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Biomedical subjects

K Kaneko

Publications and source records attributed to K Kaneko.

At least 109 records · Page 6Linked to original sources

Spontaneous blinks as a criterion of visual fatigue during prolonged work on visual display terminals.

Visual fatigue caused by prolonged work viewing a Visual Display Terminals (VDT) and of work reading a hard-copy were assessed by electromyogram (EMG) waveform and electrooculogram (EOG) waveform in spontaneous blinks as objective criteria, and by questionnaire of subjective feeling, and by task performance. The duration and the amplitude of the EMG of the orbicularis ocular muscle on the right side and the EOG of the vertical direction to the eyelid were measured for 10 subjects who participated in a figure task consisting of the addition of single-digit numbers on a VDT work or a work with a hard-copy. The mean values of the duration and the amplitude of the EMG and the EOG were evaluated by the averaging of 10 waveforms of the spontaneous blinks for all subjects. The time lag from the EMG to the EOG in the process of the generation of spontaneous blinks was also analyzed. These five parameters were evaluated during the work time. The mean values for the duration of the EMG increased gradually during the work time, but the amplitude did not show significant difference between the prework and a work time. There was no significant change of the duration of the EOG, but the mean amplitude of the EOG decreased as the work time progressed, and the time lag significantly extended. The blinks frequency increased relatively when using a VDT. The rate of fluctuation for these parameters was higher during use of a VDT than use of a hard-copy. The time lag at five hours of VDT work was extended by 90% based on the value at the pre-work. The symptoms of general fatigue and fatigue of the eyes increased linearly during the VDT work for six hours. The results indicated a significant correlation between the objective parameters for the activity of the spontaneous blinks, i.e., duration and amplitude of EMG and EOG, and the time lag between EMG and EOG, and the subjective feeling was recognized in the time course of the task. These experimental results suggested that the parameters regarding the EMG and the EOG for the spontaneous blinks were effective indices for assessing visual fatigue during prolonged VDT work.

Adult↗

Human BAC contig covering the deleted region in pancreatic cancer at 12q21.

In sporadic human primary pancreatic cancer tissues, loss of heterozygosity is frequently observed in the 1-cM region between D12S81 and D12S1719 at 12q21. Loss of this chromosome arm is known to be associate with a poor prognosis in pancreatic cancer patients. Herein we report a complete contig of human bacterial artificial chromosome (BAC) clones covering the deleted region. The region was covered by 21 BAC clones in a minimum tiling path. The clones were confirmed to exist at 12q21 by fluorescence in situ hybridization. We identified novel 40 sequence tagged sites and mapped 10 expressed sequence tags in this region. The BAC contig reported here provides an avenue for determining the complete nucleotide sequence and mining putative tumor suppressor genes in the deleted region of pancreatic cancer at 12q21.

Base Sequence↗

[Clinical study of operated nine thymic carcinomas].

Nine cases of thymic carcinoma (5 males and 4 females) were operated in our hospital between 1990 and 1998. These cases included 4 squamous cell carcinomas, 2 small cell carcinomas, 2 undifferentiated carcinomas and one adenocarcinoma. Preoperative chemotherapy were performed in 3 cases. All cases underwent median-sternotomy followed by mediastinal irradiation, 4 had total resection of the tumor, 2 had subtotal resection and 3 had exploratory thoracotomy followed by mediastinal irradiation. Adjuvant chemotherapy were administered in 4 cases and re-operation were performed in 2 cases. We applied Masaoka's clinical staging for thymoma, nine cases consisted of 6 stage III cases, 2 stage IV b cases and one stage IV a case. Within 2 years after operation, 3 cases (two complete resection cases and one exploratory thoracotomy case) were died of the carcinoma. However, two cases of squamous cell carcinoma have been alive more than 5 years after surgery followed by chemoradiation. The remaining 4 patients are alive either with or without the carcinoma after 7 to 28 months after operation. Thymic carcinoma is not so common mediastinal tumor but is expected to increase in the future. The treatment of thymic carcinoma remains a controversial matter and the survival is poor compared with invasive thymoma, but multimodal-therapy would contribute to improvement of the results in treatment for thymic carcinoma especially in squamous cell carcinoma.

Adenocarcinoma↗

Spontaneous blinks of Parkinson's disease patients evaluated by EMG and EOG.

In a study of spontaneous blinks, both electromyographic (EMG) activities from m. orbicularis oculi which is responsible for initiating closure of the eyelid and electro-oculogram (EOG) of vertical direction to the movement of the eyelid were measured in ten patients with Parkinson's disease and in thirty normal subjects. The aim of this study was to evaluate the generative mechanism of the spontaneous blinks by comparison of both the EMG and the EOG waveforms in the patients with Parkinson's disease and those in the normal subjects. The mean duration and the amplitude of both the EMG and the EOG were evaluated by the averaging of ten waveforms for the spontaneous blinks. The time lag between the onset of the generation of the EMG and the onset of the EOG signal was analyzed. The mean duration of the EMG and the mean amplitude of both the EMG and the EOG in the patients with Parkinson's disease were shorter and smaller than those in the normal subjects by the significant level of 1%, respectively. There was no difference of the time lag between the subject groups. These results suggest that the function of m. orbicularis oculi for the spontaneous blinks is reduced in patients with Parkinson's disease, because the motoneurones of the facial nucleus innervating the m. orbicularis oculi becomes hypoactive due to abnormal output of basal ganglia.

Aged↗

[A case of esophageal carcinoma with multiple liver metastases successfully treated with nedaplatin (NDP) and 5-fluorouracil (5-FU) combined with radiotherapy].

A 78-year-old male patient had esophageal carcinoma with multiple liver metastases. Chemoradiotherapy was performed. The chemotherapy consisted of protracted infusion of 5-fluorouracil (5-FU), combined with infusion of nedaplatin (NDP). Radiation of the mediastinum was administered concomitantly with chemotherapy. The patient showed a complete response (CR) of the primary lesion and a partial response (PR) of the liver metastasis for 11 months. Since liver metastasis recurred after initial treatment, chemotherapy consisting of NDP infusion combined with vindesine sulfate (VDS) infusion was performed. The patient again showed PR. Grade 3 leukocytopenia occurred during treatment, but there were no major toxicities such as thrombocytopenia, nausea, renal dysfunction or esophagitis. Survival time was one year and 7 months. In conclusion, concurrent chemoradiotherapy including NDP is effective and safe for patients with esophageal carcinoma accompanied by multiple liver metastasis. This nonsurgical approach may be an option for standard care in such cases.

Aged↗

[Acceptable definition of peripheral early lung cancer].

This study was conducted to evaluate the outcome of 88 patients who underwent surgical resection for peripheral non-small cell lung cancers less than 20 mm in diameter. Twenty-one cases with lesions smaller than 10 mm had no lymph node metastasis, intrapulmonary metastasis, pleural dissemination, or distant metastasis. The 5-year survival rate of them was 100%. However, 67 patients with tumors larger than 10 mm showed lymph node metastasis in 14 cases, intrapulmonary metastasis in 3, pleural dissemination in 2 and distant metastasis in 1. And the 5-year survival rates of patients with tumor dimensions of < or = 15 mm and < or = 20 mm were 77.9% and 74.4%, respectively. In addition, patients having adenocarcinoma categorized A and B by Noguchi's classification had no lymph node metastasis, intrapulmonary metastasis, pleural dissemination, or distant metastasis, and showed 100% of 5-year survival rate. To be defined as early cancers in terms of curability, it is thought that the 5-year survival rate of the patients with them is over 95%. Therefore, these results suggest that tumors smaller than 10 mm or adenocarcinoma less than 20 mm in diameter diagnosed as Noguchi's A and B are considered as peripheral early lung cancers.

Adult↗

Sympatric speciation: compliance with phenotype diversification from a single genotype.

A novel mechanism for sympatric speciation that takes into account complex bioprocesses within each individual organism is proposed. According to dynamical systems theory, organisms with identical genotypes can possess differentiated physiological states and may coexist 'symbiotically' through appropriate mutual interaction. With mutations, the phenotypically differentiated organisms gradually come to possess distinct genotypes while maintaining their symbiotic relationship. This symbiotic speciation is robust against sexual recombination, because offspring of mixed parentage with intermediate genotypes are less fit than their parents. This leads to sterility of the hybrid. Accordingly, a basis for mating preference also arises.

Biological Evolution↗

Intrahepatic anastomosis formation between the hepatic veins in the graft liver of the living related liver transplantation: observation by Doppler ultrasonography.

In living related liver transplantation, the right lobe has come to be used as a graft to meet the metabolic demands of adult or adolescent recipients. In harvesting the right lobe as a graft, however, there is controversy as to whether or not the middle hepatic vein (MHV) should be included and reconstructed. Anatomical intrahepatic anastomosis between the right hepatic vein (RHV) and MHV is considered to exist, but the formation process of this functional anastomosis has not been demonstrated by Doppler ultrasonography (US). In our case, a right lobe including a right branch of the MHV was used as a graft. In implanting, the RHV was anastomosed to the inferior vena cava and the right branch of the MHV was ligated. Using Doppler US, we checked the blood flow in the hepatic vein after transplantation. Within 3 days of surgery, no flow was detected in the right branch of the MHV. A flow around the right branch of the MHV was observed at postoperative day 6. At postoperative day 9, a reverse flow was detected in which the right branch of the MHV drained into the RHV via the anastomosis between them. Based on our results, it appears that a functional intrahepatic anastomosis between hepatic veins formed gradually within 10 days of ligation of an afferent branch, during which time the graft function did not deteriorate.

Adolescent↗

Detection of mutation of the p53 gene with high sensitivity by fluorescence-based PCR-SSCP analysis using low-pH buffer and an automated DNA sequencer in a large number of DNA samples.

Detection of mutations in genes responsible for hereditary diseases or tumors is important clinically. It is necessary to establish a simple technique for screening mutations in large numbers of samples. The polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) method has proved to be a useful technique for analyzing mutations or DNA polymorphisms. Non-radioisotopic versions using fluorescent dye and an automated DNA sequencer have also been exploited to extend this technique into the clinical field. We have examined mutations of exons 5-9 of the p53 gene in 112 colorectal, 28 esophageal and 33 hepatocellular carcinomas by fluorescence-based PCR-SSCP (F-SSCP) under various conditions. We found 64 types of mutations in 63, 17 and 12 cases of colon, esophageal and hepatocellular carcinomas by F-SSCP. We determined the sequence of all samples, and confirmed that all mutations were successfully detected by F-SSCP. With the low-pH buffer system, 61 types of mutants were detected, while 51 types were detected by TBE and 57 types were detected by TBE with glycerol gel. The polyacrylamide gel in TME or TBE without glycerol was tough and could be used repeatedly, but the glycerol containing gel was fragile and could not stand repeated use. Thus, use of a low-pH buffer in the electrophoresis of F-SSCP is simpler and better at detecting mutations than the conventional TBE buffer system. We believe that low-pH F-SSCP analysis is an efficient and powerful technique for examination of a large number of samples, in particular clinical specimens obtained by biopsy or surgery.

DNA Mutational Analysis↗

Origin of complexity in multicellular organisms.

Through extensive studies of dynamical system modeling cellular growth and reproduction, we find evidence that complexity arises in multicellular organisms naturally through evolution. Without any elaborate control mechanism, these systems can exhibit complex pattern formation with spontaneous cell differentiation. Such systems employ a "cooperative" use of resources and maintain a larger growth speed than simple cell systems, which exist in a homogeneous state and behave "selfishly." The relevance of the diversity of chemicals and reaction dynamics to the growth of a multicellular organism is demonstrated. Chaotic biochemical dynamics are found to provide the multipotency of stem cells.

Cell Communication↗

Haplotype-phenotype correlation in Fukuyama congenital muscular dystrophy.

In typical Fukuyama congenital muscular dystrophy (FCMD), peak motor function is usually only unassisted sitting or sliding on the buttocks, though a few patients are able to walk at some point. However, a few patients have a severe phenotype and never acquire head control. In addition, it is clinically difficult to differentiate this severe FCMD from Walker-Warburg syndrome (WWS) or from muscle-eye-brain disease (MEBD). In order to establish a genotype-phenotype correlation, we performed haplotype analysis using microsatellite markers closest to the FCMD gene (FCMD) in 56 Japanese FCMD families, including 35 families whose children were diagnosed as FCMD with the typical phenotype, 12 families with a mild phenotype, and 9 families with a severe phenotype. Of the 12 propositi with the mild phenotype, 8 could walk and the other 4 could stand with support; 10 cases were homozygous for the ancestral founder (A-F) haplotype whereas the other 2 were heterozygous for the haplotype. In the 9 severe cases, who had never acquired head control or the ability to sit without support, 3 had progressive hydrocephalus, 2 required a shunt operation, and 7 had ophthalmological abnormalities. Haplotype analysis showed that 8 of the 9 cases of the severe phenotype are heterozygous for the A-F haplotype, and the other one homozygous for the haplotype. We confirmed that at least one chromosome in each of the 56 FCMD patients has the A-F haplotype. The rate of heterozygosity for the A-F haplotypes was significantly higher in severe cases than in typical or mild cases (P < 0.005). Severe FCMD patients appeared to be compound heterozygotes for the founder mutation and another mutation. Thus, the present study yielded molecular genetic evidence of a broad clinical spectrum in FCMD.

Brain↗

Mimicking dominant negative inhibition of prion replication through structure-based drug design.

Recent progress determining the structure of the host-encoded prion protein (PrP(C)) and the role of auxiliary molecules in prion replication permits a more rational approach in the development of therapeutic interventions. Our objective is to identify a new class of lead compounds that mimic the dominant negative PrP(C) mutants, which inhibit an abnormal isoform (PrP(Sc)) formation. A computational search was conducted on the Available Chemicals Directory for molecules that mimic both the spatial orientation and basic polymorphism of PrP residues 168, 172, 215, and 219, which confer dominant negative inhibition. The search revealed 1,000 potential candidates that were visually analyzed with respect to the structure of this four-residue epitope on PrP(C). Sixty-three compounds were tested for inhibition of PrP(Sc) formation in scrapie-infected mouse neuroblastoma cells (ScN2a). Two compounds, Cp-60 (2-amino-6-[(2-aminophenyl)thio]-4-(2-furyl)pyridine-3, 5-dicarbonitrile) and Cp-62 (N'1-(¿5-[(4, 5-dichloro-1H-imidazol-1-yl)methyl]-2-furyl¿carbonyl)-4 methoxybenzene-1-sulfonohydrazide), inhibited PrP(Sc) formation in a dose-dependent manner and demonstrated low levels of toxicity. A substructure search of the Available Chemicals Directory based on Cp-60 identified five related molecules, three of which exhibited activities comparable to Cp-60. Mimicking dominant negative inhibition in the design of drugs that inhibit prion replication may provide a more general approach to developing therapeutics for deleterious protein-protein interactions.

Algorithms↗

Postnatal development of a GABA deficit and disturbance of neural functions in mice lacking GAD65.

The 65-kDa isoform of glutamic acid decarboxylase (GAD65) is believed to play an essential role for GABA synthesis in the central nervous system. Using mice with targeted disruption of the GAD65 gene (GAD65(-/-) mice) we investigated the contribution of GAD65 to GABA synthesis in different brain areas during postnatal development and in adulthood. In the amygdala, hypothalamus and parietal cortex of GAD65(+/+) mice an increase of GABA levels was observed during postnatal development, most prominently between the first and second month after birth. This increase appeared to be dependent on GAD65, as it was delayed by 2 months in GAD65(+/-) mice and was not observed in GAD65(-/-) mice. Likely as a consequence of their GABA deficit, adult GAD65(-/-) mice showed a largely abnormal neural activity with frequent paroxysmal discharges and spontaneous seizures. They furthermore displayed increased anxiety-like behaviour in a light/dark avoidance test and reduced intermale aggression, as well as a reduced forced-swimming-induced immobility indicative of an antidepressant-like behavioural change. Adult GAD65(+/-) mice did not show behavioural disturbances except for a reduced aggressive behaviour that was comparable to that in GAD65(-/-) mice. We conclude that GAD65-mediated GABA synthesis may be crucially involved in control of emotional behaviour and indispensable for a tonic inhibition that prevents the development of hyperexcitability in the maturating central nervous system. Aggressive, and possibly other social behaviour may be especially prone to regulation through GAD65-mediated GABA synthesis.

Age Factors↗