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Biomedical subjects

S Okada

Publications and source records attributed to S Okada.

At least 415 records · Page 23Linked to original sources

[Thoracoscopic surgery using voice controlled robot for spontaneous pneumothorax].

We investigated the feasibility and applicability of using voice controlled robot-assisted thoracoscopic surgery for spontaneous pneumothorax. Eleven patients with spontaneous pneumothorax were involved in this study. Five patients were treated by voice controlled robot-assisted thoracoscopic procedure and 6 by historical human-assisted thoracoscopic procedure. All procedures were successfully completed without complications. The number of times the thoracoscope required cleaning per 60-minute interval for cases involving voice controlled robot-assisted surgery were 1.4 compared to 8 per 60-minute interval for comparable cases when the robot was not used. Operative times, the amount of analgesics, the duration of indwelling chest tube, the number of recurrences after operation during thoracoscopic procedures were not statistically different. We found that use of voice-controlled robot as surgical assistant during thoracoscopic surgery for spontaneous pneumothorax is feasible.

Adolescent↗

Histopathological and morphometric study of the late effects of heavy-ion irradiation on the spinal cord of the rat.

The late effects of heavy-ion irradiation on the spinal cord of the rat were investigated histologically and morphometrically. After a single exposure of each animal's lower thoracic and lumbar spinal cord to a carbon-ion beam, the animals were observed clinically for up to 69 weeks and their spinal cords were examined histologically after sacrifice. Paralysis of the hind limbs appeared from 16 to 20 weeks after irradiation with 20 Gy or more. The first histological change seen was vacuolization in the marginal white matter, which appeared 19 to 25 weeks after irradiation with more than 10 Gy. After irradiation with more than 15 Gy, bilateral destructive cavities occurred in the white matter, especially in the lateral tract. These histological changes were similar to those reported frequently for X irradiation. The mean cross-sectional area of the blood vessels in the irradiated spinal cord increased in a manner that was dependent on dose and was significantly larger 15 to 17 weeks after irradiation with 30 Gy. Reconstruction of small destructive lesions from serial sections consistently revealed dilated veins in the centers of these lesions. The effective dose that induces 50% incidence of hind-limb paralysis and destructive cavity formation (ED50) as determined using a curve-fitting method was 18.5 and 19.5 Gy, respectively, and the latent period was shorter than that for X irradiation.

Animals↗

Chemotherapy in hepatocellular carcinoma.

Systemic chemotherapy for hepatocellular carcinoma (HCC) has been of limited value in clinical practice, because only a small portion of patients obtain significant effects, and because the toxicity of chemotherapy often outweighs the benefits. Therefore, at present, only HCC patients with no indication for standard treatments (surgical resection, percutaneous ethanol injection and transcatheter arterial embolization) undergo chemotherapy. Due to the causes of death, tumor response and survival rate, only patients with metastatic sites other than in the bone, patients with no tumor thrombus in the main portal trunk and with good hepatic reserve are good candidates for systemic chemotherapy. To improve the prognosis in HCC patients, effective chemotherapy must be developed. The recommended strategy is to include all patients with advanced HCC in well-designed phase II trials with novel anti-cancer agents or regimens, when patients can tolerate treatment. Furthermore, prospective randomized trials comparing systemic chemotherapy with other palliative therapies or the best supportive care for HCC, are necessary before a clinically available chemotherapeutic regimen can be recommended for HCC.

Antineoplastic Agents↗

[A voice-controlled robot assisted thoracoscopic surgery for pulmonary tumor].

We herein report a case of voice-controlled robot assisted thoracoscopic surgery for a right apical tumor in a 55-year-old male. The patient was referred to our hospital for further examination of an abnormal shadow on chest X-ray. A chest computed tomographic scan indicated a suspicion of malignancy. Thoracoscopic surgery using a voice-controlled robot was conducted. The thoracoscope connected with the robotic arm was inserted through the trocar. In all maneuvers (forward and backward, right and left, up and down, insertion and extraction), the robotic arm moved appropriately immediately after the voice commands were issued, and favorable operative fields were obtained. Thoracoscopic partial resection of the involved lung was successfully performed with no complications. The operative time was 140 min. The postoperative course was uneventful. Voice-controlled robotic technology innovations may become the operating surgeon's third arm in the future. They will be further used not only in laparoscopic but also in thoracoscopic surgical procedures. Regular use will lead to greater skill in thoracoscopic application with the advent of new robotically assisted endoscopic surgery.

Antitubercular Agents↗

[Concomitant cardiac and pulmonary operation, the profits of not using cardio-pulmonary bypass].

We performed off pump CABG (coronary artery bypass grafting) and right upper lobectomy with R2a lymph nodes dissection on the patient suffered from both lung cancer in the right S1 and stenotic lesion in the left anterior descending artery. Because the coronary lesion was long-segmented one, it was not suitable for percutaneous transluminal coronary angioplasty. To perform absolutely curative operation for the lung cancer, CABG was undergone simultaneously under off pump condition. It is generally feared that the cardiovascular surgery under CPB may have adverse effect for the patient with malignant lesion. Off pump CABG is expected to avoid such disadvantage of CPB, and thought to be suitable method for such a patient as we present above.

Adenocarcinoma↗

[Endoscopic treatment with laryngeal masks for the removal of tracheobronchial foreign bodies].

We studied the endoscopic removal of tracheobronchial foreign bodies from 13 patients. Eight patients were treated under local anesthesia and 5 under general anesthesia. Complications included mild bleeding during endoscopic treatment of 3 patients. One patient was placed under general anesthesia because the patient was irritable and because hemorrhage made observation difficult. Laryngeal masks were used in 4 cases, and resulted in no complications. The follow-up courses ranged from 4 months to 12 years and were uneventful for all patients. Use of a fiberoptic bronchoscope in combination with laryngeal masks facilitated the management and removal of tracheobronchial foreign bodies by providing a secure airway and by minimizing the effect on the cardiorespiratory system.

Adult↗

[Use of laryngeal mask in bronchoscopy or bronchoscopic treatment].

Laryngeal mask which is widely used in clinical anesthesiology permits establishment of airway without tracheal intubation. Flexible bronchoscopy or bronchoscopic treatment using the laryngeal mask was evaluated to determine its safety, less invasiveness, and usefulness. Fifty-two patients underwent flexible bronchoscopy or bronchoscopic treatment using laryngeal mask 54 times. Bronchoscopy was performed under either local or general anesthesia. The laryngeal mask was positioned in the larynx, as a rule without a laryngoscope. A flexible bronchoscope was introduced into the airway, passed through the rubber slit at the tip of the laryngeal mask tube, and the examination was performed. Complications observed during the course of the examinations consisted of only two cases of poorly fitting laryngeal mask and one case of catching of a part of the epiglottis in the rubber slit at the tip of the laryngeal mask tube. Both cases were not particularly problematic. There were three patients with sore throat and one with an unpleasant feeling in the pharynx following the examination, however, all of these complaints resolved within three days after the examination. Laryngeal masks are less invasive and have very little effect on either the respiratory system or the circulatory system. They may be used safely even in aged patients and appears to be highly effective for diagnostic and therapeutic bronchoscopy.

Adolescent↗

[Influence of co-administered antiepileptic drugs on nitrazepam tolerance in mice].

In the treatment of epilepsy, benzodiazepines are often administered in combination with other antiepileptic drug (s) because of the development of tolerance. In this study, the influence of concurrently administered antiepileptic drugs on tolerance to the anticonvulsant action of the nitrazepam (NZP) was studied using an animal tolerance model. Mice were given vehicle, NZP alone or NZP concurrently with one of six antiepileptic drugs (carbamazepine CBZ, phenytoin PHT, zonisamide ZNS, vigabatrin VGB, lamotrigine LTG, or flunarizine FNR) twice daily for 5 days. Tolerance was assessed by the ability of NZP to prevent pentylenetetrazol-induced clonic convulsions. Tolerance developed in mice treated with NZP alone, NZP plus CBZ, PHT, ZNS, VGB or LTG. On the other hand, mice receiving NZP + FNR showed no tolerance; there was no significant difference in seizure frequency between the vehicle group and NZP + FNR group. These data suggest that co-administration of FNR but not CBZ, PHT, ZNS, VGB or LTG may delay if not prevent development of tolerance to the anticonvulsant action of benzodiazepines.

Animals↗

[A case of juvenile type dentatorubral-pallidoluysian atrophy (DRPLA) with psychomotor retardation since infancy].

We report here a case of an 11-year-old boy with juvenile type of dentatorubral-pallidoluysian atrophy (DRPLA). His psychomotor development has been delayed since infancy and cerebellar ataxia was noted at the age of 2 years, indicating an early onset. At the age of 6 years, he had progressive myoclonus epilepsy (PME) and underwent a series of neuroradiological, electrophysiological and pathological examinations, which failed to reveal the etiology. Gene analysis performed at the age of 11 years revealed an expanded CAG repeat at the DRPLA locus in both the patient and his asymptomatic father. In the absence of a positive family history, a diagnosis of DRPLA may be difficult due to its clinical variability. We conclude that DRPLA should be taken into account in the differential diagnosis of childhood PME and that gene analysis should be performed to confirm a diagnosis of DRPLA.

Anticipation, Genetic↗

[Clearance of gadolinium contrast agent by hemodialysis: in vitro and clinical studies].

In order to evaluate the safety and pharmacokinetics of gadolinium contrast agents in patients with hemodialysis, in vitro and clinical studies were performed. Gd-DTPA and Gd-HP-DO3A solutions were dialysed by standard methods. One classic type (cellulose acetate) and two high-performance types (PMMA and polyacrylonitrile) were used. Eleven dialysis patients underwent normal dose contrast MRI followed by usual dose hemodialysis (HD). PMMA dialysis membranes were used for 8 patients and cellulose acetate membranes for 3 patients. Serum levels of gadolinium, BUN and creatinine were analyzed before and after the 1st HD and after the 2nd, 3rd and 4th HD. Side effects and edema were carefully observed. In vitro studies showed that 11.1 hours of dialysis would be necessary to remove 97% of the injected dose of contrast agent by using a first-order kinetic model of dialysis time. When dialysis membranes and contrast agents were compared, statistically significant differences were noted between dialysis membranes and all contrast agents. In the clinical study, 79.1% of the contrast agent was dialyzed after the 1st dialysis and 99.6% after the 4th dialysis. These results showed that all contrast agents and both dialysis membranes were suitable. Neither changes in laboratory parameters nor side effects were observed. The present study suggests, consequently, there are no contraindications when using the ordinary dose of contrast agent even in patients with dialysis.

Aged↗

Introduction of an osteopontin gene confers the increase in B1 cell population and the production of anti-DNA autoantibodies.

Osteopontin (OPN) is an Arg-Gly-Asp-containing phosphoprotein that is secreted by activated T cells. The concentration of serum OPN protein is elevated in autoimmune-prone MRL-lpr mice as well as in patients with systemic lupus erythematosus. Previously, it was shown that OPN induces the polyclonal activation of B cells, resulting in the augmented production of immunoglobulin, indicating that OPN plays some role in the development of autoimmune disease. However, the link between OPN and development of autoimmune disease remains unclear. To analyze the role of OPN in immune system and autoimmune diseases, we have generated two kinds of transgenic mice: one carries the immunoglobulin (Ig) enhancer/SV40 promoter and the other carries the cytomegalovirus enhancer/chicken beta-actin (CAG) promoter. In both groups of transgenic mice, the B1 cell population in peritoneal cavity was markedly increased and titer of IgM and IgG3 antibodies in the serum was considerably higher than that in wild-type mice. Most important, the titer of the IgM class of anti-double-stranded DNA antibody was significantly elevated in transgenic mice. These results strongly suggest that OPN may have an important role in the propagation and differentiation of B1 cells and production of autoantibodies.

Animals↗

Discrimination limit for purity test of human insulin by capillary electrophoresis.

Because of the inevitable noise in instrumental analysis, a purity test can overlook an illegitimate drug that contains an undesired substance in a higher amount than the prescribed limit. The lowest (average) amount of undesired substance which leads to the right results of the purity test with 95% probability is referred to here as 95% discrimination limit. This paper presents a method for predicting the discrimination limit for the purity test of human insulin in capillary electrophoresis (CE). The theory and experiments show that if the legitimate limit of a degradation product (desamido insulin) is 3.0% of the total amount of the insulin formulation, the 95% discrimination limit in the CE system used in this study is 3.24% desamido insulin. Since the statistical aspects of the purity test are provided by the interpretation of the baseline fluctuation in the instrument, the usual strategy to repeat the instrumental analysis on the same samples is unnecessary in the present study.

Chemistry Techniques, Analytical↗

Metabolic methylation is a possible genotoxicity-enhancing process of inorganic arsenics.

To elucidate if the metabolic methylation participates in the induction of inorganic arsenic-responsible genetic damage, arsenite (ARS) and its methylated metabolites, methanearsonic acid (MMAA) and dimethylarsinic acid (DMAA), were comparatively assayed for the induction of DNA damage by determining DNA repair synthesis using polymerization inhibitors such as aphidicolin (aph) and hydroxyurea (HU). When human alveolar epithelial type II (L-132) cells in culture were exposed to either one of these three arsenic compounds, DNA single-strand breaks resulting from the inhibition of repair polymerization were remarkably produced by exposure to DMAA at 5 to 100 microM, while not by that to ARS and MMAA even at 100 microM. Furthermore, a bromodeoxyuridine (BrdrU)-photolysis assay indicated that the induction of DNA repair synthesis was observed only in the case of exposure to DMAA. When L-132 cells were exposed to 100 microM MMAA in the presence of 10 mM S-adenosyl-L-methionine (SAM), which is a well-known methyl-group donor in metabolic methylation of arsenics, DNA repair synthesis was induced along with an increase in the amount of dimethylarsenic in the cells. These results indicate that metabolic methylation of inorganic arsenics to dimethylarsenics is predominantly involved in the induction of DNA damage.

Arsenic Poisoning↗

A mammalian model for Laron syndrome produced by targeted disruption of the mouse growth hormone receptor/binding protein gene (the Laron mouse).

Laron syndrome [growth hormone (GH) insensitivity syndrome] is a hereditary dwarfism resulting from defects in the GH receptor (GHR) gene. GHR deficiency has not been reported in mammals other than humans. Many aspects of GHR dysfunction remain unknown because of ethical and practical limitations in studying humans. To create a mammalian model for this disease, we generated mice bearing a disrupted GHR/binding protein (GHR/BP) gene through a homologous gene targeting approach. Homozygous GHR/BP knockout mice showed severe postnatal growth retardation, proportionate dwarfism, absence of the GHR and GH binding protein, greatly decreased serum insulin-like growth factor I and elevated serum GH concentrations. These characteristics represent the phenotype typical of individuals with Laron syndrome. Animals heterozygous for the GHR/BP defect show only minimal growth impairment but have an intermediate biochemical phenotype, with decreased GHR and GH binding protein expression and slightly diminished insulin-like growth factor I levels. These findings indicate that the GHR/BP-deficient mouse (Laron mouse) is a suitable model for human Laron syndrome that will prove useful for the elucidation of many aspects of GHR/BP function that cannot be obtained in humans.

Animals↗

Insulin and epidermal growth factor stimulate a conformational change in Rap1 and dissociation of the CrkII-C3G complex.

Insulin and epidermal growth factor (EGF) stimulation of Chinese hamster ovary cells expressing the human insulin and EGF receptors resulted in a time-dependent decrease in the ability of a Rap1 antibody (amino acid epitope 121-136) to immunoprecipitate Rap1 from whole cell detergent extracts. This was due to an apparent masking of Rap1 as heat denaturation of the whole cell detergent extracts (5 min at 100 degrees C) resulted in equal immunoprecipitation of Rap1 with this epitope-specific antibody. The time-dependent change in Rap1 immunoreactivity was paralleled with an insulin-stimulated dissociation of the CrkII-C3G complex. Similarly, EGF treatment also resulted in a time-dependent dissociation of the CrkII-C3G complex that occurred concomitant with the masking of the 121-136 Rap1 epitope. Furthermore, pretreatment of the cells with the tyrosine kinase inhibitor, genistein, decreased both the basal and insulin-stimulated tyrosine phosphorylation of CrkII that directly correlated with the amount of CrkII that was immunoprecipitated with C3G. Together, these data suggest that insulin and EGF stimulation result in the dissociation of the CrkII-C3G complex, thereby inducing an apparent conformation change in Rap1.

Animals↗

The 66-kDa Shc isoform is a negative regulator of the epidermal growth factor-stimulated mitogen-activated protein kinase pathway.

In addition to tyrosine phosphorylation of the 66-, 52-, and 46-kDa Shc isoforms, epidermal growth factor (EGF) treatment of Chinese hamster ovary cells expressing the human EGF receptor also resulted in the serine/threonine phosphorylation of approximately 50% of the 66-kDa Shc proteins. The serine/threonine phosphorylation occurred subsequent to tyrosine phosphorylation and was prevented by pretreatment of the cells with the MEK-specific inhibitor PD98059. Surprisingly, only the gel-shifted 66-kDa Shc isoform (serine/threonine phosphorylated) was tyrosine phosphorylated and associated with Grb2. In contrast, only the non-serine/threonine-phosphorylated fraction of 66-kDa Shc was associated with the EGF receptor. To assess the relationship between the three Shc isoforms in EGF-stimulated signaling, the cDNA encoding the 66-kDa Shc species was cloned from a 16-day-old mouse embryo library. Sequence alignment confirmed that the 66-kDa Shc cDNA resulted from alternative splicing of the primary Shc transcript generating a 110-amino acid extension at the amino terminus. Co-immunoprecipitation of Shc and Grb2 from cells overexpressing the 52/46-kDa Shc isoforms versus the 66-kDa Shc species directly demonstrated a competition of binding for a limited pool of Grb2 proteins. Furthermore, expression of the 66-kDa Shc isoform markedly accelerated the inactivation of ERK following EGF stimulation. Together, these data indicate that the serine/threonine phosphorylation of 66-kDa Shc impairs its ability to associate with the tyrosine-phosphorylated EGF receptor and can function in a dominant-interfering manner by inhibiting EGF receptor downstream signaling pathways.

Adaptor Proteins, Signal Transducing↗

Another critical region for deletion of 22q11: a study of 100 patients.

Deletions at 22q11.1-q11.2 present with variable manifestations usually referred to as DiGeorge or velo-cardio-facial syndrome. We previously reported that deletions observed in patients with the syndrome can be subgrouped into three types (common large deletion, proximal deletion, and distal deletion) and demonstrated the presence of a second critical region for the syndrome. In order to characterize further the second critical region, a 22q11 deletion map was constructed from the data of 100 patients, using 12 DNA markers scattered in the common large deletion, and then a phenotype-genotype correlation was analyzed. The second critical region was found to correspond to the distal deletion encompassing the HCF2, cHKAD26, and D22S935 loci, and the proximal and distal deletions do not overlap each other. Although it seems that this condition is a contiguous gene syndrome, the phenotype of patients with these two types of deletion was indistinguishable from that of patients with the common large deletion. Thus, it is plausible that several genes located in the two segments corresponding to the two deleted regions are involved in the same developmental pathway or in an extremely long-range position effect.

Chromosome Deletion↗

Change of zinc distribution in rat brain with increasing age.

Zinc (Zn) accumulation in the brain of rats of various ages was studied to look into the significance of Zn for the development and function of the brain. The Zn concentration of the cerebral hemisphere was relatively low in 1- to 11-day-old rats. The Zn concentration of the cerebellum gradually increased after birth and reached nearly a plateau at 11 days old. At 48 weeks old, the Zn concentrations of the cerebral cortex and hippocampus formation were approximately twice that of the cerebral hemisphere at the early stage after birth and significantly higher than that of the cerebellum. When 65ZnCl2 was injected into two groups of rats at 5 days and 48 weeks old for comparison, 65Zn distribution in the brain of the former group was higher than that of the latter. In the neonatal rats, the highest concentration of 65Zn was found in the cerebellum, followed by the hippocampus formation, a Zn-containing neuron-rich region. In the adult rats, the highest concentration of 65Zn was found in the CA3 and dentate gyrus of the hippocampus formation. At 48 weeks, 65Zn distribution in the cerebellum was relatively low and at about the same level as in the cerebral cortex. These results suggest that Zn is highly demanded by the cerebellum, which develops rapidly after birth. The increase in Zn concentration with increasing age may reflect the Zn requirement for functioning as an neuromodulator as well as for brain development.

Aging↗