Biomedical subjects

T Kasamatsu

Publications and source records attributed to T Kasamatsu.

At least 37 records · Page 2Linked to original sources

PubMed1998

Determinants of bone loss in a rural Japanese community: the Taiji Study.

The objective of this study was to assess the rate of bone loss and characterize its determinants, among the inhabitants of Taiji, a rural Japanese community. A cohort of 2261 inhabitants aged 40-79 years was established using resident registration in 1992. Fifty men and 50 women in each of four age strata between 40 and 79 years were randomly selected and completed a self-administered risk factor questionnaire. Baseline bone density of lumbar spine and proximal femur was measured by dual-energy X-ray absorptiometry in 1993. BMD was measured again on the same participants in 1996. The rates of change of lumbar spine BMD in men in their 40s, 50s, 60s and 70s were 0.20%, 0.34%, 0.43% and 0.28% respectively. Rates in women were -0.35%, -1.02%, -0.10% and -0.20% respectively. At the femoral neck, rates of change in BMD among men in their 40s, 50s, 60s and 70s were 0.09%, -0.07%, 0.34% and 0.31% respectively. Femoral neck rates of change among women were -0.55%, 0.02%, 0.49% and -0.25% respectively. The rate of change of lumbar spine BMD was -0.24% in premenopausal women with regular periods, -1.99% in premenopausal women with irregular periods and -0.33% in postmenopausal women. Anthropometric measurements at baseline were also related significantly to change in bone density. Baseline weight and height were statistically significant predictors of bone loss rate. These data provide estimates of the rate of bone loss among Japanese men and women aged 40-79 years. They suggest that body build and menstrual function in women are important determinants of bone loss.

Adult↗

PubMed1998

Lack of lateral inhibitory interactions in visual cortex of monocularly deprived cats.

To gain new insight into the effects of monocular deprivation, we studied the visual cortex of adult cats deprived of vision in one eye. Local field potentials were recorded in response to contrast reversal of square-wave gratings modulated in time either by pseudorandom, m-sequences or periodically. We have found that: (1) stimulation of the retinotopic locus of the recording site elicits responses with abnormal waveforms and long latencies from the deprived eye; (2) stimulation of a remote, non-retinotopic locus elicits responses from the non-deprived eye but not from the deprived eye; (3) the monocularly deprived cortex lacks lateral inhibitory interactions which are characteristic of the normal cortex; and (4) steady-state responses showed little difference in spatial-frequency tuning and contrast sensitivity between the deprived and non-deprived eye, mostly conforming to earlier field-potential data in monocular deprivation. Functional lateral interactions appear to be greatly reduced in monocularly deprived cortex.

Animals↗

PubMed1998

Roles of N-methyl-D-aspartate receptors in ocular dominance plasticity in developing visual cortex: re-evaluation.

We have re-examined whether N-methyl-D-aspartate receptors play a specific role in experience-dependent plasticity in kitten visual cortex. A specific antagonist of this glutamate receptor subtype, D,L-2-amino-5-phosphonovaleric acid, was directly and continuously infused into kitten striate cortex for one week concurrently with monocular lid suture. In the hemisphere infused with 50 mM antagonist, we found the usual shift in ocular dominance toward the open eye with only a few binocular cells remaining. The changes were accompanied by an extremely high incidence (38%) of abnormal cells lacking orientation selectivity across different ocular dominance groups. In kitten cortex infused with 10 mM antagonist concurrently with monocular deprivation for a week, recording from a drug-affected region near the infusion centre, we again found the U-shaped ocular dominance distribution with the high incidence of non-selective cells. In antagonist-infused, otherwise normal striate cortex of adult cats, we found that the proportion of binocular cells decreased by one-half in two cellular populations: one recorded during the continuous infusion of 10 mM antagonist under general anaesthesia and paralysis, and the other about two days after stopping the infusion. We also established that in vivo concentrations of chronically infused 10 mM antagonist decreased, not near-exponentially, but linearly with increasing distance from the infusion site. Thus, the effects of a directly and continuously infused, concentrated antagonist of N-methyl-D-aspartate receptors on receptive-field properties of visuocortical cells are complex. The present findings strongly suggest that the antagonist effects in the developing cortex may be due primarily to blockade of normal synaptic transmission rather than specific disruption of an experience-dependent mechanism underlying ocular dominance plasticity.

2-Amino-5-phosphonovalerate↗

PubMed1998

Relationship of parental history of high blood pressure to blood pressure: combined findings of three Japanese population samples, the INTERSALT study.

The relationship of parental history of high blood pressure (HBP) to blood pressure (BP) was estimated in three Japanese population samples, totalling 591 men and women aged 20-59 years, from the INTERSALT study. Parental history of HBP was defined as reported HBP by their father and/or mother. With adjustment for antihypertensive medication, body mass index, alcohol intake, and Na/K ratio in 24-h urine, for participants with a parental history of HBP compared to those without a history, BP was higher for three to four age-sex strata, both for systolic and diastolic pressure (SBP, DBP), by 3.3 to 6.8 and 2.7 to 5.5 mm Hg respectively, with four of these six positive associations statistically significant. This finding was stronger for persons aged 40-59 than for those aged 20-39. These data support the judgment that for persons with a parental history of HBP, BP is apt to increase more with age due to combined effects of genetic and environmental factors. Such people especially need to control their lifestyles carefully, including to maintain an optimal intake of salt (eg, <70 mmol/day) and a high potassium intake, to avoid high alcohol consumption, and keep weight moderate, for the prevention of hypertension.

Adult↗

PubMed1998

Random nuclear p53 overexpression pattern in tamoxifen-mediated endometrial carcinoma.

In a previous paper, we suggested that tamoxifen (TAM)-mediated endometrial carcinogenesis may not involve estrogenic pathways because of random estrogen receptor positivity among endometrial carcinomas with and without TAM treatment for breast cancer. DNA adduct formation (reported in rat liver and human endometrium) was considered to be a more plausible mechanism for TAM-mediated carcinogenesis. To examine the reported correlation between DNA adduct formation and p53, the present study examined p53 expression in the endometrial carcinomas reported in the previous study. Seven endometrial adenocarcinomas associated with long-term TAM treatment for breast carcinoma and 4 carcinomas without TAM treatment but with history of breast carcinoma were immunohistochemically investigated for nuclear p53 expression. The bcl-2 product was also examined. Diffuse and intense nuclear reactivity for p53 protein was present in only one TAM-related case. Essentially, no differences were observed in the bcl-2 staining patterns of TAM-treated and -untreated patients with cancer. Thus, p53 overexpression in endometrial carcinomas occurring in patients with breast cancer seems to be not specific for TAM-treated patients, and, if DNA adduct formation has any role in this type of endometrial carcinogenesis, it may not be related preferentially to p53 gene alteration. Further studies are needed to understand the precise mechanism(s) of the endometrial carcinogenesis.

Adult↗

PubMed1998

Fractures of the proximal femur: correlation with vitamin D receptor gene polymorphism.

Fractures are the feared consequences of osteoporosis and fractures of the proximal femur (FPF) are those that involve the highest morbidity and mortality. Thus far, evaluation of bone mineral density (BMD) is the best way to determine the risk of fracture. Genetic inheritance, in turn, is one of the major determinants of BMD. A correlation between different genotypes of the vitamin D receptor (VDR) and BMD has been recently reported. On this basis, we decided to determine the importance of the determination of VDR genotype in the presence of an osteoporotic FPF in a Brazilian population. We studied three groups: group I consisted of 73 elderly subjects older than 65 years (78.5 +/- 7.2 years) hospitalized for nonpathological FPF; group II consisted of 50 individuals older than 65 years (72.9 +/- 5.2 years) without FPF and group III consisted of 98 young normal Brazilian individuals aged 32.6 +/- 6.6 years (mean +/- SD). Analysis of VDR gene polymorphism by restriction fragment length polymorphism (RFLP) was performed by PCR amplification followed by BsmI digestion of DNA isolated from peripheral leukocytes. The genotype distribution in group I was 20.5% BB, 42.5% Bb and 37% bb and did not differ significantly from the values obtained for group II (16% BB, 36% Bb and 48% bb) or for group III (10.2% BB, 47.6% Bb and 41.8% bb). No differences in genotype distribution were observed between sexes or between the young and elderly groups. We conclude that determination of VDR polymorphism is of no practical use for the prediction of FPF. Other nongenetic factors probably start to affect bone mass, the risk to fall and consequently the occurrence of osteoporotic fractures with advancing age.

Age Factors↗

PubMed1997

Continuous hepatocyte growth factor supply prevents lipopolysaccharide-induced liver injury in rats.

We present a rat model in which continuous supply of hepatocyte growth factor (HGF) prevents liver injury induced by carbon tetrachloride (CCl4) and E. coli 011:B4 lipopolysaccharide (LPS). Rat fibroblasts genetically modified to secrete rat HGF were implanted in syngenic rat spleen 7 days before administration of the hepatotoxins. Rats with HGF-secreting fibroblasts in the spleen showed a dramatic resistance to CCl4- and LPS-induced liver injury. In the LPS-induced liver injury model, blood chemical analysis revealed that the increase in serum glutamic oxalacetic transaminase level and the decrease in blood sugar level were remarkably suppressed in rats with HGF-secreting cells in the spleen. Most importantly, their survival rate was greatly improved compared to other control groups of rats. Thus our results indicate a new role of HGF in liver protection during endotoxemia and convey important clinical implications for developing new therapeutic modalities in the treatment of liver failure caused by endotoxemia.

Alanine Transaminase↗

PubMed1997

Hematogenous spreading of hepatocellular carcinoma cells: possible participation in recurrence in the liver.

To detect hepatocellular carcinoma (HCC) cells in the circulating peripheral blood, we previously designed a highly sensitive reverse-transcription polymerase chain reaction (RT-PCR) method targeting alpha-fetoprotein (AFP) messenger RNA (mRNA). Using this method, we analyzed peripheral blood of in- and out-patients bearing HCC for 2 months consecutively and examined the outcome thereafter. All 11 patients with recurrence either in the liver alone or in both the liver and the lung were positive for AFP mRNA. Among 10 recurrence-free patients, 2 patients were AFP mRNA-negative and remained recurrence-free during a period of 22 months observed. Four of 8 AFP mRNA-positive, recurrence-free patients developed a clinically evident recurrence in the liver after 2 to 16 months. Seven of 8 preoperative patients were already positive for AFP mRNA and the remaining negative patient became positive during surgery. Four of 6 preoperatively positive and still-alive patients had recurrence in the liver after 2 to 9 months. None of the HCC-negative patients were positive for AFP mRNA. We actually found an AFP protein-positive cell in peripheral blood obtained from one of the AFP mRNA-positive patients by immunostaining. The present results suggest that circulating HCC cells may have some relationship with the recurrence of HCC in the liver.

Aged↗

PubMed1997

Detection of colorectal carcinoma cells in circulating peripheral blood by reverse transcription-polymerase chain reaction targeting cytokeratin-20 mRNA.

For the detection of circulating colorectal carcinoma cells, we investigated the presence of cytokeratin 20 (CK 20) mRNA in the peripheral blood of colorectal carcinoma patients. Application of our published technique resulted in analysis by reverse transcription followed by three-step nested polymerase chain reaction. This analysis could detect a single Colo 205 colon cancer cell mixed with 1 ml of blood. Our system also successfully detected the presence of CK 20 mRNA in actual patients' peripheral blood samples. Our highly sensitive and specific system for the detection of CK-20 mRNA from patients' peripheral blood thus seems to be useful for screening for circulating colorectal carcinoma cells.

Adult↗

PubMed1997

Continuous and direct infusion of drug solutions in the brain of awake animals: implementation, strengths and pitfalls.

One of the best strategies for understanding an animal's behavior is to study the function of the brain by experimentally modifying brain chemistry temporarily or on a long-term basis. This can be achieved by direct manipulation of neurochemistry of a targeted brain area with various drugs whose in vitro specificity and sensitivity are known. We assume that an animal's behavior is primarily controlled by the integrated performance of neural networks, rather than the action of a "superstar" single neuron which has narrowly tuned selectivity, in a specified brain region. Therefore, the former must be regulated by a large number of combinations of various transmitter/modulator receptors, hormones, growth factors, and other biochemically identifiable and yet unidentified substances. Under certain conditions, the activation of receptor-bound second messenger systems is thought to cause the enhanced expression of particular genes. Given the wide possibilities in manipulating brain chemistry, which may otherwise result in a variety of consequences, it is crucial to have a dependable means of sustaining the steady-state action of a drug for a sufficiently long time period at a targeted area in the brain of behaving animals. In most cases the continuous application of a drug is necessary to counteract its secondary mitigating effect, which is set in action through negative feedback loops and which in effect reduces the primary action of the drug in use. We have developed a technique to answer this need, using the Alzet osmotic minipump as the source of the continuous infusion force. A drug solution is continuously and directly infused, guided through a chronically implanted cannula, into a targeted area in the brain of behaving animals. The consequences of such an infusion are assessed, during as well as after the infusion, using various types of measurements in behavior, biochemistry, neurophysiology, pharmacology and morphology. The method has been successfully applied, for example, to the study of developmentally regulated neural plasticity in cat visual cortex. A few preconditions should be satisfied for the method to be properly applied to the brains of live animals. Those are: (1) manufacturing a suitable guide system, i.e., cannula-minipump assembly, for the infusion solution; (2) stereotaxic implantation of a cannula-minipump assembly into a selected brain region; and (3) estimating the concentration gradient of the continuously infused solution. This is crucial to assess the specificity and sensitivity of a drug for its assumed effects in vivo.

Animals↗

PubMed1997

Synthesis and miscoding specificity of oligodeoxynucleotide containing 8-phenyl-2'-deoxyguanosine.

Aryl radicals and arenediazonium ions are suspected to react with cellular DNA, resulting in C8-arylguanine adducts. 8-Phenyl-2'-deoxyguanosine (8-PhdG) was synthesized as a model adduct by reacting dG with benzenediazonium chloride and incorporated into oligodeoxynucleotides using phosphoramidite techniques. A site-specifically modified oligodeoxynucleotide containing a single 8-PhdG was then used as a template for primer extension reactions catalyzed by the intact (exo+) or 3'-->5' exonuclease-free (exo-) Klenow fragment of Escherichia coli DNA polymerase I and mammalian DNA polymerase alpha (pol alpha). Although primer extensions catalyzed by the Klenow fragments were retarded at the position of 8-PhdG, most of the primer extension passed the lesion to form the fully extended products. In contrast, primer extensions catalyzed by pol alpha were strongly blocked opposite the lesion. The fully extended products formed during DNA synthesis were analyzed to quantify the miscoding specificities of 8-PhdG. The exo- Klenow fragment incorporated primarily dCMP, the correct base, opposite 8-PhdG, along with small amounts of incorporation of dAMP. Two-base deletions were also observed. In contrast, the exo+ Klenow fragment incorporated dCMP opposite the lesion. When pol alpha was used, 8-PhdG promoted small amounts of misincorporation of dAMP and dGMP as well as one- and two-base deletions. The duplex containing 8-PhdG.dG was thermally and thermodynamically more stable than dG.dG. The duplex containing 8-PhdG.dA was thermodynamically more stable than dG.dA. We conclude that 8-PhdG is a weak miscoding lesion, capable of generating G-->T and G-->C transversions and deletions in cells.

Animals↗

PubMed1997

An endogenous dopaminergic neurotoxin, N-methyl-(R)-salsolinol, induces DNA damage in human dopaminergic neuroblastoma SH-SY5Y cells.

Recently, an endogenous neurotoxin, 1(R),2(N)-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline [N-methyl-(R)-salsolinol], was found to elicit parkinsonism in rats with selective depletion of dopamine neurons in the substantia nigra without necrotic tissue reaction. The mechanism of the cell death was examined by detection of DNA damage using a single-cell gel electrophoresis (comet) assay in human dopaminergic neuroblastoma SH-SY5Y cells. Only N-methylsalsolinol was found to induce DNA damage, whereas other catechol isoquinolines, such as (R)-salsolinol, (S)-salsolinol, and 1,2-dimethyl-6,7-dihydroxyisoquinolinium ion, did not. The (R)-enantiomer of N-methylsalsolinol damaged DNA much more profoundly than the (S)-enantiomer. Cycloheximide protected the cells from DNA damage, suggesting that an apoptotic process may account for the DNA damage. Morphological changes indicating apoptotic cell death were also confirmed. Antioxidants and deprenyl reduced DNA damage, indicating that the damage was initiated by oxidative stress and that neuroprotection by deprenyl may be partially ascribed to its prevention of DNA damage. Apoptosis induced by neurotoxins may be a mechanism underlying the cell death of dopamine neurons in the substantia nigra of Parkinson's disease.

Antioxidants↗

PubMed1997

[Application of tuberculosis medical examination radiographs to scoliosis screening in high schools].

The purpose of this study was to assess the utilization of tuberculosis examination radiographs for scoliosis screening in high schools, for early diagnosis and early treatment of adolescent idiopathic scoliosis in the health management of students. We examined 2,068 first year high school students (1,058 males and 1,010 females) in Wakayama Prefecture, who had chest X-ray photographs taken between 1994 to 1996, and 24 cases (3 males and 21 females) were identified with scoliosis of more than 10 degrees Cobb angle. Fifteen of the cases received further examinations in the hospital, and were diagnosed with definite adolescent idiopathic scoliosis, while 6 cases who did not receive hospital examinations had their abnormality of the spine noted in past periodic health examinations. In the remaining 3 students scoliosis could not be confirmed. The correlation coefficient between the Cobb angle measured in the tuberculosis examination radiographs and in the total spinal radiographs taken by the hospital was 0.815 (p < 0.001). These results suggest that the tuberculosis examination radiographs may be useful for scoliosis screening in high schools.

Adolescent↗

PubMed1997

[A case of breast cancer metastasis to the skin and bone 13 years after, and to the brain 17 years after mastectomy].

A case of breast cancer metastasis to the skin and bone 13 years after, and to the brain 17 years after mastectomy in a 54-year-old woman, is reported. In 1978, the patient, who was then 37 years old, underwent standard radical mastectomy for left breast cancer. In 1991, because of skin and bone metastasis, systemic chemotherapy with cyclophosphamide, epirubicin, and 5-fluorouracil (CAF) was performed, and she partially responded to CAF therapy. In April 1995, the patient was admitted for pain of left hip joint and left knee joint. Computed tomography of the head revealed a bleeding tumor with marked peritumoral edema. Serum levels of carcinoembryonic antigen (250 ng/ml) and CA 15-3 (810 U/ml) were increased. Bone metastases were found elsewhere in the body. Again, systemic chemotherapy with CAF was performed. CAF chemotherapy stopped the brain metastasis bleeding.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1996

Comparison of chemically induced DNA breakage in cellular and subcellular systems using the comet assay.

The alkaline comet assay, employing a single cell gel electrophoresis, is a rapid, simple and sensitive technique for visualizing and measuring DNA damage leading to strand breakage in individual mammalian cells. In this report, we describe a modified version of this assay which we used to assess DNA damage as a result of treating lysed cells with genotoxic and antimetabolic agents. By means of this modified assay, DNA is no longer held under the regulation of any metabolic pathway or membrane barrier. Using 3 direct-acting agents, hydrogen peroxide, N-methyl-N-nitrosourea, and bleomycin, we were able to induce increased DNA migration by both the standard and modified comet assays. In contrast, with 4-nitroquinoline 1-oxide, 5-fluorouracil, and methotrexate, which require cellular enzymatic activity to induce DNA damage, we succeeded in inducing increased DNA migration using the standard comet assay conditions only. In some cases, the modified comet assay might be helpful in analyzing chemical and biological characteristics of genotoxic agents when performed in combination with the standard comet assay.

4-Nitroquinoline-1-oxide↗

PubMed1996

Continuous HGF supply from HGF-expressing fibroblasts transplanted into spleen prevents CCl4-induced acute liver injury in rats.

Hepatocyte growth factor (HGF), first identified as a potent mitogen for mature hepatocytes, has been reported to have various activities. We investigated protective effect of continuous HGF supply on carbon tetrachloride (CCl4)-induced acute liver injury in rats. We transfected immortalized but not tumorigenic rat fibroblasts (Rat-1) with an expression plasmid containing the human HGF cDNA and established several cell lines expressing HGF. The biological activity of HGF produced by these cell lines was confirmed by its mitogenic effect on rat hepatocytes in vitro. Either one of the high-HGF-producer cell lines or parental Rat-1 cell line was transplanted into a syngenic rat spleen. Twelve days after transplantation, each rat was intraperitoneally injected with CCl4 and sacrificed 48 h after CCl4 injection. In rats with continuous HGF supply significantly lower serum glutamic-pyruvic transaminase (GPT) level was observed compared to its marked elevation in control rats and the degree of hepatocyte damage was slight on histological analysis. These results indicate that continuous HGF supply effectively inhibits CCl4-induced acute liver injury and may suggest the possibility that this system would be useful on various liver diseases.

Alanine Transaminase↗

PubMed1996

The cause of maintained hypercalciuria after the surgical cure of primary hyperparathyroidism is a defect in renal calcium reabsorption.

The hypercalciuria that eventually remains after the successful removal of a solitary parathyroid adenoma may originate from excessive intestinal calcium absorption, bone resorption or deficient renal reabsorption. In order to clarify this question, ten patients surgically cured from primary hyperparathyroidism (PHPx), ten age-matched normal subjects and five nephrolithiasic patients with renal hypercalciuria (RH) were studied after five days on a low calcium diet, either during fasting or after oral calcium load. Fasting serum calcium, amino-terminal and intact PTH levels and also urinary cAMP excretion were normal in every individual patient. Serum ionized calcium and inulin clearance (GFR) were used for calculations of the filtered load (FL Ca) and the fractional excretion of calcium (FE Ca). Six PHPx patients displayed fasting calciuria above the upper limit calculated for control subjects, despite having the lowest GFR and FL Ca (p < 0.05 vs control). These patients (h-PHPx) had a small calciuric response to oral calcium load. Serum 1,25-(OH)2D3 and 25OHD3 did not correlate with calciuria. Our findings exclude intestinal hyperabsorption and excessive bone resorption in h-PHPx patients, and strongly suggest a renal tubular defect in calcium reabsorption as the cause of their hypercalciuria. This defect could be primary, as in RH, but only three hPHPx patients had recurrent kidney stones before surgery. On the other hand, as a negative correlation between GFR and FE Ca was only found in PHPx patients, it seems probable that the disturbances in glomerular and tubular functions were secondary to the long standing hypercalcemic hyperparathyroidism.

Adenoma↗

PubMed1996

Identification of carcinoembryonic antigen mRNA in circulating peripheral blood of pancreatic carcinoma and gastric carcinoma patients.

To detect adenocarcinoma cells in the circulating peripheral blood, we "analyzed the presence of carcinoembryonic antigen (CEA) mRNA in the peripheral blood obtained from patients with pancreatic carcinoma (PC) or with gastric carcinoma (GC) and also, as controls, from pancreatitis or gastritis patients without carcinomas, a gastric lymphoma patient and four healthy volunteers. Because of the small number of carcinoma cells expected in the peripheral blood, the analysis was performed by the reverse transcription followed by an original two-step polymerase chain reaction. By this sensitive method, 3 of 9 PC patients and 2 of 9 GC patients were positive for CEA mRNA. Except for 1 highly advanced PC patient, 3 of 4 CEA mRNA-positive patients developed recurrence after curative resection or liver metastasis after palliative operation within 9 months after the analysis. None of the control patients was positive for CEA mRNA in the peripheral blood. The results suggest that our sensitive RT-PCR method for detecting CEA mRNA in the peripheral blood is practically useful to find the hematogenous spreading of adenocarcinoma cells.

Aged↗