Biomedical subjects

Y Sakaguchi

Publications and source records attributed to Y Sakaguchi.

At least 109 records · Page 6Linked to original sources

PubMed1992

[A case of cardiac lipoma of the anterior tricuspid leaflet].

A 42-year-old man with cardiac lipoma of the anterior tricuspid leaflet is reported. He had a chief complaint of epigastric discomfort, and a pansystolic murmur was heard at the left sternal border in the 4th intercostal space. Two-dimensional echocardiography disclosed a mobile high density stalkless mass having several areas of low density. Two-dimensional Doppler echocardiogram revealed a moderate degree of tricuspid regurgitation. These findings were more clearly visualized on transesophageal echocardiogram. MRI revealed a high signal intensity on the T1-weighted image and a high radiodensity surrounding the mass using a contrast medium of Gd-DTPA. A 2.0 x 1.3 x 0.8 cm hemispherical, lobulated and sessile yellow mass was excised by means of open heart surgery, and tricuspid valvuloplasty was performed. The mass was adipose tissue and was surrounded by fibrous tissue just under the lamina fibrosa. These findings were compatible with those of the preoperative examinations, although the preoperative diagnosis was not conclusive. This was our first case of cardiac lipoma in which the tricuspid valve was successfully excised.

Adult↗

PubMed1992

Resistance to anticancer drugs of well differentiated gastric adenocarcinoma with venous invasion.

A comparison of the chemosensitivity of well-differentiated human gastric cancer tissues was made between histological venous invasion positive (v(+)) and negative (v(-)) tissues, using the succinate dehydrogenase inhibition (SDI) test. These tissues obtained at the time of surgery were exposed to six anticancer drugs: carboquone (CQ), adriamycin (ADM), mitomycin C (MMC), aclacinomycin A (ACR), cisplatin (DDP) and 5-fluorouracil (5-FU). Chemosensitivity was judged to be positive when the succinate dehydrogenase (SD) activity of the drug exposed cells decreased to below 50% of that of control cells. Decrease in the SD activity was more apparent in the v(-) tissues than in the v(+) tissues, exposed to the anticancer drugs and in particular to ADM (P less than 0.01), MMC (P less than 0.02) and DDP (P less than 0.05). The sensitivity rates to all six anticancer drugs were lower in the v(+) tissues. The resistance rates to all drugs tested were 0% in the v(-) tissues, but 21% in the v(+) tissues. In light of these observations, patients with gastric cancer of the well differentiated type and the histological venous invasion, will probably show a less positive response to cancer chemotherapy.

Adenocarcinoma↗

PubMed1991

Usefulness of epidurally evoked cortical potential monitoring during cervicomedullary glioma surgery.

This report describes a patient with an intramedullary ependymoma at the region of the cervicomedullary junction in whom there was an abolition of somatosensory evoked potentials following median nerve stimulation. During intraoperative monitoring of cortical potentials elicited by epidural cervical cord stimulation, the tumor was removed. Posterior epidural stimulation appeared to depolarize more ascending fibers than did stimulation of a single peripheral nerve. We recommend that, in cases of operations in this vital area, epidurally evoked cortical potentials be monitored intraoperatively.

Evoked Potentials, Somatosensory↗

PubMed1991

A nationwide survey on transient hyperammonemia in newborn infants in Japan: prognosis of life and neurological outcome.

A nationwide survey of transient hyperammonemia in newborns was carried out in Japan. A total of 18 patients, consisting of 12 male and 6 female infants, were reported from 11 facilities. These neonates exhibited hyperammonemia with plasma ammonia levels in the range from 124 to 6256 micrograms/dl. Four newborn infants of the 18 died in the neonatal period, and an additional one died in the early infancy. Among the 13 infants who were alive at the time of this survey, 6 had neurological sequelae, including mental retardation, spastic quadriplegia and epilepsy. The multivariate analysis revealed that the Apgar score at 1 minute, peak plasma ammonia concentration, birth weight and sex were significant factors affecting the prognosis of life.

Ammonia↗

PubMed1991

1-Hexylcarbamoyl-5-fluorouracil alters the expression of heat shock protein in HeLa cells.

We determined the effect of 1-hexylcarbamoyl-5-fluorouracil (HCFU), a masked compound of 5-fluorouracil, on the expression of heat shock protein (HSP) in heat-treated HeLa cells. We used a monoclonal anti-72-kDa heat shock protein antibody. At 37 degrees C, HSP was predominant in the cytoplasm of cells and heating to 43 degrees C for 30 min increased the synthesis of HSP in the nucleus. When HeLa cells were treated with heat and HCFU, at a concentration which showed evidence of synergy, nuclear staining of the cells decreased. Thus, the altered expression of HSP by HCFU is related to a synergism between heat and HCFU.

Cells, Cultured↗

PubMed1991

Dipyridamole combination chemotherapy can be used safely in treating gastric cancer patients.

The feasibility of a combined chemotherapy using dipyridamole (DP) with adriamycin (ADM) and 5-fluorouracil (5-FU) was investigated. First, the chemosensitivity of gastric cancer tissues was determined by the succinate dehydrogenase inhibition test, which showed sensitivity to ADM and 5-FU is increased by DP. Next, a clinical trial of combined therapy of DP, ADM and 5-FU, as a post-operative adjuvant chemotherapy for gastric cancer patients, was performed. DP (50 mg) was given as a 1-h i.v. infusion, and ADM (20 mg) was given as a single i.v. injection. This treatment was started on post-operative day 10, and was repeated every 2 weeks. Simultaneously with these treatments, DP (300 mg) and 5-FU (150 mg) were administered post-operatively daily. A total of 63 courses of therapy in nine patients were performed. The adverse effects related to the DP infusion were flushing, headache, nausea and upper abdominal discomfort, all of a low grade. DP did not appear to alter the toxicity of ADM and 5-FU, and no severe adverse effect was noted for this combination therapy. The pharmacokinetics of DP were also investigated in five patients. The mean plasma concentration of DP increased 4.41 micrograms/ml and remained above 0.25 microgram/ml for over 6 h. This combination chemotherapy appears to be safe and may be useful clinically in treating cancer.

Adult↗

PubMed1991

The microtiter SDI test is more advantageous than the SDI test for assessing the chemosensitivity of human tumor cells.

The in vitro succinate dehydrogenase inhibition (SDI) test was adapted to be used with microtiter plates and this microtiter SDI (mSDI) test was evaluated for clinical use of chemosensitivity testing, as compared to findings with the SDI test. The optimal conditions of the mSDI test were determined: (1) 2-5 x 10(4) cells/well; (2) enzymatic disaggregation of solid tumors with the use of a mixture of 0.2% pronase, 0.25% collagenase, 0.1% DNase for 20 min at 37 degrees C; (3) addition of 10 mM sodium succinate in the colorimetric reaction; and (4) use of dimethyl sulfoxide (DMSO) as a solvent for extraction of formazan product. Good correlations were observed between the mSDI and the SDI tests when S-180 cells (r = 0.890-0.996) or 16 human fresh tumor cells (r = 0.731-0.999) were exposed to six anti-cancer drugs (carboquone, adriamycin, mitomycin C, aclacinomycin A, cisplatin, 5-fluorouracil). Thus, the mSDI test facilitates testing of a large number of drugs with minimal amounts of specimens, and is expected to replace the SDI test for chemosensitivity testing of clinical tumor cells.

Animals↗

PubMed1991

A protein-bound polysaccharide immunomodulator, PSK, does not suppress the conversion from 1-(2-tetrahydrofuryl)-5-fluorouracil to 5-fluorouracil in patients with gastric cancer.

Effects of the immunomodulator PSK on the metabolism of 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur) to 5-fluorouracil (5-FU) were examined in 10 patients with advanced gastric cancer and who had undergone curative resection. PSK is a protein-bound preparation, extracted from Coriolus versicolor and belongs to Basidiomycetes. The 5-FU concentration in the plasma was 0.024 micrograms/ml at 15 min after the intravenous injection of 400 mg of tegafur and the area under the curve of 5-FU was 0.58 micrograms.h/ml. Following administration of PSK, 3 g/day for 8-14 months, there was no change in the plasma level of 5-FU, in any patient. As the clinical dose of PSK had no apparent influence on the metabolism of tegafur to 5-FU, the combination of PSK and tegafur can be prescribed to treat patients with advanced gastric cancer.

Antibiotics, Antineoplastic↗

PubMed1991

Lid margin reconstruction with an orbicularis oculi musculocutaneous advancement flap and a conchal cartilage graft.

A simple method to reconstruct the midlateral lid margin defect is described using an orbicularis oculi musculocutaneous advancement flap and a free conchal cartilage graft. This method is easy to perform not only in the lower eyelid, but also in the upper one, provides a natural gray line and a stable lid margin without postoperative eversion, and substitutes for the Leone and van Gemert procedure.

Adult↗

PubMed1991

A histopathological study of age-related changes of the left bundle branch in the human heart.

To study age-related changes in the left bundle branch (LBB), 32 autopsied hearts were examined histopathologically using serial sections according to the method of Lev. Each division of LBB was carefully studied, i.e., the anterior and posterior radiations and the proximal, middle, and distal portions of radiations. An increase of fibrosis and fatty infiltration were observed in the LBB with aging. There was a tendency for fibrosis to be more prominent in the proximal LBB at the site of transition from bundle branch cells to Purkinje cells.

Adipose Tissue↗

PubMed1991

Human colon cancer tissues are more sensitive than rectal cancer tissues to antitumor drugs in vitro.

The chemosensitivities of 62 human colon cancer tissues, 67 rectal cancer tissues and 31 tumor-adjacent normal mucosal tissues were determined using the in vitro succinate dehydrogenase inhibition (SDI) test. These tissues obtained at the time of surgery were exposed to carboquone (CQ), adriamycin (ADM), mitomycin C (MMC), aclacinomycin A (ACR), cisplatin (DDP) and 5-fluorouracil (5-FU). The chemosensitivity was considered as positive when succinate dehydrogenase (SD) activity of the drug-treated cells decreased to below 50% of that of control cells, on day 3 of exposure. Decrease in the SD activity was noted in the colon cancer tissues, compared to the rectal cancer tissues, exposed to six antitumor drugs and in particular, to CQ (p less than 0.05), DDP (p less than 0.01) and ACR (p less than 0.05, one-sided paired t test). Decrease in the SD activity was noted in the tumor tissues, compared to the tumor-adjacent normal tissues, exposed to CQ, MMC and ACR (p less than 0.01). The sensitive rates were higher in the colon cancer tissues than the rectal cancer tissues, against all six antitumor drugs. Our findings show that the rectal cancer tissues are resistant to antitumor drugs, compared to the colon cancer tissues in vitro. When selecting antitumor drugs to treat patients with a rectal cancer, the assessment for chemosensitivity of the related tissues is crucial.

Antineoplastic Agents↗

PubMed1991

Clinical significance of abnormal Q wave disappearance in acute transmural myocardial infarction.

The clinical features of acute myocardial infarction patients in whom abnormal Q wave disappeared were analyzed. Of 201 patients, 40 (20%) (Group A) showed disappearance of Q wave in serial electrocardiograms. Regional ejection fraction of the infarcted portion improved significantly (from 24 +/- 2 to 34 +/- 4%, p less than 0.001) during chronic phase in Group A, but no such improvement was present in Group B patients who showed no change in the Q wave. Global ejection fraction was greater and percent akinetic segment was smaller in Group A than in Group B at chronic phase. Coronary occlusion occurred more often at segment 7 in Group A; in Group B, occlusion occurred more frequently upstream at segment 6, suggesting Group A had a smaller area of risk. Spontaneous recanalization was more often (57%) and complete occlusion was less frequent in Group A. These indicate that Group A is characterized by a smaller area of risk, smaller infarct size, earlier reperfusion, and greater improvement in wall motion. Twenty-eight patients (70%) of Group A lost Q wave within one month and 12 patients (30%), after 3 months or more. Electrical stunning of the myocardium may be a possible mechanism for the early disappearance of Q waves, and anatomical healing for the late disappearance of Q waves.

Electrocardiography↗

PubMed1991

Sarcoma-180 cells and human colorectal tumor cells under in vitro hypoxic conditions are more sensitive to mitomycin C and carboquone.

The effects of oxygen concentration on the chemosensitivity of mouse sarcoma-180 (S-180) cells and human colorectal cancer tissues to mitomycin C (MMC) or carboquone (CQ) were determined in vitro, since evidence had been obtained that these drugs are more effective in HeLa cells. The results were as follows: (a) S-180 cells exposed to various concentrations of MMC or CQ for 2 h under conditions of normal aeration (about 20%) or hypoxia (5.0% and 0%) were then maintained under normal conditions of aeration for 3 days. Change of viability was assessed by succinate dehydrogenase (SD) activity. With exposure of the cells to MMC or CQ, under anoxic conditions (O2:0%), SD activity decreased to a greater extent than seen in the control cells. The value for CQ was from 61.5% to about 36.2%. (b) The decrease in the SD activity of 20 colorectal cancer tissues kept under conditions of anoxia was compared with findings under normally aerated conditions, following exposure to 30 microM of MMC or 1.6 microM of CQ. On exposure to MMC or CQ under anoxic conditions, SD activity decreased significantly, compared with normally aerated conditions (P less than 0.001 for MMC; P less than 0.05 for CQ). As colorectal cancer is less sensitive than other tissues to various chemotherapeutic agents, we recommend that MMC and CQ be prescribed to treat patients with these malignant lesions.

Alkylating Agents↗

PubMed1991

Lung adenocarcinoma is more sensitive than gastric adenocarcinoma to anticancer drugs in vitro.

The chemosensitivities of 26 lung adenocarcinoma tissues were compared to those of 110 gastric adenocarcinoma tissues, using the in vitro succinate dehydrogenase inhibition (SDI) test. Tumour tissues obtained at surgery were exposed to five different anticancer drugs: carboquone (CQ), adriamycin (ADM), mitomycin C (MMC), cisplatin (DDP) and 5-fluorouracil (5-FU). The lung adenocarcinomas showed a statistically significant reduction in succinate dehydrogenase (SD) activity, compared to the gastric adenocarcinomas, after exposure to each drug. The chemosensitivity was defined as a reduction in SD activity to 50% of control or less. Lesser degrees of reduction in SD activity were defined as drug resistance. The sensitivity rates to ADM, MMC and DDP, respectively, were significantly higher in the lung than in the gastric adenocarcinomas. Tumour cells from 22 (84.6%) of the 26 lung adenocarcinoma tissues showed a sensitivity to more than three drugs, whereas the rate was only 46.4% (51/110) for the gastric adenocarcinomas. The rate of resistance to all the drugs tested was 3.8% (1/26) for the lung adenocarcinomas, in contrast to the 20.9% (23/110) seen with the gastric adenocarcinomas. Thus, while adenocarcinomas of the lung and stomach both show clinical resistance to anticancer agents, the chemosensitivity of the lung tissues is greater. In the light of these observations, attention must be directed to improving specific drug delivery systems.

Adenocarcinoma↗

PubMed1990

Thermodynamic study of protein dynamic structure in the oxygen binding reaction of myoglobin.

We examined the flash photolysis of oxy complexes of sperm whale myoglobin (Mb) on the nanosecond time scale at ambient temperatures. In this time range, we can observe the geminate reaction of Mb with the O2 ligand existing in the protein matrix after the photodissociation from the heme iron. We found that the fraction of the geminate component to the total O2 photodissociation exhibited temperature dependences. The geminate fraction decreased with rising temperature, indicating that the protein fluctuation is enhanced at high temperature because of thermal agitation. However, the temperature-dependent behavior showed a break at 20 degrees C. Concerning the geminate O2 escaping reaction from the protein matrix to the solvent region, the activation energy above 20 degrees C (0.4 +/- 0.4 kcal/mol) is significantly lower than that below 20 degrees C (5.1 +/- 0.4 kcal/mol). Thermodynamic analysis on the basis of the transition state theory indicated that the O2 escaping reaction above 20 degrees C is entropy dominated whereas that below 20 degrees C is enthalpy dominated. The results were qualitatively compatible with the theoretical prediction by J. Kottalam and D. A. Case [1988) J. Am. Chem. Soc. 110, 7690-7697). Comparing the kinetic and thermodynamic process of the O2 geminate reaction among several Mbs, we concluded that the geminate O2 reaction with Mb is governed by the dynamic motion of the protein which is sensitively controlled by the static interaction of the heme moiety with the surroundings.

Animals↗

PubMed1990

New transient species of sperm whale myoglobin in photodissociation of dioxygen from oxymyoglobin.

We carried out the flash photolysis of oxy complexes of sperm whale myoglobin, cobalt-substituted sperm whale myoglobin, and Aplysia myoglobin. When the optical absorption spectral changes associated with the O2 rebinding were monitored on the nanosecond to millisecond time scale, we found that the transient spectra of the O2 photoproduct of sperm whale myoglobin were significantly different from the static spectra of deoxy form. This was sharply contrasted with the observations that the spectra of the CO photoproduct of sperm whale myoglobin and of the O2 photoproducts of cobalt-substituted sperm whale myoglobin and Aplysia myoglobin are identical to the corresponding spectra of their deoxy forms. These results led us to suggest the presence of a fairly stable transient species in the O2 photodissociation from the oxy complex of sperm whale myoglobin, which has a protein structure different from the deoxy form. We denoted the O2 photo-product to be Mb*. In the time-resolved resonance Raman measurements, the nu Fe-His mode of Mb* gave the same value as that of the deoxy form, indicating that the difference in the optical absorption spectra is possibly due to the structural difference at the heme distal side rather than those of the proximal side. The structure of Mb* is discussed in relation to the dynamic motion of myoglobin in the O2 entry to or exit from the heme pocket. Comparing the structural characteristics of several myoglobins employed, we suggested that the formation of Mb* relates to the following two factors: a hydrogen bonding of O2 with the distal histidine, and the movement of iron upon the ligation of O2.

Animals↗

PubMed1990

Adjuvant chemotherapy enhances long-term survival of patients with advanced gastric cancer following curative resection.

We examined the effectiveness of postoperative adjuvant chemotherapy with mitomycin C (MMC), 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur), plus PSK, an immunomodulator, for patients with advanced gastric cancer who underwent histological curative resection. The effect of chemotherapy on prognostic serosal (ps) invasion [ps(-) or ps(+)] and lymph node metastasis [n(-) or N(+)] was examined. One hundred eighteen patients were in the no-chemotherapy group and 137 were on the drugs. The median follow-up time for the 86 survivors at the time of analysis was 13.8 years. With regard to prognostic factors, there were no differences between the two groups. Generalized Wilcoxon test of the two survival patterns revealed a P value of .0351, and the survival rate for 15 years was 45.7% for patients in the no-chemotherapy group and 56.9% for those of the chemotherapy group. In particular, adjuvant chemotherapy was effective for patients with ps(-)n(+) (P less than .05) and ps(+)n(-) (P less than .05), but not for those with ps(-)n(-) and ps(+)n(+). Our findings show that the concomitant prescription of MMC, tegafur, and PSK improves the 15-year survival rate for patients with advanced gastric cancer, following curative resection. As the survival rate is low for the patients with ps(+)n(+), an even more aggressive postoperative chemotherapy is recommended.

Adult↗

PubMed1990

Primary and metastatic liver lesions of clinical colorectal cancer differ in chemosensitivity.

The succinate dehydrogenase inhibition (SDI) test was used to examine eight pairs of samples obtained simultaneously from primary colorectal cancers and metastatic liver lesions. The chemosensitivity of the metastatic lesions to six antitumour drugs, carboquone (CQ), adriamycin (ADM), mitomycin C (MMC), aclacinomycin A (ACR), cisplatin (DDP), and 5-fluorouracil (5-FU), differed from that of the primary lesions - the metastatic lesions were less sensitive to all these drugs. There were no correlations of chemosensitivities between the primary and the metastatic lesions (r = -0.4331-0.4857). Thus, in patients with liver metastasis from a primary colorectal cancer, treatment with these drugs may not be so effective. When selecting antitumour drugs for metastatic liver lesions of colorectal cancer, the chemosensitivity of the primary tumour should first be assessed.

Antineoplastic Agents↗