Biomedical subjects
K Kamiya
Publications and source records attributed to K Kamiya.
[A case of recurrent breast cancer successfully treated with docetaxel].
A 53-year-old female underwent mastectomy for left breast cancer in April, 1993. She was given oral tamoxifen but this had to be discontinued due to its side effects. In March, 1998, she developed bone and lung metastases, in spite of treatment with combination chemotherapy (CEF). We thus treated here with docetaxel 90 mg three times and 40 mg six times. After the chemotherapy, she achieved complete remissions of the lung metastases and a decrease in serum CEA, CA 15-3, NCC-ST439, and BCA225. Adverse reactions to docetaxel were grade 2 alopecia, grade 4 neutropenia, dysgeusia, and fluid retention. All were tolerable. This new agent may play an important future role in chemotherapy for recurrent breast cancer.
Primary aortoduodenal fistula treated successfully with surgery in a patient with Takayasu's arteritis.
Takayasu's arteritis was originally described as a systemic inflammatory arterial disease presenting with occlusive changes. However, it has also been known to cause aneurysm formation. In this report, a patient with Takayasu's arteritis was found to have an aortoduodenal fistula. An emergency operation was carried out with resection of the saccular aneurysm and the fistula. The aorta was reconstructed with a prosthetic graft and the duodenum repaired. A pedicled omental flap was placed between the aorta and the duodenum. The postoperative recovery was uneventful, there was no evidence of persistent bleeding, and the patient was well at the 3-year follow-up. This is the first case in the English language literature of a primary aortoduodenal fistula treated successfully with surgery in a patient with Takayasu's arteritis.
Two hexameric cyanoprotein subunits from an insect, Riptortus clavatus. Sequence, phylogeny and developmental and juvenile hormone regulation.
Hemolymph of a hemipteran insect, Riptortus clavatus, contains four distinct hexameric proteins (cyanoproteins) composed of two distinct subunits, CP alpha and CP beta, which show profiles of abundance depending on developmental stage, diapause status controlled by juvenile hormone, and sex. We have isolated cDNA clones encoding the two subunits and determined the complete sequences. The nucleotide sequences predict polypeptides of 693 and 691 residues for CP alpha and CP beta, respectively, including identical 16-residue signal peptides. The deduced amino acid sequences of both CP alpha and CP beta have significant similarity to other hemocyanin-related proteins, indicating that the cyanoproteins represent hexamerins. Phylogenetic analyses show that the cyanoprotein subunits can be grouped together with other hexamerins from exopterygote insects. Developmental Northern-blot analyses suggest that the expression of the cyanoproteins is regulated at the level of transcript abundance. In addition, the expression of the CP alpha subunit in female adults has been shown to be enhanced by juvenile hormone (JH) while the expression of the CP beta subunit is suppressed by the same hormone. To our knowledge, the CP alpha subunit of R. clavatus is the first case of a JH-enhanceable hexamerin whose sequence has been determined.
Regulation of cardiac Kv1.5 K+ channel expression by cardiac fibroblasts and mechanical load in cultured newborn rat ventricular myocytes.
Of the six voltage-gated K+ channel alpha subunits detected in rat heart, the Kv1.5 channel is abundantly expressed, and its gene transcription and protein expression are reduced during cardiac remodeling. Since cardiac fibroblasts and mechanical load have been known to play important roles in myocardial hypertrophy, we studied the regulation of Kv1.5 K+ channel protein expression by these factors in cultured newborn rat ventricular myocytes, using immunofluorescent cytochemistry and Western blot analysis. Ventricular cells were isolated from 1-day-old Wistar rats and cultured for a period of 5 days. The effect of cardiac fibroblasts was examined by co-culturing myocytes with fibroblasts or incubating pure myocytes in fibroblast-conditioned growth medium (FCGM) for 72 h. In addition, a 48-h cyclic stretch at 0.5 Hz with 20% elongation in length was applied to pure myocyte cultures to mimic mechanical load. With a polyclonal antibody against rat Kv1.5 K+ channel protein, single cultured myocytes showed a weak and uniform antibody labeling. Co-culturing with fibroblasts or incubating pure myocytes in FCGM both induced a significant increase in myocyte size implying cell hypertrophy, but neither allowed normal expression of the Kv1.5 K+ channel as indicated by almost negative anti-Kv1.5 labeling. Western blots of cell proteins prepared from ventricular myocyte cultures revealed a single protein band at 75 kD recognized by the anti-Kv1.5 antibody and a 45% decrease in Kv1.5 immunoreactive protein level in the FCGM-treated preparations. Application of 1 microM losartan, an angiotensin II type I receptor blocker, significantly attenuated the FCGM-induced myocyte hypertrophy and reduction of Kv1.5 K+ channel expression. On the other hand, although no cell hypertrophy was stimulated by mechanical stretch, intense punctate antibody labeling with a 48% increase in Kv1.5 protein level was observed in the stretched myocytes. These results suggest that the protein expression of cardiac Kv1.5 K+ channel is differentially regulated by cardiac fibroblasts and mechanical load. Some soluble factors produced from cardiac fibroblasts contribute to the depressed Kv1.5 K+ channel expression in myocardial hypertrophy. This channel regulation may be mediated by angiotensin II type I receptor.
Cell cycle-related changes in the voltage-gated Ca2+ currents in cultured newborn rat ventricular myocytes.
The expression of T-type Ca2+ current (ICa,T) has been reported to change during postnatal heart development and myocardial hypertrophy, which are characterized respectively by the arrest of the cell cycle soon after birth and a switching on of DNA synthesis in the terminally differentiated cardiac myocytes. The hypothesis that there are cell cycle-related changes in cardiac Ca2+ channel expression was tested by performing whole-cell voltage-clamp recording and BromodeoxyUridine (BrdU) immunolabeling to determine the S phase of the cell cycle in the same single cultured newborn rat ventricular cells. Myocytes were isolated from 1-day-old Wistar rats and cultured for 15 days. ICa,T was detected in 27% of the 5-day cultured myocytes. The progressive loss of ICa,T during the period of 15-day incubation, which resembles the developmental changes in vivo, paralleled the decrease in the percentage of cells showing BrdU labeling. At day 5 of cell culture, the fraction of myocytes expressing ICa,T was significantly higher in the BrdU-labeled population (95%) as compared with the non-labeled cells (19%). In addition, a 72-h treatment with 20 microM nickel, an ICa,T blocker, revealed no effect on the percentage of BrdU-positive cells. L-type Ca2+ current (ICa,L) was constantly expressed throughout the 15-day cell culture. The frequency of ICa,L expression was identical between the BrdU-labeled and the non-labeled myocytes, although the latter cell population demonstrated a relatively greater current density. No differences in the inactivating kinetics of ICa,L and their reaction to beta-adrenoceptor stimulation were observed between the two groups. These findings provide convincing evidence for the cell cycle-related expression of cardiac Ca2+ channel. Cardiomyocytes at the S phase of the cell cycle predominantly express ICa,T, while the major properties of ICa,L' are unchanged during the cell cycle. Such a cell cycle-related channel expression may play a critical role in regulating the cardiac electrophysiological properties during heart development and myocardial remodeling.
Regulation of Kv4.2 and Kv1.4 K+ channel expression by myocardial hypertrophic factors in cultured newborn rat ventricular cells.
Postnatal development and myocardial hypertrophy are associated with alterations in cardiac voltage-gated K+ channels. To investigate mechanisms underlying this K+ channel remodeling, expression of Kv4.2 and Kv1.4 K+ channel alpha-subunits was examined in cultured newborn rat ventricular myocytes by Western blot analysis using polyclonal antibodies against each of the subunits. At day 5 of cell culture, Kv1.4 protein was expressed at higher level than Kv4.2; as the age of culture progressed, Kv1.4 was significantly diminished while Kv4.2 increased with time in culture and became the predominant K+ channel protein. Such K+ channel isoform switch from Kv1.4 to Kv4.2 resembles that of the development in vivo. A 72-h treatment with exogenous triiodothyronine (T3, 0.1 microM) to cultured neonatal myocytes enhanced the expression of Kv4.2 by 73% and decreased the Kv1.4 expression by 22%. The effects of T3 were associated with an increase in the protein-to-DNA ratio indicating myocyte hypertrophy. On the other hand, a 72-h treatment with cardiac non-myocyte cell (NMC)-conditioned growth medium (NCGM) or phenylephrine (20 microM) induced similar cell hypertrophy, but in sharp contrast to T3, both markedly suppressed the Kv4.2 channel protein level. In addition, the trophic and the Kv4.2-downregulating effects of NCGM could be mimicked by exogenous endothelin-1 (0.1 microM), a paracrine factor secreted from cardiac NMCs. Our observations for the first time suggest that cardiac Kv4.2 and Kv1.4 K+ channel alpha-subunits are differentially regulated by a variety of myocardial hypertrophic factors. That T3 accelerated the developmental K+ channel isoform switch from Kv1.4 to Kv4.2 in vitro indicates the critical importance of thyroid hormone in postnatal K+ channel remodeling. Cardiac NMCs and alpha-adrenoceptor activation may contribute to the reduced outward K+ channel density in hypertrophied cardiomyocytes.
Molecular phylogeny of Dipetrocarpaceae in Southeast Asia based on nucleotide sequences of matK, trnL intron, and trnL-trnF intergenic spacer region in chloroplast DNA.
To obtain a refined molecular phylogeny of dipterocarp species in Southeast Asia, nucleotide sequences of matK, the intron of trnL, and intergenic spacer region between trnL and trnF in chloroplast DNA were determined in 16 species throughout 10 genera. In the resultant trees Southeast Asian dipterocarp species were divided into two clusters. One cluster consisted of Anisoptera, Vatica, Cotylelobium, and Upuna, all with the base chromosome number of x = 11. The second cluster consisted of Hopea, Shorea, Neobalanocarpus, Dryobalanops, Parashorea, and Dipterocarpus, mostly with the base chromosome number of x = 7. Dipterocarpus was the only genus that had the base chromosome number x = 11 in the latter cluster. This result suggests that the chromosome number changed from x = 11 to x = 7 after Dipterocarpus branched in the latter cluster. Other evolutionary changes of morphological characters are also discussed.
alpha1-adrenoceptor agonists and IGF-1, myocardial hypertrophic factors, regulate the Kv1.5 K+ channel expression differentially in cultured newborn rat ventricular cells.
Interest has arisen concerning the importance of alpha-adrenergic function and insulin-like growth factor-1 (IGF-1) in cardiac remodelling. The hypothesis that these two factors may underlie the regulation of voltage-gated K+ channel expression in hypertrophied cardiomyocytes was tested by performing Western blot analysis of the Kv1.5 K+ channel alpha-subunit in cultured newborn rat ventricular cells. Myocyte size was quantified by surface area and total cell protein concentration. Cell exposure to the alpha1-adrenoceptor agonist phenylephrine (PE, 20 microM) and IGF-1 (60 ng/ml) for 72 h both induced a significant increase of cell size indicating myocyte hypertrophy, which could be separately blocked by the protein kinase C inhibitor staurosporine (20 nM) and the tyrosine kinase inhibitor genistein (15 microM). Western blots of cell proteins prepared from myocyte cultures showed a single protein band at 75 kD recognized by the anti-Kv1.5 antibody, and demonstrated a 56% reduction in the Kv1. 5 immunoreactive protein level in the PE-treated cell preparations. This suppression was not affected by staurosporine, but was remarkably attenuated by W7 (20 microM), a selective calmodulin antagonist. In contrast to PE, a 48% enhancement of the protein expression of Kv1.5 channel was induced by IGF-1 and this stimulation was specifically blocked by genistein. Our findings suggest that the differential regulation of cardiac Kv1.5 K+ channel expression can be produced by alpha1-adrenoceptor activation and IGF-1 via distinctive signalling pathways. Calmodulin-dependent kinase and tyrosine kinase contribute importantly to the alpha1-adrenoceptor-mediated decrease and the IGF-1-mediated increase in cardiac Kv1.5 K+ channel expression, respectively.
Abdominal aortic aneurysm repair with arterial branch reconstruction: utility of the temporary bypass technique.
Between June 1992 and May 1996, five patients underwent an abdominal aortic aneurysm (AAA) repair with concomitant arterial branch reconstruction. All of the patients were males ranging in age from 55 to 66 years (mean: 61.6 years). The operations were performed for a localized abdominal aortic dissection, a pseudoaneurysm after patch angioplasty of a supraceliac AAA, a pararenal AAA, a total AAA with retrograde descending thoracic aortic dissection, and a supraceliac AAA after an infrarenal AAA repair. All patients underwent bilateral renal artery (RA) reconstruction. Three patients also had a concomitant reconstruction of the superior mesenteric artery ad celiac axis. The renal arteries were preferentially reconstructed. Visceral circulation during aortic cross-clamping was maintained via a temporary bypass circuit. A temporary division of the left renal vein was necessary in two patients. Overall, the mean renal ischemia time was 17.2min (range: 10 to 32 min). There was one perioperative death due to sepsis from a graft infection. Another patient died 6 months postoperatively due to pyothorax. One patient required postoperative hemodialysis for 1 month. Based on the above findings, the temporary bypass technique is thus considered to be useful for maintaining physiologic organ perfusion during aortic clamping without the need to use any complicated devices.
Effects of thyroid status on expression of voltage-gated potassium channels in rat left ventricle.
OBJECTIVE: Thyroid hormone modifies cardiac action potentials and outward potassium currents directly and indirectly e.g. through beta-adrenergic signaling pathway. We thus examined the expression of six voltage-gated potassium channel alpha-subunits in the rat left ventricle under hypo- and hyperthyroid status, and tested roles of beta-adrenergic signaling pathway in their expressions under both status. METHODS: Hypothyroidism and hyperthyroidism were induced by administration of methimazole (MMI) for 4 weeks and by injection of L-thyroxine (T4) to the MMI-treated rats for the last 7 days, respectively. To distinguish the effects of T4 and the beta-adrenergic system, propranolol (Pro) was administered to the MMI-treated rats together with T4, and isoproterenol (Iso) was injected to MMI-treated rats for the last 7 days. The mRNA levels of Kv1.2, Kv1.4, Kv1.5, Kv2.1, Kv4.2 and Kv4.3 in the left ventricles were determined by ribonuclease protection assay. RESULTS: MMI treatment induced hypothyroidism and resulted in a significant decrease in the mRNA levels of Kv1.5, Kv2.1 and Kv4.2 (19%, 77% and 61% of control value, respectively; n = 6, p < 0.05). T4 administration induced hyperthyroidism and cardiac hypertrophy, and it increased the Kv1.5 and Kv2.1 mRNA levels over the control value (212% and 140%, respectively; n = 6, p < 0.05). Kv4.2 mRNA level was restored to the control level by T4. In contrast, the Kv1.2 and Kv1.4 mRNA levels increased in hypothyroid rats (161% and 186% of control value, respectively; n = 6, p < 0.01) and decreased in hyperthyroid rats (14% and 33% of control value, respectively; n = 6, p < 0.01). The Kv4.3 mRNA level was not altered by thyroid status. Pro did not inhibit the T4-induced hypertrophy. Iso induced cardiac hypertrophy. Pro or Iso by itself did not alter Kv mRNA levels except for Kv1.2, the message of which was decreased by Iso. CONCLUSION: Thyroid hormone differentially regulates the expression of Kv1.4, Kv1.5, Kv2.1 and Kv4.2 mRNA levels in the rat left ventricle. This effect is not mediated through beta-adrenergic signaling pathway. On the other hand, the reduction in Kv1.2 mRNA level was associated with cardiac hypertrophy induced by T4 or Iso.
Neurenteric cyst at the craniovertebral junction: report of two cases.
BACKGROUND: Neurenteric cysts are rare endothelium-lined structures. Two patients with symptomatic neurenteric cysts at the craniovertebral junction are presented. CASE PRESENTATION: Intermittent progression of neurologic symptoms delayed diagnosis for both patients. In one case, marked enlargement of the cyst was detected on serial imaging studies, and pathological examination of the excised lesion indicated rupture of the cyst. These cysts were totally resected by transoral or suboccipital approaches, as they were not firmly adherent to surrounding neural structures. The diagnosis of neurenteric cyst was confirmed by immunohistochemical analysis of the cyst wall. CONCLUSION: In view of the clinical course of these patients, we recommend early surgical resection of neurenteric cysts located at the craniovertebral junction.
Nondissection method for tibial bypass surgery using Esmarch's rubber bandage or an automatic sequential pneumatic tourniquet: long-term results.
It is suspected that operative injury to the native arteries during a vascular bypass procedure causes periarterial fibrosis contributing to late graft failure. A a nondissection method for tibial artery bypass has been developed using Esmarch's rubber bandage or an automatic sequential pneumatic tourniquet. This retrospective study examined patency and other late results in distal bypass operations using the nondissection method. Between June 1982 and July 1995, 78 tibial bypasses were performed using reversed autogenous saphenous vein grafts in 70 patients (57 men, 13 women; mean age 57.4 years). Graft patency was assessed angiographically. When a stenotic lesion was recognized, the graft was revised and considered an assisted primary patency. Primary patency rates at 1, 3, 5, and 10 years were 82.8%, 75.3%, 63.4% and 63.4%, respectively, by life-table analysis. Six grafts required revision for stenosis; one involved distal anastomotic stenosis. As a result, assisted primary patency rates resembled secondary patency rates of 87.7%, 84.3%, 80.3%, and 80.3% at the same respective intervals. In conclusion, the nondissection method improved long-term patency by preventing late distal anastomotic stenosis.
p53 gene mutation and loss of heterozygosity of chromosome 11 in methylcholanthrene-induced mouse sarcomas.
Mutations of the p53 tumor suppressor gene are the most prevalent genetic alteration observed in a wide variety of human cancers. In this study we examined 63 methylcholanthrene (MCA)-induced sarcomas from C57BL/6N x C3H/HeN F1 (BCF1) or C3H/HeN x C57BL/6N F1 (CBF1) mice for p53 gene mutations and loss of heterozygosity (LOH) of chromosome 11. Mutation analysis was done on exons 5 to 8 of the p53 gene by polymerase chain reaction-single strand conformation polymorphism analysis. This identified 53 potential mutations in 45 sarcomas. Mutations were further confirmed by direct sequencing of the region. Forty-nine of the 53 cases (94%) were missense mutations, while the rest included two nonsense mutations, one silent mutation and one insertional mutation. Spectra of base substitutions were: 25 cases (47%) of G:C-->T:A transversion, 13 cases (25%) of G:C-->A:T transition (CpG site 15%), 13 cases (24%) of G:C-->C:G transversion, a case (2%) of A:T-->T:A transversion and a case (2%) of insertion. In addition, analysis of 5 polymorphic markers of mouse chromosome 11 revealed LOH in ten cases (22%) among those carrying p53 mutations. In nine of these 10 cases, the loss involved all 5 markers. In addition, the loss was biased toward the C57BL allele (9 cases). The present study establishes the pattern of mutation of the p53 gene in MCA-induced mouse sarcomas.
Quantitative analysis of vascular endothelial growth factor in colon cancer. Clinical and experimental.
Although some studies have shown that overexpression of vascular endothelial growth factor (VEGF) mRNA or protein is correlated with the progression of human malignancies, it is still unknown whether the VEGF level in tumor tissue correlates with tumor growth or metastasis. The present clinical study enrolled 26 patients with colon cancer and revealed that the VEGF level in tumor tissue was significantly higher than in adjacent normal tissue (220.93 +/- 217.64 pg/mg protein in the tumor tissue; n = 26; 38.93 +/- 20.26 in the normal tissue; n = 26) and significantly correlated with tumor size, whereas it did not correlate with other clinicopathological variables. The animal study involved orthotopic transplantation of a human colon cancer strain into nude mice and demonstrated that the VEGF level of transplanted tumor tissue (2,318.5 +/- 1,340.9 pg/mg protein) was significantly correlated with tumor weight (1,856.4 +/- 928.9 mg), but not with the number of the liver metastatic foci. These results indicate that VEGF produced by primary tumors of colon cancers may mainly promote primary tumor growth.
Visual disturbance by lymphocytic hypophysitis in a non-pregnant woman with systemic lupus erythematosus.
The authors present the case of a patient with systemic lupus erythematosus who developed visual disturbance and amenorrhea. Though the clinical and radiological findings resembled those of pituitary adenoma, the patient was finally diagnosed as having lymphocytic hypophysitis after the operation. We briefly describe this relatively rare entity in relation to its autoimmune pathogenesis.
Dynamic structures of granulocyte colony-stimulating factor proteins studied by normal mode analysis: two domain-type motions in low frequency modes.
In this study, granulocyte colony-stimulating factor (GCSF) proteins were chosen as subjects for normal mode analysis. As helical cytokines with a four helix bundled type topology, they were classified into long chain and short chain groups by Sprang and Bazan. Normal mode calculations were also carried out with leukemia inhibitory factor (LIF), interleukin-6 (IL-6), and growth hormone (GH) as members of the long chain group and GCSF and IL-2 and IL-4 as members of the short chain group. For the GCSF families it was found that the fluctuations in the helical region are smaller than in the loop region, and it is clear that on the whole the smaller fluctuation residues belong to a large hydrophobic core region. Thus, it can be imagined how the receptor binding sites approach the receptor within the normal time-scale of pico seconds. In addition, two similar domain-type motions in low frequency modes were found with proteins in the long chain group, although we never observed any sequence similarity in the two separate two-domain regions in each protein of the long chain group. On the other hand, these two domain-type motions were not clear in proteins of the short chain group.
Dipyridamole thallium-201 single-photon emission computed tomography for prediction of perioperative cardiac events in patients with arteriosclerosis obliterans undergoing vascular surgery.
The aim of the study was to determine whether or not dipyridamole thallium-201 single-photon emission computed tomography (201Tl-SPECT) has significant additive value for predicting perioperative cardiac events in patients with arteriosclerosis obliterans (ASO) undergoing vascular surgery. Routine preoperative 201Tl-SPECT was performed in 106 consecutive patients with ASO (age 68+/-8.9 years; 91 men and 15 women). The frequency of reversible defects in a clinical high-risk group (n=44) was significantly higher than in a low-risk group (n=62; 55% vs 24%, p<0.01). Perioperative cardiac events occurred in 9 patients, including 4 cardiac deaths, 1 non-fatal myocardial infarction, and 4 cases of unstable angina. Although clinical risk stratification was useful in predicting cardiac events (19% in the high-risk group vs 2% in the low-risk group, p<0.01), the positive predictive value was low. When considering a combination of 2 or more than 2 risk factors and a large reversible defect as a predictor, the positive predictive value and specificity increased from 19% to 47% and from 64% to 91%, respectively, whereas the sensitivity remained unchanged (89%). These results suggest that the addition of 201Tl-SPECT data to clinical risk-stratified patients with ASO allows better prediction of perioperative cardiac events.