Biomedical subjects

K Sakai

Publications and source records attributed to K Sakai.

At least 451 records · Page 25Linked to original sources

PubMed1997

Implications of prodromal angina pectoris in anterior wall acute myocardial infarction: acute angiographic findings and long-term prognosis.

OBJECTIVES: This study was undertaken to assess how prodromal angina affects long-term prognosis after acute myocardial infarction. BACKGROUND: Although it has been reported that prodromal angina occurring shortly before the onset of acute myocardial infarction has protective effects against ischemia, its implication for long-term prognosis remains unclear. METHODS: We studied consecutive 350 patients with anterior myocardial infarction who underwent coronary angiography within 24 h after the onset of chest pain. Follow-up was achieved for 340 patients (97%). RESULTS: Eighty-nine patients had one or more episodes of angina within 24 h before infarction. On initial angiography, patients with prodromal angina in the 24 h before infarction had a patent infarct-related artery more frequently than did those without prodromal angina (34% vs. 22%, p = 0.03). Among 213 patients who underwent thrombolytic therapy for an occluded infarct-related artery, reperfusion was more frequently achieved in patients with prodromal angina in the 24 h before infarction (76% vs. 56%, p = 0.01). Prodromal angina in the 24 h before infarction was associated with a lower in-hospital mortality rate (6% vs. 14%, p = 0.02) and better 5-year survival (p = 0.009). There was no significant difference in survival between patients with previous angina at any time (n = 202) and those without. Multivariate analysis showed that prodromal angina in the 24 h before infarction was an independent factor related to 5-year survival after acute myocardial infarction (odds ratio 0.49, p = 0.04). CONCLUSIONS: Prodromal angina occurring shortly before the onset of infarction, but not previous angina itself, has a beneficial effect on long-term prognosis after infarction, suggesting a relation to ischemic preconditioning.

Aged↗

PubMed1997

Assessment of myocardial distribution of retrograde and antegrade cardioplegic solution in the same patients.

OBJECTIVE: In order to clarify intramyocardial delivery and distribution of retrograde cardioplegic solution in humans, we induced both ante- and retrograde methods in the same patients to compare their respective delivery and distribution using myocardial contrast echocardiography during surgery. METHODS: 15 patients consisting of nine patients with valvular heart diseases and six patients with coronary artery diseases (including two patients with myocardial infarcted areas and two patients with areas supplied by coronary collateral situation associated with totally occluded coronary arteries without myocardial infarction). Induction of cardioplegia was initially accomplished antegradely and thereafter retrogradely. RESULTS: In valvular heart disease, retrograde cardioplegic solution was distributed less homogeneously, and was not delivered to the midportion of the interventricular septum in two-thirds of the patients (6/9). The transmural myocardial distribution in the anterior, lateral, and posterior walls in the left ventricle were similar for both ante- and retrograde cardioplegic solution, while delivery to the endocardial halves was better than to the epicardial halves (endo-/epicardial intensity ration in antegrade versus retrograde: 1.31 +/- 0.24 versus 1.29 +/- 0.26; 1.19 +/- 0.05 versus 1.36 +/- 0.23; 1.33 +/- 0.28 versus 1.44 +/- 0.35, respectively (all NS)). For delivery to the right ventricle, the existence of small cardiac vein was important. In patients with small cardiac vein (34% in our study), the delivery to the right ventricular dorsal walls was shown. In coronary heart disease, retrograde cardioplegic solution was well delivered to the areas by coronary collateral situation associated with totally occluded coronary arteries, but antegrade solution was not. Neither ante- nor retro grade solution was delivered to myocardial infarcted areas. CONCLUSIONS: These results have important implications for planning strategies for myocardial protection. We think that it is necessary to fully grasp the coronary arterial and venous anatomy of individual patients and to know how to use either ante- or retrograde cardioplegia properly.

Aged↗

PubMed1997

Synaptic vesicle ultrastructural changes in the rat hippocampus induced by a combination of alpha-linolenate deficiency and a learning task.

Rats fed either a safflower oil (alpha-linolenate-deficient) or a perilla oil (alpha-linolenate-sufficient) diet through two generations (F1) showed significant differences in the brightness-discrimination learning task. In this task, correct responses were lever-pressing responses, which were reinforced with dietary pellets, and incorrect responses were those with no reinforcement. The inferior learning performance in the safflower oil group was caused mainly by the inferior ability to rectify the incorrect responses through the learning sessions. In the safflower oil group after the learning task, the average densities of synaptic vesicles in the terminals of the hippocampus CA1 region were decreased by nearly 30% as compared with those in the perilla oil group, and it is notable that this difference was not detected without the learning task. These results suggest that dietary oil-induced morphological changes in synapses in the hippocampus of rats are related to the differential learning performance and that the turnover rate of synaptic vesicles in the hippocampus may be an important factor affecting learning performance.

Animals↗

PubMed1997

Identification of human cytochrome P450 isoforms involved in the metabolism of brotizolam.

1. To identify the cytochrome P450 (CYP) isoenzyme(s) responsible for the major metabolic pathways of brotizolam in man, we examined the metabolism of brotizolam using human liver microsomes and microsomes expressing individual human CYP isoenzymes (CYP1A1, 1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1, 3A4). 2. Brotizolam was metabolized to alpha-OH- and 6-OH-brotizolam by human liver microsomes (n = 3). Vmax for alpha- and 6-hydroxylation of brotizolam were 1470 +/- 259 and 8983 +/- 7740 pmol/min/mg protein respectively, and the corresponding Km were 49 +/- 9.3 and 595 +/- 580 microM respectively. 3. Among CYP inhibitors examined (furafylline, sulphaphenazole, quinidine, ketoconazole and cimetidine), ketoconazole showed the most potent inhibitory effect on brotizolam metabolism by human liver microsomes. Ki of ketoconazole for alpha- and 6-hydroxylation were 0.05 and 0.07 microM respectively. 4. When incubated with microsomes expressing individual human CYP isoenzymes (CYP1A1, 1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1, 3A4), brotizolam was metabolized only by CYP3A4. 5. Brotizolam metabolism in human liver microsomes was almost completely inhibited by anti-CYP3A4 antiserum. 6. These results suggest that CYP3A4 is predominantly responsible for both alpha- and 6-hydroxylation of brotizolam in human liver microsomes.

Azepines↗

PubMed1997

L-ornithine decarboxylase from Hafnia alvei has a novel L-ornithine oxidase activity.

A novel activity producing gamma-aminobutyric acid (GABA) from L-ornithine in the presence of NAD(P)+ was found in the crude extract of L-ornithine-induced Hafnia alvei, in addition to L-ornithine decarboxylase (ODC) activity. The reaction system for the former activity consisted of two enzymes, L-ornithine oxidase (decarboxylating, OOD) and gamma-aminobutyraldehyde (GABL) dehydrogenase (GDH). OOD catalyzed the conversion of L-ornithine into GABL, CO2, NH3, and H2O2 in the presence of O2, and GDH dehydrogenated GABL to GABA in the presence of NAD(P)+. OOD, purified to homogeneity, had a high ODC activity and the activity ratio of ODC to OOD was almost constant throughout the purification (ODC/ OOD=160:1). The molecular mass of the OOD was about 230 kDa, probably consisting of three identical subunits of a 77 kDa peptide, and OOD had an absorption maximum at 420 nm as well as at 278 nm, the specific absorption for an enzyme containing pyridoxal phosphate (PLP). The content of PLP was estimated at about 1 mol per subunit. OOD was specific to L-ornithine, and other L-amino acids and polyamines including putrescine were inert. The enzyme was activated by PLP, but not by pyridoxamine 5'-phosphate, FAD, FMN, or pyrroloquinoline quinone, and it was inactivated by hydrazine, semicarbazide, and hydroxylamine. The holoenzyme can be resolved to the apoenzyme by incubation with hydroxylamine, and reconstituted with PLP. These properties of OOD were almost the same as those of ODC separately purified to homogeneity from H. alvei. Zn2+ and Cu2+, butanedione, and sodium borohydride inhibited both OOD and ODC in a similar manner. The OOD reaction required O2 and only the ODC reaction proceeded under anaerobic conditions. The substitution of air for oxygen in the reaction vessel and the addition of catalase-H2O, enhanced only the OOD reaction, resulting in an increase of the ratio of OOD/ODC to 1:30 and 1:4.1, respectively. These results suggested that OOD and ODC are identical and that the former is a side reaction of the latter in the presence of O2.

Aldehyde Oxidoreductases↗

PubMed1997

Neoadjuvant chemotherapy followed by concurrent chemotherapy and radiotherapy for locally advanced esophageal carcinoma with bulky upper abdominal lymphadenopathy. Case report.

A 60-year old male patient who had locally advanced esophageal carcinoma with bulky upper abdominal lymphadenopathy underwent neoadjuvant chemotherapy consisting of 5-fluorouracil (5-FU) and cisplatin (CDDP), followed by concurrent radiotherapy and chemotherapy using protracted low-dose continuous infusion of 5-FU and CDDP. The treatment brought about complete remission in the primary lesion and good partial remission in the upper abdominal lymphadenopathy. He subsequently underwent trans-hiatal esophagectomy after one cycle of adjuvant chemotherapy because local recurrence was suspected. Histopathologic study of the resected specimen demonstrated no malignant tissue in the primary lesion and the lymph nodes. The patient is still alive and disease-free at 26+ months. This result suggests that neoadjuvant chemotherapy followed by concomitant chemotherapy and radiotherapy for patients who have locally advanced squamous cell carcinoma of the esophagus with intensive abdominal lymphadenopathy may offer some chance for sterilization of local and regional metastases and longer survival.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1997

Carcinoma of the thyroid manifested as hyperthyroidism caused by functional bone metastasis.

A rare case of hyperthyroidism in the presence of a functioning bone metastasis secondary to an occult thyroid cancer is reported. A 59-year-old woman's pelvic bone metastasis was much too extensive and hypervascular to permit resection. An I-131 scan showed striking activity in the pelvic metastasis, which reflected ectopic excessive production of thyroid hormone by a functioning metastatic thyroid carcinoma. After total thyroidectomy, the patient received I-131 ablation and transcutaneous intra-arterial embolization therapy but her metastasis progressively enlarged. Microscopically, concomitant follicular and papillary cancer was found in close proximity to the thyroid. The patient now has vertebral metastases, and her hyperthyroid state still requires methymazole to prevent thyrotoxicosis.

Bone Neoplasms↗

PubMed1997

Case report: endoscopic ultrasonographic findings of mucosal prolapse syndrome.

A 41-year-old man with mucosal prolapse syndrome received endoscopic ultrasonography. The lesion was mildly hypoechoic and irregular, with extension into the muscularis propria and disappearance of the normal mucosal and submucosal layers. In addition, an enlargement of the muscularis propria, bridging towards the mucosal layer with merging of the two layers, was observed. These findings suggest the usefulness of endoscopic ultrasonography in the diagnosis of mucosal prolapse syndrome.

Adult↗

PubMed1997

Screening of H-ras gene point mutations in 50 cases of bladder carcinoma.

BACKGROUND: Mutation converts the H-ras gene into an activated oncogene in about 10% of human bladder cancers. Codons 12 and 61 are the major "hot spots" for activation. A simple and accurate method to detect point mutations in these codons may be clinically useful for early diagnosis of bladder cancer. METHODS: Bladder cancer samples from 50 patients, plus 10 samples of normal bladder mucosa, were analyzed for possible point mutation of the H-ras gene at either codon 12 or codon 61. The H-ras gene DNA segments that include these 2 codons were amplified by PCR methods, then the possible presence of a point mutation was evaluated at each codon by susceptibility of the respective DNA segments to digestion with the restriction enzyme and by dot blot hybridization assay. A bladder cancer patient who had an H-ras gene mutation was examined to see whether the mutation was also detectable in the cells released in the urine. RESULTS: Definite or possible point mutations were found in 6 (12%) out of 50 bladder cancer patients, while no mutation was detected in normal mucosa. A point mutation could also be detected in cells isolated from the patient's urine sample. CONCLUSION: The prevalence of point mutations at codon 12 or codon 61 of the H-ras gene found in this study was similar to that previously estimated for human bladder cancer by DNA transfection assay. The method we have used for detecting point mutations of the H-ras gene provides a simple and highly accurate way to detect mutated cancer cells even in the urine. It may be clinically usable for early diagnosis of bladder cancer.

Adult↗

PubMed1997

Comparison of an improved AFP kit with the intra-amniotic PSP dye-injection method in equivocal cases of preterm premature rupture of the fetal membranes.

OBJECTIVE: We developed an improved AFP kit for detecting AFP in leaked amniotic fluid. We studied the relationship between the results of the improved AFP kit and those of the intra-amniotic PSP dye-injection test (PSP test), and compared the results of two tests with the prognosis for subsequent pregnancy outcome, in order to know the diagnostic value of the two tests for preterm PROM, especially in equivocal cases. METHODS: We compared the results of the AFP kit test with those of the PSP test in 8 equivocal cases of preterm PROM (18th to 34th weeks of gestation). RESULTS: The results of the AFP kit test coincided with those of the PSP test in all 8 equivocal cases of preterm PROM. The 4 cases that tested positive resulted in preterm deliveries; and the other 4 cases that tested negative resulted in full-term deliveries. CONCLUSION: The use of the AFP kit test is useful in assessing the prognosis for subsequent pregnancy in equivocal cases of preterm PROM. The rapid and accurate AFP kit test for diagnosing preterm PROM can be substituted for the PSP test in bedside and outpatient-clinic assessments.

Adult↗

PubMed1997

Critical role for M3 muscarinic receptors in paradoxical sleep generation in the cat.

In the cat, microdialysis application of 200 microM carbachol to the peri-locus coeruleus alpha (peri-LC alpha) of the mediodorsal pontine tegmentum produced a marked (< or = 5-fold) increase in paradoxical sleep. This effect was blocked by 5-50 microM 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP), an M1/M3-selective muscarinic receptor antagonist. In contrast, the effect was not reversed by methoctramine, an M2-selective antagonist, or pirenzepine, an M1-selective antagonist, even at concentrations as high as 500 microM. In addition, unilateral application of 5 microM 4-DAMP alone to the peri-LC alpha induced both a > 60% decrease in paradoxical sleep and a state of paradoxical sleep without atonia, whereas 50 microM pirenzepine and 500 microM methoctramine had no effect. Our findings are further evidence for the important role played by the peri-LC alpha and demonstrate a critical role for M3 muscarinic cholinergic receptors in the generation of paradoxical sleep.

Animals↗

PubMed1997

Recent experience of integrated myocardial management: the newest strategy for myocardial protection.

From April 1994 until June 1996, we exclusively utilized the integrated myocardial management (IMM) proposed by Buckberg et al. at UCLA. Two hundred sixty-two consecutive patients undergoing open heart surgery at our hospital were divided into 2 groups, the non-IMM (n = 49, from July 1993 until March 1994) and the IMM (n = 213, from April 1994 until June 1996) groups. Although many older and more severely ill patients were treated with IMM, acceptable clinical outcomes with comparable safety and efficiency were obtained. Shorter durations of total cardiopulmonary bypass (CPB) and aortic cross-clamping (AXC) were needed in the IMM group despite there being many more procedures undertaken during a single cross-clamp period.

Adult↗

PubMed1997

A chance SPECT study of ictal aphasia during simple partial seizures.

We report obtaining an ictal single photon emission computed tomographic (SPECT) scan in a right-handed 51-year-old man who had an astrocytoma in the left cerebral hemisphere and simple partial seizures characterized by aphasia. An epileptic seizure producing loss of speech and right-sided facial twitching occurred by chance during a SPECT scan. During the attack, he was unable to speak, but auditory comprehension and writing were intact. Ictal SPECT showed an area of increased perfusion in the left frontal cortex, with the area of highest perfusion involving the left frontal operculum to the inferior part of the left precentral gyrus. Interictal SPECT showed hypoperfusion in the same area. These SPECT findings suggest that the frontal operculum of the dominant hemisphere is one of the regions that can give rise to epileptic aphasia.

Astrocytoma↗

PubMed1997

Reversible limbic encephalitis caused by ovarian teratoma.

A 19-year-old woman developed memory loss followed by psychosis, coma, convulsion, and central hypoventilation requiring mechanical ventilation. MRI of the brain showed minimal changes, and SPECT imaging revealed a small region of increased uptake in the cortex. Intravenous acyclovir and high-dose corticosteroids were administered without any effect. An extensive work-up revealed an elevated serum alpha-fetoprotein (AFP) concentration and the presence of an ovarian tumor. Following resection of the tumor, an immature teratoma by pathology, the patient had significant recovery of her cognitive function with some psychotic sequela. Serum anti-neuronal antibody (anti-Hu) was negative both by immunohistochemistry and by Western blot analysis. A rare combination of paraneoplastic limbic encephalitis and brainstem encephalitis was the suspected diagnosis. Because the tumor contained a neuronal component, we propose an immunologic cross-reaction as the pathomechanism, but the lack of a specific antibody may suggest cell-mediated rather than globulin-mediated immunity.

Adult↗

PubMed1997

Gastrointestinal submucosal tumors: evaluation with endoscopic US.

PURPOSE: To describe the endoscopic ultrasound (US) features of benign versus malignant submucosal tumors throughout the gastrointestinal tract. MATERIALS AND METHODS: One hundred nine patients aged 24-81 years suspected to have submucosal tumors (11 esophageal, 41 stomach, 24 duodenal, and 33 colorectal tumors) at barium studies or endoscopy underwent endoscopic US. The layer of origin, internal echo pattern, and lesion margin were analyzed by means of consensus and independent interpretation by three radiologists. RESULTS: Endoscopic US findings revealed several distinct patterns among various submucosal tumors. Sixteen (94%) of the 17 homogeneous lesions with histopathologic findings of malignancy were hypoechoic, although 29 (43%) of the 68 homogeneous lesions with histopathologic findings of benignity were similarly hypoechoic. Homogeneous lesions that were anechoic, of intermediate echogenicity, or hyperechoic were almost exclusively benign (39 [98%] of 40). In contrast, 23 (96%) of the 24 malignant lesions were heterogeneous (n = 7) or homogeneously hypoechoic (n = 16). The sizes of benign and malignant lesions were significantly different (P < .05). There was no significant difference in the echo pattern (i.e., homogeneous versus heterogeneous), but there was a significant difference in the proportion of hypoechoic versus nonhypoechoic lesions (anechoic, hyperechoic, or of intermediate echogenicity; P < .001). CONCLUSION: The differential diagnosis of gastrointestinal submucosal tumors is assisted with endoscopic US.

Diagnosis, Differential↗

PubMed1997

Renal angiotensin-converting enzyme localization in diabetic rats and the effect of low protein diet.

Recent evidence suggests a role of angiotensin-converting enzyme (ACE) in diabetic nephropathy. The effect of diabetes and low protein diet on renal immunohistochemical ACE localization was studied in streptozotocin-induced DM rats. Immunohistochemical ACE localization was reduced in DM rats, and a low protein diet partially resolved this abnormality while inhibiting the progression of diabetic nephropathy.

Albuminuria↗

PubMed1997

Hydrometrocolpos with ectopic vaginal opening to the bladder. A case report.

A case of hydrometrocolpos with vaginal opening to the bladder is presented. A newborn female presented abdominal distention and postaxial polydactyly at birth. Clinical investigation revealed hydrometrocolpos, precocious puberty, urogenital sinus and other multiple malformations. The vagina was open to the bladder with a small orifice. Vaginal pull-through surgery and closure of the communication was performed. Over a hundred cases of hydrometrocolpos have been reported previously. However, we could not find a case of hydrometrocolpos with vaginal opening to the bladder among them.

Female↗

PubMed1997

Circulating levels of soluble interleukin-6 receptor in patients with bronchial asthma.

In the search for markers of airway inflammation, we investigated the role of soluble interleukin-6 receptor (sIL-6R) in patients with bronchial asthma. Serum levels of sIL-6R were measured in 20 patients with stable asthma and in 18 healthy control subjects by means of a sandwich enzyme-linked immunosorbent assay. Such levels were also evaluated during a spontaneous attack of asthma (n = 10) as well as that after allergen inhalation (n = 7). Results were compared with those observed during the stable state and after the inhalation of methacholine. Serum levels of sIL-6R in asthmatic patients (132 +/- 31 ng/ml) significantly exceeded those of control subjects (111 +/- 16 ng/ml) (p < 0.05). These levels showed no correlation with such clinical variables as nonspecific bronchial hyperreactivity, atopic status, or serum concentration of IgE. Serum sIL-6R levels observed during an asthmatic attack versus those during the stable state (4 wk later) differed significantly. After a severe attack of asthma, such levels were significantly elevated on the second and third days, but not on Day 5. After challenge, circulating levels of sIL-6R were significantly increased 24 h after the inhalation of allergen but not of methacholine. Results suggest that serum levels of sIL-6R are increased in patients with asthma and are further increased during a spontaneous attack or that provoked by the inhalation of allergen. Thus, serum sIL-6R may reflect inflammation of the airway. Further studies are indicated to determine the clinical significance and the application of serum levels of sIL-6R in evaluating asthmatic patients.

Adult↗