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Biomedical subjects

K Kaku

Publications and source records attributed to K Kaku.

At least 19 recordsLinked to original sources
PubMed2002

Type III hyperlipoproteinema with apolipoprotein E2/2 genotype in Japan.

Limited information is available concerning type III hyperlipoproteinemia (HLP) in the Asian population. Therefore, clinical and biochemical characteristics of type III HLP were examined in 16 Japanese patients. Mean plasma triglyceride (TG) and total cholesterol (chol) levels were 381 mg/dl and 253 mg/dl, respectively, and the mean very low density lipoprotein (VLDL)-chol/plasma TG ratio was 0.27, which were lower than those reported in Western countries. Eighty percent of the patients had high plasma remnant-like particles (RLP)-chol levels above 50 mg/dl and a high RLP-chol/plasma TG ratio above 0.1. Twelve patients (75.0%) were obese. Seven patients (43.8%) had type 2 diabetes mellitus and four patients (25.0%) had impaired glucose tolerance. Six patients (37.5%) had coronary heart disease (CHD), but none had peripheral vascular disease or xanthomas. TG-rich lipoproteins from type III HLP patients with diabetes mellitus stimulated cholesteryl ester synthesis by human macrophages significantly (p < 0.001) more than those from type III HLP patients without diabetes mellitus. In conclusion, the Japanese type III HLP patients had lower plasma TG and total chol levels and a lower VLDL-chol/plasma TG ratio, but CHD was more common. The patients were characterized by a high frequency of obesity and/or glucose intolerance. The TG-rich lipoproteins from type III HLP patients with diabetes mellitus were more atherogenic.

Adult↗
PubMed2001

Downregulation of the voltage-dependent calcium channel (VDCC) beta-subunit mRNAs in pancreatic islets of type 2 diabetic rats.

The present study was undertaken to determine whether altered expression of the VDCC beta-subunits in pancreatic beta-cells could play a role in the changes in beta-cell sensitivity to glucose that occur with diabetes. Application of competitive RT-PCR procedure revealed that in normal Wistar rats, LETO and prediabetic OLETF rats, the beta(2)-subunit mRNA levels were 60-200-fold greater than the levels for the beta(3)-subunit. These findings suggest that the beta(2)-subunit as well as the beta-cell type VDCC1 alpha(1)-subunit may be the predominant form of the VDCC expressed in pancreatic beta-cells. The levels of mRNA encoding the beta-subunits and the beta-cell type alpha(1)-subunit as well as insulin were significantly reduced in diabetic rats. Perfusion experiments revealed that diabetic rats showed the higher basal insulin secretion and profoundly impaired insulin secretory responses to glucose compared with non-diabetic rats. Alternatively, impaired insulin secretory responses to glucose in high dose glucose-infused rats were recovered partly with the elevation of mRNA levels of the VDCC beta(2)- and beta(3)-subunits as well as the alpha(1)-subunit by the treatment with diazoxide. Thus, considering the possibility that the most striking effect of the VDCC alpha(1) beta-subunit coexpression in pancreatic beta-cells might occur on activation kinetics like the skeletal muscle, the impairment of further activation of the VDCCs to acute glucose challenge caused by the reduced expressions of the alpha(1) beta-subunits mRNAs in type 2 diabetic animals might be at least partly associated with the alterations in beta-cell sensitivity to glucose.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed2001

Serum contents of the free forms of alpha(1)-microglobulin and ulinastatin: relation to diseased states in patients with mood disorders.

We have found previously that the relationship between the urinary contents of alpha(1)-microglobulin (alpha(1)M) and ulinastatin (UT) in patients with mood disorder differs from that of age-matched healthy subjects. However, it has yet to be determined whether or not the difference in the relation correlates with the contents of the free forms of alpha(1)M and UT in serum and whether changes in the existing forms of alpha(1)M and UT in serum reflect the actual disease states. The relation between serum contents of the free forms of alpha(1)M and UT in 10 patients with mood disorders was different from that of 17 age-matched healthy subjects. The regression plot between scores of the Hamilton Rating Scale for Depression and ratios of the free form content to total content (F/T ratio) of UT was more informative on the depressive state than that of alpha(1)M. The F/T ratios of UT may afford a useful objective index in monitoring the diseased state of a patient with mood disorder.

Biomarkers↗
PubMed2001

[Insulin detemir(NN-304)].

A line of evidences has demonstrated that a normalization of blood glucose can prevent or delay diabetic complications. To normalize blood glucose in diabetic patients who require insulin treatment, a tailoring the time-action profile of injected insulin is needed. B29Lys-myristoyl. des-B30 human insulin(NN-304), which metabolic action is prolonged by association of the fatty acid residue to albumin in the blood and peripheral tissues, belongs to a new class of soluble long-acting insulin analogs. The aim of clinical development of NN-304 is to reduce the disadvantages of currently available long-acting insulin formulations. NN-304 might offer advantages in clinical use such as reproducing physiological basal insulin action derived from a flatter time-action profile.

Amino Acid Sequence↗
PubMed2000

Advanced glycation end products-induced gene expression of scavenger receptors in cultured human monocyte-derived macrophages.

We investigated the effects of advanced glycation end products (AGEs) on the expression of oxidized low-density lipoprotein (OxLDL) receptors in human monocyte-derived macrophages and THP-1 cells treated with PMA. Both RT-PCR procedure and Northern blot analysis revealed that AGEs induced not only the gene expression of two major OxLDL receptors, macrophage scavenger receptor (MSR) class A and CD36, but also MSR-B I and lectin-like oxidized low-density lipoprotein receptor 1. Also, as a result of gel shift assay, AGEs increased transcriptional activities of AP-1, NF-kappaB, and peroxisome proliferator-activated receptor gamma. These findings indicate that AGEs-induced enhancement of these transcriptional activities might be involved in increased levels of mRNA for some of OxLDL receptors in THP-1-cells treated with PMA. The upregulated surface expression of these receptors on macrophage membranes was closely associated with increased uptake of modified LDL, and culminated in enhanced foam cell transformation. Thus, AGEs may be involved in the cause of variable levels of foam cell formation via the increased numbers of OxLDL receptors in accelerated atherosclerotic lesions of individuals with diabetes.

Blotting, Northern↗
PubMed2000

Pharmacokinetics and pharmacodynamics of insulin aspart, a rapid-acting analog of human insulin, in healthy Japanese volunteers.

Pharmacokinetic and pharmacodynamic properties of a rapid-acting analog of human insulin, insulin aspart, were compared with those of soluble human insulin in Japanese healthy subjects. Subcutaneous single injections (0.025 and 0.05 U/kg body weight (BW)) of insulin aspart produced a significantly earlier peak of exogenous insulin level in comparison with human insulin (30.8+/-13.8 versus 61.3+/-14. 6 min, P<0.9001 for 0.025 U/kg; and 39.2+/-18.8 versus 99.2+/-53.8 min, P<0.005 for 0.05 U/kg). The peak serum level of insulin aspart was higher than that of human insulin (23.0+/-6.0 versus 9.9+/-3.1 microU/ml for 0.025 U/kg; and 30.9+/-9.2 versus 13.3+/-4.1 microU/ml for 0.05 U/kg, P<0.0001). The time to the minimal level of glucose after insulin aspart was significantly shorter compared with human insulin (P<0.05 for 0.025 U/kg BW and P<0.01 for 0.05 U/kg BW). The Delta change in blood glucose induced by insulin aspart was larger than that observed for human insulin at any dose (P<0.001). The repeated injection of insulin aspart before each meal also resulted in a rapid rise in exogenous insulin level with peak level obtained approximately 40 min after insulin aspart at any dose. When compared with results of other trials with insulin aspart, the present results showed that pharmacokinetic and pharmacodynamic profiles of the rapid-acting analog insulin aspart in Japanese subjects are no different from those in nonJapanese subjects.

Adult↗
PubMed1999

Sex- and age-related changes in urinary contents of alpha 1-microglobulin and ulinastatin in mice.

1. Using two murine strains, ICR/Jcl and senescence-accelerated-prone inbred mouse 1 (SAMP1), age-associated changes in urine indices (e.g. urine volume, creatinine contents, contents of alpha 1-microglobulin (alpha 1M) and ulinastatin (UT) and the relation of urinary contents of alpha 1M and UT were investigated. 2. Sex-related differences in the indices were not observed in ICR nor in SAMP1 mice. 3. Urine indices per 24 h of ICR mice at 6 and 14 months of age were higher than those at 3 months of age, although indices of SAMP1 mice did not change with ageing. Urinary contents of alpha 1M and UT in ICR mice at 6 and 14 months of age were higher than those in SAMP1 mice. However, contents of alpha 1M and UT expressed as the contents per creatinine did not differ between these two strains. 4. In the relation between urinary contents of alpha 1M and UT, a positive correlation was displayed both in ICR and SAMP1 mice, and the regression slope did not significantly differ with ageing in these two strains. 5. These results suggest that ageing per se is not a factor which affects the relation of urinary contents of alpha 1M and UT.

Aging↗
PubMed1999

Elevation of striatal interleukin-6 and serum corticosterone contents in MPTP-treated mice.

1. Changes in the content of striatal interleukins (IL-1 beta and IL-6) and serum corticosterone in relation to deterioration of the dopaminergic system induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; a dopaminergic neurotoxin; 20 mg/kg i.p., four administrations/12 h) in C57BL/6J mice were investigated. 2. Striatal dopamine, IL-1 beta, IL-6 and serum corticosterone were measured on days 1 and 7 post-MPTP. 3. Dopamine depletion was more severe on day 7 than on day 1 post-treatment. 4. Increases in IL-6 were observed on days 1 and 7 post-MPTP. The increase in striatal IL-6 content varied with the extent of dopamine depletion, although the IL-1 beta concentration remained unchanged compared with control values on days 1 and 7 post-treatment. 5. Serum corticosterone was not different from control on day 1 post-MPTP. However, marked increases in the serum corticosterone were observed on day 7 post-treatment. 6. These results suggest that changes in striatal IL-6 and serum corticosterone are closely associated with the severity of MPTP-induced dopaminergic degeneration.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1999

A neuropathological study of dementia in nursing homes in Shimane prefecture, Japan: evaluation of the age and gender effect.

BACKGROUND: Vascular dementia (VD) has been held responsible for the majority of all dementia cases in both epidemiological and neuropathological studies in Japan. The aim of this study was to clarify relative frequencies of dementia neuropathologically in Japanese nursing home residents over a 17-year period and to clarify the gender and age effect on the relative frequencies. METHODS: Three hundred ten aged nursing home residents (146 men and 164 women), including dementia cases in Shimane prefecture, Japan, were evaluated clinically and neuropathologically over a period of 17 years. RESULTS: One hundred twenty-two (48 men and 74 women) of the 310 autopsied (39%) had shown signs of dementia during their lives. In classifying dementia type, Alzheimer's disease (AD) accounted for 34% (41); VD 35% (42); mixed dementia 11% (14); and "other" dementia 20% (25) of all samples. As to the gender and age effect, the most characteristic findings were as follows: (a) There were only VD cases in the 57-69-year-old group; (b) the 70-79 male age group lacked any cases with only AD; (c) more AD than VD was found in elderly men; and (d) in women, AD was the major cause of dementia in total. CONCLUSIONS: VD is responsible for the major cause of dementia in the younger women and the men under 90 years of age; AD is the leading cause of dementia in the elderly men and the women over 79 years of age in nursing homes, Shimane prefecture, Japan.

Age Factors↗
PubMed1999

Impairment of the correlation between urinary contents of alpha-1-microglobulin and ulinastatin is induced by intracerebroventricularly administered interleukin-6 in mice.

We have found previously that the correlation between urinary contents of alpha-1-microglobulin (alpha1M) and ulinastatin (UT) depends on the type of neuropsychiatric disease. Since interleukin (IL)-1beta and IL-6 are closely involved in pathophysiological aspects of various neuropsychiatric diseases, effects of intracerebroventricularly (i.c.v.) administered IL-1beta and IL-6 on the correlation between urinary contents of these two glycoproteins were examined in mice, a species in which alpha1M and UT and also the correlation between the urinary contents thereof are expressed similarly to humans. Indices (volume, contents of creatinine, alpha1M and UT, and alpha1M/UT ratio) in urine collected after i.c.v. administrations of 2 and 20 ng of either IL-1beta or IL-6 were not statistically different from those of the vehicle-treated (control) groups. Neither IL-1beta (2 and 20 ng) nor the lower dose of IL-6 (2 ng) affected the positive correlation between urinary contents of alpha1M and UT. However, a higher dose of IL-6 (20 ng) nullified the positive correlation for 2 days after administration. Recovery to a positive correlation was thereafter displayed. These findings suggest that central IL-6 plays an important role in correlating urinary contents of alpha1M and UT without affecting the renal functions.

Alpha-Globulins↗
PubMed1998

Nullification of a positive correlation between urinary contents of alpha1-microglobulin and ulinastatin with intracerebroventricularly administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridinium (MPP+) in mice.

Striatal dopamine contents in C57BL/6J mice were reduced at 24 h after intracerebroventricular (ICV) administration of 1-methyl-4-phenyl-1,2, 3,6-tetrahydropyridine (MPTP) or 1-methyl-4-phenylpyridinium (MPP+) in a dose-dependent manner. A dose of 1.8 microg MPP+ significantly (P < 0.05) suppressed the dopamine contents, whereas a similar dose of MPTP did not. A definite positive correlation between urinary contents of alpha1-microglobulin (alpha1M) and ulinastatin (UT) existed in normal mice. However, this correlation was nullified by ICV administration of 18 and 36 microg MPTP or 1.8 and 18 microg MPP+. With 1.8 microg MPTP, a positive correlation between urinary contents of alpha1M and UT was displayed. The urine volume, creatinine content, glomerular filtration rate, alpha1M and UT contents, and alpha1M/UT ratio of urine collected for 24 h post-ICV administration of MPTP or MPP+, were not statistically different from those of control mice. Our findings suggest that the central effects of MPP+, a neurotoxic metabolite of MPTP, nullify the positive correlation between urinary contents of alpha1M and UT without affecting renal functions.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1998

Sequences of cDNAs encoding calmodulin, and partial structures of calmodulin kinase, and a calcium channel of kdr-resistant and -susceptible German cockroaches, Blattella germanica.

Complementary DNA sequences of genes encoding calmodulin, partial structures of calmodulin-dependent protein kinase II (CaM-kinase II) and an L-type-like calcium channel al subunit (IVS5-IVS6-EF hand region) were identified and compared between susceptible and kdr strains of German cockroach, Blattella germanica. For this purpose, polymerase chain reactions (PCR) were used to obtain their sequences using cDNA from poly(A) + RNA isolated from their heads and thoraces. No mutation differences were found in all three sequences of calcium-regulating proteins between susceptible and strain. Northern blot analysis, however, showed reduced expressions of CaM-kinase II mRNA in two kdr strains. Western blot analysis with an antibody preparation against CaM-kinase II on protein levels confirmed the above strain difference in the titer of this enzyme. In contrast, the levels of calmodulin as well as that of an L-type-like calcium channel gene expression were not different between susceptible and kdr strains.

Amino Acid Sequence↗
PubMed1997

Nullification of a positive correlation between urinary levels of alpha 1-microglobulin and ulinastatin by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice.

The relationships between urinary levels of alpha 1-microglobulin (alpha 1M) and ulinastatin (UT) were investigated in C57BL/6J mice, a species which reportedly possesses the gene similar to that of humans for synthesizing the precursor protein of alpha 1M and UT. A positive correlation was established in normal mice. However, repetitive administrations (20 mg/kg, IP, four administrations/12 h) of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) nullified the positive correlation. A similar phenomenon was induced by ICV-administered MPTP (18 and 36 micrograms) in the animals. Furthermore, L-dopa administration (50 mg/kg, IV) in MPTP-treated (1 week after the final IP administration of MPTP) mice reversed the tendency of MPTP, although the agent alone did not affect the positive correlation in normal mice. These results suggest that nullification of the positive correlation probably was induced by the central effects of MPTP. We have found previously that the lack of a positive correlation between urinary levels of alpha 1M and UT distinguishes Parkinson's disease from other neuropsychiatric diseases such as dementia (Alzheimer-type and vascular dementia), schizophrenia and mood disorders. Our present results displayed a phenomenon that the lack of correlation between urinary levels of alpha 1M and UT in patients with Parkinson's disease is reproducible in MPTP-treated mice.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1996

Effect of glycated collagen on proliferation of human smooth muscle cells in vitro.

While non-enzymatic glycation of long-lived tissue proteins such as collagen has been implicated in chronic complications of diabetes mellitus, its role in the aetiology of diabetic macroangiopathy has not been elucidated. To test the hypothesis that glycation of collagen abolishes the inhibitory effect of native collagen on the proliferation of human smooth muscle cells, we obtained smooth muscle cells from human gastric arteries and cultured them on dishes coated with glycated or non-glycated collagen. The proliferation of human smooth muscle cells in the presence of 10% fetal calf serum or platelet derived growth factor-BB (10 ng/ml) was inhibited by type 1 collagen coated on the dishes. Glycation of collagen with glucose 6-phosphate for 7 days abolished the growth-inhibitory effect of native collagen. Succinylation of collagen, which like glycation blocked the lysyl residues in collagen, also abolished the growth-inhibitory effect. Adhesion of human smooth muscle cells to collagen-coated dishes was not affected by glycation of collagen. Addition of glycated albumin to the medium did not affect the growth of human smooth muscle cells on plastic dishes. The inhibition of human smooth muscle cell proliferation by collagen was not reversed by the glycation of collagen in the presence of aminoguanidine. Results suggest that early glycation abolishes the inhibitory effect of collagen on human smooth muscle cell proliferation and may thus participate in the progression of macro-angiopathy in diabetes.

Cell Division↗