Chronic graft-versus-host disease and seizure.
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Adult↗
Biomedical subjects
K Kaku
Publications and source records attributed to K Kaku.
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↗
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↗
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↗
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↗
A novel mutation in the ferrochelatase gene associated with erythropoietic protoporphyria.
Erythropoietic protoporphyria (EPP) is a hereditary disorder caused by mutations of the ferrochelatase gene. We investigated a Japanese patient with a dominant form of erythropoietic protoporphyria for a ferrochelatase mutation. Sequence analysis of the proband's ferrochelatase cDNA revealed a T to C point mutation at nucleotide 557. This mutation resulted in the replacement of Ile by Thr at amino acid position 186, a novel mutation in erythropoietic protoporphyria. An increase in ferrochelatase activity was not observed in the crude extract of E. coli over-expressing the mutant protein compared with the control, whereas a marked increase in activity was observed in that over-expressing the wild type. Prediction of the secondary structure of ferrochelatase suggested that the Ile186-->Thr mutation changed the original beta-sheet structure to an alpha helix in the region including amino acid residue of mutation. We conclude that, in the patient, the Ile186-->Thr mutation had abolished enzyme activity, possibly by disrupting the secondary structure, thereby causing erythropoietic protoporphyria.
Adult↗
Myelodysplastic syndrome associated with hypotriploidy.
We describe a case of de novo myelodysplastic syndrome (MDS) with hypotriploidy, a condition in which polypoid chromosome abnormalities are rarely observed. A 64-year-old male was diagnosed with refractory anemia with ring sideroblasts (RARS). Cytogenetic analysis of bone marrow cells revealed 65, X,-Y,+2,+6,-7,+8,-9,-10,+11,-12, add (12) (p11.2), +14,-16,-18,-19,20,-21,-21,+3mar[11/22]/46,XY[11/22]. One month later, rapid transformation to refractory anemia with excess of blasts in transformation was observed in spite of a hematological improvement obtained by therapy with corticosteroids, anabolic steroids and pyridoxine. Two months after the diagnosis of RARS, he died of multiple organ failure. In our case, the hypotriploid chromosome abnormality may have represented a poor prognosis.
Aneuploidy↗
Insulin stimulates protein synthesis of glycogen synthase in rat hepatoma H4 cells associated with acceleration of translation rate.
To assess the regulatory mechanism of insulin action on the biosynthesis of glycogen synthase under long-term control, we investigated post-transcriptional and post-translational regulation by insulin of glycogen synthase in rat hepatoma H4 cells. Glycogen synthase protein gradually increased in response to insulin and peaked at 6 h during a 24-h insulin incubation (185% of the control), corresponding with the second peak of glycogen synthase activation measured by the activity ratio (low glucose 6-P/high glucose 6-P). The effect of insulin on synthesis of glycogen synthase protein was assessed by measuring the incorporation of [35S]-methionine into the enzyme protein during a 6-h insulin incubation. The amount of [35S]-methionine incorporation into glycogen synthase was increased in response to insulin with time, and peaked at 4 h (250% of the control). The degradation of glycogen synthase examined by measuring the rate of reduction of [35S]-methionine for 6 h after the tracer incubation for 12 h was not affected by insulin. The results indicate that (a) insulin induces glycogen synthase activity by accumulating the enzyme protein due to stimulation of protein synthesis rather than inhibition of protein degradation and (b) insulin-reduced stability of glycogen synthase mRNA is caused by acceleration of the translation rate.
Amino Acid Sequence↗
Hereditary deficiency of lactate dehydrogenase H-subunit.
We report herein the fifth family of hereditary deficiency of lactate dehydrogenase (LDH) H-subunit with an autosomal recessive inheritance including two cases of complete deficiency. Their LDH activities were low both in the serum and in the red blood cells (RBC). Electrophoretic analysis revealed that the patients with the complete deficiency had only the LDH5 isozyme. The complete deficiency was associated with marked elevation of fructose-1, 6-diphosphate (FDP) and dihydroxyacetonephosphate (DHAP) and a less marked rise in glyceraldehyde-3-phosphate (GA3P) among glycolytic intermediates in the RBC. Furthermore, hemolysis was observed in the present cases, but this finding was not included in the other reports.
Consanguinity↗
Long-term remission obtained by intensive chemotherapy against a leukemic relapse and subsequent graft-versus-host disease following an allogeneic BMT in a patient with myelodysplastic syndrome.
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Adult↗
Donor leukocyte transfusions and discontinuation of immunosuppressants to achieve an initial remission after allogeneic bone marrow transplantation in a patient with primary refractory acute leukemia.
We present a female patient who received an allogeneic bone marrow transplantation for primary refractory Philadelphia-positive acute biphenotypic leukemia. Since leukemic blasts were persistently present in peripheral blood and bone marrow, in spite of the evidence for engraftment of male donor hematopoiesis, we performed donor leukocyte transfusions and discontinued immunosuppression. An initial complete remission was obtained 15 weeks after allogeneic bone marrow transplantation, and lasted for 24 weeks. We concluded that the prominent mechanism for the eradication of the refractory leukemic clone in the patient was the graft-versus-leukemia effect.
Adult↗
The new oral hypoglycemic agent, CS-045, inhibits the lipid peroxidation of human plasma low density lipoprotein in vitro.
Several lines of evidence have revealed that the oxidative modification of low-density lipoprotein (LDL) is probably associated with the genesis of the atherosclerotic region. CS-045 is a new (thiazolidine) class of oral hypoglycemic agent which has a hindered phenol in the side chain (an analogue of alpha-tocopherol). The present results indicate that CS-045 had a relatively high antioxidative potency in inhibiting the lipid peroxidation of human plasma LDL in vitro induced by 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) compared with that of alpha-tocopherol. These findings suggest that CS-045 may be useful in preventing the progression of atherosclerosis in diabetic patients.
Administration, Oral↗
Characterization of the binding sites for [3H]glibenclamide in rat liver membranes.
The specific binding sites for sulfonylureas in the rat liver membrane fraction were demonstrated and characterized. [3H]Glibenclamide binding to the liver membrane was specific, time- and temperature-dependent, and reversible. Scatchard analysis showed a single class binding site. The dissociation constant (Kd) for glibenclamide was 1.1 microM and the binding capacity (Bmax) was 50 pmol/mg protein. [3H]Glibenclamide binding could be displaced by other sulfonylureas. Half-maximal inhibition of binding (IC50) for glimepiride, gliclazide, acetohexamide, tolbutamide and chlorpropamide was 4.2 microM, 74 microM, 0.33 mM, 0.60 mM, 1.2 mM, respectively. Each value is close to the reported blood concentration when a therapeutic dose of each drug is administered orally. The order of IC50 values is coincident with the order of potency of the clinical hypoglycemic effect of these drugs. We had shown that these concentrations of sulfonylureas stimulate 6-phosphofructo-2-kinase in the liver or hepatocytes and inhibit phosphoenolpyruvate carboxykinase in the hepatoma cells. The specific binding sites demonstrated here may play some roles when sulfonylureas affect carbohydrate metabolism in the liver.
Animals↗
Mitoxantrone and etoposide in breast milk.
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Adult↗
Agranulocytosis induced by macrolide antibiotics.
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Aged↗
HepG2/erythrocyte glucose transporter (GLUT1) gene in NIDDM: a population association study and molecular scanning in Japanese subjects.
To evaluate the role of mutations in the glucose transporter (GLUT1) gene in Japanese patients with non-insulin-dependent diabetes mellitus (NIDDM), we first conducted a population association study using the XbaI polymorphism of the gene. A polymerase chain reaction (PCR)-based assay was developed and used for the analysis. When analysed in 91 diabetic patients and 87 non-diabetic control subjects, the distribution of the genotype frequency was significantly different between the two groups (p = 0.0025). The (-) allele was significantly associated with NIDDM (odds ratio 2.317, 95% confidence interval 1.425-3.768). To identify possible mutation(s) in the GLUT1 gene, which was in linkage disequilibrium with the (-) allele, all ten exons of the gene were analysed by PCR single-strand conformation polymorphism (SSCP) analysis in 53 diabetic patients with at least one (-) allele. Variant SSCP patterns were detected in exons 2, 4, 5, 7, 9 and 10. Sequence analysis revealed that all the variants represented silent mutations. One of the variants in exon 2, GCT (Ala15)-->GCC(Ala), created a HaeIII restriction site. This polymorphism was common in Japanese subjects with heterozygosity of 0.36 and polymorphism information content 0.29. We conclude that the structural mutation of GLUT1 is rare and not likely to be a major genetic determinant of NIDDM in Japanese subjects. The XbaI (-) allele of the GLUT1 gene appeared to be a genetic marker of NIDDM in Japanese subjects. The possibility of the presence of mutation(s) in the regulatory region of the gene or in another locus nearby could not be excluded.
Alleles↗
Extrapancreatic effects of sulfonylurea drugs.
Extrapancreatic action of sulfonylurea (SU) drugs were extensively summarized. Hypoglycemic SU drugs stimulate glycolytic pathway and inhibit gluconeogenic pathway in the liver through regulating key enzymes such as the bifunctional enzyme PFK2/F-2,6-P2ase and PEPCK. It is possible that SUs improve the primary defects in NIDDM through both pancreatic and extrapancreatic actions.
Animals↗