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Biomedical subjects

A Katoh

Publications and source records attributed to A Katoh.

At least 55 records · Page 3Linked to original sources

Obstacles encountered in the use of the medical record and cancer registry abstract in breast cancer research.

A historical-prospective study is being conducted to determine whether there is a relationship between obesity and breast cancer recurrence and survival in African-American women. The primary data sources for the study are the medical record and cancer registry abstract. It has been found that data items such as occupation, menopausal status, height, weight, estrogen receptor and progesterone receptor values, stage, tumor size, number of positive nodes, family history of cancer, and tumor status are not always documented. Suggestions for improving documentation of the primary data sources are provided.

Abstracting and Indexing↗

Modulation of cisplatin sensitivity and accumulation by interferon alpha-2A in human squamous carcinoma cell lines.

This study was undertaken to elucidate the mechanism(s) of potentiation of cisplatin (CDDP) cytotoxicity by interferon alpha-2a (IFN alpha-2a) in human squamous carcinoma cell lines SCC-25 and SCC-4. IFN alpha-2a treatment significantly increased the cytotoxicity of CDDP in both cell lines in a dose-dependent manner. In SCC-25 cells, the cytotoxicity of CDDP was increased by about 2- and 4-fold, respectively, by treating the cells with 400 and 800 IU/ml IFN alpha-2a. Sensitivity of SCC-4 cells to CDDP was increased by about 3- and 7-fold, respectively, by 400 and 800 IU/ml IFN alpha-2a treatment. Drug uptake experiments revealed approximately 1.4- to 5-fold higher platinum accumulation in IFN alpha-2a-treated cells as compared to respective controls. Cellular levels of glutathione (GSH) and GSH transferase, which have been suggested to be important determinants of tumor cell sensitivity to CDDP, were not altered by IFN alpha-2a treatment in either of the cell lines. Northern blot analysis showed a moderate increase (about 30-40%) in the level of MT-IIA mRNA by IFN alpha-2a treatment in these cells. Our results suggest that IFN alpha-2a-mediated sensitization of SCC-25 and SCC-4 cell lines to CDDP in vitro may be due to an increase in intracellular platinum accumulation.

Antineoplastic Agents↗

Disappearance of giant negative T waves in patients with the Japanese form of apical hypertrophy.

OBJECTIVES: The present study investigated the long-term changes in the electrocardiographic (ECG) hallmarks of the Japanese form of apical hypertrophy. BACKGROUND: Giant negative T waves and tall R waves in the left precordial leads are the ECG hallmarks of the Japanese form of apical hypertrophy. However, the long-term course is largely unknown. METHODS: Twenty-nine patients with apical hypertrophy (26 men, 3 women, mean age +/- SD 50.4 +/- 8.2 years) who showed left precordial giant negative T waves (< or = -10 mm) and tall R waves (> or = 26 mm) and spade configuration in the left ventriculogram were followed up for 10.9 +/- 3.7 years. RESULTS: The intermediate follow-up ECGs (5 to 9 years) showed disappearance of giant negative T waves in 31% and of tall R waves in lead V5 in 6%. At the long-term follow-up study (> or = 10 years), loss of giant negative T waves increased to 71%, with average T wave negativity in lead V4 or V5 decreasing from -16.5 +/- 5.1 to -6.9 +/- 4.2 mm. These T wave changes were associated with decreases in R wave amplitude in lead V5 from 40.7 +/- 9.6 to 26.1 +/- 13.8 mm, with loss of tall R waves in lead V5 in 38% of patients and development of abnormal Q waves in two patients. CONCLUSIONS: During the long-term follow-up of the Japanese form of apical hypertrophy, giant negative T waves disappeared in association with decreases in R wave amplitude in lead V5, indicating that these ECG hallmarks are clinical features that evolve progressively during the natural course of the disease.

Adult↗

Mice devoid of the glial fibrillary acidic protein develop normally and are susceptible to scrapie prions.

Glial fibrillary acidic protein (GFAP) is an intermediate filament protein specifically expressed in astrocytes in the CNS. To examine the function of GFAP in vivo, the Gfap gene was disrupted by gene targeting in embryonic stem cells. Mice homozygous for the mutation were completely devoid of GFAP but exhibited normal development and showed no obvious anatomical abnormalities in the CNS. When inoculated with infectious scrapie prions, the mutant mice exhibited neuropathological changes typical of prion diseases. Infectious prions accumulated in brains of the mutant mice to a degree similar to that in control littermates. These results suggest that GFAP is not essential for the morphogenesis of the CNS or for astrocytic responses against neuronal injury. The results argue against the hypothesis that GFAP plays a crucial role in the pathogenesis of prion diseases.

Animals↗

[Artificial insemination using the husband's frozen sperm in a patient with chronic myelogenous leukemia after bone marrow transplantation].

A 37-year-old man with chronic myelogenous leukemia (CML) was scheduled to receive a bone marrow allograft from an HLA-matching sibling. He was married without children, and desired to have a child in the future. Sperm was collected before transplantation and frozen for preservation. Induction therapy performed using 8 mg/kg of busulfan, 120 mg/kg of cyclophosphamide, splenic irradiation (4.5Gy), and total body irradiation (10Gy), and then allogenic bone marrow transplantation (BMT) was carried out. His post-transplantation course was uneventful and cyclosporin therapy was finished on day 187. The Philadelphia chromosome disappeared on day 20 after BMT and PCR analysis was negative for the bcr/abl rearrangement, suggesting the possibility of cure. Accordingly, artificial insemination was attempted using the frozen sperm. His wife became pregnant after the 4th attempt and a healthy baby was delivered. Transplantation recipients often become sterile because they receive ultra-high doses of chemotherapy and irradiation. However, it is still possible to have children if sperm or ova are preserved prior to transplantation. This is thought to improve the quality of life after BMT.

Adult↗

Behavioral and electroencephalographic properties of duloxetine (LY248686), a reuptake inhibitor of norepinephrine and serotonin, in mice and rats.

Duloxetine is a dual inhibitor of norepinephrine and serotonin reuptake. Duloxetine (3.13-50 mg/kg p.o.) significantly prevented tetrabenazine (1 and 50 mg/kg s.c.)-induced ptosis in mice and rats. Moreover, duloxetine (1.56-12.5 mg/kg p.o.) also inhibited reserpine (1 mg/kg s.c.)-induced hypothermia in mice. When duloxetine (12.5-100 mg/kg p.o.) and 5-hydroxytryptophan (80 and 100 mg/kg i.p.), a precursor of serotonin, were administered simultaneously to mice and rats, head movement behavior and tremor were observed. In addition, duloxetine (25-100 mg/kg p.o.) significantly attenuated immobility in forced swimming in mice, as equally effective as commonly used antidepressant drugs. Duloxetine (12.5-25 mg/kg p.o.) significantly decreased rapid eye movement sleep and slow-wave deep sleep and increased the awake period, as shown in the rat EEG. However, duloxetine (25-200 mg/kg p.o.) did not affect salivation and lacrimation induced by oxotremorine (1 mg/kg s.c.), a cholinergic agonist, whereas it (25-50 mg/kg) reduced the oxotremorine-induced tremor in part. These results indicated that duloxetine produced behavioral and electroencephalographic responses resulting from the inhibition of norepinephrine and serotonin reuptake in vivo, and that it had a weak anticholinergic action. Therefore, duloxetine may be clinically useful as an antidepressant.

5-Hydroxytryptophan↗

The substrate specificity of Saccharomyces cerevisiae myristoyl-CoA: protein N-myristoyltransferase. Polar probes of the enzyme's myristoyl-CoA recognition site.

Saccharomyces cerevisiae myristoyl-CoA:protein N-myristoyltransferase (Nmt1p) is a monomeric enzyme that is essential for vegetative growth. Nmt1p catalyzes the co-translational transfer of myristate from CoA to the amino-terminal Gly of cellular proteins in an ordered Bi Bi reaction mechanism that initially involves binding of myristoyl-CoA to the apoenzyme. Forty one fatty acid analogs were synthesized to define features in the acyl chain of myristoyl-CoA which are important determinants of its recognition by Nmt1p's acyl-CoA binding site as well as to help us deduce the structure of the binding site itself. These analogs included dicarboxylic acids, omega-nitrocarboxylic acids, analogs equivalent in length to C13:0-C15:0 which contain electronegative halogens at their omega-termini, hydroxytetradecanoic acids with hydrogen replaced by OH from C3 to C13, and azidophenyl-containing fatty acids with the linear azide unit attached either meta or para to phenyl and with variations in the length of their methylene chains. These compounds were converted to their CoA derivatives using Pseudomonas acyl-CoA synthetase and then surveyed as substrates for purified Nmt1p in an in vitro assay system that included an octapeptide derived from residues 1-8 of the human immunodeficiency virus Pr55gag polyprotein precursor. The results suggest that the myristoyl-CoA binding site contains a conical-shaped "receptor" that interacts with the omega-terminus of the bound acyl chain of acyl-CoAs. The acuteness of this cone determines the enzyme's capacity to accommodate steric bulk at the omega-terminus as well as Nmt1p's sensitivity to the distance between the eclipsed C5-C6 bond of a bound acyl chain and its omega-terminus. The activity profile of the various analog-CoAs also indicates that the enzyme's myristoyl-CoA binding site can accommodate fatty acid analogs with marked increases in polarity at their omega-terminus (compared to C14:0) as long as their chain length is equivalent to that of myristate.

Acyl Coenzyme A↗

An examination of obesity and breast cancer survival in post-menopausal women.

A historical prospective study was conducted at the Mercy Hospital of Pittsburgh, Pennsylvania (USA), to study the role of post-menopausal obesity in the recurrence and survival of breast cancer. Records from 301 post-menopausal women diagnosed with breast cancer from 1977 to 1985 were followed for at least 5 years from data supplied by the Tumor Registry and medical records. Data collected included age, height, weight, race, hormone receptor status, stage and size of tumour, number of positive nodes, site of distant metastasis, first course of treatment, and 5 year recurrence and survival. Forty-five per cent of patients were obese (n = 136), while 55% were non-obese (n = 165). Obesity was defined by the Quetelet index (patients with values > 27 were considered obese). The recurrence rates for the obese and non-obese groups were 40% and 39% respectively, and were not significantly different. Univariate and multivariate analyses showed that there was no significant association between obesity in post-menopausal women and likelihood of recurrence of or death from breast cancer.

Aged↗

Interleukin-2 in neoadjuvant therapy potentiates inhibitory activity of 5-fluorouracil and interferon in experimental liver metastases.

Our previous studies showed that interferon (IFN) used in combination with 5-fluorouracil (5-FU) was effective in inhibiting colorectal tumor cell metastases to the liver in nude mice. Furthermore, IFN was also effective in neoadjuvant therapy and allowed the combination treatment (5-FU + IFN) to be delayed for 2-3 weeks following i.s. injections of tumor cells. In this study, we have examined the potential of interleukin-2 (IL-2) to substitute for IFN in neoadjuvant therapy. IL-2 was found to be equally effective, if not superior, to IFN as a neoadjuvant in inhibiting liver and lung metastases with 5-FU + IFN. Moreover, the effect of IL-2 was demonstrable even after 1 week, whereas IFN did not have an effect until 2 weeks of neoadjuvant dosing. These studies demonstrate IL-2 to be more effective than IFN as an immunomodulatory agent in combination with 5-FU + IFN for the inhibition of liver metastases in nude mice.

Animals↗

Fusarium merismoides Corda NR 6356, the source of the protein kinase C inhibitor, azepinostatin. Taxonomy, yield improvement, fermentation and biological activity.

Fungal strain NR 6356, Fusarium merismoides Corda, was discovered as the source of the protein kinase C (PKC) inhibitor, azepinostatin. The strain was identified based on its growth on potato sucrose agar, slender conidial shape, characteristic polyphialide and production of abundant chlamydospores. Fusarium aquaeductuum Lagh. IMI 103658 and Fusarium sp. NR 7222 were also found to produce the same inhibitor. After single colony isolation and medium optimization trials, a more than 30-fold increase in the production of azepinostatin over the original culture was achieved. Azepinostatin selectively and potently inhibited rat brain PKC with an IC50 value of 70 nM. Other enzymes utilizing ATP, including hexokinase, were not affected. The Ki of azepinostatin for PKC was 0.5 nM. The inhibition of PKC was competitive with ATP and uncompetitive with histone.

Anti-Bacterial Agents↗

[Anaphylactoid reaction after intravenous administration of Gd-DTPA].

An anaphylactoid reaction due to Gd-DTPA was observed in a patient who had disposition of asthma bronchiale. Five minutes after injection of Gd-DTPA, the patient developed laryngeal edema and erythema over the whole body. The patient recovered after treatment. It may be advisable to tighten indications for Gd-DTPA study on patients with allergic disposition. Gd-DTPA should be used with the same care against the anaphylactoid reaction as iodinated contrast media.

Adolescent↗

Effects of percutaneous transluminal mitral valvuloplasty on plasma catecholamine levels during exercise.

Elevation of plasma catecholamine levels during exercise in patients with mitral stenosis correlated with the severity of the disease. We investigated the plasma norepinephrine changes in six patients before and after percutaneous transluminal mitral valvuloplasty (PTMV) during continuously graded ergometer exercise. Peak exercise intensity was increased from 65.8 W to 87.5 W after PTMV. Plasma norepinephrine level at 60 W workload intensity was decreased from 2308 +/- 864 pg/ml to 841 +/- 233 pg/ml after PTMV (p < 0.05). We concluded that PTMV decreased the plasma norepinephrine level during exercise in the patients with mitral stenosis. Percutaneous transluminal mitral valvuloplasty is a novel procedure for the improvement of symptoms in patients with mitral stenosis.

Adult↗

The responses of left ventricular end-systolic pressure-diameter relationship to acute pressure overload induced by aortic constriction.

The aim was to investigate the responses of the left ventricular (LV) end-systolic pressure-diameter relationship (ESPDR) to acute pressure overload. ESPDRs were made by 2-min ascending and descending aortic constrictions before and after administration of propranolol and atropine sulphate (both 0.2 mg kg-1 i.v.) in eight open-chest dogs with the pericardium preserved. LV anterior-posterior diameter was measured with ultrasonic crystals. In the ascending aortic constriction, end-diastolic pressure (EDP) and end-diastolic diameter (EDD) were unchanged and ESPDR shifted to the left. In the descending aortic constriction, EDP and EDD increased from 6.8 +/- 0.7 to 8.8 +/- 0.9 mmHg (P < 0.01) and from 32.7 +/- 1.4 to 34.5 +/- 1.6 mm (P < 0.05) and ESPDR shifted to the right. After administration of propranolol and atropine sulphate, cases having smaller changes in EDD during 2 min constriction (0.3 +/- 0.3 mm in all cases of ascending, 0.3 +/- 0.2 mm in four cases of descending aorta) showed a leftward shift of ESPDR. The remaining four cases of descending aortic constriction with larger changes in EDD (1.8 +/- 0.8 mm, P < 0.05) showed a rightward shift of ESPDR. An inverse curvilinear correlation was found between percentage changes in EDD and in the slopes. These results suggest that the responses in ESPDR to acute pressure overload were determined by not only changes in the contractile state but also the interplay between adaptation to acute pressure overload (the Anrep effect) and pre-load.

Animals↗

Ontogenesis and distribution of epidermal growth factor immunoreactivity and binding activity in the mouse fetal and neonatal tissues.

Epidermal growth factor (EGF) immunoreactivity, EGF binding activity, and their ontogenic changes were investigated in placenta, amnion, and various organs of mouse fetus and neonate. EGF immunoreactivity was detected in all organs examined such as fetal and neonatal liver, brain, lung, intestine, placenta, and amnion. The fetal tissues having relatively higher EGF content were amnion, liver, and intestine. The tissue distribution of EGF immunoreactivity in the fetus did not differ from that in neonate. As for its ontogenesis, EGF immunoreactivity was almost constant during fetal development in liver, brain, and placenta, whereas it gradually increased in intestine. Scatchard plot analysis of EGF receptor, which was also demonstrated in all organs studied, revealed that EGF receptor in these tissues showed curvi-linear profile and its affinity was very high. Unlike EGF immunoreactivity, EGF binding activity showed tissue distributional difference between fetus and neonate except skin; EGF binding activity was relatively high in heart, kidney, lung, and intestine in the fetus, whereas it was high in liver, kidney, heart, and lung in the neonate. As for its ontogenesis, EGF receptor increased in liver as gestation proceeded, while it decreased in intestine. These results suggest that the biological importance of EGF in fetal development may be variable among fetal organs despite the ubiquitous existence of EGF and its receptor in many fetal tissues.

Animals↗

Effects of changes in afterload on regional wall motion in acute ischemic canine heart.

The aim of the present study was to examine effects of changes in afterload on regional myocardial motion in acute ischemia. Ischemic and non-ischemic segment lengths of the left ventricular free wall were measured by miniature ultrasonic gauges in eleven open chest dogs with the pericardium preserved. In a stable state after left anterior descending coronary artery occlusion, peak left ventricular pressure was varied by the infusion of angiotensin II (n = 8) and sodium nitroprusside (n = 8). To exclude effects of preload on the responses, end-diastolic lengths of the non-ischemic region before and during infusion of each drug were matched with vena caval occlusion. When peak left ventricular pressure elevated from 113 +/- 2 (mean +/- S.E.)mmHg to 145 +/- 6, in isovolumetric contraction phase, degree of active shortening in the non-ischemic region and that of paradoxical expansion of the ischemic region did not change. In ejection phase, active shortening of the non-ischemic region decreased from 1.38 +/- 0.11 mm to 1.06 +/- 0.10 but that of the ischemic region remained unchanged. Stroke volume decreased from 14.5 +/- 1.3 ml to 10.8 +/- 1.0. When peak left ventricular pressure decreased from 111 +/- 4 mmHg to 101 +/- 6, in isovolumetric contraction phase, active shortening of the non-ischemic region decreased from 0.90 +/- 0.13 mm to 0.76 +/- 0.15 and paradoxical expansion of the ischemic region reduced from -0.95 +/- 0.11 mm to -0.80 +/- 0.11. In ejection phase, shortening of the non-ischemic region increased from 1.05 +/- 0.13 mm to 1.31 +/- 0.15 but that of the ischemic region did not change. Stroke volume increased from 11.5 +/- 1.3 ml to 14.0 +/- 1.4. These results indicate that in acute ischemia, changes in isovolumetric shortening of the non-ischemic region and paradoxical expansion of ischemic region are related with each other in isovolumetric contraction phase when afterload is altered and suggest that stroke volume is affected by the shortening of ejection phase in the non-ischemic region.

Angiotensin II↗

Metastasis of B16F10 mouse melanoma inhibited by lovastatin, an inhibitor of cholesterol biosynthesis.

Lovastatin (LST) is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, a rate-limiting enzyme that regulates the biosynthesis of cholesterol. This drug is used clinically to treat patients with hypercholesterolemia. Numerous studies have also suggested an important, if not essential, role of the cholesterol biosynthetic pathway to cell growth and proliferation. In fact, recent studies demonstrating the inhibitory effects of LST on various tumor cells have drawn much attention. We now describe a novel action of LST that inhibited experimental lung metastasis of the highly metastatic B16F10 mouse melanoma in nude mice. Further, when used in in vitro studies, LST pretreatment of B16F10 cells resulted in inhibition of attachment, motility, and invasion, which are key steps in the dynamic sequence of events that comprise the metastatic cascade. Our studies also suggested that the antimetastatic effect of LST on B16F10 cells is probably not mediated by a growth inhibitory action. We submit that these observations identify an antimetastatic agent with potentially useful clinical application.

Animals↗

Design and synthesis of regioselective cleaving reagents for oligonucleotides.

Reaction of methyl 2,3-anhydro-alpha-D-ribofuranoside with allylmagnesium chloride selectively took place at the 2-C position to afford methyl 2-C-allyl-2-deoxy-alpha-D-arabinofuranoside. 1-O-Acetyl-2,3,5-tri-O-benzoyl-beta-D-ribofuranose reacted with allylic alcohols in the presence of BF3.OEt2 to give the corresponding allyl beta-D-ribofuranosides. The allyl group in these compounds were converted into a variety of functional groups which include bromoacetoxy, oxylanyl, tosyloxy, and azide.

Allyl Compounds↗

Systemic administration of a cholecystokinin analogue, ceruletide, protects against ischemia-induced neurodegeneration in gerbils.

The neuroprotective action of a cholecystokinin octapeptide analogue, ceruletide, was evaluated in models of cerebral ischemia using Mongolian gerbils. Ceruletide significantly suppressed the hyperactivity and amnesia induced by ischemia when injected s.c. 30 min before 5-min occlusion of the bilateral common carotid arteries at room temperature or immediately after their reperfusion. Ceruletide also reduced behavioral changes in ischemic gerbils whose body temperature was maintained at 37 degrees C during the 3-min occlusion. In these groups, delayed neuronal cell death in the hippocampal CA1 area following ischemia was markedly attenuated by s.c. administration of ceruletide. On the other hand, ceruletide could not inhibit the behavioral changes or the neurodegeneration induced in the hippocampal CA1 area by 5-min occlusion at 37 degrees C. These findings indicate that peripheral injection of ceruletide produces a neuroprotective action against moderate cerebral ischemia, which is the first evidence suggesting the efficacy of ceruletide in neurodegenerative diseases.

Amnesia↗