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Biomedical subjects

T Kuno

Publications and source records attributed to T Kuno.

At least 73 records · Page 4Linked to original sources

Continuous subcutaneous insulin injection for self-care of young patients with insulin-dependent diabetes mellitus.

Continuous subcutaneous insulin injection was used for the self-care of five patients aged 10-18 years with insulin-dependent diabetes mellitus. After an introduction to the concept and procedures for continuous subcutaneous injection, the patients soon became familiar with self-care using an insulin pump at home and at school. Three months later, the control of blood glucose improved with smaller doses of insulin in four cases and milder hypoglycemia was observed compared to when using multiple injections. Significantly decreased variations and lowered means of early morning blood glucose values were observed and seemed to explain the reason for better glycemic control. Buffered regular insulin continuously injected by pumps brought a more stable nocturnal blood glucose level compared to isophane insulin injected at bedtime, the absorption of which seemed to vary considerably. On the contrary, unbuffered regular insulin injected by pumps brought frequent nocturnal hypoglycemia, sudden worsening of glycemic control and skin infections and thus, was deemed inadequate for continuous subcutaneous injection.

Adolescent↗

The fission yeast pmk1+ gene encodes a novel mitogen-activated protein kinase homolog which regulates cell integrity and functions coordinately with the protein kinase C pathway.

We have isolated a gene, pmk1+, a third mitogen-activated protein kinase (MAPK) gene homolog from the fission yeast Schizosaccharomyces pombe. The predicted amino acid sequence shows the most homology (63 to 65% identity) to those of budding yeast Saccharomyces Mpk1 and Candida Mkc1. The Pmk1 protein contains phosphorylated tyrosines, and the level of tyrosine phosphorylation was increased in the dsp1 mutant which lacks an attenuating phosphatase for Pmk1. The level of tyrosine phosphorylation appears constant during hypotonic or heat shock treatment. The cells with pmk1 deleted (delta pmk1) are viable but show various defective phenotypes, including cell wall weakness, abnormal cell shape, a cytokinesis defect, and altered sensitivities to cations, such as hypersensitivity to potassium and resistance to sodium. Consistent with a high degree of conservation of amino acid sequence, multicopy plasmids containing the MPK1 gene rescued the defective phenotypes of the delta pmk1 mutant. The frog MAPK gene also suppressed the pmk1 disruptant. The results of genetic analysis indicated that Pmk1 lies on a novel MAPK pathway which does not overlap functionally with the other two MAPK pathways, the Spk1-dependent mating signal pathway and Sty1/Spc1/Phh1-dependent stress-sensing pathway. In Saccharomyces cerevisiae, Mpk1 is involved in cell wall integrity and functions downstream of the protein kinase C homolog. In contrast, in S. pombe, Pmk1 may not act in a linear manner with respect to fission yeast protein kinase C homologs. Interestingly, however, these two pathways are not independent; instead, they regulate cell integrity in a coordinate manner.

Amino Acid Sequence↗

One case of pemphigus vulgaris observed in the oral cavity.

We report on a case of pemphigus vulgaris with lesions in the oral cavity as well as an outline of differential diagnosis and treatment. Changes in the pemphigus antibodies in blood assisted in judging the therapeutic effects along with the therapeutic course.

Adult↗

Fat-soluble vitamins in cord blood and colostrum in the south of China.

Certain diseases have been associated with micronutrient deficiencies in China, and nutritional assessments have become important means of preventing such diseases. In the present study, fat-soluble vitamins including vitamins A, D, E, K, and beta-carotene in the cord blood and colostrum of Chinese subjects in Guilin, China, were assayed and compared with those of Japanese subjects in Osaka, Japan. These vitamins were analyzed by high-performance liquid chromatography. Vitamin A and E levels in the cord blood and colostrum of the Chinese group showed almost the same values as those of the Japanese group. There was also no significant difference in vitamin D level in cord blood between the two groups, while significantly lower levels of beta-carotene and cryptoxanthin, and a higher level of PIVKA-II (protein induced in vitamin K absence) in cord blood were observed in the Chinese group. These findings pointed to a restricted intake of green-yellow vegetables in the Chinese group and an increased risk of hemorrhagic disease in newborn of that group is suggested.

China↗

Delayed changes in neural visinin-like calcium-binding protein gene expression caused by acute phencyclidine administration.

Phencyclidine (PCP) induces a psychotomimetic state that closely resembles schizophrenia, and PCP-treated animals can serve as a model for schizophrenia. The effects of PCP on the gene expression of NVP-1, a novel Ca(2+)-binding protein, were studied in rats. After 24 hours, the NVP-1 mRNA level in the nucleus accumbens showed a significant decrease of 42%. This result suggests that alterations in Ca(2+)-binding protein may be involved in the pathology of PCP-induced psychosis and, presumably, schizophrenia.

Actins↗

Surgical advancement of the mandible through sagittal ramus osteotomy.

The sagittal split-ramus osteotomy (SSRO) technique has gained widespread acceptance, for it can be easily adapted to correct a wide variety of mandibular abnormalities. However, in spite of its many advantages, numerous investigators have reported postoperative relapse following mandibular advancement surgery. SSRO was performed on four patients with deficiency of mandibular growth which had led to characteristic protrusion of the maxilla. In three of the four cases, postoperative skeletal relapse occurred, which was corrected by postoperative orthodontic treatment.

Adult↗

Isolation and characterization of CAJ1, a novel yeast homolog of dnaJ.

A novel member of the Escherichia coli dnaJ family, designated CAJ1, was isolated from a yeast expression library using antiserum against a yeast calmodulin-binding fraction. Although CAJ1 contains neither a Gly-rich region nor a Cys-rich repeat, as are found in other DnaJ relatives, it contains a leucine zipper-like motif.

Amino Acid Sequence↗

Interaction of tacrolimus(FK506) and its metabolites with FKBP and calcineurin.

Tacrolimus(FK506) is a strong immuno-suppressant and shows its activity through inhibiting IL-2 mRNA transcription by forming pentameric complex with intracellular receptor(FK506 binding protein 12 kDa or FKBP12), Ca2+, calmodulin, and calcineurin. Here, we report the binding activity to FKBP12, the pentameric complex formation and Con-A response inhibiting activities of 7 metabolites. C15-demethylated metabolite(M-3) needed higher quantity to compete in Con-A assay and in pentamer formation assay, although it binds more strongly to FKBP12. The result suggests that the ability to form a pentameric complex is not a two step reaction with the first binding to FKBP12, but a single step reaction by components for the pentamer formation.

Animals↗

Immunological approach to identify calmodulin-stimulated phosphatase isozymes from bovine brain.

Molecular cloning of human, mouse and rat brain CaM-stimulated phosphatase has suggested the existence of two genes for the alpha subunit of the enzymes. A alpha and A beta fragments of A alpha and A beta from rat brain library have been expressed in bacteria to produce specific anti-calcineurin A alpha and anti-calcineurin A beta antibodies (Kuno et al., J Neurochem 58: 1643-1651, 1992). Alternative mRNA splicing gives rise to additional calcineurin isozymes with some containing an insertion sequence of ATVEAIEADE. Antibody against synthetic peptide of this insertion sequence has been raised in this study. Three CaM-stimulated phosphatase isozymes previously purified from bovine brain (BPI, BPII, BPIII) (Yokoyama & Wang, J Biol Chem 266: 14822-14829, 1991), along with the bacterially expressed rat A alpha and A beta fragments, were analyzed by two calcineurin alpha subunit monoclonal antibodies VJ6 and VD3, the rat anti-calcineurin A alpha and anti-calcineurin A beta specific polyclonal antibodies, and the insertion peptide antibody. The bovine brain CaM-stimulated phosphatase isozymes BPI and BPIII reacted with both anti-calcineurin A alpha and anti-calcineurin A beta antibodies. While BPII reacted with anti-calcineurin A alpha but not anti-calcineurin A beta antibody, it differed from the expressed A alpha fragment in immunoreactivity towards the monoclonal antibodies. The results show that the bovine brain CaM-stimulated phosphatase isozymes cannot be simply categorized as derived from A alpha or A beta genes products.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

cDNA cloning of an alternatively spliced isoform of the regulatory subunit of Ca2+/calmodulin-dependent protein phosphatase (calcineurin B alpha 2).

A cDNA encoding the regulatory subunit of Ca2+/calmodulin-dependent protein phosphatase, calcineurin B (CNB), was isolated from a rat testis cDNA library. It differs from the cDNA obtained from a rat brain cDNA library by an addition of 138 base pairs in the coding region. The codon of the clone from a testis library corresponding to the initiation codon of the clone from a brain library is not ATG but AAG, 5'-noncoding regions of these cDNAs are also different. The addition in the coding region results in the gain of 46 amino acids at the N-terminus. These findings suggest that two distinct isoforms of CNB alpha are derived from the same gene through a process involving alternative utilization of two promoters. We designate the brain type isoform as CNB alpha 1 and the longer isoform as CNB alpha 2. Northern blot analysis and reverse transcriptase-polymerase chain reaction (RT-PCR) followed by Southern blot analysis suggest that CNB alpha 2 is specifically expressed in the testis, and its expression is developmentally regulated.

Amino Acid Sequence↗

Calyculin A and okadiac acid inhibit human platelet aggregation by blocking protein phosphatases types 1 and 2A.

Two potent inhibitors of protein phosphatase type 1 (PP1) and type 2A (PP2A), calyculin A (CAL-A) and okadaic acid (OKA), inhibited human platelet aggregation induced by thrombin, collagen and 9,11-epithio-11,12-methano-thromboxane A2 (STA2). IC50 values of CAL-A and OKA for STA2-induced aggregation were 53 nM and 3.5 microM, respectively. These drugs also inhibited thrombin-induced [14C]serotonin secretion of platelets. CAL-A and OKA elicited phosphorylation of certain proteins with an apparent M(r) (x 10(-3) of 200, 60, 50 and 20 light chain of myosin (MLC). Agonist-induced 47,000 M(r) protein phosphorylation was strongly inhibited by these compounds, whereas phosphorylation of 20,000 M(r) MLC was enhanced. The increase in 50,000 M(r) protein phosphorylation by CAL-A and OKA was observed in the presence of agonists, and the 50,000 M(r) phosphorylation may be involved in the inhibition of platelet activation by these compounds. Subcellular analysis of the phosphatase activity in human platelets showed that MLC phosphatase activity was present mainly (approx. 78%) in the cytosolic fraction. Chromatography of human platelet extract on heparin-Sepharose resolved two peaks of MLC phosphatase activity: PP2A in 0.1 M NaCl eluate and PP1 in 0.5 NaCl eluate. PP2A and PP1 isozymes (PP1 alpha, PP1 gamma and PP1 delta) have also been identified in human platelets, by cross-reactivity with polyclonal antibodies against PP2A and PP1 isozymes, respectively. These results suggest that PP1 and/or PP2A may play an important role in the process of platelet activation by regulating levels of phosphorylation of certain proteins.

Blood Platelets↗

A variant form of hypobetalipoproteinaemia associated with ataxia, hearing loss and retinitis pigmentosa.

A six-year-old Japanese boy had ataxia, mental retardation, peripheral neuropathy, proximal myopathy, hearing loss, retinitis pigmentosa and deficiencies in apolipoprotein AI, B, CII and CIII. His clinical features except for hearing loss resembled those of abetalipoproteinaemia or symptomatic hypobetalipoproteinaemia, but his apolipoprotein abnormalities were distinct from these disorders. He had apolipoprotein B-100 with a normal molecular weight. Although most of his neurological manifestations were compatible with those of vitamin E deficiency, their early onset and the presence of hearing loss was unusual for that condition. There has been slight deterioration of ataxia during two years follow-up despite high-dose vitamin E supplementation. Other abnormalities in lipid metabolism might be associated with the neurological damage in this case.

Ataxia↗

Comparison of the functional occlusal plane in adults with class III malocclusion showing open bite and non-open bite.

A retrospective study of lateral cephalograms of 24 Japanese adults with Class III malocclusion was made in order to compare the angles of the horizontal plane between open bite and non-open bite cases. The following results were obtained: i) There was no significant difference in the angle of the NF-upper occlusal plane between the open bite and non-open bite groups. ii) There were significant differences between the two groups in the angle of the SN-upper and lower occlusal planes, the FH-upper and lower occlusal planes and MP-lower occlusal plane. There was also a significant difference between the groups in the distance from the Xi point to the upper occlusal plane. iii) In both the open bite and non-open bite groups there was a wide variation in occlusal plane angles, compared with normal cases.

Adolescent↗

Effects of recombinant human erythropoietin (rHuEPO) on nutritional status of hemodialysis patients: investigation of direct anabolic effects of rHuEPO.

To investigate whether the nutritional improvement achieved by recombinant human erythropoietin (rHuEPO) treatment is the result of anemia correction with rHuEPO or the direct anabolic effects of rHuEPO per se, nutritional assessment was performed in 2 studies (study I and II) on hemodialysis (HD) patients. Nutritional assessment included blood biochemistry determinations, anthropometric measurements, daily protein intake (DPI) and dialysis efficiency. In study I, 5 HD patients who had not been given rHuEPO and had a hematocrit (Hct) of < or = 25%, were administered rHuEPO at the initial dose of 96.2 U/kgBW. Nutritional assessment of these patients was performed before rHuEPO treatment and every 4 weeks until the 24th week after rHuEPO treatment. In study II, the same nutritional assessment as in study I except for DPI, was performed in 2 groups with the same Hct level and dialysis regimen; an EPO group (n = 8) previously given rHuEPO (88.2 +/- 13.7 U/kgBW, 25.8 +/- 2.5 mos) and a non-EPO group (n = 8) not given rHuEPO. In study I, the mean Hct level was significantly increased 4 weeks after rHuEPO treatment (23.3 +/- 0.6 to 26.9 +/- 0.9%). However, the nutritional parameters and dialysis efficiency were nearly constant over 24 weeks, suggesting either the absence of a short-term direct anabolic effect of rHuEPO or masking of such an effect due to general condition improvement by anemia correction with rHuEPO. In study II, no significant differences in nutritional assessment were confirmed between the groups, suggesting that a long-term direct anabolic effect of rHuEPO may not exist and nutritional improvement may result from correction of anemia with rHuEPO.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Detection of HTLV-1 provirus DNA in T-cell neoplasms].

Using polymerase chain reaction (PCR) amplification and Southern hybridization, gag, pol, env and pX region genes of HTLV-1 provirus were detected in T-cell malignancy such as adult T-cell leukemia/lymphoma (ATLL), mycosis fungoides in leukemic phase (MF) and, CD8-leukemia. The gag, pol, and/or env regions, were not amplified in some cases of ATLL, which was considered to be induced by mutation, but not deletion. However, the pX-1 and pX-2 regions could be amplified in all cases examined. As it is suggested that the pX gene plays an important role in leukemogenesis, the mutation may not occur in this region gene. Interestingly, the pX-2 was amplified in the cases with MF and CD8-leukemia as well. The amplified products were hybridized to the HTLV-1 pX sequence, even though the products contained DNA fragments with a size larger than expected as well as those of an expected size. These results indicated the possibility that the virus having sequence identical with HTLV-1 pX is integrated in the tumor cells of MF and CD8 leukemia.

Base Sequence↗

Isolation and characterization of SSE1 and SSE2, new members of the yeast HSP70 multigene family.

Two new members of the Saccharomyces cerevisiae heat-shock protein 70 multigene (HSP70) family were isolated from a yeast expression library using antisera made against a yeast calmodulin-binding fraction. They are designated as SSE1 and SSE2, because their predicted amino acid (aa) sequences are highly homologous to each other (76% identical), and share homology with known members of the yeast HSP70 multigene family, but their homologies (13 to 28% identity) are not high enough to place them in known subfamilies. SSE1 and SSE2 are thought to encode polypeptides of 693 aa with calculated M(r)'s of 77,408 and 77,619, respectively. The SSE1 mRNAs were moderately abundant during steady-state growth at 23 degrees C, and increased a few-fold upon upshift to 37 degrees C. SSE2 mRNAs were present at low level during steady-state growth at 23 degrees C, and greatly increased upon upshift to 37 degrees C. Disruption of SSE1 results in slow-growing cells at any temperature. No phenotypic effects of the mutation in SSE2 were detected, and the growth property of the sse1sse2 double mutant was the same as that of the sse1 single mutant.

Amino Acid Sequence↗