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Biomedical subjects

T Konishi

Publications and source records attributed to T Konishi.

At least 91 records · Page 5Linked to original sources
PubMed1999

Intermittently audible the "third heart sound" as a sign of complete atrio-ventricular block in patients with a VVI pacemaker.

BACKGROUND: It is not known that an S3 can be audible intermittently. We have recognized this in patients with VVI pacing in whom sinus rhythm has been preserved. SUBJECTS AND METHODS: Subjects consisted of consecutive 39 patients with VVI pacemaker implantation and preservation of sinus rhythm. We tried to find out what percentage of these patients have an intermittent S3 and also to elucidate the mechanism of this sound by Doppler echocardiography. The PP interval and RR intervals were measured and ¿PP-RR¿/RR was calculated. One doctor carried out auscultation from the left sternal border to the apex for 5-6 consecutive beats while the patients held their breath. Transmitral flow velocity was measured by pulsed Doppler echocardiography with a paper speed of 100 cm/sec. A wave velocity was measured when a P wave coincided with late diastole. E wave velocity was measured when no A wave was present in early diastole. The maximal summation of E and A waves (E+A) velocity was measured. RESULT: An intermittent S3, being audible in 21 patients (group A) and not audible in 18 patients (group B), coincided with maximal E+A velocity. There was no statistical age difference between the two groups. Both maximal E+A velocity, and A velocity were higher in group A than group B (116.2 cm/sec Vs 90.8 cm/sec P<0.0001, 80.6 cm/sec Vs 56.4 cm/sec P<0.0001 respectively), while E velocity was not statistically different (68.3 cm/sec Vs 60.3 cm/sec). In 5 of 9 cases in whom an intermittent S3 was not audible regardless of more than 100 cm/sec of E+A velocity, the calculated ¿PP-RR¿/RR was less than 0.1. CONCLUSION: An intermittently audible S3 is one of the physical signs of complete atrio-ventricular block. It occurs when a strong atrial contraction develops exactly at the time of rapid left ventricular filling. However, when the PP and RR intervals are too close, the S3 may be difficult to discern.

Adult↗
PubMed1999

Rb independent inhibition of cell growth by p15(INK4B).

The INK4 cyclin dependent kinase inhibitors (CDKI), such as p15(INK4B) and p16(INK4A), block cell cycle progression from G to S phase. This is mediated by inhibition of phosphorylation of proteins, including the retinoblastoma susceptibility protein (Rb), by cyclin dependent kinases. Ectopic over-expression of the p16(INK4A) CDKI can inhibit growth of cell lines depending on Rb status. Cell lines lacking Rb, with few exceptions, are resistant to growth inhibition by p16(INK4A). The effects of ectopic over-expression of p15(INK4B) in cell lines with and without wild type Rb were examined by measuring cell recovery. Proliferation was inhibited in cells lacking Rb as well as in cells with wild type Rb expression. Experiments analyzing the effectiveness of chimeric p15(INK4B)/p16(INK4A) proteins indicated that the Rb independent growth inhibition required N-terminal residues of p15(INK4B). Linker insertion mutation of p15(INK4B) showed that the inhibition was dependent on intact ankyrin structures. Double staining flow cytometry found that the growth inhibition correlated with a decrease in cells in G2/M phases of the cell cycle. These findings are consistent with Rb independent inhibition of the progression from G1 to S caused by overexpression of p15(INK4B).

Carrier Proteins↗
PubMed1999

Enhancement of cellulose production by expression of sucrose synthase in Acetobacter xylinum.

Higher plants efficiently conserve energy ATP in cellulose biosynthesis by expression of sucrose synthase, in which the high free energy between glucose and fructose in sucrose can be conserved and used for the synthesis of UDP-glucose. A mixture of sucrose synthase and bacterial cellulose synthase proceeded to form UDP-glucose from sucrose plus UDP and to synthesize 1,4-beta-glucan from the sugar nucleotide. The mutant sucrose synthase, which mimics phosphorylated sucrose synthase, enhanced the reaction efficiency (Vmax/Km) on 1,4-beta-glucan synthesis, in which the incorporation of glucose from sucrose was increased at low concentrations of UDP. Because UDP formed after glucosyl transfer can be directly recycled with sucrose synthase, UDP-glucose formed appears to show high turnover with cellulose synthase in the coupled reaction. The expression of sucrose synthase in Acetobacter xylinum not only changed sucrose metabolism but also enhanced cellulose production, in which UDP-glucose was efficiently formed from sucrose. Although the level of UDP-glucose in the transformant with mutant sucrose synthase cDNA was only 1.6-fold higher than that in plasmid-free cells, the level of UDP was markedly decreased in the transformant. The results show that sucrose synthase serves to channel carbon directly from sucrose to cellulose and recycles UDP, which prevents UDP build-up in cellulose biosynthesis.

Journal Article↗
PubMed1999

Influence of gravity on pulmonary venous flow velocity patterns: analysis of left and right pulmonary venous flow velocities in left and right decubitus positions.

BACKGROUND: The pulmonary venous flow signal measured by transesophageal echocardiography is generally recorded from the left upper pulmonary vein in the left lateral decubitus position, whereas that by transthoracic echocardiography is from the right upper pulmonary vein in the left semi-lateral decubitus position. The purpose of this study was to evaluate the influence of the postural change on the peak flow velocities of the left and right pulmonary veins and whether the parameters of the left and right pulmonary venous flow can be used interchangeably. METHODS AND RESULTS: The study group consisted of 37 patients with normal left ventricular filling pressure and in whom the systolic forward flow signals from both pulmonary veins recorded in the left and right lateral decubitus positions were clear enough to differentiate as biphasic. The peak early systolic (peak S1) and diastolic velocities were significantly increased when the pulmonary vein was on the recumbent subject's upper side, whereas the peak late systolic velocity (peak S2) was significantly increased when the pulmonary vein was on the recumbent subject's lower side. The peak S1 was higher than the peak S2 when the pulmonary vein was on the recumbent subject's upper side, whereas the reverse relation was seen when the pulmonary vein was on the recumbent subject's lower side. CONCLUSIONS: We should take into consideration the body position and the side on which the pulmonary vein is situated in evaluating the peak flow velocities of the pulmonary veins.

Adult↗
PubMed1999

Extended aortic replacement in acute dissection by the separated elephant trunk technique.

BACKGROUND: Extensive aortic replacement in acute dissection is currently not a widely accepted method of treatment. METHODS: We developed a safe method for extended aortic repair including the aortic arch in type A acute dissection, and describe here its application in 5 cases. This method was based on a modification of the elephant trunk method and several other strategies. Most of the procedures were carried out under simple hypothermic circulatory arrest. RESULTS: All patients recovered within 2 days without recurrent nerve injury. One patient suffered from unilateral upper arm palsy due to severe innominate dissection. Patients were all discharged and early postoperative computed tomography (CT) showed thrombotic obliteration around the elephant trunk. Follow-up CT after 4 to 18 months confirmed that thromboexclusion proceeded down to the distal end of the elephant graft in 1 patient and to the diaphragmatic level in 3 patients. Total obliteration was observed in the remaining 1 patient. CONCLUSIONS: This technique enables extended aortic repair in acute dissection with no increase in morbidity, and effectively promotes thromboexclusion of the dissected lumen to a wider extent than conventional methods.

Aged↗
PubMed1999

Role of transforming growth factor-beta1 and decorin in development of central fibrosis in pulmonary adenocarcinoma.

Transforming growth factor-beta1 (TGF-beta1) is known as the growth factor that stimulates the synthesis of extracellular matrix. Recently, TGF-beta has been found to control the growth of cancer cells. Small chondroitin-dermatan sulfate (decorin) is an abundant extracellular matrix component. TGF-beta1 stimulates the synthesis of decorin, and decorin is considered to bind TGF-beta1. The activity of decorin in neutralizing TGF-beta1 activity suggests that decorin serves as a negative-feedback regulator of TGF-beta1 activity. To investigate the role and relationship of TGF-beta1 and decorin in the formation of central fibrosis in pulmonary adenocarcinoma, we performed an immunohistochemical study of TGF-beta1 and decorin in 61 cases of T1 pulmonary adenocarcinoma. Positive stainings for TGF-beta1 were shown in 40 cases and negative in 21 cases. Twenty-seven of 32 cases with central fibrosis were positive for TGF-beta1. Positive staining for TGF-beta1 was significantly related to the appearance of central fibrosis in pulmonary adenocarcinoma. When central fibrosis was composed of proliferative connective tissue with loose staining for decorin, cancer cells showed intense staining for TGF-beta1. When central fibrosis was composed of old fibrotic tissue with dense staining for decorin, cancer cells showed weak staining for TGF-beta1. Our results suggest that TGF-beta1 has an important role in the formation of central fibrosis in pulmonary adenocarcinoma, and decorin may play a role as a negative feedback regulator in the production of TGF-beta1 in pulmonary adenocarcinoma.

Adenocarcinoma↗
PubMed1999

Endovascular stent graft repair of aortopulmonary fistula.

Two patients who had aortopulmonary fistula of postoperative origin with hemoptysis underwent successful repair by means of an endovascular stent graft procedure. One patient had undergone repeated thoracotomies two times, and the other one time to repair anastomotic aneurysms of the descending aorta after surgery for Takayasu's arteritis. A self-expanding stainless steel stent covered with a Dacron graft was inserted into the lesion through the external iliac or femoral artery. The patients recovered well, with no signs of infection or recurrent hemoptysis 8 months after the procedure. Endovascular stent grafting may be a therapeutic option for treating patients with aortopulmonary fistula.

Anastomosis, Surgical↗
PubMed1999

Identification of human cytochrome P450 isoforms involved in the metabolism of S-2-[4-(3-methyl-2-thienyl)phenyl]propionic acid.

1. To identify the cytochrome P450 (CYP) isoenzymes responsible for the major metabolic pathways of S-2-[4-(3-methyl-2-thienyl)phenyl] propionic acid (S-MTPPA) in man, the metabolism of S-MTPPA was examined using human liver microsomes and microsomes containing cDNA-expressed CYP isozymes (CYP1A2, 2A6, 2B6, 2C9-Arg, 2C9-Cys, 2C19, 2D6-Val, 2E1 and 3A4). 2. S-MTPPA was mainly oxidized to the 5-hydroxylated metabolite of the thiophene ring (MA6) with human liver microsomes in the presence of NADPH. The formation of MA6 was inhibited by SKF 525-A, suggesting that CYP plays role in the formation of MA6. 3. Eadie-Hofstee plots for the 5-hydroxylation of S-MTPPA in the range 5-100 microM were linear for all samples studied, suggesting that the formation of MA6 by human liver microsomes follows simple Michaelis-Menten kinetics. Apparent Vmax = 1.42+/-0.64 nmol/min/mg protein; Km = 12+/-5 microM. 4. Among the CYP inhibitors examined (alpha-naphthoflavone, sulphaphenazole, omeprazole, quinidine and troleandomycin), sulphaphenazole (a CYP2C9 inhibitor) showed the most potent inhibitory effect on the 5-hydroxylation of S-MTPPA by human liver microsomes. 5. When incubated with microsomes containing cDNA-expressed CYP isozymes, S-MTPPA was substantially oxidized to MA6 only by CYP2C9. 6. These results suggest that formation of the major metabolite of S-MTPPA, MA6, in human liver microsomes is catalysed predominantly by a single CYP isoenzyme, namely CYP2C9.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1999

Prevention and repair of cerebral ischemia-reperfusion injury by Chinese herbal medicine, shengmai san, in rats.

The protective activity of Shengmai San, a traditional Chinese herbal medicine, was studied in cerebral ischemia-reperfusion injury in rats. Shengmai San consists of three herbal components, Panax Ginseng, Ophiopogon Japonicus and Schisandra Chinensis and is routinely being used for treating coronary heart disease. When Shengmai San was injected directly into rat duodenum 2h before cerebral ischemia by bilateral carotid artery occlusion, thiobarbituric acid reactive substance (TBARS) formation during reperfusion following ischemia was almost completely suppressed in the brain. The loss of glutathione peroxidase activity after the ischemia-reperfusion was also effectively prevented by the Shengmai San pre-administration whereas the activity was considerably decreased in the damaged brain. It was found that Shengmai San also effectively suppressed the TBARS formation even when it was administered after 45 min reperfusion following ischemia, indicating that Shengmai San improves the oxidative damage already established in the brain. Likewise, the decrease of glutathione peroxidase activity was minimized in the damaged brain by the post-administration of Shengmai San. On the other hand, none of the Shengmai San components were active in protecting the ischemia-reperfusion brain damage when they were independently administered. These experiments suggest the potential of Shengmai San in both preventive and therapeutic usages for cerebral ischemia-reperfusion injury.

Animals↗
PubMed1999

Paroxysmal kinesigenic choreoathetosis locus maps to chromosome 16p11.2-q12.1.

Paroxysmal kinesigenic choreoathetosis (PKC), the most frequently described type of paroxysmal dyskinesia, is characterized by recurrent, brief attacks of involuntary movements induced by sudden voluntary movements. Some patients with PKC have a history of infantile afebrile convulsions with a favorable outcome. To localize the PKC locus, we performed genomewide linkage analysis on eight Japanese families with autosomal dominant PKC. Two-point linkage analysis provided a maximum LOD score of 10.27 (recombination fraction [theta] =.00; penetrance [p] =.7) at marker D16S3081, and a maximum multipoint LOD score for a subset of markers was calculated to be 11.51 (p = 0.8) at D16S3080. Haplotype analysis defined the disease locus within a region of approximately 12.4 cM between D16S3093 and D16S416. P1-derived artificial chromosome clones containing loci D16S3093 and D16S416 were mapped, by use of FISH, to 16p11.2 and 16q12.1, respectively. Thus, in the eight families studied, the chromosomal localization of the PKC critical region (PKCR) is 16p11.2-q12.1. The PKCR overlaps with a region responsible for "infantile convulsions and paroxysmal choreoathetosis" (MIM 602066), a recently recognized clinical entity with benign infantile convulsions and nonkinesigenic paroxysmal dyskinesias.

Adolescent↗
PubMed1999

Pre-operative chemoradiation therapy with 5-fluorouracil and low-dose daily cisplatin for esophageal cancer: a preliminary report.

BACKGROUND: A combination of chemotherapy and radiotherapy (chemoradiation therapy; CRT) has recently been developed to improve the survival of esophageal cancer patients. However, the optimal choice of chemotherapeutic agents and their doses, as well as chemotherapy and radiotherapy regimens, remain unclear. METHODS: Based on recent advances in knowledge on the radiosensitizing and biochemical modulation effects of chemotherapeutic agents, we have recently developed concurrent CRT which consisted of continuous 5-fluorouracil (5FU) administration (600 mg/m2/day, days 1-5) combined with a low dose of daily cisplatin administration (10 mg/m2/day, days 1-5, and 5 or 10 mg/m2/day, days 8-12 and 15-19) before each fraction of radiation (2 Gy each). To evaluate the efficacy and safety of our concurrent CRT, 10 esophageal cancer patients received one or one and a half courses of the CRT. RESULTS: All patients tolerated and completed a full course of the CRT. The effectiveness of the CRT on the primary tumor included pathologically or endoscopically complete responses in three patients (30%), partial response in five (50%), no response in two (20%) and tumoral downstaging (T-classification) in five (50%). Grade 2 and Grade 3 toxicity, seen in six patients, did not affect surgical operation. No patients showed CRT-related deaths. Eight patients (80%) underwent resection with no operative mortality. Of these, two patients (25%) showed pathologically or endoscopically complete responses, and four (50%) showed partial response. Three patients died of cancer after resection. The two inoperable patients showed a pathologically complete response and partial response, respectively. They were relieved of their cancer-related complaints and were living without hospitalization at the time of this analysis. CONCLUSIONS: These results suggest that the concurrent CRT based on the theoretical backgrounds is effective and has acceptable toxicities with maintaining its efficacy for the treatment of esophageal cancer patients.

Aged↗
PubMed1999

Massive gastrointestinal hemorrhage in systemic lupus erythematosus: successful treatment with corticosteroid pulse therapy.

Although mesenteric vasculitis due to systemic lupus erythematosus (SLE) is relatively uncommon, it is the most dangerous manifestation associated with high mortality. We describe the case of a SLE patient with life-threatening gastrointestinal hemorrhage due to mesenteric vasculitis in whom methylprednisolone pulse therapy was quite effective in controlling the hemorrhage and resulted in a satisfactory long term outcome. A 47-yr-old woman presenting with high fever, rash, and melena was diagnosed with SLE from positive antinuclear antibodies, anti-dsDNA, and low complement titers. Although fever and rash subsided with administration of prednisolone, massive hematemesis appeared with melena. Endoscopy demonstrated bleeding ulceration of the antrum, which was intractable despite intensive antiulcer therapy and transfusion. Surgical exploration revealed ileal penetration, and multiple bleeding ulcerations were observed over the resected ileum as well as the antral ulceration. However, bleeding persisted after surgery and surgical findings prompted us to select methylprednisolone pulse. Hemorrhage responded promptly to the therapy, and the patient has remained well since then for >10 yr. Our report indicates that corticosteroid pulse may serve as one of the therapeutic options for SLE with massive hemorrhage due to widespread mesenteric vasculitis.

Anti-Inflammatory Agents↗
PubMed1999

Partial pressure of oxygen is lower in the left upper pulmonary vein than in the right in adults with atrial septal defect: difference in P(O2) between the right and left pulmonary veins.

BACKGROUND: The right-to-left shunt at the atrial level is responsible for arterial hypoxemia in patients with atrial septal defect. OBJECTIVES: This study investigated the mechanism of arterial hypoxemia in patients with atrial septal defect by measuring the P(O2) in both the right and left upper pulmonary veins. SUBJECTS AND METHOD: We prospectively measured the P(O2) in the femoral artery and the right and left upper pulmonary veins during cardiac catheterization in 13 adults (median age, 53 years) and 7 children (median age, 7 years) with secundum atrial septal defect. The adults and children were studied consecutively. Contrast echocardiography was performed to evaluate right-to-left shunt in all adults. RESULTS: Among the children, there were no patients showing arterial hypoxemia, and there was no difference in the P(O2) (+/-SD) between the right and left upper pulmonary veins (right, 100+/-3.8 mm Hg vs left, 100+/-7.8 mm Hg; p = 0.92). However, arterial hypoxemia was present in 11 of the 13 adult patients, although contrast echocardiography showed more than a moderate degree of right-to-left shunt in only four adults. The P(O2) was lower in the left upper pulmonary vein than it was in the right upper pulmonary vein in all adult patients (right, 91.6+/-13.8 mm Hg vs left, 73.0+/-11.5 mm Hg; p < 0.0001). CONCLUSION: The P(O2) was lower in the left upper pulmonary vein than it was in the right upper pulmonary vein in adults with atrial septal defect. Care must be taken in measuring pulmonary blood flow if the P(O2) in the left upper pulmonary vein is low enough to influence oxygen content. The decreased P(O2) in the left upper pulmonary vein may contribute to arterial hypoxemia in addition to right-to-left shunt at the atrial level in adults with atrial septal defect.

Adult↗
PubMed1999

Long-term open-trial of mizoribine with prednisolone in 24 patients with multiple sclerosis: safety, clinical and magnetic resonance imaging outcome.

OBJECT: Mizoribine (MZR), imidazole nucleotide, inhibits purine synthesis and helper T cell functions. It is used as an immunosuppressant in chronic rheumatic arthritis in Japan. Twenty-four patients with relapsing-remitting and chronic progressive multiple sclerosis (MS) were studied for the long-term effects of MZR over 8 years. METHODS: Average daily MZR doses of 200 mg along with prednisolone (PSL) were administered in the patients studied. Ten of 24 patients were treated for more than 5 years. RESULTS: The mean relapse rate per year at entry (1.50 +/- 0.24, mean +/- SE, n = 22) decreased [0.46 +/- 0.24 (n = 19)] after two years. In 70% of the patients, the disability did not worsen. Eleven of 18 patients showed a mild decrease of the total lesion size in magnetic resonance imaging (MRI). CONCLUSION: MZR was well tolerated and could be used for long-term in MS as an adjunctive immunosuppressant to PSL, and the PSL doses could be decreased. A further randomized controlled trial with PSL is necessary.

Adolescent↗
PubMed1999

[Improving the anti-tumor activity of 5-fluorouracil by methotrexate].

The first clinical application of biochemical modulation (BCM) of 5-fluorouracil (5-FU) was the sequential MTX/5-FU regimen proposed in 1977 by Bertino for the treatment of colorectal cancer. In Japan, sequential MTX/5-FU therapy was mainly used as a new method of treating gastric cancer, and attracted a great deal of attention because it proved effective in many cases of advanced gastric cancer that had been unresponsive to the previous chemotherapy, particularly scirrhous gastric cancer with poor prognosis. Its therapeutic efficacy varied according to histologic type, it was effective in cases of peritoneal dissemination and disseminated intravascular coagulopathy (DIC), it was associated with fewer adverse effects, and it was a multidrug chemotherapy based on a clear rationale. With sequential MTX/5-FU therapy as a starting point, fundamental studies of BCM and its clinical applications have expanded rapidly in Japan. This paper provides an outline of sequential MTX/5-FU therapy from the aspects of its mechanism of action, indications, therapeutic efficacy, relevance to adjuvant therapy, counter-measures to adverse effects, and emergence of resistance to the drugs involved. The high therapeutic efficacy of this therapy in certain histologic types is also discussed, and its combined use with other forms of BCM, as in triple BCM (LV/5-FU + CDDP/5-FU + MTX/5-FU), is introduced.

Animals↗