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Biomedical subjects

K Higuchi

Publications and source records attributed to K Higuchi.

At least 523 records · Page 29Linked to original sources
PubMedDate not supplied

Pathobiology of the senescence-accelerated mouse (SAM).

Routine postmortem examinations and the pathobiological features revealed by systematically designed studies have shown several pathologic phenotypes that are often characteristic enough to differentiate among the various SAM strains: senile amyloidosis in SAMP1, -P2, -P7, -P9, -P10, and -P11; secondary amyloidosis in SAMP2 and -P6; contracted kidney in SAMP1, -P2, -P10, and -P11; immunoblastic lymphoma in SAMR1 and -R4; histiocytic sarcoma in SAMR1 and -R4; ovarian cysts in SAMR1; impaired immune response in SAMP1, -P2, and -P8; hyperinflation of the lungs in SAMP1; hearing impairment in SAMP1; degenerative temporomandibular joint disease in SAMP3; senile osteoporosis in SAMP6; deficits in learning and memory in SAMP8 and -P10; emotional disorders in SAMP8 and -P10; cataracts in SAMP9; and brain atrophy in SAMP10. These are all age-associated pathologies, the incidence and severity of which increase with advancing age. The SAM model in which these pathobiological features have been carefully monitored will be a valuable tool in the clarification of the pathogenic mechanisms of age-associated pathologies and in the research for effective methods to modulate or ameliorate these pathologies.

Aging↗
PubMedDate not supplied

In vitro study of the mechanisms of senescence acceleration.

Accelerated senescence can be considered to be an aging process that occurs after development and maturity and is characterized by a higher rate of increase in the degree of senescence than seen in the "normal senescence process." We devised culture methods to determine precise population doublings in cultured fibroblast-like cell lines and subsequently compared the aging process, in vitro, in cell lines established from either accelerated senescence-prone or- resistant strains of mice to obtain evidence of accelerated aging. Fibroblast-like cell lines were established from the dorsal dermis of the newborn accelerated senescence-prone mice of the SAMP11 strain and from accelerated senescence-resistant mice of the SAMR1 strain. All cell lines from both strains showed senescence as evidenced by a crisis in growth; then were immortalized. However, in cell lines from the SAMP11 strain, this growth crisis occurred more rapidly and at earlier population doubling levels than in cell lines from the SAMR1 strain. The methods and materials should aid in the elucidation of mechanisms linked to accelerated senescence in mice.

Aging↗
PubMedDate not supplied

Immune abnormality in relation to nonimmune diseases in SAM mice.

A series of related strains of senescence-accelerated mouse (SAM) shows strain-unique age-related diseases, such as amyloidosis, deficit in learning and memory, osteoporosis, and brain atrophy, while many of these disease-prone mouse (SAMP) strains have impaired immune activity as young adults, and have a short life span, probably not due directly to the diseases. Because the mean life span was prolonged and the time of the disease onset was delayed by a low-calorie dietary condition or a specific pathogen-free environment, both of which ameliorate the impaired immune activity, the enhancement of immune activity may help decrease the deteriorative process of aging, to that seen in ordinary strains of mice. Studies using the SAMP model may help elucidate the role of immunity in the aging process. Herein, we review the cellular and genetic basis of the immune abnormality in SAMP mice, then discuss the relationship between immune abnormality and development of the age-related disease, senile amyloidosis, findings obtained on SAMP hybrid mice and congenic mice for disease-related genes. Activation of the gene(s) for senile amyloid per se shortened the life span, and the early development of the immune dysfunction primarily seems to be both genetically and physiologically independent of amyloidosis, although the disease may be indirectly modified in the aged with depressed immune activity.

Aging↗
PubMedDate not supplied

Management and design of the maintenance of SAM mouse strains: an animal model for accelerated senescence and age-associated disorders.

The Senescence-Accelerated Mouse (SAM) was established by inbreeding and pedigree selection based on the life span, degree of senescence, as well as the incidence and degree of several age-associated disorders. At first, SAM strains were developed under conventional conditions, but now some strains are also maintained under specific pathogen-free conditions. There are many methods used to maintain such strains of mice; our methods will be introduced as one example of how to develop and maintain strains of mice used in aging research.

Aging↗
PubMedDate not supplied

Automated diagnosis of heart disease in patients with heart murmurs: application of a neural network technique.

This study was conducted to test a three-layered artificial neural network analysis of phonocardiogram recordings to diagnose, automatically and objectively, the condition of the heart in patients with heart murmurs. The data were recorded simultaneously in each of 49 patients with a heart murmur through eight microphones attached to the skin surface with adhesive tape, and were analysed by computer. The diagnosis was automated using a three-layered neural network technique. The neural network generated correct answers in over 70% of cases. Furthermore, about 80% of cases of two concurrent diseases were identified correctly. However, ventricular septal defects were incorrectly classified as aortic stenosis or aortic regurgitation, and patent ductus arteriosus was not diagnosed correctly. Accurate diagnoses can frequently be obtained using a neural network, but accuracy can be improved with further data accumulation.

Artificial Intelligence↗
PubMedDate not supplied

Unique mutations in mitochondrial DNA of senescence-accelerated mouse (SAM) strains.

Mitochondrial DNA (mtDNA) is exclusively inherited maternally and hence could offer a good method for tracing the lineage of mouse strains. We examined the mtDNA sequence of senescence-accelerated mouse (SAM) strains as well as other laboratory strains of inbred mice to deduce the ancestral strain of SAM. Four unique mutations were identified at bases 2256, 10,847, 11,181, and 13,053 in SAM strains. The mutations were not found in other mouse strains including AKR/J, one of the parental strains of SAM. Comparison of the mtDNA sequences also led to the consensus mtDNA sequence of laboratory strains of inbred mice. The seven laboratory strains of common inbred mice showed polymorphisms at base 9348, thymine repeat from base 9818, and adenine repeat from base 9821, and could be classified into five types by combination of the differences. Although we could not identify mouse strains with the same type of mtDNA as SAM in this study, the polymorphisms would provide a promising clue to ascertain the ancestral strain(s) of SAM. The polymorphism in mtDNA could be used to ascertain the genealogy of other mouse strains as well.

Aging↗
PubMedDate not supplied

Induction of allogeneic tumour- and lymphokine-activated lymphocytes against hepatocellular carcinoma.

For clinical application of adoptive immunotherapy against hepatocellular carcinoma (HCC), it is not easy to prepare tumour specific effector cells such as cytotoxic T lymphocytes (CTL). To induce potent and broad-spectrum effectors, allogeneic cultured hepatoma cell lines (JHH-4 and HuH-6) were used as stimulators of peripheral blood lymphocytes (PBL) instead of autologous HCC cells. Allogeneic tumour- and lymphokine-activated killer cells (ATLAK) were generated by a mixed culture of lymphocytes and allogeneic cultured tumour cells with recombinant interleukin-2 (rIL-2). The tumour-killing activity of ATLAK induced by HuH-6 was confirmed against HuH-6 and other different HCC cell lines (JHH-2, HuH-7 and PLC). These activated lymphocytes were significantly more potent than lymphokine-activated killer cells (LAK) in [51Cr]-releasing assay. The JHH-4 stimulated ATLAK was reactive not only with JHH-4 but also with JHH-2. The lysis of allogeneic targets could be partially inhibited by anti-CD8 and anti-CD3 but not by anti-CD4. Anti-tumour cytotoxicity in these cultures might be mediated by CD3+CD56- and CD3+CD56+ effectors. These results imply that adoptive immunotherapy for HCC with ATLAK may be more feasible than that with LAK.

Antibodies, Monoclonal↗
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The protective effect of pyrroloquinoline quinone and its derivatives against carbon tetrachloride-induced liver injury of rats.

Pyrroloquinoline quinone (PQQ) and its derivative, oxazo pyrroloquinoline (OPQ-G), protected rats from experimental liver injury induced by carbon tetrachloride (CCl4) in vivo. This effect was observed after an intraperitoneal injection of 5 mg/kg PQQ or OPQ-G, which was given twice, 10 min and 1 h before CCl4 administration. Pyrroloquinoline quinone protected primary cultured rat hepatocytes from CCl4 toxicity in vitro. This protection was most effective at a concentration of 3 mumol/L PQQ. Pyrroloquinoline quinone derivatives (oxazo pyrroloquinoline, methyl-thioethyl oxazo pyrroloquinoline and PQQ-allylester) also protected the hepatocytes from CCl4 toxicity. Pyrroloquinoline quinone and its derivatives inhibited the lucigenin-enhanced chemiluminescence from isolated hepatocytes initiated by CCl4. These results suggest that eliminating free radicals is one of the protective mechanisms of PQQ and its derivatives against CCl4-induced liver injury.

Acridines↗
PubMedDate not supplied

Hepatocellular carcinoma in 13 patients with hepatitis C virus-associated chronic hepatitis.

Thirteen of 81 patients with chronic hepatitis and positive hepatitis C virus (HCV) antibody developed hepatocellular carcinoma (HCC) during a follow-up period of 54 +/- 38 months. The histopathological findings in HCC-bearing liver in these patients included six cases of chronic persistent hepatitis [CPH; mean hepatitis activity index (HAI) score: 5.8] and seven cases of chronic aggressive hepatitis (CAH) 2A, or 2B (HAI) score: 13.6). Multiple biopsies of the liver in six cases revealed that five cases, including four with CPH at the time of HCC diagnosis, previously had histopathological findings identical to CAH 2A, and another case constantly had CPH during the 8-year follow-up. These findings suggest that HCV-associated HCC can occur even in patients with HCV antibody positivity and inactive or mild chronic hepatitis. This is of interest in the pathogenetic mechanisms of HCV-associated HCC.

Carcinoma, Hepatocellular↗
PubMedDate not supplied

Effects of an infusion of branched-chain amino acids on neurophysiological and psychometric testings in cirrhotic patients with mild hepatic encephalopathy.

Psychotropic action of a branched-chain-enriched amino acid solution (Aminoleban) was quantitatively and visually examined in six cirrhotic patients with mild hepatic encephalopathy (grades I and II) using electrophysiological and psychometric methods. Neurophysiological effects of the amino acid solution were observed by comparing topographic spectrum analyses of electroencephalography (EEG) before and immediately after an intravenous 3 h infusion of the solution. The delta wave in the frontal region diminished from 61 +/- 13 to 12 +/- 4% (P < 0.01) and the alpha wave in the occipital region increased from 11 +/- 3 to 51 +/- 11% (P < 0.01). Latencies of the P3 wave in visual evoked potentials, which were topographically recorded in the occipital region, shortened from 220 +/- 32 to 148 +/- 19 ms (P < 0.01). Latencies of the P300 wave in event-related potentials, which were topographically recorded in the centro-temporal region, shortened from 493 +/- 81 to 360 +/- 93 ms (P < 0.05). Topographic reaction pattern of P300 was irregular toward the occipital or parietal region in cirrhotic patients. The EEG frequency power spectrum, illustrated by the colour density spectral array of computer-aided polysomnography analysis, clearly showed a gradual increase of the alpha wave spectrum and a gradual decrease of the delta wave spectrum after initiation of the infusion. These immediate neurophysiological changes were confirmed by improvement of quantitative psychometric tests including number connection test, reaction time to sound, and digit symbol and block design tests of Wechsler Adult Intelligence Scale.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids, Branched-Chain↗
PubMedDate not supplied

Analyses of proliferating cell nuclear antigen-positive cells in hepatocellular carcinoma: comparisons with clinical findings.

Proliferating tumour cells in 92 patients with hepatocellular carcinoma (HCC) were identified by an immunohistochemical method using a monoclonal antibody against proliferating cell nuclear antigen (PCNA). The rate of PCNA-positive cells in HCC tissues was positively correlated with histological grade and the tumour size and T factor of the tumour. In order to analyse the relationship between prognostic factors and cumulative survival rate after obtaining tumour specimens, 49 patients whose clinical courses could be followed after needle biopsy were selected for evaluation. These patients were treated by medical therapy alone. Analyses of prognostic factors by Cox's proportional hazard model revealed that the patient's prognosis was significantly correlated with PCNA-positive rates as well as the tumour size and mode of therapy. Moreover, the cumulative survival rates were significantly (P < 0.001) higher in patients with rates of PCNA-positive cells < 15% than in those with > or = 15%, even when tumour sizes were under 50 mm or tumours demonstrated the same degree of histological differentiation. These findings indicate that the PCNA-positive rate in biopsied tissues provides useful prognostic information in patients with HCC treated only by medical therapy.

Adult↗
PubMedDate not supplied

Interleukin-6 functions as an autocrine growth factor in a cholangiocarcinoma cell line.

The tumour cells of a human cholangiocarcinoma cell line, HuCC-T1, were found to express mRNA of interleukin-6 (IL-6) and to secrete a large amount of biologically active IL-6 in the culture medium at the concentration of 22.6 ng/mL. Interleukin-6 was demonstrated in the cytoplasm of the cells by immunohistochemical staining. Furthermore, these cells showed the presence of receptors for IL-6 on the surface, and DNA synthesis of the cells was stimulated by the exogenous addition of recombinant human IL-6 into the culture medium. The cell growth was significantly inhibited in the presence of anti-human IL-6 antibody in the culture medium. These findings indicate that IL-6 is one of the autocrine growth factors of this cell line in vitro.

Cholangiocarcinoma↗
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Thermal enhancement of pirarubicin (THP-adriamycin) by mild hyperthermia in vitro.

It has been demonstrated that hyperthermia can enhance the cytotoxicity of several anticancer drugs. Pirarubicin (THP-adriamycin) is a less cardiotoxic derivative of adriamycin. The thermal enhancement of cytotoxicity of pirarubicin was studied at various elevated temperatures in vitro by using a Chinese hamster cell line, V79. Cell survival curves were obtained at elevated temperatures for V79 cells treated with heat given alone or in combination with pirarubicin, and D0, the treatment time to reduce cell survival from S to S/e, was obtained for each cell survival curve. The relationship between the logarithm of the D0 and the treatment temperature for cells treated with heat alone was biphasic with a breaking point at 43 degrees C, although that for cells treated with a combination of heat and pirarubicin was exponential with no breaking point. The slope of this relationship for heat alone > 43 degrees C was -0.72 +/- 0.094 h/degree C which was not significantly different from the slope for combined heat and pirarubicin, -0.64 +/- 0.032 h/degree C. The results indicated that the cytotoxicity of pirarubicin was thermally enhanced specifically by mild hyperthermia. Pirarubicin uptake into the V79 cells during hyperthermia was independent of the treatment temperature (37, 42, and 44 degrees C), suggesting that the thermal enhancement of pirarubicin was not due to the increased drug-uptake at elevated temperatures. Based on these results, it is predictable that hyperthermia combined with pirarubicin is more effective below 43 degrees C which is easily achievable clinically.

Animals↗
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Detection of alpha-fetoprotein mRNA in seminoma.

The classic testicular tumor marker alpha-fetoprotein (AFP) is associated with nonseminomatous germ cell tumors, including embryonal carcinoma, yolk sac tumor, and teratoma. AFP is not considered to be produced by pure seminoma. However, postmortem studies have demonstrated that 30 to 45% of patients who died of seminoma initially diagnosed harbored nonseminomatous metastases and had an elevated serum AFP. We analyzed AFP expression by immunohistochemistry and by nested reverse transcription-polymerase chain reaction (RT-PCR) in 10 seminomas, 3 embryonal carcinomas, and 1 immature teratoma, diagnosed by traditional clinical methods. Positive immunohistochemical staining was observed in all embryonal carcinomas and in the teratoma but not in the seminomas. AFP mRNA, however, was found in 6 of 10 seminomas, in all embryonal carcinomas, and in the teratoma. The nucleotide sequence of PCR products was identical with that of the AFP gene. We conclude that the analysis of AFP gene expression by nested RT-PCR would be useful for detecting minute quantities of nonseminomatous germ cell elements in classic seminoma. Moreover, the existence of AFP mRNA suggests the possibility that seminoma cells can differentiate into nonseminomatous germ cells.

Adult↗
PubMedDate not supplied

Survival of the Brånemark implant in partially edentulous jaws: a 10-year prospective multicenter study.

A total of 127 partially edentulous patients, treated according to the Brånemark protocol, was followed for 10 years after completion of prosthetic treatment. The patients ranged in age from 18 to 70 years, and 57% were female. Four hundred sixty-one implants were placed in 56 maxillae and 71 mandibles. In 125 patients, 163 fixed partial prostheses were attached to the implants; a majority of the prostheses (83%) were located in posterior regions. At the end of the 10-year period, 73% of the implants could be traced either as failed or in function, providing cumulative implant survival rates of 90.2% and 93.7% for the maxilla and mandible, respectively. Of the original fixed prostheses, 63% (cumulatively 86.5%) were still in use, whereas the level of continuous cumulative prosthesis function, including primary and remade restorations, was 94.3% at the end of the evaluation period. Marginal bone resorption at the implants was low (mean = 0.7 mm), and mucosal health was good. No severe complications apart from the above-mentioned implant and prosthetic failures were reported. The Brånemark Implant System is a safe and predictable method for restoring partially edentulous patients, as demonstrated by this 10-year follow-up investigation.

Adolescent↗
PubMedDate not supplied

Effect of Helicobacter pylori culture supernatant on acute reflux esophagitis in a rat model.

BACKGROUND/AIMS: Prevalence of Helicobacter pylori, especially cagA-positive strains is inversely related to gastroesophageal reflux disease. The aim of this study was to examine whether H. pylori culture supernatants affect acute esophagitis induced by acid or mixed reflux in rats. METHODOLOGY: Three different H. pylori strains were used. Acute esophagitis was induced in 59 male Wistar rats by ligation of both the transitional regions between the forestomach and glandular portion, and the pylorus or the lower part of duodenum. After operation, the rats were either left untreated or treated with intragastric injection of either vehicle or H. pylori culture supernatants and were sacrificed 6 or 24 hours later. Esophagitis index, depth of esophageal lesions, esophageal epithelial degeneration, and infiltration of inflammatory cells were examined. RESULTS: Gross esophageal erosions and ulcers were observed up to mid-esophagus in all animals. H. pylori culture supernatants did not affect esophageal mucosal injury and no histologically significant differences were found among rats. CONCLUSIONS: H. pylori culture supernatants, regardless of cagA gene expression, did not affect acute esophagitis induced by acid or mixed reflux. This finding suggests that no powerful protective factors against reflux-induced mucosal injury were produced by H. pylori.

Acute Disease↗
PubMedDate not supplied

Immunohistochemical studies of age-associated amyloid deposition in the joint of senescence-accelerated mouse (SAM).

The senescence-accelerated mouse (SAM) is a murine model of accelerated senescence and consists of the senescence-accelerated prone mouse (SAM-P) and senescence-accelerated resistant mouse (SAM-R), the latter of which shows normal aging characteristics. SAM shows a high incidence of age-associated microscopic amyloid deposition in synovial joints and intervertebral discs and the lesion is histologically quite similar to that of humans. The amyloid fibril protein of these mice is well characterized as a murine systemic senile amyloid (ASSAM). Twenty SAM-P and three SAM-R mice were used for this immunohistological study. Synovial joints and intervertebral discs were stained by immunoperoxidase method (PAP) using anti-ASSAM and anti-mouse AA antibodies and compared with birefringence in a Congo-red-stained section. Positive staining was observed in annulus fibrosus of the intervertebral discs, blood vessels, synovia, and on the surfaces of the meniscus and articular cartilage, exactly at the same site where green birefringence in Congo-red staining was observed. Both ASSAM and AA existed in the articular structures of SAM and the incidence of AA was significantly correlated with systemic signs of inflammation at autopsy. Among blood vessels, synovium and articular cartilage, there was no one tissue where amyloid deposited earlier than others. It was postulated that amyloid is transported via synovial fluid as its fibrillar form or as a precursor and that it deposits on the surface of articular cartilage.

Aging↗