Biomedical subjects

Y Nakashima

Publications and source records attributed to Y Nakashima.

At least 91 records · Page 5Linked to original sources

PubMed2000

Concurrent expressions of metallothionein, glutathione S-transferase-pi, and P-glycoprotein in colorectal cancers.

PURPOSE: Because the status of the inherent drug-resistance of colorectal cancers remains obscure, human colorectal cancers with no neoadjuvant therapy were retrospectively investigated regarding the expression of three drug-resistant proteins: metallothionein, glutathione S-transferase-pi, and P-glycoprotein. METHODS: Paraffin-embedded tissues of 130 colorectal cancers (Dukes A, 20; B, 49; C, 41; D, 20) obtained by surgical resections from 1982 to 1989 were used. The three proteins were immunostained by the streptavidin-biotin complex method. The immunostaining was judged to be positive if more than 5 percent of cells showed positive staining by use of cell analysis system. The data were compared with clinicopathologic features (Dukes A-D) and patients' prognosis (Dukes AC). RESULTS: Metallothionein, glutathione S-transferase-pi, and P-glycoprotein were positively expressed in 91 (70 percent), 30 (23 percent), and 98 (75 percent), respectively. A total of 120 (86 percent) expressed at least one drug-resistant protein. No intergroup differences were observed between positive and negative expressions of the proteins and their clinicopathologic features except tumor location. Rectal cancers positively expressed P-glycoprotein and three proteins more frequently. Twenty-six (20 percent), 65 (50 percent), and 21 (16 percent) cancers positively expressed one, two, and three proteins, respectively. The disease-free survival rates of patients with Dukes A through C cancer with positive staining for one, two, and three proteins were 100, 94, and 83 percent (at 1 year); 100, 72, and 51 percent (at 3 years); and 94, 66, and 38 percent (at 5 years), respectively (Kaplan-Meier with log-rank test; P = 0.016). In the multivariate Cox analysis, age, Dukes stage, tumor size, and glutathione S-transferase-pi were independent prognostic factors. CONCLUSIONS: The patients with concurrent expression of drug-resistant proteins in their cancers had worse prognoses. Examining drug-resistant proteins in colorectal cancers may be useful in selecting adjuvant chemotherapy and in predicting prognosis more accurately.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2000

Evaluation of new TNM lung cancer classification.

OBJECTIVE: A new staging system for lung cancer was proposed by the Union Internationale Contre le Cancer in 1997, with Stages I and II subdivided and T3N0M0 assigned as stage IIB. We studied the usefulness of this new classification. METHODS: Subjects were 753 patients with non-small-cell lung cancer undergoing pulmonary resection and follow-up data were retrospectively reviewed. RESULTS: A significant difference was seen between stage IA and IB survival--70.4% vs 52%. No significant difference was seen between survival for T3N0M0, T1N1M0 and T2N1M0--35.3%, 42.3%, and 43.8%--at 5 years. We found, however, that the prognosis for T3N2M0 tumors--6.5% 5-year survival--is too poor to be grouped with other N2 diseases having a better prognosis--23.9% 5-year survival. Significant differences were also seen in the survival of T3N0 or T3N1 patients by organ and diseases involving the rib, diaphragm, or mediastinum may be classified as T4. CONCLUSION: The new staging system predicts patient outcome fairly well and the modification is well grounded. It appears, however, to be appropriate to subdivide T3 tumors by invaded organs and T3N2M0 disease may be better classified as stage IIIB. The classification of pulmonary metastasis appears to require further improvement.

Adult↗

PubMed2000

Postmortem absorption of dichloromethane: a case study and animal experiments.

A case of accidental death after occupational exposure to an atmosphere containing dichloromethane (DCM) is reported. The concentrations of DCM in the blood and tissues of a 40-year-old man who died while observing an industrial washing machine filled with DCM vapour were blood 1660 mg/l, urine 247 mg/l, brain 87 mg/kg, heart muscle 199 mg/kg and lungs 103 mg/kg which are 3-7 times higher than previously reported fatal levels. The body was left undiscovered in the machine filled with DCM vapour for about 20 h. The present study was designed to determine whether all the DCM detected in the tissues and body fluids had been inhaled while alive using rats as the experimental model. The concentrations of DCM in the tissues and body fluids of a rat that died from DCM poisoning and was left for 20 h in a box containing DCM vapour were the same as those in the tissues and body fluids of a rat that had died from an injected overdose of barbiturates and had then been placed in the DCM box in a similar manner. Moreover, the concentrations of DCM in the tissues and body fluids of the carcasses that were exposed to the DCM vapour increased gradually throughout the period of exposure. These findings imply that DCM is able to penetrate the tissues and body fluids of rat carcasses through a route other than inhalation such as through the skin.

Adult↗

PubMed2000

Presence and possible role of the spliced isoform of the P2X1 receptor in rat vascular smooth muscle cells.

An alternatively spliced isoform of the P2X1 receptor (P2X1a) was cloned from rat mesenteric artery. The spliced isoform does not have the 27 amino acids that are in the middle of the putative extracellular loop domain of the P2X1 original subunit (P2X1). Reverse transcriptase polymerase chain reaction (RT-PCR) revealed co-localization of P2X1a mRNA and P2X1 mRNA in vascular and other smooth muscle tissues and heart, but not in the spinal cord. In HEK293 cells transfected with P2X1 cDNA, ATP (1 microM) evoked an inward current which strongly desensitized, and an intense signal for GFP (green fluorescent protein) fused with P2X1 was detected at the membrane. Neither of these results was obtained in HEK293 cells expressing P2X1a alone. The fluorescent GFP signal was detected at the membrane when GFP-fused P2X1a was co-expressed with P2X1, and no significant difference in the ATP-activated current was noted between cells expressing P2X1 and those coexpressing P2X1 and P2X1a. These results indicate that the 27-amino-acid sequence (175-201) is important for protein trafficking to the membrane and for the formation of a functional P2X1 receptor. Our results also show that P2X1a is transported to the membrane when P2X1a is co-expressed with P2X1, although the co-expression of P2X1a does not modify the channel's current properties.

Alternative Splicing↗

PubMed2000

Cloning, sequence analysis, and expression of Lactobacillus casei phage PL-1 lysis genes.

The genes encoding the host cell wall-lytic proteins were searched in the genome DNA of phage PL-1 active against Lactobacillus casei ATCC 27092 by comparing the amino acid sequences with those of others using a computer software of the DDBJ data base. The gene regions found were cloned into E. coli by inserting PCR-amplified DNA fragments into the EcoRI site of pUC 19, and the nucleotide sequences were determined. One of the ORFs (hol) consisted of 270 bp encoding 90 amino acids. The hol product (holin) possessed a putative secretion signal, two putative transmembrane helices, and a highly charged C-terminus. Another ORF (lys) consisted of 1050 bp encoding an N-acetylmuramoyl-L-alanine amidase of 350 amino acids. The gene lys was expressed in E. coli using pCALn expression vector, and the purified gene product hydrolysed the amide linkage in the peptidoglycans of L. casei. The amino acid sequence of PL-1 amidase showed a high homology to those of Lactococcus lactis phage rlt and Listeria monocytogenes phage A511. It was suggested that the N-terminal region was involved in enzyme activity and the C-terminal region in binding the enzyme to the cell wall substrate, respectively.

Amidohydrolases↗

PubMed2000

Pathomorphologic study on the mechanism of fatty change in small hepatocellular carcinoma of humans.

BACKGROUND/AIMS: Fatty change is frequently observed in small hepatocellular carcinoma (HCC) of the early stage. However, the mechanism of fatty change and its pathomorphological features in small HCC are not yet fully understood. These issues are addressed here. METHODS: Histological examinations were conducted on 260 HCC nodules (< or =3 cm in diameter) which were surgically obtained from 249 patients. According to the distribution pattern, fatty changes were classified into two types: 'diffuse type' when the change was found throughout the cancerous nodule; and 'focal type' when the change was localized in part of the nodule. To study the pathogenesis of fatty change in HCC in relation to angioarchitecture, the number of arterial tumor vessels and intratumoral portal tracts in 104 of the 260 nodules was counted. RESULTS: Fatty change was found in 51 of the 260 nodules (19.6%), the frequency was highest (36.4%) in the nodules whose diameter was 1.1 to approximately 1.5 cm, and the frequency decreased with the increase in tumor diameter. Small well-differentiated HCCs were often associated with a diffuse type fatty change. With the increase in tumor diameter, moderately differentiated cancerous tissues without associated fatty change appeared, and the focal type was found more frequently. According to the angioarchitecture, in HCCs < or =1.5 cm, the number of intratumoral arteries was significantly smaller in HCCs with fatty change (p<0.05), though the number of intratumoral portal tracts was not significantly different compared with HCCs without fatty change. CONCLUSION: These findings suggest that fatty change of small HCC is closely related to the tumor size, the histological grade and insufficient development of the arterial tumor vessels.

Arteries↗

PubMed2000

Irsogladine upregulates expressions of connexin32 and connexin26 in the rat liver.

A gap junction is the channel for cell-to-cell communication and plays an important role in the maintenance of tissue homeostasis, control of cell growth and differentiation, and prevention of experimental hepatocarcino-genesis. Irsogladine, an antiulcer drug, augments gap junctional intercellular communication in gastric mucosa, but the effect of irsogladine on the liver remains uncertain. In this study the effects of irsogladine on the liver were investigated from the viewpoints of gap junctional protein connexin (Cx)32 and Cx26 in rats. Twelve rats were divided into a control group (n=6) and the irsogladine group (n=6) in which irsogladine (20 mg/kg per day) was administered orally for 3 days before sample collection, and the two groups were compared in regard to liver enzymes (serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH)), serum- and tissue-calcium concentrations, immunohistochemical expressions of Cx32 and Cx26, and RT-PCR analysis. In immunohistochemistry, analyzed using an image processor for analytical pathology (IPAP), the number of Cx32-positive spots was higher and the area of Cx26-positive spots were larger in the irsogladine group than those in the control group (P=0.036 and P=0.00032, respectively). In RT-PCR analysis, the mRNA of Cx32 or Cx26 in the irsogladine group showed a tendency to be higher than in the control group, but not significantly (Cx32, P=0.70; Cx26, P=0.07). Another 30 rats were used for measurements of cyclic-adenosine monophosphate (c-AMP) of the liver. c-AMP concentration was increased 1 h after the administration of irsogladine, which partially explained how the Cxs were upregulated. These findings may suggest that irsogladine upregulates Cx32 and Cx26 expressions in the liver of rats.

Journal Article↗

PubMed2000

Relationship between oxidative stress and apoE phenotype in Alzheimer's disease.

OBJECTIVE: To investigate the relationship between oxidative stress and apoE phenotype in dementia of Alzheimer type (DAT). MATERIAL AND METHODS: Hydroxyl radical content in blood, superoxide dismutase (SOD) activity in red blood cells (RBC) and plasma, Cu,Zn-SOD protein content in RBC, and apoE phenotype were determined in 24 DAT patients and 25 controls. RESULTS: DAT patients with the apoE4 phenotype showed higher hydroxyl radical levels than DAT patients without the apoE4 phenotype or controls. SOD activities and Cu,Zn-SOD protein levels in RBC of DAT patients with and without the apoE4 phenotype showed no significant differences, but values in both patient groups were lower than in controls. The apoE4 phenotype was more prevalent in DAT patients than in controls. DAT patients with the apoE4 phenotype were younger at disease onset than DAT patients without the apoE4 phenotype. CONCLUSION: Our findings suggest that apoE4 and SOD individually influence oxidative stress in DAT.

Aged↗

PubMed2000

Angiogenesis and its regulation: roles of vascular endothelial cell growth factor.

Neovascularization is well known to occur in human atherosclerotic plaques, proliferative retinopathies, and malignant neoplasias. However, its pathophysiologic roles and mechanisms still remain unclear. In this study, histochemical examination of atherosclerotic plaques showed that vascular endothelial cell growth factor (VEGF) was expressed by the smooth muscle cells and foamy macrophages in the atherosclerotic intimas. The number of VEGF-positive cells was positively correlated with the number of intimal blood vessels. Moreover, VEGF gene transfer into rabbit carotid arteries using the hemagglutinating virus of Japan (HVJ)-liposomes showed that VEGF overexpression could induce the angiomatoid proliferation. In diabetic rats, VEGF was overexpressed in diabetic retinas, and thus the local overexpression of VEGF seemed to play an important role in the development of blood-retinal barrier breakdown in simple diabetic retinopathy. These results indicated that the VEGF can act as a local and endogenous regulator of endothelial cell functions and that VEGF induces the neovascularization under pathophysiologic conditions. On the other hand, the transfer of a decoy for the cis-element in the promoter region of the angiogenic factors would be an effective method for regulating angiogenesis, because other angiogenic factors' expression promoted by such cis-element could be simultaneously suppressed. Therefore, this method may supply a useful therapeutic tool for the regulation of pathologic angiogenesis.

Animals↗

PubMed2000

The contribution of residual renal function to overall nutritional status in chronic haemodialysis patients.

BACKGROUND: The benefits of residual renal function (RRF) in peritoneal dialysis patients have been described frequently. However, previous reports have shown that RRF diminished faster in haemodialysis (HD) patients than in peritoneal dialysis patients, and in most of the studies in HD patients, RRF was ignored. In this study, the RRF in chronic HD patients was studied to assess its impact on patients' nutritional status. METHODS: In 41 chronic HD patients with at least a 2-year history of HD treatment, RRF was determined by a urine collection for 7 consecutive days. Nutritional parameters, such as percentage body fat, fat-free mass index, serum albumin concentration and normalized protein catabolic rate, were also measured. RESULTS: In all 41 patients, mean weekly total Kt/V urea was 4.88 and renal Kt/V urea was 0.65. RRF was well correlated with serum albumin concentration, but dialysis Kt/V urea was not. One year after the start of this study, RRF and nutritional indices were re-examined and patients were classified into two groups: with RRF, preserved residual renal diuresis over 200 ml/day (mean, 720 ml; range, 230-1640 ml), N=23; and without RRF, persistent anuria (mean, 51 ml; range, 0-190 ml), N=18. At the start of this study, the mean serum albumin concentration and mean normalized protein catabolic rate in patients with RRF were 3.84 g/dl and 1.16 g/kg/day, respectively, which were significantly higher than those in patients without RRF (P=0.02 and P=0.0002, respectively), despite total (renal+dialysis) Kt/V urea being equal in both groups. During the 1-year study period, there was no significant change in total Kt/V urea in either group. Mean serum albumin concentration increased to 4.05 g/dl in patients with RRF, but did not change significantly (from 3.66 to 3.62 g/dl) in patients without RRF. The same trend was observed in all other parameters. CONCLUSION: Over half of our HD patients had sufficient RRF. RRF itself may have a beneficial effect on nutritional parameters, and it is important to determine RRF over time, even in chronic HD patients.

Aged↗

PubMed2000

Heart rate and plasma cyclic AMP responses to isoproterenol infusion and effect of beta-adrenergic blockade in patients with postural orthostatic tachycardia syndrome.

To clarify the pathophysiological mechanism of postural orthostatic tachycardia syndrome (POTS). the responses of heart rate and the plasma cyclic AMP (cAMP) level to isoproterenol infusion in the supine position were evaluated in 10 POTS patients and 10 age-matched controls. Also, the effect of beta-adrenergic blockade on POTS was assessed using the headup tilt test. The POTS patients consisted of two men and eight women, with a mean age of 19.7 years (range. 15-28 years). An exaggerated increase of both heart rate and the plasma cAMP concentration after isoproterenol infusion at a low dose (1 microg/min) was observed in the POTS patients, but not in control subjects. Seven POTS patients received oral beta-blocker therapy. In five of these, symptoms were abolished and there was a smaller heart rate increase during the head-up tilt test. These data suggest that POTS may be more prevalent in young women and that beta-adrenergic hypersensitivity may play a role in the mechanisms of this syndrome. However, a larger series of patients need to be studied in the future.

Adolescent↗

PubMed2000

Conditions for the evolution of soldier sperm classes.

There has been wide disagreement as to whether sperm competition among animals can produce a soldier class of sperm to fight against other males. Utilizing mathematical models, we analyze the appropriate conditions for the evolution and maintenance of a soldier sperm class. We conclude that: (1) soldier sperm evolve even if one soldier sperm can kill or block less than one competing sperm; (2) soldier sperm evolve faster when there is a large variance in the number of competing sperm; (3) soldier ratio increases until reproductive sperm are too scarce to fertilize all ova or a sperm intensely refuses to become a soldier; and (4) soldier sperm are more likely to be smaller than reproductive sperm. Our models suggest that the conditions for the evolution of a soldier sperm class are not stringent.

Animals↗

PubMed2000

Successful treatment of severe orthostatic hypotension with cardiac tachypacing in dual chamber pacemakers.

Orthostatic hypotension is an evolving and disabling disease usually observed in elderly patients with dramatic consequences on morbidity, mortality, and impairing the quality of life. We studied the effects of the pacing rate and AV interval on the blood pressure drop in the upright position in two patients with previously implanted pacemakers for sinus node dysfunction. Although the AV interval did not affect the blood pressure drop in the upright position, tachypacing at 100 paces/min improved it dramatically and prevented syncope. Cardiac tachypacing is a useful therapeutic option in severe refractory orthostatic hypotensive patients, especially those with chronotropic incompetence.

Aged↗

PubMed2000

Ventricular pacing failure after a single oral dose of pilsicainide in a patient with a permanent pacemaker and paroxysmal atrial fibrillation.

A single oral dose of pilsicainide, a Class Ic antiarrhythmic drug, is a widely used and highly effective therapy for termination of recent onset atrial fibrillation. We report on a patient in which ventricular pacing failure occurred immediately after a single oral dose of pilsicainide. It did not exhibit a parallel relationship between the change in the pacing threshold and plasma concentration of pilsicainide, and the recovery period for the ventricular pacing threshold was longer than that of the plasma concentration of pilsicainide in this patient. Careful attention should be paid when a single oral dose of pilsicainide for termination of recent onset atrial fibrillation is used in patients with permanent pacemakers.

Administration, Oral↗

PubMed2000

Single oral administration of pilsicainide versus infusion of disopyramide for termination of paroxysmal atrial fibrillation: a multicenter trial.

A single oral dose of pilsicainide (PLS) is effective in terminating acute-onset atrial fibrillation (AF). However, the effectiveness of this single oral treatment has not been compared with the infusion of other antiarrhythmic drugs. The effects of a single oral dose of PLS on the termination of AF were compared with an infusion of disopyramide (DISO) in a multicenter trial. Seventy-two patients with electrocardiographically confirmed, symptomatic, paroxysmal AF (< 48-hour duration) were randomized to receive either a single 100- to 150-mg dose of PLS versus a 2 mg/kg (maximum dose = 100 mg) infusion of DISO. Successful defibrillation was defined as termination of AF within 2 hours of drug administration. Conversion of AF to sinus rhythm was achieved within 2 hours in 29 of 40 patients (73%) treated with PLS, and in 18 of 32 patients (56%) treated with DISO (NS). The mean time to return of sinus rhythm was 60 +/- 30 minutes in the PLS group versus 23 +/- 18 minutes in the DISO group (P < 0.001). DISO was particularly effective in terminating nocturnal AF, whereas PLS had a stable circadian effect. PLS was significantly more effective than DISO between 6 AM and 12 PM (64% vs 17%, P < 0.05). No adverse effect was observed in either group. In conclusion, a single oral dose of PLS was as effective as an infusion of DISO to restore sinus rhythm in patients with recent-onset AF. PLS consistently terminated AF regardless of its time of onset.

Administration, Oral↗

PubMed2000

Does the lack of hyperkinesis during dobutamine stress echocardiography predict the functional significance of coronary arterial stenosis?

The clinical implication of the lack of hyperkinesis during dobutamine stress echocardiography (DSE) has not been determined. We hypothesized that a lack of hyperkinesis during graded doses of dobutamine infusion would reflect the severity of coronary flow abnormality distal to the stenosis and provide the functional significance of coronary arterial stenosis. The aim of the present study was to investigate the prevalence of the lack of hyperkinesis in patients with normal coronary arteries and to determine its value in patients with single-vessel disease. A total of 63 consecutive patients who subsequently revealed angiographically normal coronary arteries underwent DSE. Thirty-one consecutive patients with angina and single-vessel disease also underwent both DSE and exercise thallium single-photon emission computed tomography (SPECT). According to the response of wall motion during low and peak doses of dobutamine infusion, patients were divided into three groups (group A, hyperkinesis was present during both low dose and peak stress; group B, hyperkinesis was present only during low dose; group C, no hyperkinesis). SPECT images were divided into 16 segments, and thallium uptake at each segment was scored from 0 (normal) to 3 (severe defect). Thallium uptake score index (TSI) was calculated as total thallium score divided by 16 at stress and delayed image. The prevalence of group A, B and C was 56 (89%), 3 (5%), and 4 (6%) in patients with normal coronary arteries. The corresponding values were 11 (35%), 8 (26%), and 12 (39%) in patients with single-vessel disease (P < 0.0001). In patients with single-vessel disease, there was no significant difference in percent diameter stenosis (group A, 59% +/- 8%; group B, 69% +/- 16%; group C, 67% +/- 13%) and the prevalence of proximal stenosis (45%, 25%, and 42%) among three groups. However, TSI at stress image was significantly lower in group A (0.21 +/- 0.14) than in group B (0.45 +/- 0.20, P < 0.05) and group C (0.53 +/- 0.27, P < 0.01). TSI at delayed image was also significantly lower in group A (0.07 +/- 0. 11) than in group C (0.18 +/- 0.15, P < 0.05). Because the lack of hyperkinesis during DSE was observed in 11% of patients with normal coronary arteries, it does not always predict the presence of significant coronary artery stenosis. However, this finding related to the severity of perfusion abnormality by exercise thallium SPECT in patients with single-vessel disease. These results suggest that the lack of hyperkinesis during dobutamine infusion would predict functional significance of coronary arterial stenosis and provide myocardial perfusion status distal to the stenosis in patients with single-vessel disease.

Aged↗

PubMed2000

Effects of a slow-release nifedipine on 24-hour ambulatory blood pressure and ischemic changes on 24-hour ambulatory electrocardiogram in patients with severe coronary artery disease.

Calcium antagonists have long been used as first-line drugs for hypertension and angina. However, deleterious effects have also been reported in patients treated with calcium antagonists. Thus, we evaluated the effect of a slow-release twice-daily formulation of nifedipine in 10 patients with severe coronary artery disease. Twenty-four-hour ambulatory electrocardiography (AECG) and blood pressure monitoring (ABPM) were performed simultaneously to detect any association between ischemic episodes on the ECG and changes in blood pressure (BP) and heart rate with and without nifedipine. Increased oxygen demand due to an increased systolic BP and heart rate was associated with ischemic episodes without nifedipine, while those with nifedipine were accompanied by a fall in diastolic BP and a rapid increase in heart rate. This slow-release twice-daily formulation of nifedipine may induce myocardial ischemia through a heart-rate increase and a decrease in coronary blood flow due to lower diastolic BP in patients with severe coronary artery disease. A once-daily formulation of nifedipine might be of great value for such patients.

Aged↗

PubMed2000

Rapid purification of human DNase I using mouse monoclonal anti-DNase I antibodies and characterization of the antibodies.

Five anti-human deoxyribonuclease I (DNase I) monoclonal antibodies were obtained from BALB/c mice immunized with DNase I purified from human urine. Four of them inhibited DNase I enzyme activity, as did a rabbit polyclonal antibody; these 4 did not have immunostaining ability. The remaining one had immunostaining ability but no inhibitory activity. A Sepharose 4B column conjugated with 1 of the 4 antibodies that had inhibitory activity effectively adsorbed and eluted the DNase I enzyme; this did not occur with the rabbit polyclonal antibody. We showed that adding an immunoaffinity chromatography step made the purification of human DNase I easier and faster than the conventional procedure.

Animals↗