indicated for high-risk patients or surgically inaccessible lesions in stenotic disorders of the internal carotid artery. However, there are several complications reported, including intimal dissection and restenosis. The present case emphasizes the usefulness of emergency stenting when occlusion of the internal carotid artery is complicated during percutaneous transluminal angioplasty.

Aged↗