Biomedical subjects

Y Hishikawa

Publications and source records attributed to Y Hishikawa.

At least 37 records · Page 2Linked to original sources

PubMed1999

Multi-institutional randomized trial of external radiotherapy with and without intraluminal brachytherapy for esophageal cancer in Japan. Japanese Society of Therapeutic Radiology and Oncology (JASTRO) Study Group.

PURPOSE: With the aim of improving the results of treatment of esophageal cancer, we designed this multi-institutional, randomized trial to establish the optimal irradiation method in radical radiation therapy for esophageal cancer by clinically evaluating external irradiation alone and in combination with intraluminal brachytherapy. METHODS AND MATERIALS: The study population consisted of patients with squamous cell carcinoma who were expected to be successfully treated with radical radiation therapy. The patients who could be given intraluminal brachytherapy at the end of external irradiation of 60 Gy were stratified into 2 groups. Patients assigned to receive external irradiation alone received boost irradiation of 10 Gy/week on a schedule similar to the previous one, and with the same or smaller irradiation field. Intraluminal brachytherapy was performed, as a rule, with the reference dose point set at a depth of 5 mm of the esophageal submucosa, and a total of 10 Gy was irradiated at a daily dose of 5 Gy, on a once-weekly schedule with low-dose-rate or high-dose-rate brachytherapy equipment. RESULTS: A total of 103 patients were registered, 94 of whom were analyzable, with 8 ineligible, and 1 for whom complete information was unavailable. The overall cumulative survival rate was 20.3% at 5 years. The cause-specific survival rate was 31.8% at 5 years. The cause-specific survival rate at 5 years was 27% in the external irradiation alone group and 38% in intraluminal brachytherapy combined group. There was no significant difference between the 2 groups (p = 0.385). However, in the patients with 5 cm or less tumor length, the cause-specific survival rate was 64% at 5 years in the intraluminal brachytherapy combined group, which showed a significant improvement over 31.5% in the external irradiation alone group (p = 0.025). In the patients with Stage T1 and T2 disease, cause-specific survival rates tended to be better in the intraluminal brachytherapy combined group than in the external irradiation alone group (p = 0.088). In the patients with more than 5 cm tumor length or Stage T3-4 disease, there were no significant differences between the two groups by treatment methods (p = 0.290). The incidence of early and late complications did not differ according to whether intraluminal brachytherapy was used. CONCLUSION: For the purpose of establishing the usefulness of intraluminal brachytherapy, further prospective randomized studies are necessary to evaluate the efficacy in tumors with short length and those with shallow invasion, or to assess the usefulness of intraluminal brachytherapy, as additional irradiation in large advanced tumors have been shown to have disappeared by diagnostic imaging after chemoradiotherapy with 60 Gy/6w external irradiation.

Adult↗

PubMed1999

Melatonin secretion rhythm disorders in patients with senile dementia of Alzheimer's type with disturbed sleep-waking.

BACKGROUND: There is growing evidence that the dysregulation of circadian rhythms may play an important role in irregular sleep-waking in demented elderly. In this study, we investigated daily variation of the pineal hormone melatonin, which has been reported to possess hypnogenic and synchronizing effects, in patients with senile dementia of Alzheimer's type. METHODS: Serum melatonin secretion rhythms in inpatients with senile dementia of Alzheimer's type (SDAT group, n = 10, average age = 75.7 years) with disturbed sleep-waking and nondemented elderly (ND group, n = 10, age = 78.3 years) without clinical sleep disorders in the same facility were monitored under a dim light condition without excessive physical exercise. RESULTS: The SDAT group showed a significantly higher degree of irregularities in actigraphically recorded rest-activity (R-A) rhythm during the 7-day baseline period compared with the ND group. The SDAT group simultaneously showed significantly reduced amplitude, larger variation of peak times, and diminished amount of total secretion in the melatonin secretion rhythm compared with the ND group. There were significantly positive correlations between the severity of R-A rhythm disorder and the reduced amplitude as well as diminished amount of total melatonin secretion. CONCLUSIONS: The SDAT patients with disturbed sleep-waking possessed melatonin secretion rhythm disorders that may play an important role in irregular sleep-waking in demented elderly.

Aged↗

PubMed1999

Thalidomide increases both REM and stage 3-4 sleep in human adults: a preliminary study.

Polysomnography was used to assess the effect of thalidomide on human sleep. This compound significantly increased the time spent in REM and stage 3-4 sleep as compared with placebo. On the other hand, thalidomide significantly decreased the time spent in stage 1, while the time spent in stage 2 was unchanged. The effect of thalidomide on REM and stage 3-4 sleep is unique as compared with other hypnotics. Although the mode of action of this compound is unknown, further studies on thalidomide should help in our understanding of the mechanisms of sleep regulation.

Adult↗

PubMed1999

The effects of benzodiazepine (triazolam), cyclopyrrolone (zopiclone) and imidazopyridine (zolpidem) hypnotics on the frequency of hippocampal theta activity and sleep structure in rats.

In order to investigate the relative efficacy and safety of zopiclone and zolpidem, we compared the effects of higher doses of zopiclone and zolpidem on the frequency of hippocampal theta activity and sleep structure with that of triazolam. Rats were divided into triazolam treatment group (1 mg/kg, 5 mg/kg), zopiclone treatment group (20 mg/kg, 100 mg/kg) and zolpidem treatment group (20 mg/kg, 100 mg/kg). Rats were injected intraperitoneally with these drugs or their vehicle. Polygraphic sleep recording and visual frequency analysis of the hippocampal EEG activity in REM sleep were carried out for 6 h after each injection. Zolpidem, unlike triazolam and zopiclone, had a much milder reducing-effect on the frequency of hippocampal theta activity and suppressing-effect on REM sleep. These results suggest that zolpidem may prove to be a safer hypnotic drug which has fewer or milder side effects than are benzodiazepine and cyclopyrrolone hypnotics.

Animals↗

PubMed1999

Different effects of L-type and T-type calcium channel blockers on the hypnotic potency of triazolam and zolpidem in rats.

We examined the effects of an L-type Ca2+ channel blocker, nilvadipine (0.5 and 2.0 mg/kg), and that of a T-type Ca2+ channel blocker, flunarizine (10.0 and 40.0 mg/kg), on the hypnotic potency of both a benzodiazepine (BZ)-hypnotic, triazolam (1.0 mg/kg), and a non-BZ hypnotic, zolpidem (20.0 mg/kg), in rats. The polysomnogram was recorded for 6 h after administration of the vehicle solution alone, or after one of the Ca2+ channel blockers, with or without one of the hypnotics. Both Ca2+ channel blockers prolonged the increased total time of non-rapid eye movement (non-REM) sleep induced by either hypnotic. In the case of triazolam, however, the non-REM sleep-enhancing effect induced by nilvadipine was greater than that induced by flunarizine. These findings indicate that the hypnotic action of triazolam is potentiated more strongly by an L-type Ca2+ channel blocker than by a T-type Ca2+ channel blocker.

Animals↗

PubMed1999

Metallothionein expression correlates with metastatic and proliferative potential in squamous cell carcinoma of the oesophagus.

The goal of this study is to clarify whether the expression of metallothionein (MT) could affect the prognosis and the metastatic potential of squamous cell carcinoma (SCC) of the oesophagus. In paraffin-embedded specimens resected from 57 patients, MT mRNA and protein expressions were detected by in situ hybridization and immunohistochemistry respectively. The expression of MT was evaluated in respect of clinicopathologic variables and patients' survival. MT mRNA expression was significantly associated with the proportion of lymph node metastasis (71% in MT mRNA-positive tumours vs 42% in MT mRNA-negative tumours; P = 0.0343) and that of distant metastasis (29% in MT mRNA-positive tumours vs 5% in MT mRNA-negative tumours; P = 0.0452). In respect of MT protein expression, the frequency of distant metastasis was more common in MT-positive tumours than in MT-negative tumours (30% in MT-positive tumours vs 8% in MT-negative tumours; P = 0.0446). The survival rate of the patients with MT protein-negative tumours was significantly better than that of the patients with MT protein-positive tumours (P = 0.0340). There was a positive correlation between the expression of MT protein and that of proliferating cell nuclear antigen (P = 0.0018). Therefore, we conclude that MT expression, both at the mRNA and protein levels, may be a potential marker predicting metastatic and proliferative activities of oesophageal SCC.

Aged↗

PubMed1999

Panic attacks in patients with chronic schizophrenia: a complication of long-term neuroleptic treatment.

Panic attacks meeting the diagnostic criteria for panic disorder (DSM-III-R) were found in nine (20%) of 45 patients suffering chronic schizophrenia for more than 5 years. The scores of the Hamilton Depression Rating Scale and the Simpson Angus Scale were significantly higher in the group of patients with panic attacks. They also tended to be taking neuroleptics in larger doses than in the other group. The present report suggests that long-term treatment with neuroleptics is closely related to the manifestation of panic attacks in chronic schizophrenia. It also suggests that when panic attacks are seen frequently in patients taking high doses of neuroleptics, dose reduction of neuroleptics should be considered.

Adult↗

PubMed1999

Prognostic significance of perioperative blood transfusions in resectable thoracic esophageal cancer.

OBJECTIVE: The perioperative blood transfusions have been associated with tumor recurrence and decreased survival in various types of alimentary tract cancer. There exist, however, contradictory studies showing no relationship between blood transfusions and survival. For patients with esophageal cancer, only one report suggested that blood transfusions did not by itself decrease the chance of cure after esophagectomy. METHODS: Among 235 patients with primary squamous cell carcinoma of the thoracic esophagus between December 1979 and March 1998, 143 patients (60.9%) underwent esophagectomy with curative intent (RO). To exclude the effects of surgery-related postoperative complications, 14 patients who died within 90 days during the hospital stay were excluded. Thus, clinicopathological characteristics and prognostic factors were retrospectively investigated between patients with no or few transfusions (< or = 2 units) (n = 58), and much transfused patients (> or = 3 units) (n = 71). RESULTS: Sixty-three patients are alive and free of cancer, and 66 patients are dead. A total of 98 patients (76%) received blood transfusions, whereas 31 patients (24%) had no transfusion. The amount of blood transfused was 1 or 2 units in 27 patients (27.6%), 3 or 4 units in 33 (33.7%), 5 or 6 units in 20 (20.4%), and > or = 7 units in 18 (18.4%). The 5-yr survival rate for patients with no or few transfusions was 69%, whereas that for much transfused patients was 31.7% (p < 0.0001). The much transfused patients had more prominent ulcerative tumor, longer time of operation, more estimated blood loss, and more marked blood vessel invasion than the group with no or few transfusions. The factors influencing survival rate were tumor location, Borrmann classification, size of tumor, depth of invasion, number of lymph node metastases, time of operation, amount of blood transfusions, lymph vessel invasion, and blood vessel invasion. Among those nine significant variables verified by univariate analysis, independent prognostic factors for survival determined by multivariate analysis were number of lymph node metastasis (0 or 1 vs > or = 2, p < 0.0001), amount of blood transfusions (< or = 2 units vs > or = 3 units, p < 0.0001), and blood vessel invasion (marked vs non-marked, p = 0.0207). CONCLUSIONS: There is an association between high amount of blood transfusions and decreased survival for patients with resectable esophageal cancer. To improve the prognosis, surgeons must be careful to reduce blood loss during esophagectomy with extensive lymph node dissection and subsequently must minimize blood transfusions.

Aged↗

PubMed1999

The fragment of complement 3a lacking the primary 9 amino acids induces promoting activity on mouse voluntary running.

We have newly found that interleukin-2 (IL-2) increases mouse voluntary running 24 hours, but not 30 minutes, after the injection. We suspected that IL-2 induced a substance increasing the voluntary running for 24 hours after injection. Serum obtained from mice 24 hours after the IL-2 treatment was fractioned with the use of an ion-exchanger and an ultra-filtration method, and the amino acid sequence analysis indicated that the substance purified from the effective fraction was a fragment of mouse complement 3a (C3a) lacking the primary 9 amino acids. The 20 amino acid peptide synthesized according to the fragment showed the activity increasing the voluntary running, but the 20 amino acid peptide synthesized according to the C3a itself did not. The effect of the synthesized peptide was demuted by haloperidol but not by a specific dopamine 2 antagonist (-)sulpiride. The present findings clearly indicate that IL-2 produces the C3a fragment lacking the primary 9 amino acids which directly promotes the voluntary running, and that the effect of the fragment is mediated by an activity of haloperidol on the neurons, except for the dopamine 2 antagonism.

Amino Acid Sequence↗

PubMed1999

Effects of repeated selective serotonin reuptake inhibitor paroxetine treatments on mouse forced swimming.

Studies were performed in the mouse forced swimming model, a well known experimental depression model, in order to detect the mechanism of the antidepressive effects induced by repeated serotonin reuptake inhibitor (SSRI) dosing. Five-day repeat dosing of a typical SSRI, paroxetine, increased climbing, a distinctive antidepressive behavior, 1 h after but not 1 h before treatment. The coinjection of paroxetine and serum in mice treated with four repeated doses of paroxetine distinctively increased the behavior, but the coinjection of paroxetine and serum in mice without paroxetine did not. These results indicate that repeated dosing of paroxetine produces a serum substance related to the antidepressive effects induced by serotonin neuron activities. Furthermore, the behavior induced by 5-day repeated dosing of paroxetine was decreased by 100 and 10 micrograms/kg of ketanserin (5-HT2 antagonist) and 100 micrograms/kg of LY-278584 (5-HT3 antagonist). The present findings strongly suggest that repeated dosing of paroxetine produces a serum substance stimulating the antidepressive neuronal pathway sensitively mediated by 5-HT2 and 5-HT3 receptor activity.

Animals↗

PubMed1999

The role of P-glycoprotein in human gastric cancer xenografts in response to chemotherapy.

BACKGROUND: To clarify the contribution of P-glycoprotein (P-GP) to drug resistance of gastric cancer, the correlation between chemosensitivity of the tumor and expression of P-GP was examined using human gastric cancer xenografts in nude mice. METHODS: Two strains, P-GP-positive and -negative, were established using primary explants from patients who had not received chemotherapy. Their stable growth was obtained by serial passages as subcutaneous tumors in nude mice. Mitomycin C (MMC, 3.25 mg/kg), adriamycin (ADR, 6mg/kg), or cisplatin (CDDP, 6mg/kg) was administered intraperitoneally once a week for 3 weeks. RESULTS: In the P-GP-negative strain, all three drugs significantly suppressed the tumor growth, while in the P-GP-positive strain, only MMC did so. However, the growth inhibition of MMC was apparently greater in the P-GP-negative strain than in the positive tumor. The expressions of metallothionein (MT), glutathione-S-transferase-pi (GST-pi), and p53 were not different between the strains. Bcl-2 was expressed only in the P-GP-negative strain. Induction of P-GP expression was observed in some specimens after treatment with MMC and with CDDP. CONCLUSIONS: P-GP might affect inherent and acquired resistance against chemotherapeutic agents in gastric cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1998

Single and repeated electroconvulsive shocks activate dopaminergic and 5-hydroxytryptaminergic neurotransmission in the frontal cortex of rats.

1. The effect of electroconvulsive shock (ECS) on the extracellular concentration of dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) was examined in the frontal cortex of rats with the use of in vivo microdialysis. 2. The extracellular concentration of DOPAC, HVA and 5-HIAA was largely increased after the first ECS treatment. The increase after the eighth ECS treatment tended to be attenuated or was significantly attenuated as compared to that after the first ECS treatment. The baseline concentration of DOPAC and 5-HIAA was significantly increased after repeated ECS, though that of DA and HVA did not show any significant change after repeated ECS. 3. These results suggest that the activating effect of repeated ECT on 5-hydroxytryptaminergic (5-HT) and DA neurotransmission, (especially on 5-HT neurotransmission), is significant in improving depression both in patients with Parkinson's disease (PD) and in those who do not suffer from PD.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1998

A negative component on event related potential recorded in the drowsy state.

Behavior of event related potential (ERP) components in the drowsy state was examined in nine subjects using oddball paradigm. A component with peak latency of 300 msec, N300, was superimposed on ERP in the drowsy state. N300 appeared also in stage 1 of NREM sleep and closely resembled vertex sharp wave evoked by sound stimulation in both scalp distribution and peak latency. It was suggested that N300 recorded in the drowsy state and vertex sharp wave recorded in stage 1 of NREM sleep are generated by the identical synchronizing mechanism in the brain.

Adult↗

PubMed1998

Some sensory stimuli generate spontaneous K-complexes.

The present study was performed in order to determine whether spontaneous K-complex are induced by sensory stimuli. Electroencephalogram (EEG) segments in stage 2 sleep containing an evoked K-complex or spontaneous K-complex were separately averaged with respect to the peak of N300, one of the main components constituting the K-complex. Small negative and positive components were found immediately before the main components of spontaneous K-complex in averaged EEG. These two components were judged to correspond to N100 and P200 induced by the sound stimulus. The present findings suggest that the spontaneous K-complex is not a spontaneous phenomenon but that it is induced by sensory stimuli.

Adult↗

PubMed1998

Cortical activity of REM sleep often occurs earlier than other physiological phenomena.

N300 appearing in response to sound stimulus was used as an index to determine the occurrence of cortical activity characterizing REM sleep. In 5/10 subjects, marked reduction of N300 amplitude occurred even in the period of 0.5-2.5 min immediately preceding the appearance of muscle atonia characterizing REM sleep. Neither muscle atonia nor rapid eye movements appeared prior to the marked reduction of N300 amplitude in any subject. This suggests that the cortical activity characterizing REM sleep sometimes occurs a few minutes (or less) earlier than other physiological phenomena.

Adult↗

PubMed1998

Prevalence of sleep-related respiratory disorders in 101 schizophrenic inpatients.

We studied the prevalence of sleep-related respiratory disorders (SRRD) in 101 schizophrenic inpatients (64 men and 37 women) and in 48 healthy volunteers (control group: 22 men and 26 women) using ambulatory pulse-oximetric devices. Those with a desaturation index (DI) > or = 5 were classified as having SRRD. The prevalence of SRRD in the schizophrenic patients (men 21.9%, women 13.5%) was not higher than that in the control group (men 30.7%, women 13.6%). Gender difference in the prevalence of SRRD was not observed in schizophrenic group. This was probably because the schizophrenic women took an increased amount of sleeping pills. Neuroleptics were shown to be least effected on SRRD.

Adult↗

PubMed1998

Sleep-disordered breathing in a patient with congenital myopathy.

A case of adult onset myopathy who showed a peculiar sleep-related respiratory disorder (SRRD) is reported. She recovered from respiratory failure after tracheostomy and/or with the aid of the respirator used only during the night. Sleep study without the use of respirator revealed that her sleep was highly fragmented by frequent arousal responses due to inspiratory effort but not by apnea or hypopnea. To our knowledge this type of SRRD has not been described.

Arousal↗

PubMed1998

Randomized, dim light controlled, crossover test of morning bright light therapy for rest-activity rhythm disorders in patients with vascular dementia and dementia of Alzheimer's type.

The authors compared the therapeutic effect of morning bright and dim light exposure on rest-activity (R-A) rhythm disorders in patients with vascular dementia (VD) and patients with dementia of Alzheimer's type (DAT). Participants in this study were 12 patients with VD (M/F = 5/7; average age = 81 years) and 10 patients with DAT (M/F = 4/6; average age = 78 years). They were exposed to 2 weeks of bright light (BL; 5000-8000 lux) and 2 weeks of dim light (DL; 300 lux) in the morning (09:00-11:00) in a randomized crossover design in which the 2-week treatment period took place between pretreatment (1 week) and posttreatment (1 week) periods. Continuous R-A monitoring was performed at 1-minute intervals throughout the study using an actigraph around the nondominant wrist. The BL exposure for 2 weeks induced a significant reduction in both nighttime activity and percentages of nighttime activity to total activity compared with the pretreatment period, as well as compared with the DL condition in the VD group, but not in the DAT group. These findings support the assumption that the therapeutic efficacies of morning BL exposure are prominent in VD patients and are mainly due to its photic effect rather than nonphotic effects such as the intensification of social interaction accompanying light therapy.

Activity Cycles↗