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Biomedical subjects

K Kino

Publications and source records attributed to K Kino.

At least 19 recordsLinked to original sources
PubMed1998

Non-equivalent cooperation between the two nucleotide-binding folds of P-glycoprotein.

To identify the roles of the two nucleotide-binding folds (NBFs) in the function of human P-glycoprotein, a multidrug transporter, we mutated the key lysine residues to methionines and the cysteine residues to alanines in the Walker A (WA) motifs (the core consensus sequence) in the NBFs. We examined the effects of these mutations on N-ethylmaleimide (NEM) and ATP binding, as well as on the vanadate-induced nucleotide trapping with 8-azido-[alpha-32P]ATP. Mutation of the WA lysine or NEM binding cysteine in either of the NBFs blocked vanadate-induced nucleotide trapping of P-glycoprotein. These results suggest that if one NBF is non-functional, there is no ATP hydrolysis even if the other functional NBF contains a bound nucleotide, further indicating the strong cooperation between the two NBFs of P-glycoprotein. However, we found that the effect of NEM modification at one NBF on ATP binding at the other NBF was not equivalent, suggesting a non-equivalency of the role of the two NBFs in P-glycoprotein function.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

T cell epitopes in Japanese cedar (Cryptomeria japonica) pollen allergens: choice of major T cell epitopes in Cry j 1 and Cry j 2 toward design of the peptide-based immunotherapeutics for the management of Japanese cedar pollinosis.

Japanese cedar pollinosis is caused by exposure to Japanese cedar (Cryptomeria japonica) pollen, of which two components, Cry j 1 and Cry j 2, are believed to be the major allergens. T cell lines specific to either Cry j 1 or rCry j 2 were reactive to various portions of each panel of overlapping peptides derived from Cry j 1 or Cry j 2. Two peptides, p211-225 and p108-120, from among six major T cell epitopes identified in Cry j 1 sequence, and three peptides, p182-200, p344-355, and p66-80, from among five in Cry j 2, were chosen to design an artificial polypeptide (named Cry-consensus) based on a difference among the types of the restriction molecules capable of presenting these peptides. After construction of a DNA encoding these peptides in order, Cry-consensus was expressed in Escherichia coli. Five of six T cell epitopes, except for Cry j 2 p344-355, in Cry-consensus were recognized by the T cell clones specific to each peptide. PBMC from allergic patients induced higher proliferation under stimulation from Cry-consensus than individual peptides. Eighty-eight percent of the PBMC (15 of 17) showed proliferation under the Cry-consensus stimulation. Thus, several major T cell epitopes from Cry j 1 and Cry j 2 can be chosen in the design of peptide-based immunotherapeutics for the management of Japanese cedar pollinosis in subjects having various types of HLA class II molecules.

Adult↗
PubMed1998

Extreme right lobar atrophy of the liver: a rare complication of autoimmune hepatitis.

Lobar atrophy is a rare morphologic change of the liver. We describe a 73-year-old woman with mild liver dysfunction and history of Sjögren's syndrome who had right hepatic lobar atrophy. Serum biochemistry levels were as follows: albumin, 4.5 g/dl; total bilirubin, 1.0 mg/dl; alanine aminotransferase, 25 international units/l; aspartate aminotransferase, 27 international units/l; alkaline phosphatase, 333 international units/l; and gamma-glutamyl transpeptidase, 332 international units/l. Serological data were as follows: rheumatoid factor, 27.9; anti-nuclear antibody, 1:640; and antismooth muscle antibody, 1:80. Viral markers for hepatitis B were all negative. Anti-hepatitis C virus (anti-c-100) was negative. Portal hypertension developed thereafter, and the patient died of hepatic failure at age 76. Postmortem examination revealed autoimmune hepatitis with moderate fibrosis, portal vein thrombus, and complete obstruction of the right hepatic duct due to hepatolithiasis. Terminal hepatic failure resulted from combination of decreased hepatic volume due to the right lobar atrophy, exacerbation of autoimmune hepatitis in the remnant left hepatic lobe, decreased portal venous blood flow due to thrombosis, portal hypertension, and cholangitis with hepatolithiasis. This is the first reported case of hepatic lobar atrophy due to autoimmune hepatitis. From a clinical standpoint, patients with hepatic lobar atrophy, even if asymptomatic, should be followed up with careful attention to progression of liver diseases, portal hypertension, and biliary complications.

Aged↗
PubMed1998

[Nerve paralysis after third molar extraction].

This paper described the incidence of inferior alveolar nerve paralysis following surgical removal of impacted third molars. The investigated cases were 789 patients with 1,299 teeth that were surgically extracted. Eight (0.6%) patients had the inferior alveolar nerve paralysis and one (0.08%) had lingual nerve paralysis. As for the patients with inferior alveolar nerve paralysis, the incidence was 0.4% in those aged 20 to 29 years, 0.6% in those aged 30 to 39 years, and 3.5% in those aged over 40 years. This study showed that the incidence of inferior alveolar nerve paralysis occurred more frequently in older age cases and in the cases in which the root splitting or the removing the surrounding bone was needed.

Adult↗
PubMed1997

Alteration of substrate specificity by mutations at the His61 position in predicted transmembrane domain 1 of human MDR1/P-glycoprotein.

In CFTR, a member of the ABC superfamily and a chloride channel, amino acid substitutions in its transmembrane domains 1 and 6 (TM1, TM6) have been reported to modulate the anion selectivity or ion conductance of the ion channel. In P-glycoprotein, no amino acid substitution in TM1, but some in TM6, have been reported to modify the substrate specificity of this protein. In this work, we demonstrated the involvement of His61, which is in the middle of the predicted TM1, in the function of P-glycoprotein. His61 was replaced by all other amino acid residues, and each of the mutant cDNAs was introduced into drug-sensitive human carcinoma cells, KB3-1. The drug-resistance profile of cells stably expressing each mutated P-glycoprotein was investigated by comparing their relative resistance to vinblastine, colchicine, VP16, and adriamycin. The resistance to vinblastine was increased by replacing His61 by amino acids with smaller side chains, while it was lowered by replacing by amino acids with bulkier side chains. The reverse effect was observed for resistance to colchicine and VP16. The resistance to adriamycin was increased by replacing by amino acids with bulkier side chains except Lys or Arg, which have a basic side chain. We also showed that the replacement of His61 by Phe and Lys greatly impaired the efflux of calcein AM, while the replacement had no effect on the efflux of rhodamine 123. These results suggest that an amino acid residue at position 61 in TM1 is important in deciding the substrate specificity of P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Immortalization of mutant p53-transfected human fibroblasts by treatment with either 4-nitroquinoline 1-oxide or X-rays.

The study of in vitro cell transformation is valuable for understanding the multistep carcinogenesis of human cells. The difficulty in inducing neoplastic transformation of human cells by treatment with chemical or physical agents alone is due to the difficulty in immortalizing normal human cells. Thus, the immortalization step is critical for in vitro neoplastic transformation of human cells. We transfected a mutant p53 gene (mp53: codon 273Arg-His) into normal human fibroblasts and obtained two G418-resistant mp53-containing clones. These clones showed an extended life span but ultimately senesced. However, when they were treated with either 4-nitroquinoline 1-oxide or X-rays, they were immortalized. The immortalized cells showed both numerical and structural chromosome abnormalities, but they were not tumorigenic. The expression of mutant but not wild type p53 was detected in the immortalized cells by RT-PCR. Expression of p21, which is located downstream of p53, was remarkably reduced in the immortalized cells, resulting in increased cdk2 and cdc2 kinase activity. However, there was no significant difference between the normal and immortalized human cells in expression of another tumor suppressor gene, p16. These findings indicate that the p53-p21 cascade may play an important role in the immortalization of human cells.

4-Nitroquinoline-1-oxide↗
PubMed1997

Simultaneous multilayer arthrotomography of the temporomandibular joint using photostimulable phosphor computed radiography.

OBJECTIVE: To compare the image quality of photostimulable phosphor computed radiography (CR) with that of a conventional screen-film system for simultaneous multilayer arthrotomography of the temporomandibular joint (TMJ). METHODS: X-ray attenuation, resolution and granularity was compared. Simultaneous multilayer tomography of TMJ was performed using a skull phantom and diagnostic quality of bone structures estimated. The clinical outcome is demonstrated in two typical cases. RESULTS: X-ray attenuation was larger with CR. Granularity was more prominent in edge-enhanced CR images and was associated with inferior diagnostic quality. However, it was improved by using a higher tube voltage. Clinical CR without edge enhancement showed a similar resolution to the conventional system but this decreased with enhancement. In an enhanced arthrotomogram, the boundary between contrast medium, bone and soft tissue were clearly defined and a fibrous adhesion also easily seen. CONCLUSION: Photostimulable phosphor CR is an acceptable alternative for simultaneous multilayer arthrotomography of the TMJ.

Adult↗
PubMed1997

Production of chicken chimeras from injection of frozen-thawed blastodermal cells.

To execute a strategy for reconstituting genetic resources from cryopreserved blastodermal cells, experiments were conducted to optimize conditions for producing chimeric chickens from frozen-thawed blastodermal cells. Stage X blastodermal cells were collected from Barred Plymouth Rock embryos and dispersed. Cells were resuspended in 10% dimethyl sulfoxide in Dulbecco's modified Eagle's medium (DMEM) containing 20% fetal bovine serum, and distributed into plastic ampules. Cell suspensions were seeded to induce ice formation at -7 C, cooled from -7 to -35 C at 1 C/min and then ampules were plunged into liquid nitrogen. Thawing was done by plunging the ampules into warm water (37 C) for 3 min. After centrifugation, the supernatant was replaced with DMEM, and dead or broken cells were removed by density gradient centrifugation. Approximately 500 cells were injected into irradiated Stage X White Leghorn recipient embryos. Following incubation, several somatic chimeras were produced. The frequency of somatic chimerism when fresh (unfrozen) cells, or cells that were frozen and selected by density gradient centrifugation on Percoll or Nycoprep were injected into recipient embryos was 84, 79, and 85%, respectively. The percentage of donor-derived pigmentation in the down of these chimeric chickens was 79, 50, and 58%, respectively. Germline chimerism was determined by mating the chimeras that survived to sexual maturity to Barred Plymouth Rocks. Nine of 16 birds (56.2%) injected with fresh cells, 2 of 26 birds (7.7%) injected with cells that were frozen and selected by density gradient centrifugation on a Percoll gradient, and 3 of 26 birds (11.5%) injected with cells that were frozen and selected on a Nycoprep gradient showed germline transmission; the percentage of donor-derived progeny in these chimeras were 29.5, 5.2, and 6.8%, respectively. The Barred Plymouth Rock donor stock was "reconstituted" by inter se mating of germline male and female chimeras. These data demonstrate that the strategy described here for reconstituting genetic resources from cryopreserved blastodermal cells via chimeric intermediates can be performed successfully.

Animals↗
PubMed1997

Manipulation of blastodermal cells.

Blastodermal cells isolated from newly laid, unincubated eggs are virtually uncommitted cells that exhibit many of the properties of pluripotential stem cells. They can be transferred from donor to recipient embryos and contribute to both somatic tissues and the germline. Blastodermal cells that have been maintained in culture for 7 d express the epitopes ECMA-7 and SSEA-1, which are also expressed by mouse embryonic stem cells. After culture for up to at least 7 d, blastodermal cells retain the ability to differentiate into somatic tissues and the germline both in vivo and in vitro. Proliferation in the absence of differentiation of blastodermal cells is stimulated by the presence of Leukemia Inhibitory Factor (LIF) and other ligands that interact with the gp130 receptor, and differentiation is stimulated by exposure to retinoic acid. Blastodermal cells also possess high levels of telomerase activity, which is shared by immortalized cells and cells within the germline. Blastodermal cells can be transfected and will express foreign genes both in vivo and in vitro. Transfected cells can be isolated by fluorescence activated cell sorting and can be cryopreserved without losing their ability to contribute to either somatic tissues or the germline. These properties of blastodermal cells make them ideal vectors for introducing genetic modifications to the germline.

Alkaline Phosphatase↗
PubMed1997

Hyperproduction of L-threonine by an Escherichia coli mutant with impaired L-threonine uptake.

An efficient production strain for L-threonine fermentation was derived from Escherichia coli by multiple rounds of mutation programs that aimed at deregulation of the L-threonine biosynthetic pathway and blocking of L-threonine degradation pathways. When the optimum amount of DL-methionine was added, this strain KY10935, an L-methionine auxotroph, gave 100 g/liter L-threonine after 77 h cultivation. In this strain, key enzymes in the L-threonine biosynthetic pathway were highly derepressed, but some were inhibited by lower concentrations of L-threonine than the accumulated level. Such incomplete deregulation of the pathway was accounted for by the intracellular concentration of L-threonine being lower than the extracellular level. In an assessment of L-threonine transport in terms of phenotypic growth responses to the amino acid, L-threonine-auxotrophic mutants with a lesion in the L-threonine operon were derived from strain KY10935 by selection for auxotrophy for dipeptide L-alanyl-L-threonine or glycyl-L-threonine, the transport systems of which were different from those of L-threonine. All three independent mutants isolated needed an extraordinarily high concentration (10 mg/ml) of L-threonine, but grew in the presence of a low concentration (10 micrograms/ml) of either dipeptide, indicating that strain KY10935 had impaired L-threonine uptake. These results suggested that the strain had an unusual mechanism of L-threonine hyperproduction: the inability to take up L-threonine that had accumulated extracellularly decreased the steady-state level of intracellular L-threonine, freeing the remaining regulatory steps of feedback inhibition.

Amino Acids↗
PubMed1997

[Malignant tumors in a Japanese geriatric hospital].

We studied the cases of 909 patients with malignant tumors (497 men and 412 women) who were admitted to Tokyo Metropolitan Geriatric Hospital from April 1994 to July 1995. The mean age was 78.6 years (range: 60 to 103 years). The most common tumors were gastric cancer, colo-rectal cancer, and lung cancer. However, the most common tumors in those who died (n = 263) were gastric cancer, lung cancer, and liver cancer. In 425, abnormalities were found during routine health checks or incidental laboratory examinations, while the patients were asymptomatic. On the first admission, 23.4% were found distant metastases. The rate of complications with other diseases was 82.3%. About one third (31.2%) were informed of their situation, and 18.5% had not received any treatment for their malignancies. In 63%, performance status at the time of discharge was the same as that measured on admission or better.

Aged↗
PubMed1997

[Gastric cancer in the elderly--relationship between macroscopic appearance and histological type in autopsy specimens].

OBJECTIVE: We sought to clarify the characteristics of gastric cancer in the elderly. METHODS: We examined 349 specimens of gastric cancers. All specimens were obtained at autopsy from patients who were over 65 years old. We analyzed the relations among five factors: age of the patient, histological type, macroscopic appearance, grade of invasion and location. RESULTS: Older patients were more likely to have papillary adenocarcinoma, tubular adenocarcinoma, and Borrmann-2 and 3 lesions. Papillary and tubular adenocarcinoma together accounted for 14 of 84 Borrmann-4 lesions (16.3%). Borrmann-1 signet-ring-cell carcinomas were observed in two cases. Tubular adenocarcinomas made up 31 in 38 depressed-type early carcinomas (81.6%). Over half of the papillary and tubular adenocarcinomas were confined to the mucosal or submucosal layers, but over 60% of the poorly differentiated adenocarcinomas or signet-ring-cell carcinomas had invaded the extraserosal layer. Papillary and tubular adenocarcinomas were commonly found in the lower part of the stomach, but poorly differentiated adenocarcinomas and signet-ring-cell carcinomas were found in all parts of the stomach. CONCLUSIONS: Unlike specimens obtained during surgery, many of those obtained at autopsy were from older patients, and the gastric cancers were advanced. Compared to many reports about specimens obtained during surgery, tubular or papillary adenocarcinomas are not a few histological type in Borrmann-4 lesions in this study. Surgical specimens of depressed-type early cancer in younger patients are most commonly found to be signet-ring-cell carcinoma, but tubular adenocarcinoma was common in this study. We found many differences between specimens obtained at autopsy and during surgery. These findings indicate that autopsy studies can reveal some otherwise-obscure characteristics of gastric cancer in the elderly.

Adenocarcinoma↗
PubMed1997

[Coronary artery bypass grafting using arterial grafts in a patient with rheumatoid arthritis requiring steroid therapy].

We report a 58-year-old man with rheumatoid arthritis (RA) who underwent successful coronary artery bypass grafting (CABG) for stable angina after myocardial infarction. He had been receiving prednisolone for 9 years. Selective coronary angiography revealed 99% stenosis in the left anterior descending branch (LAD; seg. 6). Before going on cardiopulmonary bypass, the inferior epigastric artery (IEA) was anastomosed to the left internal thoracic artery (LITA) in end-to-side fashion. The LITA was anastomosed to LAD (seg. 7) and the IEA was anastomosed to the first diagonal branch (seg. 9). The postoperative course was uneventful and postoperative angiography showed both grafts were well patent. He is now doing well with no angina attack. The stumps of the LITA and IEA were examined pathologically with the atherosclerotic changes of both grafts relatively mild. We consider the arterial grafts are useful for CABG even in the patient with RA requiring steroid therapy.

Angina Pectoris↗
PubMed1997

[Successful open commissurotomy and resection of dysplastic myxomatous tissue on the leaflet edges in a neonate and an early infant with critical aortic stenosis].

A neonate and an early infant with critical aortic stenosis successfully underwent open commissurotomy and resection of dysplastic myxomatous tissue on the leaflet edges using cardiopulmonary bypass. Case 1: A 31-day-old boy admitted to our unit with shock. Echocardiography demonstrated critical aortic stenosis and severe left ventricular dysfunction (EF = 15%). Case 2: A 12-day-old boy suddenly deteriorated and required resuscitation with ventilation and inotropic support. Emergency operation was required in both cases using cardiopulmonary bypass with systemic hypothermia (30 degrees C). In both cases, the aortic valve was bicuspid and dysplastic with gelatinous myxomatous tissue on the leaflet edges. Commissurotomy and resection of myxomatous tissue were performed. Their postoperation courses were uneventful and they have been free from medication at present. These results suggest that aortic commissurotomy and resection of myxomatous tissue under direct vision may be preferable for critical aortic stenosis with dysplastic aortic valve.

Aortic Valve↗
PubMed1997

[Transverse submammary skin incision for congenital cardiac surgery].

Submammary skin incision has been accepted as cosmetic approach for open heart surgery. During November 1990 to February 1995, 39 ASD patients under 15 years old were operated with either median or submammary skin incision in Okayama University Medical School. For these patients, retrospective study was carried out to determine whether submammary skin incision made surgical procedure complex and whether patients were satisfied with the scar by submammary skin incision. There were 14 submammary skin incision (Group S) and 25 median skin incision (Group M). There was no significant difference in patients profile between the two groups except for sex. Operative time, cardiopulmonary bypass time and aortic cross clamp time had no significant difference between the two groups. Postoperative ICU stay and hospital stay also did not differed between the two groups. Questionnaires for evaluation of the subjective operation scar was sent with 32 answers (82%). There was no significant difference on questionnaire findings. However for the patients without hypertrophic scar, more patients in Group S were significantly satisfied with their scars. Submammary skin incision was safe and easy. It could be alternative of median skin incision. If hypertrophic scar formation could be prevented, more patients would be satisfied with submammary skin incision than median skin incision.

Cardiac Surgical Procedures↗