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Biomedical subjects

Y Takagi

Publications and source records attributed to Y Takagi.

At least 73 records · Page 4Linked to original sources

Influence of the angiotensin II receptor antagonist losartan on diuretic-induced metabolic effects in elderly hypertensive patients: comparison with a calcium channel blocker.

OBJECTIVE: Diuretic therapy frequently induces undesirable biochemical changes and side effects. We compared metabolic effects of a low-dose diuretic (D) given in combination with an angiotensin II receptor antagonist, losartan (L), with those resulting from a diuretic given in combination with a calcium channel blocker, slow-release nifedipine (N). MATERIAL AND METHODS: Thirty-seven elderly patients with mild to moderate hypertension (mean age: 71 +/- 3 years) were treated with either L+D (n = 18) or N+D (n = 19) for 1 year. Diuretic therapy included low-dose trichlormethiazide or low-dose furosemide in numbers of patients that were similar between L+D and N+D groups. Blood pressure, serum electrolytes, uric acid, blood glucose, renal function and lipid parameters were measured at baseline, 6 months and 1 year. RESULTS: Effective blood pressure control was observed in both groups at 6 months, and with further improvement at 1 year. Serum potassium was significantly decreased from baseline at 6 months (p < 0.01) and 1 year (p < 0.01) in the N+D group, but not in the L+D group. Serum uric acid was significantly increased from baseline at 6 months (p < 0.01) and 1 year (p < 0.01) in the N+D group, but had minimally decreased at 1 year in the L+D group (p < 0.1). Blood glucose, renal function and lipid parameters did not change in either group. CONCLUSION: The combination of losartan and low-dose diuretics effectively treated hypertension in elderly patients while minimizing the metabolic consequences of diuretic therapy. Larger trials will be necessary to confirm this finding.

Aged↗

[Factors in popularizing home nutritional therapy (HNT) in Japan-analysis of nurse's awareness].

Home nutritional therapy (HNT) is not popular in Japan as compared with American countries. The purpose of this study was to clarify the role of nurses in popularizing HNT. We sent out questionnaires to 469 nurses working at the O University affiliated Hospital, and got 265 responses. As a result, the following two factors were considered to affect the popularization of HNT. 1. Nurses had only a superficial knowledge of the activities of the nutrition support team (NST), and medical care by NST had not been spread. 2. In HNT, there were several gaps between ideals and the real role of nurses.

Awareness↗

[Clinical enzymology].

Clinical Enzymology is an important discipline of Clinical Chemistry and Laboratory Medicine. We review the significant aspect of clinical enzymology from the theoretical as well as the empirical points of view.

Biomarkers↗

[Aldolase].

Aldolase (EC 4.1.2.13) plays an important role in glucose metabolism. Aldolase has a molecular weight of 160 kDa and has three isozymes, namely aldolase A, B and C. The enzyme is probably present in all cells; it occurs in particularly large quantities in the muscles, liver and brain. An increase in serum aldolase is found in myotonic muscular disease, such as progressive muscular dystrophy and polymyositis. The enzyme rises in myocardial infarction, reaches a maximum within 24-48 hours and returns to normal in the course of five days. In these muscular diseases, aldolase A isozyme is elevated. Aldolase activity, especially B isozyme, in serum rises to very high levels in acute hepatitis, but is slightly elevated in cirrhosis, chronic hepatitis and obstructive jaundice. Aldolase becomes elevated in serum with malignant tumors, and isozyme A is predominant in serum. Erythrocytes are also rich in aldolase, and the enzyme rises in hemolytic anemia.

Acute Disease↗

[Creatine kinase and its isozymes].

Creatine kinase (CK; EC 2.7.3.2) is found in a variety of striated and smooth muscles, and the brain, and is an important enzyme regulator of high-energy phosphate production and utilization within contractile tissues. Serum CK activity is measured routinely as a sensitive indicator of injuries to the skeletal muscle and myocardium. CK has three isozymes (CK-MM, CK-MB and CK-BB) in cytoplasm and two isozymes (non-sarcomeric and sarcomeric) in mitochondria. CK isozymes provide more specific information about injured tissue because of their tissue distribution. CK-MM is useful in skeletal muscle diseases, such as muscle dystrophy, CK-MB in acute myocardial infarction (AMI), and CK-BB in brain damage and malignant tumor of the gastro-intestinal tract. CK-MB is measured either by enzyme activity or mass concentration and is measured as a marker not only in the diagnosis of AMI but also in suspected AMI and unstable angina. Mitochondrial CK, a useful indicator for pinpointing the severeness of muscle injuries, and CK-linked immunoglobulin are recognized as macro-CK because of their large molecular size.

Angina, Unstable↗

Phosphorylation of c-Jun NH(2)-terminal kinase and p38 mitogen-activated protein kinase after transient forebrain ischemia in mice.

We investigated the activation of c-Jun NH(2)-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) during transient forebrain ischemia to clarify the roles of these stress kinases during brain ischemia. Mice were subjected bilateral common carotid artery (BCCA) occlusion for 20 min followed by reperfusion. Immunohistochemical analysis and Western blot analysis for active JNK and active p38 MAPK were performed at 0, 5, 10, 30 and 150 min after reperfusion. After 5 min of reperfusion, active JNK and p38 MAPK immunoreactivities were enhanced in neurons in the cerebral cortex and hippocampus; this activation peaked at 30 min of reperfusion. Stress kinases activation dominantly occurred in the similar regions, in which neurons with fragmented DNA were detected at 72 h after reperfusion. Western blot analysis indicated that JNK 1, JNK 2 and p38 MAPK were activated at 10 and 30 min after reperfusion. These findings indicate that JNK and p38 MAPK pathways may play important roles in neuronal death during brain ischemia.

Animals↗

Activation of mitogen-activated protein kinases after transient forebrain ischemia in gerbil hippocampus.

We investigated the expression, activation, and distribution of c-Jun N-terminal kinases (JNKs), p38 mitogen-activated protein kinases (p38s) and extracellular signal-regulated kinases (ERKs) using Western blotting and immunohistochemistry in gerbil hippocampus after transient forebrain ischemia to clarify the role of these kinases in delayed neuronal death (DND) in the CA1 subfield. Immunoblot analysis demonstrated that activities of JNK, p38, and ERK in whole hippocampus were increased after 5 min of global ischemia. We used an immunohistochemical study to elucidate the temporal and spatial expression of these kinases after transient global ischemia. The immunohistochemical study showed that active JNK and p38 immunoreactivities were enhanced at 15 min of reperfusion and then gradually reduced and disappeared in the hippocampal CA1 region. On the other hand, in CA3 neurons, active JNK and p38 immunoreactivities were enhanced at 15 min of reperfusion and peaked at 6 hr of reperfusion and then gradually reduced but was continuously detected 72 hr after ischemia. Active ERK immunoreactivity was observed transiently in CA3 fibers and dentate gyrus. Pretreatment with SB203580, a p38 inhibitor, but not with PD98059, an ERK kinase 1/2 inhibitor, reduced ischemic cell death in the CA1 region after transient global ischemia by inhibiting the activity of p38. These findings indicate that the p38 pathway may play an important role in DND during brain ischemia in gerbil. Components of the pathway are important target molecules for clarifying the mechanism of neuronal death.

Animals↗

Adhesion-dependent tyrosine phosphorylation of enabled in Drosophila neuronal cell line.

Cell culture consisting of Drosophila BG2-c6 cells and laminin revealed its value for the analysis of the integrin-mediated activity of extracellular matrix (Takagi, Y., et al. (1998) Neurosci. Lett. 244, 149-152). To elucidate Drosophila integrin cascade further, we report here our characterization on the tyrosine phosphorylation in BG2-c6 cells, coupling with their spreading on extracellular matrix. Large-scale culture of Drosophila Kc167 cells provided a sufficient amount of extracellular matrix (including laminin) for performing biochemical analysis on the signal transduction in BG2-c6 cells. Several proteins underwent significant tyrosine phosphorylation in an adhesion-dependent manner. Among them, the heavy phosphorylation of Enabled (a substrate for Abelson tyrosine kinase) was noteworthy because of the proposed function of Enabled in cell adhesion. Together with our previous results, we propose a model for signal transduction activated by cell adhesion for the first time in Drosophila.

Animals↗

Preparation of 5-(2,6-dideoxy-2-fluoro-alpha-L-talopyranosyloxy)-6-hydroxynap htho[2,3- f]quinoline-7,12-dione (FT-Alz), a new-type, potentially antitumor substance with various biological activities.

The title compound (6), its structure being imaginatively created, has been prepared through coupling of alizarine blue (2), a classical dye, and 3,4-di-O-acetyl-2,6-dideoxy-2-fluoro-alpha-L-talopyranosyl bromide (3). Compound 6 has considerably higher and different antitumor activity from that of doxorubicin or its analogue (10), and, further, has properties to reverse multidrug resistance (by P-glycoprotein), to inhibit topoisomerase II, and to induce apoptosis.

Animals↗

Parathyroid hormone-activated volume-sensitive calcium influx pathways in mechanically loaded osteocytes.

This paper documents for the first time a volume-sensitive Ca(2+) influx pathway in osteocytes, which transmits loading-induced signals into bone formation. Stretch loading by swelling rat and chicken osteocytes in hypo-osmotic solution induced a rapid and progressive increase of cytosolic calcium concentration, [Ca(2+)](i). The influx of extracellular Ca(2+) explains the increased [Ca(2+)](i) that paralleled the increase in the mean cell volume. Gadolinium chloride (Gd(3+)), an inhibitor of stretch- activated cation channels, blocked the [Ca(2+)](i) increase caused by hypotonic solutions. Also, the expression of alpha1C subunit of voltage-operated L-type Ca(2+) channels (alpha1C) is required for the hypotonicity-induced [Ca(2+)](i) increase judging from the effect of alpha1C antisense oligodeoxynucleotides. Parathyroid hormone (PTH) specifically potentiated the hypotonicity-induced [Ca(2+)](i) increase in a dose-dependent manner through the activation of adenyl cyclase. The increases induced by both PTH and hypotonicity were observed primarily in the processes of the osteocytes. In cyclically stretched osteocytes on flexible-bottomed plates, PTH also synergistically elevated the insulin-like growth factor-1 mRNA level. Furthermore, Gd(3+) and alpha1C antisense significantly inhibited the stretch-induced insulin-like growth factor-1 mRNA elevation. The volume-sensitive calcium influx pathways of osteocytes represent a mechanism by which PTH potentiates mechanical responsiveness, an important aspect of bone formation.

Animals↗

Association of transforming growth factor beta1 genotype with spinal osteophytosis in Japanese women.

OBJECTIVE: To examine the possible relationship between a T-->C polymorphism at nucleotide position 29 of the transforming growth factor beta1 (TGFbeta1) gene and genetic susceptibility to radiographic spinal osteophytosis. METHODS: A total of 540 postmenopausal Japanese women were subjected to radiography of the spine and determination of bone mineral density (BMD) for the lumbar spine and total body. Changes in lumbar intervertebral discs were examined in 67 individuals with either osteoporosis or spinal osteophytosis by magnetic resonance imaging (MRI). TGFbeta1 genotype was determined with an allele-specific polymerase chain reaction assay. The serum concentration of TGFbeta1 was measured in 29 control subjects and in 36 patients with spinal osteophytosis. RESULTS: Among all study subjects, the prevalence of radiographic spinal osteophytosis in individuals with the CC genotype was greater than that in those with the TC or TT genotype. Logistic regression analysis, adjusted for age, height, body weight, time since menopause, smoking status, body fat, lean mass, and either lumbar spine or total body BMD, demonstrated that the frequency of the C allele in subjects with spinal osteophytosis was significantly greater than that in those without this condition. Comparison among control, osteoporosis, and spinal osteophytosis groups also revealed that the C allele was more prevalent in subjects with osteophytosis than in controls, even after adjustment for BMD. In contrast, as previously shown, the frequency of the C allele was lower in osteoporosis patients than in controls. The intervertebral disc area and the ratio of disc area to vertebral body area, as determined by MRI, were also lowest in subjects with the CC genotype. The serum concentration of TGFbeta1 increased with the number of C alleles in both controls and patients with spinal osteophytosis. CONCLUSION: The T29-->C polymorphism of the TGFbeta1 gene exhibited inverse patterns of association with genetic susceptibility to spinal osteophytosis and with osteoporosis. Although radiographic evaluation of osteophytes might not reflect the actual disease severity, the C allele, which protects against osteoporosis, may be a risk factor for genetic susceptibility to spinal osteophytosis.

Aged↗

Sarpogrelate reduces mechanical hemolysis in patients with heart valve prostheses.

OBJECTIVE: We evaluate the clinical efficacy of sarpogrelate, an antiplatelet drug that improves red blood cell deformability, to reduce the intravascular hemolysis problems suffered frequently by patients implanted with heart valve prostheses. SUBJECTS: Subjects were 34 patients undergoing mechanical heart valve replacement and having serum lactate dehydrogenase concentrations 20% above the maximum normal range. METHOD: Sarpogrelate was given daily, 100 mg orally for the first 6 months and 200 mg thereafter. RESULTS: Average serum lactate dehydrogenase decreased significantly from 423 +/- 108 IU/l, to 391 +/- 83 IU/l with the 100 mg dose, and to 361 +/- 86 IU/l with the 200 mg dose. The percentage of reticulocytes decreased from 15.5 +/- 5.3/1000 to 15.3 +/- 5.7/1000 at the 100 mg dose and 13.1 +/- 4.0/1000 at the 200 mg dose. Serum iron concentrations increased significantly from 63.2 +/- 24.8 micrograms/dl to 76.2 +/- 16.2 micrograms/dl at the 100 mg dose, and to 70.9 +/- 26.2 micrograms/dl with the 200 mg dose. CONCLUSION: Sarpogrelate is a useful drug for patients with implanted heart valve prostheses and subsequent high serum lactate dehydrogenase because it works as an antiplatelet drug and reduces mechanical hemolysis.

Adult↗

Effect of avicatonin (chicken carbocalcitonin) on galvanic skin response: a randomized, prospective, double-blind, controlled study for an objective assessment of pain.

In an attempt to objectively evaluate the analgesic effect of avicatonin (chicken carbocalcitonin), galvanic skin response (GSR) was recorded in 18 patients with osteoporosis or osteopenia and backache in a randomized, prospective, double-blind, controlled study. Backache on examination and in daily living was assessed weekly by scores utilizing a questionnaire. After two measurements 1 week apart on induction of backache with a maximum anterior flexion of the back from a supine position, either 20 units of avicatonin or inactive placebo was intramuscularly injected once a week for 4 consecutive weeks. In the avicatonin group but not in the placebo group, the area under the curve (AUC) of GSR tracing was decreased, giving a significant difference between the avicatonin and placebo groups after the second week. The pain score obtained by questionnaire decreased in both groups, suggesting a placebo effect. Galvanic skin response may provide a breakthrough to the objective and reliable evaluation of the biological response to pain which could not be accomplished by questionnaires based on subjective impression markedly influenced by emotional and psychological factors.

Aged↗

DNA fragmentation in central nervous system vascular malformations.

Recent studies have shown that apoptosis plays an important role in vascular remodeling. We examined central nervous system vascular malformations for the presence of DNA fragmentation which is the evidence of apoptosis. We hypothesize that vascular remodeling through apoptosis may be responsible for recurrence or hemorrhage in these lesions. We examined the specimens of central nervous system vascular malformations by in situ end labeling (ISEL) of fragmented DNA. Moreover, we examined the expression of Caspase-3 which is apoptosis-related proteins in these lesions by immunohistochemistry. DNA fragmentation was observed in all 15 arteriovenous malformation (AVM) specimens. ISEL-positive cells were mainly distributed in the endothelium, media and perivascular tissue. In cavernous hemangioma (CH), DNA fragmentation was also observed in all 5 specimens. ISEL-positive cells were distributed in the endothelium, subendothelium and intercavernous matrix. Thirteen out of 15 AVM lesions stained positive for Caspase-3. Caspase-3 immunoreactivity was mainly distributed in the endothelium, media and perivascular tissue. This distribution was similar to that of ISEL positive cells. As for CHs, all 5 lesions stained positive for Caspase-3. Caspase-3 immunoreactivity was distributed in the endothelium, subendothelium and intercavernous matrix. Our findings indicate that apoptotic cell death and vascular remodeling play a role in the development and maintenance of vascular malformations.

Adolescent↗

Increase of intestinal calcium absorption and bone mineral density by heated algal ingredient (HAI) in rats.

Active absorbable calcium (AAACa) produced by adding HAI (heated algal ingredient) to oyster shell calcium (AACa) is quite efficiently absorbed from the intestine and can increase bone mineral density in elderly osteoporotic patients. HAI was produced by heating the seaweed Cystophyllum fusiforme under reduced pressure, extracting with 6N HCL, and partially neutralizing it. Butanol-ethanol extraction then yielded active HAI fraction A, corresponding to about 1% in weight. The active HAI fraction increased intestinal Ca absorption as shown by a dose-dependent increase of plasma Ca in young male parathyroidectomized rats maintained on a low-Ca diet by administration through a stomach tube with a constant dose of AACa. The action of the active fraction A to maintain bone mass was then tested in young male rats kept on a low-Ca diet for 2 weeks. Bone weight, trabecular bone density, and strength-strain index as indices of bone strength measured by peripheral computed tomography (pQCT) tended to increase when the active HAI fraction was given along with Ca. HAI increased intestinal Ca absorption and prevented the decrease of bone density in rats kept on a low-Ca diet.

Animals↗

Peripheral computed tomography (pQCT) detected short-term effect of AAACa (heated oyster shell with heated algal ingredient HAI): a double-blind comparison with CaCO3 and placebo.

Trabecular bone density at the distal radius and cortical bone density at the midradius were measured in four randomized groups of women before and after 4 months administration of AAACa, oyster shell heated under reduced pressure with addition of heated algal ingredient (HAI) (group A); AACa, the same preparation without HAI (group B); CaCO3 (group C); and placebo (group D) in a double-blind system using peripheral quantitative computed tomography (pQCT) with lumbar spine density measurement by dual-energy X-ray absorptiometry (DXA). Groups A, B, and C received 900 mg/day elemental calcium and D received none. In subjects of group A, but not B, C, and D, radial trabecular bone density increased significantly, to 106.2% +/- 2.1% of the initial value (mean +/- SEM). The increase of trabecular bone density was significantly different from the placebo group (D) only in AAACa (group A) and not in AACa (group B) and the calcium carbonate (group C). Cortical bone density increase was also greater in group A (but not in B and C) than in D. Lumbar spine density did not change significantly. AAACa was apparently more effective, increasing trabecular bone density more than AACa and CaCO3 containing the same amount of elemental calcium.

Absorptiometry, Photon↗