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Biomedical subjects

A Kono

Publications and source records attributed to A Kono.

At least 37 records · Page 2Linked to original sources
PubMed1999

[Three-years changes in disability and mortality associated with daily life patterns among the home frail elderly].

PURPOSE: The purpose of this study was to eximine 3-year changes in disability and mortality in relation to the daily life patterns among the frail elderly living at home. METHODS: Subjects were 50 frail elderly living at home who were interviewed at baseline, in July to September, 1995. By detailed time budgets, five daily life patterns were classified: Lying-rest, Sitting-rest, Hobby, Walking, and Housework. Information on ADL was obtained from visiting nurses or mailed questionnaires in June 1998 (3 years later). RESULTS: Within the 3-year period, 15 people (30%) died. At the follow up, 27 people (54%) were living at home, three (6%) were hospitalized, and four (8%) were institutionalized. In 31 analyzed samples, ADL scores significantly decreased during the 3-year period. As for the ability to perform each activity, it was found that only the elderly in Housework life pattern maintained their ADL. The elderly in Lying-rest life and Sitting-rest life patterns were more likely to die. CONCLUSION: Decline in ADL among home frail elderly was found for the 3 years. It was suggested that community health care for preventing disability progress among home frail elderly were important over a long time. Housework life patterns were seemed to be associated with physical performance.

Activities of Daily Living↗
PubMed1998

A disrupted cholecystokinin A receptor gene induces diabetes in obese rats synergistically with ODB1 gene.

Otsuka Long-Evans Tokushima fatty (OLETF) rats develop hyperglycemia, hyperinsulinemia, and mild obesity, which are characteristic of human non-insulin-dependent diabetes mellitus. We have shown that two recessive genes, ODB1 mapped on the X chromosome and ODB2 mapped on chromosome 14, are involved in the induction of the diabetes in OLETF rats. Recently we found that OLETF rats are the naturally occurring cholecystokinin type A receptor (CCKAR) gene knockout rats. In this study, we focused on the genotype of CCKAR gene and the ODB1 gene in regulation of glucose homeostasis in the F2 cross of the OLETF rats. Relatively high plasma glucose levels were observed in the F2 offspring with the homozygously disrupted CCKAR gene. A synergistic effect for increasing plasma glucose levels in F2 rats between disrupted CCKAR gene and the ODB1 gene was shown. The CCKAR gene was found to map very close to ODB2 by a linkage analysis using microsatellite markers. These results suggest that CCKAR gene maintains normoglycemia in rats.

Animals↗
PubMed1998

Overexpression of cholecystokinin-B/gastrin receptor gene in the stomach of naturally occurring cholecystokinin-A receptor gene knockout rats.

We examined the cholecystokinin (CCK)-B/gastrin receptor, H+/K+-ATPase and somatostatin gene expression, the histology and immunohistochemistry of gastrin and somatostatin of the stomach, plasma gastrin levels, and gastric acid secretion in naturally occurring CCK-A receptor gene knockout (Otsuka Long-Evans Tokushima fatty, OLETF) rats. The CCK-B/ gastrin receptor, H+/K+-ATPase and somatostatin mRNAs were determined by Northern transfer analysis. The gastric acid secretion and the plasma gastrin level were measured in vivo. The levels of CCK-B/gastrin receptor mRNA in the forestomach and the glandular stomach in OLETF rats were 2-fold higher than those of control rats, although those of H+/ K+-ATPase and somatostatin mRNAs were not different. Histological examination revealed thickening of the fundic mucosa, and hyperplasia and hypertrophy of parietal cells, although immunohistochemistry of gastrin and somatostatin revealed no significant difference from the control rats. Gastric acid secretion stimulated by gastrin or histamine was enhanced, whereas the fasting plasma gastrin level was not significantly different from that in control rats. The overexpression of CCK-B/gastrin receptor mRNA and the hyperfunction of parietal cells were observed in rats without CCK-A receptor gene expression.

Animals↗
PubMed1998

Alteration of the CDKN2A gene in pancreatic cancers: Is it a late event in the progression of pancreatic cancer?

Various genetic changes are involved in progression of various cancers. We examined alterations (deletion, sequence abnormalities, methylation) of the CDKN2A gene in cell lines and tumor tissues of pancreatic cancers. Some alterations of this gene were found in all the 12 cell lines examined. In the primary lesions of pancreatic cancers, homozygous or hemizygous deletion were found in 8 of 24 ductal carcinoma and 4 of 9 other types of carcinomas. It appears that there is an association between the alteration of this gene and tumor size, regional lymph node metastasis and hematogenous distant metastasis in the ductal carcinoma, but not in the other types of carcinomas. All the 5 liver metastatic lesions of the ductal carcinoma examined revealed homozygous or hemizygous deletion and 3 bp deletion. These results suggest that inactivation of the CDKN2A gene occurs more frequently in cell lines than in pancreatic cancer tissues. Such genetic events on the CDKN2A gene may play an important role possibly at a later step in the progression of pancreatic ductal carcinoma.

Adult↗
PubMed1998

Effect of retinoic acid on morphological changes of human pancreatic cancer cells on collagen gels: a possible association with the metastatic potentials.

Pancreatic carcinoma is an invasive and metastasizing type of malignancy. We established six pancreatic cancer cell lines from human pancreatic carcinomas, three highly metastatic lines (KP-1NL, KP-4, and SUIT-2) and three minimally metastatic lines (KP-2, KP-3, and BxPC-3). The three highly metastatic cell lines grew in a fibroblastoid pattern on collagen gels, whereas the three minimally metastatic cell lines grew in an epithelioid pattern under similar conditions. Western blot and Northern blot analyses indicated much higher levels of E-cadherin in the three minimally metastatic cell lines relative to the three highly metastatic cell lines. When the effect of all-trans-retinoic acid on the growth patterns of the three highly metastatic lines was examined, we observed a dramatic change from fibroblastoid to epithelioid growth in SUIT-2 cells. Although all six cell lines had comparable levels of retinoic acid receptor-gamma, retinoic acid receptor-beta was expressed only in SUIT-2 cells. Treating SUIT-2 cells with retinoic acid also induced the upregulation of E-cadherin expression. When SUIT-2 cells were treated with retinoic acid receptor-specific agonists, 13-cis-retinoic acid and Am555S, a morphological change from fibroblastoid to epithelioid growth was induced. Retinoic acid receptor-specific antagonists, LE135 and LE540, inhibited retinoic acid-induced change of the growth patterns. The effect of retinoic acid and its derivatives on the growth pattern was discussed in a possible association with their antimetastatic activities of pancreatic cancer.

Cadherins↗
PubMed1998

[Daily life patterns associated with 18-months changes of disability among frail elderly living at home].

The purpose of this study was to investigate daily life patterns associated with changes of disability over 18-months among frail elderly living at home. Subjects were 50 frail elderly living at home who were interviewed at baseline, in July-September 1995. By detailed time budgets among them, five life patterns were classified. Lying-rest life pattern, Sitting-rest life pattern, Hobby life pattern, Walking life pattern, and Houseworking life pattern. Activities of daily living (ADL) measured by Extended ADL Index consisted of 8 items of Barthel Index and 4 items of TMIG Index of Competence. Information for follow-up were obtained from home health nurses or mail-questionnaires February-March in 1997. The results were as follows: All samples were able to be followed. Seven people died within the 18 months follow-up. Overall change of score on ADL was not seen between baseline and follow-up study. ADL improvement was seen in 45.0% and 43.7% had declines. Daily life patterns were not correlated with changes in ADL score. However, analysis of decline in ability to perform each activities, relative associations (not statistically significant) were found for changes in function and daily life patterns. Lying-rest life pattern and Sitting-rest life pattern elderly were more likely to decline in ADL than Walking life pattern and HouseworKing life pattern elderly. Hobby life pattern elderly only declined in walking. These findings support previous studies showing that disability of home frail elderly could be improved. Daily life pattern among them would be a helpful predictor of changes in specific physical performance over years.

Activities of Daily Living↗
PubMed1997

Disrupted cholecystokinin type-A receptor (CCKAR) gene in OLETF rats.

OLETF rats develop hyperglycemia, hyperinsulinemia and mild obesity, which is characteristic of human non-insulin-dependent diabetes mellitus (NIDDM). We cloned and sequenced the cholecystokinin type-A receptor (CCKAR) gene in the rats. Comparing the DNA sequences of the OLETF CCKAR gene and LETO CCKAR gene, normal gene, we found a deletion in the OLETF gene, 6847 bases in length, which was flanked by two 3-base-pair direct repeats (5'-TGT-3') at positions -2407/-2405 and 4441/4443, numbered according to the LETO gene sequence, one of which was lost. The promoter region, the first and second exons were missing in the mutant. The region upstream and downstream of the deletion, including exons 3, 4 and 5, was conserved between the two strains, and did not contain any base changes. We found that the gene mapped to chromosome 14 in rats. OLETF rats are the naturally occurring knockout animals with the homozygously disrupted CCKAR gene.

Animals↗
PubMed1997

Decreased level of light-induced Fos expression in the suprachiasmatic nucleus of diabetic rats.

We assessed light-induced Fos-immunoreactive cells in the suprachiasmatic nucleus of diabetic rats. The number of Fos-immunoreactive cells significantly decreased in diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats as compared with control Long-Evans Tokushima Otsuka (LETO) rats. In contrast there was no decrease in the number of Fos-immunoreactive cells in young OLETF rats which have not yet developed diabetes. Two months after the administration of streptozotocin (STZ) to Wistar rats, the number of Fos-immunoreactive cells significantly decreased, although 1 week after the administration of STZ, the number had not yet changed in these STZ-induced diabetic rats. These results suggest that chronic diabetic (hyperglycemic) conditions may affect the light entraining responses in the suprachiasmatic nucleus (SCN).

Animals↗
PubMed1997

Mouse cholecystokinin type-A receptor gene and its structural analysis.

The mouse cholecystokinin type-A receptor (CCK(A)R) gene was cloned and sequenced, and the exon/intron boundaries were determined by cDNA cloning. The gene, approximately 10 kb in length, contains the entire coding region, and consists of five exons. The deduced amino acid sequence was homologous with that of other species, with the exception of an additional DNA sequence encoding 7 amino acids in exon 5. A region of the 5' end of exon 2 appeared to be alternatively spliced, and generated an isoform shorter by 52 bases. The shorter isoform may encode an 48 amino acid open reading frame due to frameshift of translation. These two mRNA isoforms were expressed equally in the mouse gallbladders.

Alternative Splicing↗
PubMed1997

Apoptosis in the pancreas of genetically diabetic rats with a disrupted cholecystokinin (CCK-A) receptor gene.

In a previous study, we reported that the pancreatic wet weight in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, cholecystokinin-A (CCK-A) receptor-defective because of a congenital gene abnormality, was significantly lower than in control rats (Long-Evans Tokushima Otsuka; LETO) from 3 weeks of age. In this study we examined apoptosis of pancreatic acinar cells in OLETF rats at 5 to 6 weeks of age in comparison with that in LETO rats. We present here direct morphologic evidence of apoptosis in OLETF rats, using a 3'-OH nick end-labeling method for detecting cells with DNA strand breaks and electron microscopy. Nick end-labeling revealed a small number of positively labeled acinar cells in OLETF rats. On electron microscopic examination, small numbers of apoptotic cells were seen in the lobules in OLETF rats but not in LETO rats. These results suggest that apoptosis plays an important role in the destruction of acinar cells of OLETF rats and induces atrophy of the pancreas.

Animals↗
PubMed1997

Antitumor effect of DX-8951, a novel camptothecin analog, on human pancreatic tumor cells and their CPT-11-resistant variants cultured in vitro and xenografted into nude mice.

DX-8951 is a novel water-soluble derivative of camptothecin. We evaluated the effects of DX-8951 on the growth of several pancreatic tumor cell lines in vitro and in vivo. In vitro cytotoxic activity of DX-8951 against SUIT-2 and KP-1N cells, as indicated by IC50 value, was several times more potent than that of SN-38, an active metabolite of CPT-11, and dozens of times more potent than that of SK&F104864 (topotecan). DX-8951 also showed the greatest cytotoxicity against CPT-11-resistant variants, SUIT-2/CPT-11 and KP-1N/CPT-11 cells, and the cross-resistance of these cells to DX-8951 was lower than that to SN-38 and SK&F104864. Topoisomerase I inhibitory activity of DX-8951 was about three-fold stronger than that of SN-38, as measured in crude nuclear extract obtained from SUIT-2 cells. DX-8951 induced DNA fragmentation, a specific feature of apoptosis, in SUIT-2 cells more effectively than SN-38. DX-8951 exhibited potent antitumor effects against SUIT-2 in a solid tumor model and in a liver metastasis model, in which tumor cells were xenografted subcutaneously and intrasplenically, respectively, into nude mice. The in vivo effects were closely similar to or somewhat superior to those of CPT-11. DX-8951 also showed significant antitumor effects against SUIT-2/CPT-11 solid tumors, against which CPT-11 had no effect. These results suggest that, on the basis of its strong antitumor activity and effectiveness against CPT-11-resistant tumors, DX-8951 may be a useful therapeutic agent in the treatment of human cancer. The potent cytotoxicity of DX-8951 may result from strong inhibition of topoisomerase I, which may then trigger apoptotic cell death.

Animals↗
PubMed1997

Nucleotide and amino acid sequence variations in the L1 open reading frame of human papillomavirus type 6.

Human papillomavirus (HPV) type 6 induces benign tumors such as condyloma acuminata and laryngeal papilloma. The HPV-6 DNA has been thought to be a heterogeneous group of subtypes and variant-types. To examine sequence variations of the HPV-6 L1 ORF, we analyzed by single-strand conformation polymorphism (SSCP) and by DNA sequencing 21 specimens from condyloma acuminata and laryngeal papilloma that harbor HPV-6 DNA. PCR products of HPV-6 DNA were digested with 6 restriction enzymes yielding 8 fragments, which were then analyzed by SSCP. The resolution patterns showed that the L1 coding sequences were separated into three SSCP groups, I, II, and III, and two minor groups, (I) and (III). By sequencing the five representatives of each SSCP group and by comparing these sequences with those of HPV-6a [Hofmann et al., 1995] and HPV-6b [Schwarz et al., 1983], we identified base substitutions at 20 positions in the L1 coding region and an amino acid substitution in one case.

Adolescent↗
PubMed1996

An experimental model of bone metastasis by human lung cancer cells: the role of parathyroid hormone-related protein in bone metastasis.

In the formation of bone metastasis, osteoclastic bone resorption is necessary before the expansion of tumor cells from bone marrow to bone, and several cytokines, which possess osteoclast-stimulating activity, could be involved in this step. In this paper, we describe a bone metastasis model in nude mice using human lung squamous cell carcinoma-derived cells (HARA), in which the parathyroid hormone-related protein (PTHrP) gene, one of the most potent osteoclast-activating factors, is strongly expressed. The injection of HARA cells (1 x 10(5)) into the left cardiac ventricle resulted in tumor colonies exclusively in the skeletal system at 4 and/or 8 weeks after inoculation. An anti-PTHrP antibody injected via a tail vein reduced the incidence of bone metastases, number of tumor colonies, and tumor volume after the inoculation of HARA cells. The injection of another line of human lung squamous cell carcinoma-derived cells (QG-56), in which the PTHrP gene is not expressed, resulted in no bone metastasis. These findings suggest that PTHrP plays an important role in the formation of bone metastasis.

Animals↗
PubMed1996

Isolation of DNA sequences amplified at chromosome 19q13.1-q13.2 including the AKT2 locus in human pancreatic cancer.

In the human pancreatic cancer cell line PANC1, we detected several DNA fragments with abnormally intensified signals by restriction landmark genomic scanning. Major five of these fragments were cloned. All of the cloned fragments were mapped at the 19q13.1-13.2 region where the AKT2 oncogene was located. Southern blotting using the cloned DNA fragments and a fragment of AKT2 cDNA as probes revealed that the AKT2 gene was amplified in 3 of 12 pancreatic cancer cell lines analyzed including PANC1 and in 3 of 20 primary pancreatic cancers. The AKT2 gene was overexpressed in the 3 cell lines with the amplified gene. The results suggest that the AKT2 gene is a candidate oncogene activated by amplification in some human pancreatic cancers.

Base Sequence↗
PubMed1996

Improved tumor detection by anti-CEA chimeric Fab oligomers with disulfide linkages in a pancreatic-carcinoma-xenograft model.

We have investigated the effect of Fab oligomerization on imaging efficacy in a pancreatic-carcinoma xenograft model in mice. Recombinant mouse/human chimeric Fab of the anticarcinoembryonic antigen (CEA) monoclonal antibody A10, which has been shown to react specifically with gastrointestinal cancers, was used in this study. Fab homo-oligomers (dimers and trimers) were prepared by linkage of chimeric Fab with N-succinimidyl-3-(2-pyridyldithio)-propionate. Oligomers with S-S bonds showed 10-fold higher binding activity against human CEA than Fab, while the binding activity of oligomers was similar to that of F(ab')2. In mice bearing pancreatic-carcinoma xenografts, tumor uptake of S-S oligomers was significantly greater than that of monomeric Fab, while there was no difference in tumor uptake between S-S Fab trimers and F(ab')2. S-S oligomers showed more rapid clearance rates and uniform percolation in the tumor nodules than F(ab')2. At 18 hr after injection, clear scintigraphic detection of the pancreatic-carcinoma tumors was obtained with 123I-labeled S-S Fab dimers. At 24hr, improved tumor imaging was shown for 123I-labeled S-S Fab oligomers with slightly visible uptake in normal tissues, similar to that of F(ab')2. S-S oligomers of chimeric A10 Fab may be useful as rapid diagnostic tools of pancreatic carcinomas.

Animals↗
PubMed1996

Pancreatic endocrine dysfunction in rats not expressing the cholecystokinin-A receptor.

Cholecystokinin (CCK) has been suggested to modulate insulin output. We have shown that Otsuka Long-Evans Tokushima Fatty (OLETF) rats show little or no expression of the CCK-A receptor gene in the pancreas. We examined whether the CCK-A and CCK-B receptor genes are expressed in the islets and the role of CCK-A receptor in insulin secretion. Gene expressions of CCK receptors were determined by the reverse-transcriptase polymerase chain reaction (RT-PCR) followed by Southern blot hybridization and Northern transfer analysis using LETO rats as controls. Pancreatic endocrine function was examined in perfusion (exogenous CCK stimulation) and meal ingestion (endogenous CCK stimulation) studies. CCK-A receptor mRNA was detected in the islets of LETO rats but not OLETF rats. Expression of the CCK-B receptor gene was detected in both strains by RT-PCR. Insulin secretion was impaired in OLETF rats, but the insulin contents of OLETF and LETO rats were not different. No abnormalities were detected histologically in either strain. These results suggest that the occurrence of pancreatic endocrine dysfunction in OLETF rats may be due to a defect in expression of the CCK-A receptor gene, not to insulin deficiency.

Animals↗
PubMed1996

Clinical implications of renal cyst in primary aldosteronism.

The present study surveyed 69 patients with aldosteronoma to study the clinical implications of renal cysts demonstrated in computed tomography. Patients who had cysts (n = 16, 23.2%) were older and had a longer duration of hypertension and more severe hypokalemia than those without cysts (n = 53). Patients with cysts therefore had longer-term, more severe hypokalemia than those without cysts. Endogeneous creatinine clearance (Ccr), measured in 61 patients, was significantly lower in patients with cysts (58.4 +/- 7.1 ml/min, n = 16) than in those without cysts (77.3 +/- 7.1 ml/min, n = 45, P = 0.0039). This significant difference was observed even after adjusting for covariables (age, duration of hypertension, and serum potassium) between the two groups by analysis of covariance (ANCOVA). No significant difference was observed in gender, blood pressure, serum creatinine, plasma aldosterone, or PRA. Age, serum potassium levels, and systolic and diastolic blood pressure were the significant determinants in predicting Ccr in a backward stepwise multiple regression analysis (r = 0.505, n = 61, P = 0.0025). Cysts were graded into four classes on the basis of number and size. Cyst grading correlated negatively with Ccr at a Spearman rank correlation (rho = -0.33, n = 61, P = 0.0103). The incidence of chronic renal failure was significantly higher in patients with cysts (18.8%) than in patients without (0%) in a Fischer's exact probability test (P = 0.0107). Thus, both renal cysts and dysfunction arose and/or developed from common roots, i.e., the duration and severity of hypokalemia, in primary aldosteronism. In addition, we surveyed 27 patients with pheochromocytoma. Patients with renal cysts (n = 8) had a significantly longer duration of hypertension than those without cysts. No significant difference was observed in Ccr between patients with and those without cysts. Thus, a significant link between renal cysts and Ccr was a specific feature of primary aldosteronism, but not of pheochromocytoma. In summary, the renal cysts in primary aldosteronism should be recognized as a significant complication representing the extent of renal injury and dysfunction.

Adolescent↗