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Biomedical subjects

K Ishida

Publications and source records attributed to K Ishida.

At least 181 records · Page 10Linked to original sources

The effects of intermittent exposure to hypoxia during endurance exercise training on the ventilatory responses to hypoxia and hypercapnia in humans.

The present study was performed to investigate the effects of a combination of intermittent exposure to hypoxia during exercise training for short periods on ventilatory responses to hypoxia and hypercapnia (HVR and HCVR respectively) in humans. In a hypobaric chamber at a simulated altitude of 4,500 m (barometric pressure 432 mmHg), seven subjects (training group) performed exercise training for 6 consecutive days (30 min x day(-1)), while six subjects (control group) were inactive during the same period. The HVR, HCVR and maximal oxygen uptake (VO2max) for each subject were measured at sea level before (pre) and after exposure to intermittent hypoxia. The post exposure test was carried out twice, i.e. on the 1st day and 1 week post exposure. It was found that HVR, as an index of peripheral chemosensitivity to hypoxia, was increased significantly (P < 0.05) in the control group after intermittent exposure to hypoxia. In contrast, there was no significant increase in HVR in the training group after exposure. The HCVR in both groups was not changed by intermittent exposure to hypoxia, while VO2max increased significantly in the training group. These results would suggest that endurance training during intermittent exposure to hypoxia depresses the increment of chemosensitivity to hypoxia, and that intermittent exposure to hypoxia in the presence or absence of exercise training does not induce an increase in the chemosensitivity to hypercapnia in humans.

Adult↗

Quantity of prelocalized maternal factor is associated with the timing of initiation of an epidermis-specific gene expression of the ascidian embryo.

We produced half-egg-volume ascidian embryos by dividing the unfertilized egg of Halocynthia roretzi at the equatorial plane, and investigated the timing of the initiation of the expression of three tissue-specific genes, a muscle-specific actin gene HrMA4, a notochord-specific gene As-T and an epidermis-specific gene HrEpiC in the half-egg-volume embryos of the animal side and those of the vegetal side. The timing of the onset of HrMA4 and As-T expression in both the animal- and vegetal-half embryos and that of HrEpiC expression in the animal-half embryos were essentially the same as that of normal embryos. In contrast, the timing of HrEpiC expression in the vegetal-half embryos was delayed by one division cycle compared with the normal embryos. This delay was partially recovered by increasing the amount of unfertilized egg cytoplasm of the animal hemisphere, suggesting that the timing of HrEpiC expression is regulated by the amount of a maternal factor which is distributed abundantly in the animal hemisphere of the unfertilized egg.

Actins↗

The role of CD4+ and CD8+ T-cells in host morbidity and innate resistance to angiostrongylus cantonensis in the mouse.

Strain-dependent differences in host morbidity and mortality due to Angiostrongylus cantonensis infection have been established between C57BL/6 and BALB/c mice; C57BL/6 mice show rapid worm killing with low morbidity, whereas BALB/c mice indicate slow worm killing with high morbidity and mortality. To determine the possible roles of CD4+ and CD8+ T-cells in host morbidity and innate resistance to A. cantonensis infection we treated C57BL/6 and BALB/c mice with anti-CD4 or anti-CD8 monoclonal antibody and examined the changes in host morbidity and worm-killing activity. Our study indicates that anti-CD4 antibody treatment interferes with worm killing and improves the morbidity of A. cantonensis-infected BALB/c mice, whereas anti-CD8 antibody treatment fails to improve the morbidity. Tumor necrosis factor-alpha (TNF-alpha, or cachectin) production in infected mice was not correlated with host morbidity. Anti-IL-5 monoclonal antibody treatment also failed to affect the morbidity of infected BALB/c mice, although their worm-killing activity was restrained as shown in anti-CD4-treated mice. These findings clearly indicate that the morbidity of infected BALB/c mice is regulated by some unknown CD4+ T-cell-dependent mechanism but not by an IL-5-, eosinophil-, or TNF-alpha-dependent mechanism.

Angiostrongylus cantonensis↗

Cochlear otosclerosis 30 years after stapedectomy confirmed by CT, MRI.

A 64-year-old Japanese male patient, status post-stapedectomy, presented with progressive, bilateral SNHL of 30 years' duration. CT showed extensive demineralization of the otic capsule, suggestive of otospongiotic change in both ears. There were no hyperostotic lesions found, which would have been suggestive of otosclerotic change. MRI showed a morphologically intact membranous labyrinth in both ears, with no obstruction of the cochlear lumen. It was concluded that the patient has progressive otospongiotic change of the otic capsule, but no otosclerotic change.

Calcification, Physiologic↗

Thiopental and propofol impair relaxation produced by ATP-sensitive potassium channel openers in the rat aorta.

ATP-sensitive potassium channel openers are used as vasodilators in the treatment of cardiovascular disorders. The effects of i.v. anaesthetics on arterial relaxation induced by ATP-sensitive potassium channel openers have not been studied. Therefore, in this study, we have examined if thiopental (thiopentone) and propofol affect the vascular response to the ATP-sensitive potassium channel openers, cromakalim and pinacidil, in the isolated rat aorta. Rings of rat thoracic aortas without endothelium were suspended for isometric force recording. Concentration-response curves were obtained in a cumulative manner. During submaximal contractions with phenylephrine 0.3 mumol litre-1, relaxation after cromakalim 0.1-30 mumol litre-1, pinacidil 0.1-30 mumol litre-1 and papaverine 0.1-300 mumol litre-1 was demonstrated. Thiopental 30-300 mumol litre-1, propofol 10-100 mumol litre-1, 10% Intralipid 45 microliters or glibenclamide 5 mumol litre-1 were applied 15 min before addition of phenylephrine. During contractions with phenylephrine, cromakalim and pinacidil induced concentration-dependent relaxation. A selective ATP-sensitive potassium channel antagonist, glibenclamide 5 mumol litre-1, abolished this relaxation, whereas it did not affect relaxation produced by papaverine. Thiopental concentrations > 30 mumol litre-1 significantly impaired relaxation produced by cromakalim or pinacidil. Propofol concentrations > 10 mumol litre-1 also significantly reduced relaxation produced by cromakalim or pinacidil, whereas Intralipid was ineffective. Thiopental 300 mumol litre-1 and propofol 100 mumol litre-1 did not alter relaxation produced by papaverine. These results suggest that the i.v. anaesthetics, thiopental and propofol, impaired vasodilatation mediated by ATP-sensitive potassium channels in vascular smooth muscle cells.

Adenosine Triphosphate↗

Pharmacokinetics of cisplatin in combined cisplatin and 5-fluorouracil therapy: a comparative study of three different schedules of cisplatin administration.

BACKGROUND: Cisplatin is widely used in combination chemotherapy against a variety of tumors; however, the optimal administration schedule of cisplatin is still controversial. To clarify the pharmacokinetic differences according to the administration schedules of cisplatin, we compared three different administration schedules of cisplatin such as single short-term infusion, daily short-term infusion and daily continuous infusion in combination with 5-fluorouracil. Preliminary clinical responses and toxicities were also investigated. METHODS: A total of 12 courses in combination of cisplatin and 5-fluorouracil therapy was studied. The schedules of cisplatin tested were as follows: single short-term infusion (80 mg/m2, day 1,2 h div., n = 4), daily short-term infusion (20 mg/m2, days 1 to 5, 2 h div., n = 4), daily continuous infusion (100 mg/m2, 120 h, n = 4). In all schedules, 5-fluorouracil was continuously administered at a dose of 800 mg/m2/day on days 1 to 5. The area under the time-concentration curve (AUC) and the maximum concentration (Cmax) of total and free Pt were investigated. RESULTS: The highest AUC of total and free Pt and the lowest Cmax of free Pt were observed in the daily continuous infusion (total AUC; 162.53 +/- 18.39 micrograms h/ml, free AUC; 5.50 +/- 0.9 micrograms h/ml, free Cmax; 0.07 +/- 0.01 microgram/ml, mean +/- SEM). Two patients in the single short-term infusion and one patient in the daily continuous infusion indicated partial responses clinically. No nephrotoxicity or ototoxicity was observed. All toxicities were mild and tolerable in all regimens; however, the incidence of GI toxicity in daily continuous infusion seemed to be relatively higher. CONCLUSIONS: Daily continuous infusion of cisplatin gave the best pharmacokinetic results and to evaluate the clinical advantage of this schedule a prospective randomized trial should be conducted with sufficient numbers of patients.

Aged↗

DNA adduct level induced by 2-amino-3,4-dimethylimidazo[4,5-f]-quinoline in Big Blue mice does not correlate with mutagenicity.

In previous experiments we analyzed the mutant frequency (MF) and mutational types in various organs of lacI transgenic mice which were fed a diet containing 300 p.p.m. 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), a food-borne mutagen/carcinogen. To clarify the relationships between mutational type and adduct molecular species and between adduct level and MF we analyzed adducts in the same DNA samples. The DNA adduct in the liver, heart, colon, forestomach and bone marrow was determined by the modified intensification method of 32P-post-labeling at time points 1, 4 and 12 weeks. Only a single spot corresponding to N2-(deoxyguanosin-8-yl)MeIQ 5'-monophosphate was detected in DNA from all organs at all time points examined, with a recovery of 48%. The difference in mutation type between bone marrow and other organs detected in the previous experiment was not explained by adduct molecular species. At 4 and 12 weeks administration the adduct levels were highest in the liver and then heart, colon, forestomach and bone marrow in decreasing order, with values of 28.3, 8.4, 3.3, 1.3 and 0.4 molecule/10(7) nucleotides at 12 weeks. Based on our previously reported data, lacI MF was highest in the colon and those in the liver, bone marrow and forestomach were 10-60% of that of the colon; no increase in MF was detected in the heart, where no DNA replication is expected except for vascular endothelial cells. There was no direct relationship between MF and adduct level. The MF may be the product of adduct level and cell proliferation rate.

Animals↗

Relationship between maximal pulmonary ventilation and arterialized venous blood potassium and dopamine concentrations obtained at exhaustion in man.

This study was performed to test the hypothesis that potassium concentration in arterialized blood may be closely related to maximal pulmonary ventilation (V.Emax) obtained at exhaustion during maximal exercise in man. Eleven healthy men performed bicycle exercise with incremental loading at 60 rpm until exhaustion. Pulmonary ventilation (V.E), oxygen uptake (V.O2), and heart rate (HR) were determined continuously throughout the experiment. Arterialized venous blood samples were collected to measure potassium ([K+]), lactate ([La]), hydrogen ion (pH), catecholamine ([CA]), and dopamine ([DA]) concentrations. A significant correlation (r = 0.98-0.88) between V.E and [K+], [La], and pH during exercise was observed in all subjects. Furthermore, a close relationship was found in this study between dopamine concentration measured at exhaustion ([DA]0) and maximal pulmonary ventilation per kilogram of body weight (V.Emax/W) (r = -0.668, p < 0.05) or maximum oxygen uptake per kilogram of body weight (VO2MAX/W) (r = 0.720, p < 0.05). However, no significant correlation was found between V. Emax/W and [K+]0 (r = 0.202, NS), [La]0 (r = -0.096, NS), and pH0 (r = 0.344, NS). These results suggest that dopamine may play a more important role in the determination of maximal pulmonary ventilation during exercise in man than K+ or pH.

Adolescent↗

[Study of optokinetic nystagmus and spino-motor functions with cyclo-rotatory optokinetic stimulus].

It has been shown that the neural channels from the otolith organs and the vertical semicircular canals connect to the cyclo-rotatory oculomotor system. However, only a few studies have been conducted to examine the relationship between the cyclo-rotatory optokinetic (COK) and the vestibular inputs. Accordingly, we have analyzed the cyclo-rotatory oculomotor output evoked by a COK stimulus, in 30 subjects; 21 normal adults, 4 elderly persons, and 5 persons with unilateral vestibular dysfunction. In addition, the spinal motor output was simultaneously recorded and comparatively analyzed. The increase in COK nystagmus (COKN) was less than that in horizontal and vertical OKN. There was a significant decline in the maximum slow phase eye velocity in the elderly subjects as well as in the subjects with unilateral vestibular dysfunction, compared to that in the normal adult subjects. Regarding the spinal motor output, in the subjects with unilateral vestibular dysfunction, a pronouned increase in the sway distance from the center of gravity was found with COK stimulus forward the lesioned side. However, with the COK stimulus, there was no significant correlation between the output functions of the cyclorotatory oculomotor system and those of the spinal motor system.

Adult↗

[Evaluation of optokinetic afternystagmus (OKAN) induced by cyclo-rotatory optokinetic stimulation (C-OKst)].

It is not known whether the optokinetic afternystagmus (OKAN) can be evoked by cyclo-rotatory optokinetic stimulation (C-OKst) or not. Accordingly, this study was designed to investigate the problem by using a rotating white dome with random dots. Optokinetic nystagmus (OKN) and OKAN in standing upright, supine, and prone positions were recorded and analyzed with an infrared-ray CCD camera and computed picture analyzer. During stimulation, rotatory OKN showed clearly, but there was no slow-rise component. The OKAN was continuously recorded and analyzed. The component of this OKAN was found only in the head-horizontal direction (yaw axis) in all different head positions. It appeared fairly constantly in the prone posture. The velocity storage mechanism (VSM) had to be charged by the C-OKst, but the OKAN (1st phase) appeared only in the yaw axis, not in the roll axis.

Adult↗

Magnetic resonance imaging of the paranasal sinuses in divers.

BACKGROUND: CT and magnetic resonance imaging (MRI) frequently reveal asymptomatic paranasal sinus mucosal hypertrophy in the general population. HYPOTHESIS: Divers can suffer asymptomatic paranasal sinus mucosal injury secondary to barotrauma. METHODS: We examined 20 professional divers by MRI and compared them to 20 normal controls. Paranasal sinus mucosal hypertrophy was defined as mucosal thickening of 3 mm or greater. RESULTS: Nine divers had paranasal sinus mucosal hypertrophy vs. four controls (p = 0.09). There was no significant relationship between paranasal sinus hypertrophy and age, diving history, alcohol consumption, or smoking. CONCLUSION: Divers had a tendency toward paranasal sinus mucosal hypertrophy.

Adult↗

[Treatment of patients with recurrent esophageal carcinoma].

From 1987 to 1997, 211 patients with thoracic esophageal carcinoma underwent radical surgery. The 5 year survival rate was 87% in pTNM stage I, 64% in stage II A, 57% in stage II B, and 31% in stage III. The survival curve was improved by postoperative chemotherapy including CDDP/5-FU as compared with surgery alone. Relapse occurred in 59 of these patients (28%). Lymphatic recurrence was recognized in 32 patients, hematogenic recurrence in 19, mixed type in 4, and intramural or local recurrence in 4 patients. In spite of through lymph node dissection, postoperative lymphatic recurrence was most frequent at the upper mediastinum and neck. Among hematogenic metastases, pulmonary and hepatic metastases were observed at equal incidences. The 1 year survival rate and median survival period of the patients with recurrent carcinoma were 36% and 191 days (26-1,122), respectively. There was no significant difference in prognosis between lymphatic and hematogenic recurrence. The prognosis for patients who underwent active therapy for recurrence (42 cases) was significantly better than for those who underwent only palliative therapy (17 cases). Resection of the site of recurrence was performed in 4 cases. The combination therapy of resection or irradiation and combined chemotherapy with CDDP and 5-FU resulted in a better prognosis (median survival period was 504 days) than irradiation alone or chemotherapy alone. In conclusion, early diagnosis and active multimodality therapy were important to improve the prognosis of recurrent esophageal carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗

Mutations in the human homologue of the Drosophila patched gene in esophageal squamous cell carcinoma.

The human homologue (PTCH) of the Drosophila segment polarity gene patched has recently been identified as a tumor-suppressor gene for nevoid basal cell carcinoma syndrome and for sporadic basal cell carcinomas of the skin. We analyzed 30 esophageal squamous cell carcinomas (ESCC) for intrageneic mutations of the PTCH gene by polymerase chain reaction-single-strand conformation polymorphism analysis followed by DNA sequencing. We identified two somatic PTCH mutations (7%) in 30 ESCC. These were a nonsense mutation (CAG to TAG at codon 361) in exon 8 and a missense mutation (CAG to CTG, Gln to Leu at codon 816) in exon 14. These tumors exhibited loss of heterozygosity at the polymorphic site of the PTCH gene. These results indicate that inactivation of the PTCH gene via a two-hit mechanism occurs in a subset of ESCC.

Amino Acid Substitution↗

Upregulation of transforming growth factor-beta after panretinal photocoagulation.

PURPOSE: To determine whether upregulation of transforming growth factor-beta (TGF-beta) gene expression occurs after panretinal photocoagulation (PRP). To quantitate two TGF-beta isoforms in the aqueous and vitreous humors and to localize TGF-beta 2-like immunoreactivities (TGF-beta 2-LI) and TGF-beta 2 mRNA in the retina after PRP. METHODS: PRP was performed on Brown Norway rats by using an argon-green laser. Sensory retina, aqueous and vitreous humors were collected from the rats on days 1, 3, and 7 after PRP, and semiquantitative polymerase chain reaction analyses were carried out. TGF-beta 2 in the aqueous and vitreous humors was quantitated by enzyme-linked immunosorbent assay. Localization of TGF-beta 2-LI was demonstrated by immunohistochemistry, and that of TGF-beta 2 mRNA by in situ reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Gene expression of both TGF-beta 1 and -beta 2 was upregulated by PRP. Expression of TGF-beta 2 was greater than that of beta 1 (12.8-fold increase versus 3.24-fold increase, respectively, compared with control level on day 3). TGF-beta 2 concentration was increased in the vitreous humor (4.37-fold increase, P < 0.01) but not in the aqueous humor (the same level compared with control) on day 1. TGF-beta 2-LI and TGF-beta 2 mRNA were detected in cells of the outer retinal layer and in retinal pigment epithelial cells adjacent to the laser burns. CONCLUSIONS: PRP upregulates expression of TGF-beta 2 in the retina, and increased TGF-beta 2 concentrations are found in the retina and the vitreous humor. Retinal pigment epithelial cells and sensory retina around the laser burn appear to play a major role in the upregulation.

Animals↗

Contribution of E-selectin to cellular infiltration during endotoxin-induced uveitis.

PURPOSE: The selectin family is a group of early-reactive adhesion molecules that plays a role in the rolling phase of leukocytes in cellular infiltration. It has been reported that P-selectin is expressed on vascular endothelium in the iris-ciliary body 15 minutes after lipopolysaccharide (LPS) treatment in endotoxin-induced uveitis (EIU) and may contribute to the initial phase of ocular inflammation. The objective of the present study was to identify the expression pattern of E-selectin, another member of the selectin family, and to investigate the role of E-selectin during the course of EIU. METHODS: Endotoxin-induced uveitis was induced in male Lewis rats by a footpad injection of 200 microg LPS. The time-dependent expressions of E-selectin in EIU in the iris- ciliary body and the retina were studied by immunohistochemistry using wholemounts and paraffin-embedded sections and by monitoring the level of E-selectin mRNA expression. A monoclonal antibody to E-selectin and a control antibody were each injected intravenously to evaluate the effects of E-selectin inhibition on ocular inflammation at the time of maximum uveitis. In the anterior uvea, the effect was evaluated by the number of infiltrated cells and by the protein concentration in the aqueous humor 24 hours after LPS treatment; in the retina, the myeloperoxidase (MPO) activity was measured 48 hours after LPS treatment. The effect of the combined injection of anti-P-selectin and anti-E-selectin antibodies was also studied. It was then determined whether the delayed inhibition of E-selectin (6, 12, or 24 hours after LPS injection) could contribute to the early resolution of the uveitis. RESULTS: E-selectin immunoreactivity was observed on the vessel walls of the iris and retina 7 hours after LPS treatment in wholemounts and paraffin-embedded sections and remained positive for 24 hours after LPS treatment. The expression of E-selectin messenger RNA gene peaked at 6 hours and again at 18 hours after LPS treatment in the iris- ciliary body and retina. The expression returned to the basal level 24 hours after LPS treatment in the iris- ciliary body and 48 hours after LPS treatment in the retina. The selective inhibition of E-selectin significantly blocked the cellular infiltration into the aqueous humor (P < 0.005) but had a milder effect on the protein concentration in the aqueous humor (P=0.0536). The inhibition of E-selectin and P-selectin almost abrogated cellular infiltration (P < 0.001). Myeloperoxidase activity in the retina 48 hours after LPS treatment was again significantly decreased by the inhibition of E-selectin alone and by the inhibition of E-selectin and P-selectin (P < 0.0001). A single injection of anti-E-selectin antibody 6, 12, or 24 hours after LPS injection effectively blocked cellular infiltration in the aqueous humor 24 and 48 hours after LPS treatment. CONCLUSIONS: In EIU, E-selectin may be expressed on the vascular endothelium and remain after the period of expression of P-selectin and until approximately the time of maximum uveitis. The present results suggest that, in contrast to the role of P-selectin as an initiator of cellular infiltration, E-selectin may contribute to continuing cellular infiltration into the inflammatory site during inflammation, and its inhibition may contribute to the early resolution of the uveitis.

Animals↗

Sudden death following psychiatric electroconvulsive therapy: a case report.

We report a case of sudden death following psychiatric electroconvulsive therapy (ECT). A schizophrenic patient with manic excitement (39-year-old male) in a mental hospital died while vomiting immediately after ECT. The cause of death was diagnosed as asphyxia due to aspiration of vomitus (choking). It is now considered that ECT is an effective treatment for a range of psychiatric disorders and the benefit-risk ratio is equal to or greater than that of psychoactive drugs. Recently, however, there have been 2 other forensic autopsy reports of death due to ECT in Japan. These cases suggest that more effort and careful management are necessary to prevent the accidental deaths.

Adult↗

Infant death presumably due to exertional self-overheating in bed: an autopsy case of suspected child abuse.

We report a case of accidental infant death presumably due to exertional self-overheating in bed. On a winter morning, a 9-month-old female baby was found dead in her bed at home. She had been confined to the bed overnight by her father, totally covered with a blanket and a thick quilt, because her night crying disturbed his sleep. The clothing and bedclothes were extremely wet with sweat. Many petechial hemorrhages were observed in the upper chest and thoracic viscera. The blood was concentrated, indicative of dehydration. Histological and immunohistochemical investigation revealed findings of shock and myolysis in the cardiac and skeletal muscles. There was no evidence of natural diseases. The main cause of death was diagnosed as circulatory collapse from overheating (hyperpyrexia and dehydration; heat stroke/exhaustion) probably precipitated by struggling in the closed space. Although there was no apparent evidence of battering or any other repetitive physical violence, this case was regarded as an atypical type of fatal child abuse.

Bedding and Linens↗