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Biomedical subjects

K Nagano

Publications and source records attributed to K Nagano.

At least 19 recordsLinked to original sources

Cytohistologic assessment of antitumor effects of intraperitoneal hyperthermic perfusion with mitomycin C for patients with gastric cancer with peritoneal metastasis.

For 15 patients with refractory gastric cancer and peritoneal metastasis, intraperitoneal hyperthermic perfusion (IPHP) using mitomycin C combined with extensive surgery was prescribed. The antitumor effects were assessed cytohistologically in pre-IPHP and post-IPHP specimens of the abdominal effusion and peritoneal tissue. Gastric cancer cells in the abdominal effusion and/or lavage vanished from post-IPHP peritoneal exudate obtained from the pouch of Douglas. Peritoneal tissues from nine patients were harvested just after the IPHP treatment. All the nuclei of cancer cells were pyknotic in three of nine patients, and two of these three patients are alive with no local recurrence; one patient died of hepatic metastasis. In the remaining six patients, four with preoperative ascitic effusion and positive post-IPHP histologic findings died of peritoneal, intraabdominal, and pericardial metastases. The other two had some residual microscopic foci in the subperitoneal deep layer; one patient died of pleural recurrence, and the other is alive with no evidence of recurrence 42 months after the IPHP. Among the other six patients, whose post-IPHP peritoneal tissues were not available because of disappearance of disseminating foci as a result of the IPHP, two are living with no recurrence and, of the remaining four patients, three died of hepatic and intraabdominal metastases and the other one died of other causes. The histologic findings are suggestive of the following: (1) uniform heat and drug distribution in the abdominal cavity with IPHP treatment, except for an area adjacent to the inflow point of the perfusate; and (2) limited penetration of heat and drug through the subperitoneal layer. Thus, IPHP treatment results in complete destruction of cancer cells in the abdominal effusion and on and just beneath the peritoneum.

Adult

Ammonia: a possible promotor in Helicobacter pylori-related gastric carcinogenesis.

Helicobacter pylori (HP) has been shown to possibly be a pathogen of gastric carcinoma. HP has urease activity and produces ammonia in the stomach. In this study, the role of ammonia on gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were investigated in rats. After 24 weeks pretreatment with MNNG (83 mg/l), 0.01% ammonia or tap water as a drinking water was administered for 24 weeks. The ammonia-treated rats showed a significantly higher incidence of gastric cancer (percent of animals with tumors and number of tumors per rat). Ammonia would thus appear to have an important role in HP-related human gastric carcinogenesis.

Adenocarcinoma

Effects of proton pump inhibitor on gastric mucosa hemodynamics and tissue oxygenation in anesthetized rats.

Proton pump inhibitors have been reported to have a cytoprotective action in addition to the anti-secretory action of acid. The precise mechanism, however, remains obscure. In this study, the effects of proton pump inhibitors (omeprazole and NC-1300) on gastric mucosa hemodynamics and tissue oxygenation were investigated using organ reflectance spectrophotometry in a hemorrhagic shock-reperfusion model involving anesthetized rats. Neither drug affected gastric mucosa hemodynamics nor tissue oxygenation in the basal state before hemorrhage. During the hemorrhagic shock state, however, these drugs maintained tissue oxygenation and reduced ulcer formation, although they did not show a significant effect on gastric mucosa blood volume. The results suggest that both proton pump inhibitors have an anti-ulcer action by maintaining mucosal oxygenation in addition to the anti-secretory activity of acid.

2-Pyridinylmethylsulfinylbenzimidazoles

The influence of pelvic nerve transection on the neuromuscular system of the canine urinary bladder.

We previously reported that bladder overdistension led to denervation and subsequent supersensitivity of the detrusor muscle to acetylcholine. Therefore, to exclude the influence of bladder overdistension, we produced a low-pressure bladder in female mongrel dogs using an indwelling urethral catheter, and performed pelvic neurectomy (decentralization). We examined the effects of decentralization on the neuromuscular system of the bladder. The contraction response levels of bladder strips in dogs 1 and 2 weeks after neurectomy was low, and significantly different from that of bladder strips in the control group. The dose-response curves of dogs 4 and 8 weeks after neurectomy showed a shift to the left when compared to those of the control group, indicating a significant increase in sensitivity of the bladder strips. Many cholinergic terminal and varicosity profiles had a normal ultrastructure in all of the groups subjected to neurectomy, while some had degenerating profiles representing clear axoplasm without any recognizable organelles. Microphotographs of bladder obtained from dogs with spontaneous catheter loss showed degenerating axons, which were observed more frequently than in bladders kept empty with indwelling urethral catheters. Micturition in the dogs with spontaneous catheter loss was achieved by overflow incontinence without catheterization. These findings suggest that post-synaptic nerve degeneration may be augmented by impairment of micturition, followed by decentralization. Our observations also suggest that post-synaptic nerve degeneration (denervation) plays an important role in the increased sensitivity of the detrusor muscle to acetylcholine in the parasympathetically decentralized urinary bladder, whether denervation is due to trans-synaptic degeneration or impairment of micturition.

Acetylcholine

Computer-assisted two-dimensional analysis of gastric mucosal hemoglobin distribution using electronic endoscopy.

An electronic endoscope was modified to assess the imaging of two-dimensional distribution of gastrointestinal mucosal hemoglobin with the aid of a computer and image analyzing system. The band-pass filters ranging from 530-470 nm (G'), and 770-830 nm (IR) replaced ordinary filters in a conventional electronic endoscope (Olympus V-10 or EVIS-200). As the hemoglobin is the most abundant biological pigment in the gastrointestinal mucosa absorbing the green light with little absorption in the infrared region, we used the algorithm of 32 [log2(Vir/Vg)] as a reflection of hemoglobin content in the surface mucosa. The algorithm had a good correlation with the spectrophotometrically measured hemoglobin concentration. The mucosal distribution of hemoglobin was displayed in patients with gastric ulcer. In conclusion, the computer and image analyzing system were successfully applied in an attempt to determine gastric mucosal hemoglobin content and its distribution. The possible applications of computers in endoscopic image analysis are discussed.

Adult

Identification and characterization of the cis-elements regulating the rat AMOG (adhesion molecule on glia)/Na,K-ATPase beta 2 subunit gene.

We have identified a positive regulatory cis-acting element of the adhesion molecule on glia (AMOG)/Na,K-ATPase beta 2 subunit gene as GAGGCGGGG at position -87 to -79 by transient transfection assay using B103 cells (rat neuroblastoma cell line). The newly identified AMOG regulatory element (AMRE) enhanced the promoter activity in a mutually compensating manner with the Sp1 element at position -147 to -142. AMRE acts as a positive regulatory element not only in B103 cells but also in 3Y1 (rat embryo cell line) cells to roughly the same extent and in MDCK (canine kidney cell line) cells to a lesser extent. AMRE also enhances other gene promoters, such as myelin basic protein (MBP) and herpes simplex virus (HSV) thymidine kinase (TK) gene promoters. The element is not a typical enhancer element because when it is introduced downstream of the HSV TK promoter, it has no enhancing activity.

Adenosine Triphosphatases

Ethanol stimulates immunoreactive endothelin-1 and -2 release from cultured human umbilical vein endothelial cells.

The present study employed enzyme-immunoassay to examine the effect of ethanol on endothelin-1 and/or -2(ET1 + 2) release from human umbilical vein endothelial cells. Thirty minutes of exposure to ethanol increased the release of immunoreactive ET1 + 2 from cultured endothelial cells in a dose-dependent manner. However, ethanol at concentrations of less than 400 mM did not induce any LDH release from the endothelial cells. Trypan blue exclusion test revealed that 400 mM solution of ethanol decreased the cell viability to 7.7%. Thus, ethanol was found to directly stimulate ET1 + 2 release from cultured human umbilical vein endothelial cells. This reaction of vascular endothelial cells against ethanol may be related to ethanol-induced cardiovascular diseases such as hypertension, myocardial infarction and stroke, as well as fatal alcohol syndrome.

Cells, Cultured

Housekeeping Na,K-ATPase alpha 1 subunit gene promoter is composed of multiple cis elements to which common and cell type-specific factors bind.

Na,K-ATPase alpha 1 subunit gene (ATP1A1) is one of the housekeeping genes involved in homeostasis of Na+ and K+ in all animal cells. We identified and characterized the cis-acting elements that regulate the expression of ATP1A1. The region between -155 and -49 was determined as a positive regulatory region in five cultured cell lines of different tissue origins (MDCK, B103, L6, 3Y1, and HepG2). The region was divided into three subregions: from -120 to -106 (including the Sp1 binding site), from -102 to -61, and from -58 to -49 (including an Sp1 consensus sequence). Cell type-specific factors binding to the middle subregion (from -102 to -61) were detected by gel retardation analysis, using nuclear extracts prepared from MDCK and B103 cells. Two gel retardation complexes were formed in the B103 nuclear extract, and three were formed in the MDCK nuclear extract. DNA binding regions of these factors were located at -88 to -69 and differed from each other in DNase I footprinting experiments. These factors also showed different binding characteristics in gel retardation competition and methylation interference experiments. The identified cis element was named the ATP1A1 regulatory element. The core sequence of this element is found in several other genes involved in cellular energy metabolism, suggesting that the sequence is a common regulatory element responsive to the state of energy metabolism.

Animals

Effect of intravascular ethanol on modulation of gastric mucosal integrity: possible role of endothelin-1.

The influences of intravascular ethanol on gastric mucosal integrity and its relation to gastric circulation were investigated in rats. Ulcer formation of the gastric mucosa correlated with the blood ethanol concentration in the presence of 150 mM HCl in the rat stomach. Furthermore, the gastric mucosal hemoglobin concentration (IHb) and hemoglobin oxygen saturation (ISO2), estimated using organ reflectance spectrophotometry, decreased in a concentration-dependent manner with blood ethanol. In isolated, vascularly perfused rabbit stomach, various concentrations (10-400 mM) of ethanol infused into the celiac artery increased the perfusion pressure and released endothelin-1 (ET-1) from the gastric vasculature in a concentration-dependent manner. Moreover, a significant correlation existed between changes in the perfusion pressure and ET-1 concentration in effluents from the gastric vasculature. Furthermore, anti-ET-1 antibody reduced 100 mM ethanol-induced vasoconstriction in a concentration-dependent manner. The results indicate that intravascular ethanol increases the susceptibility of gastric mucosa to injury induced by intraluminal HCl by causing gastric vasoconstriction mediated by ET-1. Thus intravascular ethanol may play an important role in the mechanism of ethanol-induced gastric mucosal injury.

Animals

Regulation of Na,K-ATPase gene expression by thyroid hormone in rat cardiocytes.

Synthesis and activity of the enzymatic equivalent of the sodium pump, Na,K-ATPase, are regulated by thyroid hormone in responsive tissues. The purpose of this study was to determine whether triiodothyronine (T3) regulates the level of the messenger RNA (mRNA) coding for Na,K-ATPase alpha- and beta-subunits in the heart. The expression of Na,K-ATPase mRNAs in in vitro myocardial cells was directly assayed by Northern and slot blot hybridization using Na,K-ATPase alpha- and beta-isoform-specific cDNA probes. Exposure of cultured neonatal rat cardiocytes to 10(-8) M T3 resulted in 1) threefold to fourfold increase in alpha 1- and beta 1-mRNA accumulation, with a maximum elevation at 48 hours, 2) sevenfold increase in alpha 2-mRNA accumulation with a peak elevation at 72 hours, and 3) transient threefold increase in alpha 3-mRNA within the first 24 hours followed by a deinduction thereafter. The increase in alpha 1-mRNA accumulation by T3 occurred over the physiological T3 concentration range with an EC50 of 5 x 10(-10) M. This was associated with a twofold increase in alpha 1-subunit protein accumulation and an increase in Na,K-ATPase transport activity. The half-life of alpha 1-mRNA analyzed by actinomycin D chase was less than 3 hours and was not affected by T3. Transfection experiments with the luciferase reporter gene revealed that thyroid hormone response sequences are located within the 5'-flanking regions of each alpha-isoform gene.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

[Two kindreds with familial Alzheimer's disease--analysis of the APP717 mutation and the mutated genes for the prion protein].

Numerous Caucasian familial Alzheimer's disease (FAD) pedigrees have been described in the literature, while only 21 Japanese FAD families have been reported to date. Here we report the clinical findings and the result of molecular genetic analysis of 4 patients from two FAD kindreds, OS-2 and OS-3. The proband in OS-2 family has developed loss of recent memory and place disorientation age at 43. A brain CT showed severe diffuse cortical atrophy. Her younger brother had dementia at 42 years and her mother and other 3 siblings had also dementia symptoms suspected to be Alzheimer's disease. The proband in OS-3 family showed declining recent memory at 49 years and developed dysphagia, gait disturbance and emotional incontinent with cerebral atrophy at 52 years. His father and elder brother demonstrated dementia signs at 60 and 54 years old, respectively. Recently it was reported that affected members from 2 Caucasian kindreds with FAD had missense mutation in exon 17 of the gene for amyloid precursor protein (APP). Patients from three different Japanese kindreds with FAD also showed the same mutation on the APP gene. Amino acid substitution (Val-Ile) at codon 717 by this mutation is responsible for FAD in at least some kindreds. We used genomic DNA from 4 affected members of 2 families to determine whether the disease in these families is associated with a APP717 mutation and the mutated codons, 102, 117, 129, 178 and 200, on the gene for protease-resistance prion protein (PrP) which cause transmissible dementia, Creutzfelt-Jacob disease (CJD) and Gerstmann-Strausler syndrome (GSS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[Pharmacokinetic and clinical studies of cefprozil fine granules in children].

Cefprozil (CFPZ, BMY-28100) is a new oral cephem antibiotic without an ester linkage. Pharmacokinetic and clinical studies using CFPZ 10% fine granules were performed in pediatric patients. 1. Pharmacokinetic investigation Peak serum concentrations of CFPZ after dose of 7.5 mg/kg and 10 mg/kg were, respectively, 3.65 +/- 0.24 micrograms/ml and 6.38 +/- 3.23 micrograms/ml at 1-2 hours. The average half-life with 7.5 mg/kg administration was 0.90 +/- 0.16 hours and that with 10 mg/kg was 1.29 +/- 0.50 hours. The urinary excretion of CFPZ was about 45% (35.3-50.0%) in 6 hours. 2. Clinical investigation Enrolled in the study were 22 patients including 4 with pharyngitis, 3 with tonsillitis, 3 with bronchitis, 5 with pneumonia, 4 with urinary tract infection, and 1 each with pertussis, purulent lymphadenitis and otitis media. Responses were excellent in 14 patients, good in 5 patients and fair in 1 patient. In the assessment of the bacteriological efficacy, 8 out of 17 strains of organism identified previous to the treatment were eradicated, 5 strains were found replaced by other bacteria and 4 strains persisted, hence the eradication rate was 76.5%. 3. No adverse reactions attributable to the drug were observed. From the above results, it has been concluded that CFPZ is a highly effective and safe agent for moderate respiratory and urinary tract infections in children.

Administration, Oral

[A recovered case of serious lung tuberculosis on wanderer].

This report is a case study of a vagrant whose state of tuberculosis showed noteworthy improvement due to clinical treatment. A 54-year-old male, vagrant, was admitted to the hospital in a state of preshock because of a serious stage of lung tuberculosis. The clinical course was severe, but after three months of intensive care the patient recovered. It was noted that the echocardiogram taken after recovery revealed improvement when compared with the one taken upon admission, which showed remarkable right ventricular overload. Furthermore, anti-tuberculosis agents proved to be very effective in this case. The patients respiratory functions improved more markedly than had been expected. The reason for reporting this case study is to bring attention to the improvements in the patient's clinical course and echocardiographic findings. These suggest that tuberculosis in vagrants may differ from the usual stage of tuberculosis diagnosed in elderly persons in terms of response to anti-tuberculosis agents and potential recovery.

Antitubercular Agents

[Experimental and clinical evaluation of functional electrical stimulation of the anal sphincter].

To determine the most effective parameter of functional electrical stimulation of the anal sphincter (FES), the present study was carried out in female mongrel dogs anesthetized with alpha-chloralose urethane. When spontaneous and rhythmic micturition contractions of the bladder were present, they were more effectively inhibited by the stimulation with low frequency (5 to 10 Hz). Based on the results of this experiment 18 patients with urge incontinence were treated by maximal electrical stimulation with the following parameters. The duration for each stimulus was 0.2 msec, frequency 5 Hz, amplitude 30 to 150 volts. Every patient received ten treatments for two weeks, each lasting for 30 minutes. A clinical cure for urge incontinence was noted in 12 patients. As for urodynamic studies, FES increased significantly the volumes of the first desire to void (FDV) and maximum desire to void (MDV); however, it did not increase significantly the maximum urethral closure pressure or residual urine volume. Eighteen patients were divided into two groups; an unstable bladder group and a neurogenic bladder group. In the latter, the increases in volumes of FDV and MDV were significant. Second, 18 patients were divided into two groups according to the administration of lack of anticholinergic agents. For subjective symptoms, the rate of improvement of urge incontinence was significantly higher in the group administered the agents. These findings suggested that FES was very useful for the treatment of urge incontinence, with its efficacy augmented by the administration of anticholinergic agents.

Aged

[A study on the relationship between solvent abusers and alcoholism in the parental generation].

In recent years, attention has been paid to the fact that alcoholism and/or drug addiction runs in families. Few studies have investigated the relationship between solvent abuse in adolescents and alcoholism in their parents. Two hundred and ten solvent abusers who came to Serigaya-en, alcoholism and drug addiction treatment hospital, during from 1983 to 1989, were examined from the following two standpoints. The proportion of solvent abusers with alcoholic parents (A group), what characteristics the solvent abusers in A group had as compared with those whose parents were not alcoholic (NA group). The findings were summarized as follows; 21.4% of the subjects had an alcoholic (FH-RDC) parent. They were approximately two years older than those in the NA group at the first examination. The solvent abusers of the A group presented with: 1) more experiences of parental death and/or separation prior to the age of 15; 2) a higher frequency of school refusal in elementary or junior high school; 3) poorer socioeconomic status; 4) a longer duration of solvent abuse; 5) more abuse of addictive drugs other than solvent; 6) a more severe psychopathology; 7) a higher incidence of chronic organic diseases among their parents; 8) a higher incidence of solvent abuse among their siblings. The present study indicates that: 1) many a solvent abuser come from alcoholic families; 2) parental alcoholism is responsible not only for solvent abuse, but also for the development of addictions, (e.g., prolonged solvent abuse, developing into alcoholism or poly-substance abuse); 3) clinical and socioeconomic deterioration occurs not merely in the individual abusers but also in other family members, especially in the A group. The results lead the author to stress the importance of focusing the therapy upon the family itself.

Adolescent

The response of the detrusor muscle to acetylcholine in patients with infravesical obstruction.

We previously examined the effects of overdistension on the neuromuscular system of canine urinary bladders and reported that bladder overdistension led to nerve degeneration and subsequent supersensitivity through a decrease of blood supply to the bladder. We have accordingly in this study evaluated these changes in human subjects with infravesical obstruction. The responses to acetylcholine of bladder strips obtained from patients with detrusor instability were not significantly different from those of bladder strips from patients without detrusor instability, but the dose-response curve of these groups showed a shift to the right compared to that of the unobstructed control patients. As compared with the response of bladder strips in patients without an episode of retention, the response in patients who received prostatectomy within 30 days demonstrated no significant difference, although in patients who received prostatectomy after more than 30 days there was a statistical difference. These results indicated a significant decrease in sensitivity of the detrusor muscle in patients with infravesical obstruction and suggest that bladder overdistension caused by infravesical obstruction may lead to supersensitivity of the detrusor muscle secondary to denervation.

Acetylcholine

Effect of ethanol on endothelin-1 release from gastric vasculature.

The effects of ethanol on gastric vasculature in isolated vascularly perfused rabbit stomach was investigated. The isolated stomach was perfused with Krebs-Henseleit solution containing 3% dextran bubbled with 95% O2 and 5% CO2 at a rate of 12 ml/min. After mixture and perfusion of 10 mM to 400 mM of ethanol, perfusion pressure and endothelin-1 concentration in effluent from gastric vasculature were measured. Perfusion pressure and endothelin-1 concentration in effluent increased in a dose-dependent manner with increasing ethanol concentrations. In conclusion, the data suggest that ethanol may stimulate the release of endothelin from gastric vasculature and may cause gastric ischemia due to vasoconstriction resulting in acute gastric mucosal injury.

Animals