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Biomedical subjects

T Sako

Publications and source records attributed to T Sako.

At least 55 records · Page 3Linked to original sources

Circadian rhythm in peak expiratory flow: alteration with nocturnal asthma and theophylline chronotherapy.

We investigated changes in the circadian rhythm of peak expiratory flow (PEF) in seven persons with nocturnal asthma for a 24h span when (1) they were symptom free and their disease was stable, (2) their asthma deteriorated and nocturnal symptoms were frequent, and (3) they were treated with theophylline chronotherapy. Subjects recorded their PEF every 4h between 07:00 and 23:00 one day each period. Circadian rhythms in PEF were assessed using the group-mean cosinor method. The circadian rhythm in PEF varied according to asthma severity. Significant circadian rhythms in PEF were detected during the period when asthma was stable and when it was unstable and nocturnal symptoms were frequent. When nocturnal symptoms were present, the bathyphase (trough time) of the PEF rhythm narrowed to around 04:00; during this time of unstable asthma, the amplitude of the PEF pattern increased 3.9-fold compared to the symptom-free peiiod. No significant group circadian rhythm was detected during theophylline chronotherapy. Evening theophylline chronotherapy proved to be prophylactic for persons whose symptoms before treatment had occurred between midnight and early morning. Changes in the characteristics of the circadian rhythm of PEF, particularly amplitude and time of bathyphase, proved useful in determining when to institute theophylline chronotherapy to avert nocturnal asthma symptoms.

Adult↗

Effects of epinephrine and lactate on the increase in oxygen consumption of nonexercising skeletal muscle after aerobic exercise.

The purpose of this study was to measure O2 consumption of nonexercising skeletal muscles (VO2nonex) at rest and after aerobic exercise and to investigate the stimulant factors of O2 consumption. In experiment 1, we measured the resting metabolic rate of the finger flexor muscles in seven healthy males by 31P-magnetic resonance spectroscopy during a 15 min arterial occlusion. In experiment 2, the VO2nonex of the finger flexor muscles was measured using near infrared continuous wave spectroscopy at rest, immediate postexercise, and 3, 5, 10, 15, and 20 min following a cycling exercise at a workload corresponding to 50% of peak pulmonary O2 uptake for 20 min. We also monitored deep tissue temperature in the VO2nonex measurement area and determined catecholamines and lactate concentrations in the blood at rest and immediate postexercise. VO2nonex at rest was 1.1 +/- 0.1 microM O2/S (mean +/- standard error) and VO2nonex after exercise increased 59.6 +/- 7.2% (p < 0.001) from the resting values. There were significant correlations between the increase in VO2nonex and the increase in epinephrine concentration (p < 0.01), and between the increase in VO2nonex and the increase in lactate concentration (p < 0.05). These results suggest that epinephrine and lactate concentrations are important VO2nonex stimulant factors.

Adult↗

Quantification of ischemic muscle deoxygenation by near infrared time-resolved spectroscopy.

The purpose of this study was to quantify muscle deoxygenation in human skeletal muscles using near infrared time-resolved spectroscopy (NIRTRS) and compare NIRTRS indicators and blood saturation. The forearm muscles of five healthy males (aged 27-32 yrs.) were monitored for changes in hemoglobin saturation (SO2) during 12 min of arterial occlusion and recovery. SO2 was determined by measuring the temporal profile of photon diffusion at 780 and 830 nm using NIRTRS, and was defined as SO2-TRS. Venous blood samples were also obtained for measurements of SvO2, and PvO2. Interstitial PO2(PintO2) was monitored by placing an O2 electrode directly into the muscle tissue. Upon the initiation of occlusion, all parameters fell progressively until reaching a plateau in the latter half of occlusion. It was observed at the end of occlusion that SO2-TRS (24.1 +/- 5.6%) agreed with SvO2 (26.2 +/- 6.4) and that PintO2 (14.7 +/- 1.0 Torr) agreed with PvO2 (17.3 +/- 2.2 Torr). The resting O2 store (oxygenated hemoglobin) and O2 consumption rate were 290 microM and 0.82 microM s-1, respectively, values which reasonably agree with the reported results. These results indicate that there was no O2 gradient between vessels and interstisium at the end of occlusion.

Adult↗

Systemic kappaAL amyloidosis associated with bovine leukocyte adhesion deficiency.

Histopathologic and immunohistochemical examinations were conducted on a 5-year-old Holstein-Friesian cow with systemic kappaAL amyloidosis associated with bovine leukocyte adhesion deficiency. Amyloid deposits were present in the perivascular and intercellular spaces of the visceral organs, such as the liver, kidneys, pancreas, adrenal glands, and upper alimentary tract. Amyloid was stained positively with Congo red with or without 5% potassium permanganate pretreatment and had green birefringence observed under polarized light. Immunohistochemically, amyloid reacted strongly against anti-bovine IgG (H+L) and anti-bovine kappa-light chain and reacted weakly against bovine X-light chain antibodies but was negative for anti-human amyloid AA antibody. This is the first description of AL amyloidosis immunohistochemically related to immunoglobulin kappa-light chains of precursor protein in cattle.

Amyloid↗

Establishment of a human colon cancer cell line (PMF-ko14) displaying highly metastatic activity.

A new human colon cancer cell line (PMF-ko14) derived from a peritoneal disseminated tumor has been established and maintained for over 25 months. In tissue culture, the cells grew in a mainly monolayered sheet with a population doubling time of about 27 h. Chromosome counts at the 60th passage ranged from 79 to 84 with a modal number of 83. Flow cytometry of the cell surface antigen expression indicated that CD49b, CD29, carcinoembryonic antigen (CEA), sialyl Lewis a (sLea), and CD49c were positive in more than 70% of the cells. The nude mouse xenograft models indicated are: subcutaneous or intraperitoneal injection model, spleen injection-liver metastasis model, and orthotopic implantation-spontaneous metastasis model. As PMF-ko14 has highly metastatic activity it should prove to be a useful tool for research in biological behavior of metastatic colon cancer.

Animals↗

Human pulmonary dirofilariasis presenting as a small nodule with a cavity.

A 73-year-old woman had a 4-year history of lung fibrosis from collagen vascular disease. She presented with a complaint of dry cough. A chest radiograph showed a 2-cm solitary pulmonary nodule with a small cavity in the right lower lobe. Preoperatively, we performed computed tomography of the chest and measured tumor markers. Video-assisted thoracotomy was performed because we could not rule out lung cancer. Pathologic analysis confirmed the presence of a granuloma with Dirofilaria immitis. In Japan, the incidence of human dirofilariasis has steadily increased and must be considered in the workup of cavitary pulmonary nodules.

Aged↗

Generation of polymeric immunoglobulin receptor-deficient mouse with marked reduction of secretory IgA.

We generated mouse lacking exon 2 of polymeric Ig receptor (pIgR) gene by a gene-targeting strategy (pIgR-deficient mouse; pIgR-/- mouse) to define the physiological role of pIgR in the transcytosis of Igs. pIgR-/- mice were born at the expected ratio from a cross between pIgR+/- mice, indicating that disruption of the pIgR gene in mice is not lethal. pIgR and secretory component proteins were not detected in pIgR-/- mice by Western blot analysis. Moreover, immunohistochemical analysis showed that pIgR protein is not expressed in jejunal and colonic epithelial cells of pIgR-/- mice, whereas IgA+ cells are present in the intestinal mucosa of pIgR-/- mice as well as wild-type littermates. Disruption of the pIgR gene caused a remarkable increase in serum IgA concentration and a slight increment of serum IgG and IgE levels, leaving serum IgM level unaltered. In contrast, IgA was much reduced but not negligible in the bile, feces, and intestinal contents of pIgR-/- mice. Additionally, IgA with a molecular mass of 280 kDa preferentially accumulated in the serum of pIgR-/- mice, suggesting that transepithelial transport of dIgA is severely blocked in pIgR-/- mice. These results demonstrate that dIgA is mainly transported by pIgR on the epithelial cells of intestine and hepatocytes, but a small quantity of IgA may be secreted via other pathways.

Animals↗

A comparison of the plasma fructose concentrations in dogs and cats and changes in the fructose concentrations in dogs following intravenous administration of fructose.

The plasma concentrations of fructose, glucose, free fatty acids (FFA) and triglycerides (TG) were measured in dogs and cats. Changes in these concentrations were investigated in dogs by an intravenous fructose tolerance test (IVFTT) at a dose of 0.1 g/kg body weight. Fructose concentrations in the plasma of dogs were significantly higher than those of cats. There was no significant difference in plasma glucose concentrations between dogs and cats. Plasma FFA concentrations decreased and TG concentrations increased after feeding in both dogs and cats. During the IVFTT, the plasma fructose concentrations in the dogs increased rapidly to a peak by 2 min and then decreased to half of the peak by 5 min after the administration of fructose. Administration of fructose resulted in an increase in the plasma TG concentrations and reduced plasma FFA concentrations in the dogs. Only 4%, of the administered fructose was detected in the urine of dogs following IVFTT. Plasma fructose was considered to be rapidly absorbed and metabolized in both dogs and cats. However, as with glucose metabolism, there appear to be some differences in fructose metabolism between dogs and cats.

Animals↗

Preliminary studies on hepatic carnitine palmitoyltransferase in dairy cattle with or without fatty liver.

The hepatic mitochondrial carnitine palmitoyltransferase (CPT) activity was measured by fluorimetric assay in dairy cows with or without fatty liver. CPT activities in 13 lactating cattle and in 6 non-lactating cows were 304.4+/-86.6 micromol CoA/min per g protein and 169.3+/-84.8 micromol CoA/min per g protein, respectively. This difference was significant (p < 0.05). CPT activities in early lactation (0-110 days after calving), mid-lactation (111-220 days after calving) and late lactation (over 220 days after calving) were 278.9+/-68.0, 312.4+/-124.1 and 320+/-59.3 micromol CoA/min per g protein, respectively. There was no significant difference between the values at different stages of lactation. The CPT activity in 10 lactating cows with fatty liver unrelated to calving was 201.3+/-80.0 micromol CoA/min per g protein. CPT activity in 10 cattle with fatty liver was significantly lower than that in normal lactating cattle. Based on these findings, clinical fatty liver unrelated to calving appears to be associated with a decrease in hepatic CPT activity.

Animals↗

Comparison of the activities of enzymes related to glycolysis and gluconeogenesis in the liver of dogs and cats.

Activities of enzymes related to glucose metabolism were measured in canine and feline liver. There were no significant differences in plasma glucose and immunoreactive insulin concentrations between dogs and cats. Glucokinase activities were absent in feline liver, however, activities of other glycolytic enzymes such as hexokinase, phosphofructokinase and pyruvate kinase, were significantly higher than those in canine livers. Activities of rate limiting enzymes of gluconeogenesis such as pyruvate carboxylase, fructose-1, 6-bisphosphatase and glucose-6-phosphatase in feline livers were significantly higher than those in canine livers.

Animals↗

Nasal nocardiosis in a calf.

Nasal nocardiosis was found in a female Japanese Black calf, 11 months of age. Macroscopically, the posterior half of the left nasal passage was completely obstructed by yellowish brown caseous substance and the mucosa was irregularly thickened. In the brain, a few soft brown foci were present in the olfactory bulb and frontal lobe. Microscopically, there were closely packed granulomas in the nasal cavity and brain. The lesions were characterized by a center of cellular debris surrounded by epithelioid macrophages, neutrophils, lymphocytes and multinucleated giant cells of the Langhans type. Special stains revealed the presence of a large number of filamentous branching gram-positive, partially acid-fast organisms in these epithelioid cells and giant cells, and in cellular debris.

Animals↗

[Progress of the stroke registry system by public health centers, and factors associated with its advancement].

In Japan, a community-based stroke registry was started in 1992 based on the policy of the central government. There are mainly two objectives in this registry system. One is to analyze factors related to the incidence of stroke, and the other is to support home care of stroke patients after leaving the hospital. This system has experienced many difficulties, such as obtaining appropriate information smoothly from the hospitals. Therefore, we investigated all 895 public health centers in Japan through a questionnaire sent by mail, in February 1996. We obtained valid replies from 612 (68%) of the public health centers by March 1996. Results showed that 75% of health centers have established a stroke registry system. Some health centers have promoted the system since 1984. In these systems, the flows of information are mainly of two types: ones which flow to the health centers from the hospitals and the ones which flow to the municipalities. In the former, the number of registered cases were significantly higher and the registry was functioning better than the latter. It has become clear that the health center plays a key role in the successful development of a stroke registry system.

Cerebrovascular Disorders↗

Stereoselective serum protein binding of ketoprofen in liver diseases.

The stereoselective binding of ketoprofen (KP) to human serum was studied in patients with liver diseases and was compared with that of normal volunteers. The serum protein binding of racemic KP was found to be decreased in hepatic patients whereas, interestingly, the stereoselectivity of KP was increased. The ratio of unbound concentrations of the KP enantiomers (FR/FS) showed positive linear correlation with albumin concentrations. Inhibition of KP binding to human serum albumin (HSA) induced by lithocholate, lithocholate sulfate and bilirubin was studied. The data presented in this paper strongly suggest that the variation of stereoselective binding of KP in patients suffering from liver diseases was mainly caused by the decrease of HSA levels and secondly by the stereoselective inhibition induced by the increased concentrations of bile acid and its metabolite.

Adult↗

Comparison of glucokinase activities in the peripheral leukocytes between dogs and cats.

Activities of hexokinase (HK), glucokinase (GK) and pyruvate kinase (PK), were measured. The expression of GK mRNA was investigated using reverse transcription-polymerase chain reaction (RT-PCR) in leukocytes (WBC) of dogs and cats. No significant differences between dogs and cats were found in concentrations of blood glucose and plasma insulin. Dog WBC showed GK activities and the specific fragment with predicted size of 574 bp containing conserved region including glucose- and ATP-binding domains of GK as determined with RT-PCR. However, in cat WBC, the activities and specific fragment of GK were absent. After fasting, the activities and gene expression of GK decreased greatly in the dog WBC. The cat WBC had significantly higher activities of HK and PK than dog WBC.

Animals↗

A comparison of the activities of certain enzymes related to energy metabolism in leukocytes in dogs and cats.

The activities of Na+,K(+)-ATPase in plasma membrane, of cytosolic enzymes and of glutamate dehydrogenase (GlGD) in mitochondria were measured in leukocytes (WBC) from dogs and cats to clarify the differences in energy metabolism in these cells. Feline WBC had significantly higher activities of hexokinase (HK), pyruvate kinase (PK) and LDH with pyruvate as substrate than did canine WBC. Canine WBC had significantly higher activities of glucokinase (GK) and GlDH than did feline WBC. Feline WBC had unique characteristics of energy metabolism in that the activities of the cytosolic enzymes under anaerobic conditions were significantly higher than those in canine WBC. It therefore appears that there are distinct differences in glucose-metabolism in WBC between dogs and cats. WBC enzyme activities are considered to reflect the metabolic state in the whole body of the animal. It is therefore suggested that changes in the activities of certain glycolytic enzymes in WBC may be useful as a diagnostic indicator in some types of metabolic disease in dogs and cats.

Alanine Transaminase↗

Alterative expression of the collagenase and adhesion molecules in the highly metastatic clones of human colonic cancer cell lines.

Human colonic carcinoma cell lines, KM12C, KM12SM and KM12L4, were previously established and their in vivo metastatic potentials have been well evaluated. The highly metastatic cell lines KM12SM and KM12L4 were derived from the parental low metastatic cell line KM12C in vivo. To evaluate the metastatic behavior of these cell lines in vitro, we examined colony formation on monolayers of the pulmonary arterial endothelial (CPAE) cells. On day 4, the highly metastatic cell lines showed an approximately 2-fold increase in number of colonies on CPAE cell monolayers relative to the parental KM12C cell line. To investigate what evidence is correlated with their metastatic and invasive abilities, Northern blot analysis and flow cytometry were performed in all cell lines. According to the results of Northern blot analysis, the levels of matrix metalloproteinase (MMP)-2 and c-met mRNA expression were increased in highly metastatic cell lines as compared with the parental cell line. We also examined the cell-surface expression of several adhesion molecules by flow cytometry. The levels of expression of sialyl Lewisa antigen (sLe(a)) in KM12SM and KM12L4 were twice higher than that in KM12C. However, the levels of expression of E-cadherin in KM12SM and KM12L4 were decreased to half that in KM12C. The alterative expression of the collagenase and adhesion molecules might contribute to their metastatic/invasive abilities of these cell lines both in vivo and in vitro.

Antigens, CD↗

Role of the kringle domain in plasminogen activation with staphylokinase.

We have evaluated the effect of lysine binding sites in kringle structures on the activation of plasminogen with plasmin and staphylokinase (SAK) complex and on the binding of plasminogen to SAK. Activation of native plasminogen (Glu-plasminogen) by a catalytic amount of plasmin-SAK complex increased in the presence of epsilon-amino-n-caproic acid (EACA) and then decreased with higher concentrations of EACA. By contrast, activation of modified plasminogen (Lys-plasminogen) decreased in an EACA-concentration-dependent manner. This decrease was explained by a more than 10-fold higher Km for activation of Lys-plasminogen with a catalytic amount of plasmin-SAK complex in the presence of EACA. EACA was a competitive inhibitor with Ki 0.23 mM. In addition, the Km for activation of mini-plasminogen, which lacks first four kringle structures (K1+2+3+4), was at least 3.5-fold higher than that for the activation of Lys-plasminogen. Furthermore, EACA showed a negligible inhibitory effect on the activation of mini-plasminogen by the plasmin-SAK complex. We observed a similar biphasic effect of EACA on the binding of Glu-plasminogen to SAK and a dose-dependent effect on the Lys-plasminogen binding to SAK by gel filtration methods. Since EACA binds to plasminogen via lysine binding sites in the kringle structure, we propose that the lysine binding site in K1+2+3+4 domain plays a role in the activation of plasminogen by plasmin SAK complex, and in the binding of plasminogen to SAK.

Aminocaproic Acid↗