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Biomedical subjects

T Konishi

Publications and source records attributed to T Konishi.

At least 109 records · Page 6Linked to original sources

[Twenty-five years of progress in the treatment of esophageal and gastric cancers].

As we approach the year 2000, it seems useful to look back at the progress that has been made in medicine. The author has had 25 years' experience in gastrointestinal surgery for esophageal and gastric cancers. Twenty-five years ago in the field of gastrointestinal cancer diagnosis, double-contrast radiography was the leading technology and the development of fiberscopes led to an increasing number of early cancers being detected by endoscopy combined with biopsy. The treatment of advanced cancers relied heavily on the surgical knife, with the aim of complete removal of cancer cells by through and extended combined resection. Today, greater importance is placed on limited resection that allows for the preservation of function. The combined use of chemotherapy and radiotherapy is also regarded as important in some areas, reflecting a great change in therapeutic trends. This paper examines the author's 25 years of experience as a clinical surgeon, and, in doing so, provides an outline of the changes in the treatment of esophageal and gastric cancers during the last quarter of this century. Based on this, and with a view to the 21st century, the author hopes to contribute to new developments in the treatment of esophageal and gastric cancers.

Antineoplastic Combined Chemotherapy Protocols↗

Feasibility of simultaneous stress 99mTc-sestamibi/rest 201Tl dual-isotope myocardial perfusion SPECT in the detection of coronary artery disease.

UNLABELLED: This study assesses feasibility and diagnostic accuracy of simultaneous stress 99mTc-sestamibi/rest 201 TI dual-isotope myocardial perfusion SPECT with Moore's correction method, in which contamination originating from lead x-rays produced in a collimator was subtracted in the 201TI windows. METHODS: Eighty-one patients with suspected coronary artery disease received exercise 99mTc-sestamibi injection, followed by rest 201TI injection 50 min later, and dual-isotope SPECT was performed (group 1). These results were compared with coronary angiographic findings. Furthermore, to estimate the accuracy of Moore's correction method, 201TI crosstalk into the 99mTc acquisition window (group 2A, n = 20) and 99mTc crosstalk into the 201TI acquisition windows (group 2B, n = 20) were studied. For group 2A, stress 99mTc-sestamibi SPECT (single 99mTc-sestamibi SPECT) was performed, followed by 201TI injection at rest and dual-isotope SPECT acquisition 50 min later. For group 2B, rest 201TI SPECT (single 201TI SPECT) was performed, followed by 99mTc-sestamibi injection at rest and dual-isotope SPECT acquisition 30 min later. RESULTS: Sensitivity and specificity in group 1 were 83% and 99%, respectively, when > or =75% coronary artery narrowing was considered significant. In groups 2A and 2B, SPECT images were divided into 24 segments, and relative regional uptake in each segment was obtained. In group 2A, relative regional uptake of single 99mTc-sestamibi SPECT correlated well with that of dual-isotope SPECT (r = 0.942). In group 2B, relative regional uptake of single 201TI SPECT correlated well with that of dual-isotope SPECT (r = 0.935). Furthermore, in low 201TI uptake segments with relative regional uptake in both single- and dual-isotope SPECT of < or =70%, the degree of concordance between single- and dual-rest 201TI was considered to be high with Bland-Altman analysis and the kappa statistic. Comparison of perfusion defect type demonstrated that, of 22 stress defects within infarct zones, 95% were irreversible and 5% were reversible. In contrast, of 28 stress defects within stenosed vessel zones in noninfarct zones, 89% were reversible and 11% were irreversible (P < 0.0001 versus infarct zones). CONCLUSION: Simultaneous dual-isotope imaging with Moore's correction method is feasible, with acceptable accuracy for detection of coronary artery disease and a small amount of crosstalk into each window.

Aged↗

[Partial seizures during the course in patients with absence epilepsy].

We studied the incidence and clinicoelectrographic features of partial seizures in 46 patients with absence epilepsy. Ten patients (21.7%) showed obvious partial seizure symptoms during the course. Five patients had absence attacks with partial seizure symptoms, the ictal EEGs being a generalized 3 Hz spike-wave burst complex preceded by focal discharges. These absence attacks may be partial seizures with secondary bilateral synchronization, which originated from the frontal lobe. Three patients initially had partial seizures related to the frontal lobe, followed by absence attacks 8 months to 2.6 years after the start of CBZ therapy. The appearance of absence attacks may have been triggered by CBZ administration. Two patients had partial seizures at the relapse of epilepsy after the discontinuation of AED therapy for childhood absence epilepsy. This change of seizure types may be associated with the CNS maturation, or with localized cortical hyperexcitability subsequent to the foregoing generalized seizures. The prognosis of absence attacks in the all patients were excellent, and comparable to that of typical absence attacks. Our results suggest that localized cortical areas, especially the frontal lobe, are commonly involved in absence epilepsy. More detailed clinical observation is necessary to understand the pathogenesis of absence epilepsy.

Adolescent↗

[Subacute motor neuronopathy associated with myasthenia gravis and thymoma].

We reported a 63-year-old woman, suffered from myasthenia gravis with thymoma who later developed subacute motor neuronopathy after thymectomy. She noticed distally dominant muscle weakness and atrophy of bilateral upper extremities without sensory loss 4 month after thymomectomy. Her muscle weakness did not improve by intravenous administration of anti-cholinesterase (Tensilon test). Electrophysiological examinations showed no decremental response of examined muscles during repetitive nerve stimulation, nor motor nerve conduction block nor demyelination of affected peripheral nerves. Laboratory study demonstrated positive anti-acetylcholine receptor, anti-nuclear and SS-A antibodies. On immunohistochemistry, the patient's sera positively stained human and rat anterior horn cell cytoplasm as well as axoplasm of spinal white matter and root nerve axon, suggesting the presence of anti-axon antibody, possibly against neurofilament or tubulin components. The biopsied muscle specimen showed neurogenic muscle changes, but with no evidence of vasculitis nor cellular infiltration. Therapeutic trial of plasmapheresis was effective for her muscle weakness. Further recovery of weakness and muscle atrophy of hand muscles was obtained by combined therapy of intravenous and oral corticosteroid administration and plasmapheresis. These clinical, electrophysiological and histological findings suggested that antibodies against neuronal component might be responsible for her motor neuronopathy associated with myasthenia gravis. The findings of our case study may support the idea that some cases of motor neuron disease are caused by auto-immune mechanism.

Autoantibodies↗

[Minimally invasive surgery for single valvular heart disease].

Two patients underwent valve surgery using the minimally invasive approach. A 51-year-old man underwent mitral valve repair for chronic mitral regurgitation due to prolapse of the posterior mitral leaflet. The left-half of his sternum was cut in "C" shape below the level of the second intercostal space, and all of the arterial or venous cannulas were inserted via this single access. A 37-year-old man underwent aortic valve replacement for aortic valve regurgitation due to infective endocarditis. Right upper partial sternotomy between the first and fourth intercostal space was selected for this aortic valve surgery. The median skin incisions were as small as 12 and 9 cm. Postoperative recovery was very smooth. Minimally invasive approach using selected partial sternotomy provides acceptable results with a good exposure, and is an alternative approach to valve surgery.

Adult↗

[A case of multiple liver metastases from breast cancer successfully treated with intra-arterial administration of docetaxel].

Docetaxel is an excellent agent with a high antitumor effect for the treatment of advanced/recurrent breast cancer. A 55-year-old female with metastatic liver tumors from breast cancer showed a remarkable response to intra-arterial administration of docetaxel (20 mg/week, or 40 mg/2 weeks). Since CT and MRI imaging revealed multiple metastases in the liver, intra-arterial chemotherapy was selected. No critical side effect was found during this chemotherapy. A CT scan 3 months after chemotherapy showed a partial response. We conclude that this intra-arterial chemotherapy using docetaxel will be safe and useful for liver metastases from breast cancer.

Adenocarcinoma, Scirrhous↗

Effects of hyper +Gz acceleration on brainstem and auditory cortical evoked potentials and cerebral blood flow in anesthetized rats.

Hypergravity acceleration along the long axis of the body (Gz) causes severe cardiovascular dysfunctions. Many studies have been conducted along this line. However, most previous studies used rather a short duration of hyper-Gz application, up to 30 sec, because application of large hyper-Gz brings animals into death. In order to elucidate effects of long duration of Gz application, we made experiments with Gz load for as long as 1000 sec. Cardiovascular dysfunctions and reduction of arterial blood pressure were usually accompanied by reduction of cerebral blood flow, leading subjects into loss of consciousness and into death. Recently, we studied the effects of +Gz load on evoked potentials. The present experiments shows effects of +Gz on brainstem auditory response and auditory evoked potentials.

Acceleration↗

In vivo studies on chiral inversion and amino acid conjugation of 2-[4-(3-methyl-2-thienyl)phenyl]propionic acid in rats and dogs.

The relationship between chiral inversion and stereoselective amino acid conjugation of a new nonsteroidal anti-inflammatory agent, R, S-2-[4-(3-methyl-2-thienyl)phenyl]propionic acid (R,S-MTPPA) was investigated in rats and dogs. Only the S-enantiomer was found in plasma after oral administration of S-MTPPA to both species. In contrast, the R- and S-enantiomers were both detected after the dosing of R-MTPPA. In rats, the area under the curve of S-MTPPA in plasma was only 9% of that of R-MTPPA when R-MTPPA was dosed, whereas in dogs it was 2.5 times larger than that of the R-enantiomer. After administration of R-MTPPA, both enantiomers appeared in the urine. In rats, a small amount of S-enantiomer was found in the urine, whereas in the case of dogs the amount of the S-enantiomer was larger than that of the R-enantiomer. It appears that R-MTPPA is chirally inverted to S-MTPPA in both rats and dogs, although the extent of chiral inversion is greater in dogs than in rats. In dogs, the taurine conjugate was detected in plasma, urine and feces as a major metabolite after oral administration of either R- or S-MTPPA. In this case, only S-MTPPA-taurine was detected in the urine after the administration of S-MTPPA, and it was also the main component after administration of R-MTPPA.

Administration, Oral↗

Integration of SV40 in human osteosarcoma DNA.

Simian virus 40 (SV40) has been demonstrated in several types of tumors, including osteosarcoma, by polymerase chain reaction (PCR). We detected SV40 sequences by PCR, followed by hybridization, in nine of 35 osteosarcoma tumors and one of 11 osteosarcoma explants. PCR can detect fewer than one virus per cell but gives little detail of the gross structure and abundance of the virus. Analysis by Southern blotting of total DNA from ten osteosarcomas, positive for SV40 by PCR, found viral integration in half of these. Analysis showed integration of one to four copies per cell of rearranged SV40. No SV40 was detectable on blots of the remaining five SV40+ osteosarcomas, perhaps because of the lesser sensitivity of direct hybridization. Inactivation of the p53 and Rb tumor suppressors is a key activity of SV40 T-antigen. Unexpectedly, correlation of these findings with our prior studies indicated that five of ten osteosarcomas positive for SV40 DNA had mutations of p53, and two had deleted Rb. Apparently clonal integration with pre-existing alteration of a tumor suppressor gene, suggests that SV40 may play a role in the final conversion to malignant osteosarcoma.

Adolescent↗

Transmembrane 4 superfamily as a prognostic factor in pancreatic cancer.

Several members of the transmembrane 4 superfamily (TM4SF) have been reported to be related to tumor progression and metastasis. The aims of our study were to clarify the relationship between TM4SF and pancreatic cancer and to determine the prognostic significance of TM4SF in human pancreatic cancer. The mRNA levels for MRP-1/CD9, KAI1/CD82 and ME491/CD63, which belong to the TM4SF gene family, were evaluated in 40 resectable pancreatic adenocarcinomas using reverse transcriptase-PCR. MRP-1/CD9 gene expression was associated with lymph node status, and with pathological status. Moreover, MRP-1/CD9 expression was inversely associated with histo-pathological grading. KAI1/CD82 gene expression was inversely associated with tumor status. ME491/CD63 gene expression, however, was conserved in all pancreatic cancers. The overall survival rate for the 22 patients whose tumors had decreased MRP-1/CD9 gene expression was strikingly lower than that for the 18 patients with MRP-1/CD9-positive tumors. The overall survival rate of the 15 patients who were KAI1/CD82-positive was significantly higher than that of the 25 patients with decreased KAI1/CD82 gene expression. In a multivariate analysis using the Cox proportional hazards model, MRP-1/CD9 and KAI1/CD82 status was found to be the most significant.

Adenocarcinoma↗

Increased thrombin-antithrombin III complex during an episode of paroxysmal atrial fibrillation.

Thrombin-antithrombin III complex (TAT) is a marker of thrombin generation, indicating increased coagulability. To investigate whether paroxysmal atrial fibrillation (PAf) is associated with an increased coagulation system, we measured TAT within 24 h after the documentation of PAf in 50 patients with structurally normal hearts. The mean age of the study population was 62 years old. In 32 patients, PAf was documented during routine physical examinations, electrocardiograms or echocardiograms and in the remaining 18 patients, it was reproducibly documented on more than two Holter electrocardiograms. Group I consisted of 38 TAT data sets from 38 patients who did not receive anticoagulant therapy during PAf episodes. At least one week after starting anticoagulant therapy, TAT was measured again in ten patients in whom there was evidence of PAf on the day of measurement. In the remaining 12 patients, PAf occurred while the patients were receiving anticoagulation. Group II consisted of 22 TAT data sets from 22 patients who received anticoagulation during PAf episodes. The average TAT value was 5.8 ng/ml in group I, while it was 2.8 ng/ml in group II (P<0.0001). TAT was greater than 5 ng/ml in 15 of the 38 patients in group I, and in four of the 22 patients in group II. In 20 symptomatic patients, we measured TAT again when the patients maintained sinus rhythm under the same anticoagulant therapy; four patients were receiving and 16 patients were not receiving anticoagulation therapy. TAT decreased from 6.4 to 2.3 ng/ml on average when PAf disappeared and sinus rhythm was maintained (P=0.0009). Increase in the coagulation system occurred transiently during or shortly after PAf episodes in about 40% of PAf patients. As patients with prior anticoagulation had a relatively low TAT value, anticoagulant therapy might be useful in patients with PAf.

Adolescent↗

Mutations in exon 7 and 8 of p53 as poor prognostic factors in patients with non-small cell lung cancer.

This study was performed to clarify the different effects of each mutant exon of p53 as indicators of a poor prognosis in patients with non-small cell lung cancer (NSCLC). Tumor tissues of 204 patients with NSCLC were analysed; 96 tumors were stage I, 22 stage II, and 86 stage III. DNA was extracted from frozen specimens and polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and direct sequencing were performed to investigate mutations of p53 from exon 5 to exon 8. Seventy-five patients with NSCLC (36.8%) had mutations in p53 which included 72 cases of missense mutations and three cases of non-missense mutations. The overall survival rate of patients with mutant p53 adenocarcinomas was strikingly worse than that of patients whose tumors had wild-type p53 (35.7% vs 53.8%; P=0.041), but no significant difference in survival was found in the patients with NSCLC and squamous cell carcinoma. Mutations in exon 5 of p53 occurred in 33 cases (16.2%), mutation in exon 6 was detected in only one case (0.5%), mutations in exon 7 in 20 cases (9.8%), and mutations in exon 8 in 18 cases (8.8%). The overall survival rate of patients with mutations in exon 7 was worse than that of patients with wild-type p53 in NSCLCs and adenocarcinomas (42.9% vs 56.0%; P=0.025 and 33.3% vs 53.8%; P=0.048, respectively), whereas the overall survival of patients with mutations in exon 5 was almost the same as that of patients with wild-type p53. In addition, the overall survival rate of patients with mutations in exon 8 was strikingly worse than that of patients with wild-type p53 in NSCLCs, adenocarcinomas and squamous cell carcinomas (22.9% vs 56.0%; P<0.001, 19.0% vs 53.8%; P=0.004 and 33.3% vs 62.5%; P=0.042, respectively). Multivariate analysis with the Cox regression model of patients with NSCLC, adenocarcinoma and squamous cell carcinoma indicated that mutations in exon 8 were best correlated with the overall survival rate, followed by lymph node status (P<0.001, P=0.015 and P=0.006, respectively), and mutations in exon 7 of NSCLC were also revealed to have good correlation, followed by lymph node status and mutations in exon 8 (P=0.031). Mutation of p53 was a poor prognostic factor for adenocarcinoma as described previously. Moreover, mutations in exon 8 were more useful indicators of prognosis not only for adenocarcinoma but also for NSCLC. Worse overall survival of the patients with mutations in exon 8 of p53 was suggested to be associated with codon 273 mutations as well as mutations between codon 280 and 285 included into the H2 alpha helix corresponding to residues 278-286. These results suggested that abnormal conformation of H2 alpha helix might play an important role not only in the loss of normal function but also in the acquisition of tumorigenesis. Investigation of mutations in exon 8, especially codon 273 mutation and mutant H2 alpha helix was considered to be a clinically useful approach for determining the prognosis of patients with NSCLC.

Adenocarcinoma↗

Stereoselective determination of R,S-2-[4-(3-methyl-2-thienyl)phenyl]propionic acid and its taurine conjugates in dog urine by high-performance liquid chromatography.

Two high-performance liquid chromatographic methods for the stereoselective determination of R,S-2-[4-(3-methyl-2-thienyl)-phenyl]propionic acid (R,S-MTPPA), a new anti-inflammatory agent, and its taurine conjugates (R,S-MTPPA-TAU) in dog urine have been developed and validated. The urine samples were subjected to solid extraction or TLC preparation, then R,S-MTPPA and R,S-MTPPA-TAU were separated on Chiralcel OD and Chiral AGP columns, respectively, with ultraviolet absorbance detection at 272 nm. The dose-response relationships for enantiomers of R,S-MTPPA and R,S-MTPPA-TAU were linear in the concentration ranges of 0.5-50 (r>0.9993) and 5-200 microg/ml (r>0.9982), respectively. Recoveries of all tested enantiomers from dog urine were roughly 90% within the above concentration ranges. Intra- and inter-day reproducibilities were sufficient for metabolic studies. These methods were applied to stereoselective determination of the enantiomers in dog urine after administration of either S- or R-MTPPA.

Animals↗

Assay of protein-bound lipoic acid in tissues by a new enzymatic method.

A new enzymatic method for the determination of protein-bound lipoic acid was established. Bound lipoyl groups were liberated in the form of lipoyllysine by protease digestion and assayed by lipoamide dehydrogenase (NADH:lipoamide oxidoreductase, EC 1.8.1.4)-mediated NADH oxidation. NADH oxidation was coupled to reduction of the lipoyl disulfide group. Fluorescence kinetics of NADH oxidation were markedly enhanced by the addition of glutathione disulfide, recycling the enzyme-mediated lipoyl/dihydrolipoyl conversion. In the presence of a large excess of glutathione disulfide, NADH oxidation follows pseudo-first-order kinetics in terms of lipoyllysine concentration. A good linear correlation is obtained between the oxidation rate and lipoyllysine concentration up to 5 microM and the calibration curve indicates that the detection limit could be 100 nM lipoyllysine. The method was applied to protease lysates of bovine, rat, and rabbit tissues to determine lipoyllysine levels. Kidney and liver were found to have the highest content of lipoyllysine in the range of 3.9 to 4.6 nmol/g rat or rabbit wet tissue or 11.6 to 13.1 nmol/g bovine acetone powder.

Animals↗

A combination of laser therapy, radiation therapy, and stent placement for the palliation of complete malignant bronchial obstruction.

We treated a complete obstruction of the left mainstem bronchus due to nonresectable recurrent esophageal carcinoma with a combination of laser therapy, radiation therapy, and the placement of an expandable metallic stent. The patient survived 1 year after the first therapy, with good quality of life. We conclude that a combination of laser ablation, radiotherapy, and stent placement can improve survival and quality of life for the patients with complete malignant bronchial obstruction.

Aged↗

Complete response of esophageal cancer achieved by combination therapy with 5-fluorouracil, low-dose cisplatin, and radiation: report of a case.

To improve the survival rate of patients with esophageal cancer, several protocols of a preoperative combination of chemotherapy and radiotherapy, known as chemoradiation therapy, have been developed, recently characterized by the combination of 5-fluorouracil (5-FU), cisplatin, and radiation. Although some of these combinations have been demonstrated to be effective, the optimal chemoradiation dose and schedule are not yet precisely established. Recent investigations have elucidated that the radiosensitizing effects of cisplatin are able to be achieved more effectively by the daily administration of cisplatin before each fraction of radiation. Based on these investigations, we report herein the case of a patient with esophageal cancer with direct invasion to the trachea, in whom a complete response was achieved by the continuous administration of 5-FU, 600 mg/m2 per day, from days 1-5 combined with the daily administration of low-dose cisplatin, 10 mg/m2 per day before each fraction of radiation, given as 2Gy each time, throughout the entire treatment period of 3 weeks beginning on day 1. The benefits of our preoperative chemoradiation therapy included no severe side effects, down-staging and resectability of the tumor, as well as a pathological complete response, which could prolong the survival time. Our experience of this case prompts us to recommend the concurrent daily preoperative chemoradiation therapy for patients with locally advanced esophageal cancer.

Antimetabolites, Antineoplastic↗

Hybrid-type stabilizer for off-pump direct coronary artery bypass grafting.

We have developed a mechanical stabilizer for use in off-pump direct coronary artery bypass grafting. We consider it an improvement on the sucker-type stabilizer, although it uses the mechanisms of the compressor-type. Our hybrid stabilizer effectively immobilizes the local heart surface with light compression and low evacuation. We believe that its use will eliminate the need for further immobilization and thus reduce cardiac invasiveness.

Anastomosis, Surgical↗