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Biomedical subjects

K Kanegae

Publications and source records attributed to K Kanegae.

At least 19 recordsLinked to original sources

The mature form of adrenomedullin correlates with brain natriuretic peptide in plasma of chronic hemodialysis patients.

AIM: Adrenomedullin (AM), a hypotensive and natriuretic peptide, consists of an amidated mature form (mAM) and an intermediate form in human plasma, of which only mAM exerts biological activity. Like atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), plasma levels of mAM are reported to be significantly elevated in hemodialysis (HD) patients, suggesting that mAM may be stimulated partly by increased body fluid volume in a manner similar to the natriuretic peptides. Here, we examined the relationship between mAM levels and ANP or BNP levels and the effect of HD on plasma mAM in HD patients. PATIENTS AND METHODS: We measured plasma levels of mAM, total AM (tAM), ANP and BNP before and after HD in patients on long-term HD (n = 22, mean age 56.3 +/- 3.2 years) using radioimmunoassay. RESULTS: Baseline mAM (2.7 +/- 0.3 fmol/ml) and tAM (23.6 +/- 2.0 fmol/ml) were significantly higher in HD patients than in healthy subjects (1.1 +/- 0.2 fmol/ml, 9.0 +/- 2.1 fmol/ml, respectively). HD significantly reduced the levels to 1.2 +/- 0.2 fmol/ml and 13.8 +/- 1.4 fmol/ml, respectively, although tAM levels were still elevated compared to healthy subjects. Similar plasma ANP and BNP levels were obtained in HD patients. There were significant correlations between mAM and tAM levels before and after HD and between HD-induced changes in mAM and tAM levels. In the pre-HD state, levels of both mAM and tAM correlated significantly with BNP levels, but the correlation of BNP with mAM was closer than that with tAM. In contrast, no correlations were observed between the 2 forms of AM and ANP. Changes in mAM levels during HD also correlated significantly with BNP but not ANP levels, although the changes in tAM did not correlate with those of the 2 natriuretic peptides. CONCLUSION: Our results suggest that the secretion/metabolism of mAM may be regulated in a manner similar to that of BNP in HD patients.

Adrenomedullin↗

Pressure-induced expression of monocyte chemoattractant protein-1 through activation of MAP kinase.

BACKGROUND: In glomerular hypertension, mesangial cells (MC) are subjected to at least two physical forces: a high pressure and mechanical stretch. In 5/6 nephrectomized rat, a model of progressive glomerular sclerosis associated with glomerular hypertension, monocyte chemoattractant protein-1 (MCP-1) is expressed in glomeruli, suggesting the possible role of MCP-1 in the pathogenesis of glomerular sclerosis; however, whether pressure directly affects MCP-1 expression remains undetermined. Here we examined the effects of pressure on MCP-1 expression in cultured rat MC and the signal transduction pathways that lead to MCP-1 expression. METHODS: Pressure was applied to MC by instilling compressed helium gas into sealed plates. MCP-1 mRNA and protein levels in MC were detected by reverse transcription-polymerase chain reaction (RT-PCR) or Northern blotting and ELISA or Western blotting, respectively. Mitogen-activated protein (MAP) kinase activity was measured with the catalytic activity of p42/p44 MAP kinase and anti-phospho p42/p44 MAP kinase antibody. A transient transfection assay that specifically modulates MAP kinase kinase (MEK) activity was carried out. RESULTS: MCs subjected to external pressure expressed MCP-1 mRNA rapidly and transiently with the peak level noted at 10 minutes and 80 mm Hg pressure. MCP-1 protein levels in cell lysates and culture medium also significantly increased after pressure loading. Pressure rapidly increased the phosphorylation level and activity of p42/p44 MAP kinase. Treatment of MC with a MAP kinase kinase (MEK) inhibitor, PD98059, suppressed levels of both pressure-induced MAP kinase activities and MCP-1 mRNA expression. The constitutively activated type of MEK1 induced MCP-1 expression (13.7-fold) even in non-pressurized MC. CONCLUSIONS: Our results indicate that pressure per se can induce MCP-1 via activation of MAP kinase pathway, suggesting that glomerular hypertension might be involved in the progression of renal diseases through the expression of MCP-1 in MC.

Animals↗

Oral supplementation of branched-chain amino acid improves nutritional status in elderly patients on chronic haemodialysis.

BACKGROUND: Anorexia may be associated with decreased plasma levels of branched-chain amino acids (BCAA). In malnourished elderly haemodialysis (HD) patients, oral BCAA supplementation may improve anorexia, resulting in improved nutritional status. METHODS: Among 44 elderly (age >70 years) patients on chronic HD, 28 patients with low plasma albumin concentration (<3.5 g/dl) were classified as the malnourished group; they also suffered from anorexia. The other 16 patients did not complain of anorexia and were classified as the well-nourished group. We performed a 12-month, placebo-controlled, double-blind study on the malnourished group. Fourteen patients each received daily oral BCAA supplementation (12 g/day) or a placebo in random order in a crossover trial for 6 months. Body fat percentage, lean body mass, plasma albumin concentration, dietary protein and caloric intakes, and plasma amino acid profiles were monitored. RESULTS: Lower plasma levels of BCAA and lower protein and caloric intakes were found in the malnourished group as compared to the well-nourished group. In BCAA-treated malnourished patients, anorexia and poor oral protein and caloric intakes improved within a month concomitant with the improvement in plasma BCAA levels over the values in well-nourished patients. After 6 months of BCAA supplementation, anthropometric indices showed a statistically significant increase and mean plasma albumin concentration increased from 3.31 g/dl to 3.93 g/dl. After exchanging BCAA for a placebo, spontaneous oral food intake decreased, but the favourable nutritional status persisted for the next 6 months. In 14 patients initially treated with a placebo, no significant changes in nutritional parameters were observed during the first 6 months. However, positive results were obtained by BCAA supplementation during the subsequent 6 months, and mean plasma albumin concentration increased from 3.27 g/dl to 3.81 g/dl. CONCLUSIONS: Normalization of low plasma levels of BCAA by oral supplementation can reduce anorexia and significantly improve overall nutritional status in elderly malnourished HD patients.

Administration, Oral↗

Synergistic interaction of integrin and angiotensin II in activation of extracellular signal-regulated kinase pathways in vascular smooth muscle cells.

Integrins, major adhesion receptors and angiotensin II activate extracellular signal-regulated kinase (ERK) pathways and result in a mitogenic response such as the proliferation of vascular smooth muscle cells (VSMCs). We investigated mechanisms of collaboration or synergism between integrins and angiotensin II involving ERK pathways in VSMCs. Integrin activation by cell adhesion to fibronectin increased the phosphorylation level of focal adhesion kinase (FAK) upstream of the ERK pathway. angiotensin II induced a high increase in the phosphorylation level of FAK with integrin activation, but not in suspended cells. Integrin activation increased phosphorylation levels of ERK kinase (MEK) and ERK phosphorylation as well. Angiotensin II-induced MEK and ERK phosphorylation were retained even in suspended cells. Furthermore, with integrin activation, angiotensin II induced a much larger increase in the phosphorylation levels of MEK and ERK. These results suggest that simultaneous stimulation of integrin and angiotensin II receptors cause synergistic interaction in the activation of ERK pathway, possibly via phosphorylation of FAK, which may play a critical role in angiotensin II-mediated mitogenic response in VSMCs.

Angiotensin II↗

FDG uptake and glucose transporter subtype expressions in experimental tumor and inflammation models.

UNLABELLED: Although FDG uptake is closely related to the expression of the glucose transporter (GLUT) in malignant tumors, such a relationship has not been fully investigated in inflammatory lesions. The aim of our study was to determine the expression of GLUT subtypes in experimental inflammatory lesions and to compare the results with those in malignant tumors in relation to FDG accumulation. METHODS: Rats were inoculated with a suspension of Staphylococcus aureus or allogenic hepatoma cells (KDH-8) into the left calf muscle. Five days after S. aureus inoculation (n = 9) and 14 d after KDH-8 inoculation (n = 11), [(14)C]FDG was injected intravenously and its accumulation in the infectious and tumor tissues was determined as the percentage activity of the injected dose per gram of tissue (%ID/g). The expression of glucose transporters (GLUT-1 to GLUT-5) was investigated by immunostaining the infectious tissues (n = 6) and the tumor tissues (n = 6). Immunohistochemical grading was assessed semiquantitatively by 5 observers. RESULTS: The [(14)C]FDG uptake was significantly higher in the tumor lesion than in the inflammatory lesion (2.04 +/- 0.38 %ID/g vs. 0.72 +/- 0.15 %ID/g; P < 0.0001). The tumor and inflammatory tissues highly expressed GLUT-1 and GLUT-3. The GLUT-1 expression level was significantly higher in the tumor tissue than in the inflammatory tissue (P < 0.05). CONCLUSION: The results based on our models showed a high FDG uptake and high GLUT-1 expression level not only in the tumor lesion but also in the inflammatory lesion. The higher GLUT-1 expression level in the tumor lesion may partially explain the higher FDG accumulation in the tumor than in the inflammatory lesion.

Animals↗

The contribution of residual renal function to overall nutritional status in chronic haemodialysis patients.

BACKGROUND: The benefits of residual renal function (RRF) in peritoneal dialysis patients have been described frequently. However, previous reports have shown that RRF diminished faster in haemodialysis (HD) patients than in peritoneal dialysis patients, and in most of the studies in HD patients, RRF was ignored. In this study, the RRF in chronic HD patients was studied to assess its impact on patients' nutritional status. METHODS: In 41 chronic HD patients with at least a 2-year history of HD treatment, RRF was determined by a urine collection for 7 consecutive days. Nutritional parameters, such as percentage body fat, fat-free mass index, serum albumin concentration and normalized protein catabolic rate, were also measured. RESULTS: In all 41 patients, mean weekly total Kt/V urea was 4.88 and renal Kt/V urea was 0.65. RRF was well correlated with serum albumin concentration, but dialysis Kt/V urea was not. One year after the start of this study, RRF and nutritional indices were re-examined and patients were classified into two groups: with RRF, preserved residual renal diuresis over 200 ml/day (mean, 720 ml; range, 230-1640 ml), N=23; and without RRF, persistent anuria (mean, 51 ml; range, 0-190 ml), N=18. At the start of this study, the mean serum albumin concentration and mean normalized protein catabolic rate in patients with RRF were 3.84 g/dl and 1.16 g/kg/day, respectively, which were significantly higher than those in patients without RRF (P=0.02 and P=0.0002, respectively), despite total (renal+dialysis) Kt/V urea being equal in both groups. During the 1-year study period, there was no significant change in total Kt/V urea in either group. Mean serum albumin concentration increased to 4.05 g/dl in patients with RRF, but did not change significantly (from 3.66 to 3.62 g/dl) in patients without RRF. The same trend was observed in all other parameters. CONCLUSION: Over half of our HD patients had sufficient RRF. RRF itself may have a beneficial effect on nutritional parameters, and it is important to determine RRF over time, even in chronic HD patients.

Aged↗

Use of fusion images of I-131 metaiodobenzylguanidine, SPECT, and magnetic resonance studies to identify a malignant pheochromocytoma.

Pheochromocytoma is a chromaffin tumor in which 10% are extra-adrenal and 10% are malignant. I-131 metaiodobenzylguanidine (MIBG) scintigraphy has an important role in the identification of these tumors and investigation of metastatic lesions. The authors describe a 36-year-old woman who underwent resection of a malignant left adrenal pheochromocytoma who was thought to have metastases in the liver and para-aortic lymph nodes. Fusion images of I-131 MIBG SPECT and magnetic resonance studies were obtained to properly identify the metastatic lesions. These fusion images helped greatly in subsequent surgery.

3-Iodobenzylguanidine↗

Relationship among 201T1 uptake, nuclear DNA content and clinical behavior in metastatic thyroid carcinoma.

UNLABELLED: A prospective study of 201TI uptake was performed to compare 201TI uptake with nuclear deoxyribonucleic acid (DNA) content and clinical behavior of tumors in metastatic thyroid carcinoma and to assess the significance of 201TI uptake in evaluating clinical characteristics of thyroid carcinoma. METHODS: Fifty-six patients with metastases of differentiated thyroid carcinoma had 201TI scintigraphy. Grade of 201TI uptake was semiquantitatively assessed according to tumor-to-background ratio on 2-h late scan. Nuclear DNA content was analyzed within 3 wk of 201TI study by flow cytometry using biopsy material and was classified as diploidy or aneuploidy. Patients were followed up to examine incidence of tumor growth and/or anaplastic transformation. RESULTS: DNA content was diploidy in 48 patients and aneuploidy in 8 patients. 201TI uptake in the DNA-aneuploid group (2.61 +/- 0.29) was significantly higher than that in the DNA-diploid group (1.82 +/- 0.35, P < 0.01 for both groups). Tumor growth was observed in all patients with DNA aneuploidy but in only 5 of 48 patients with DNA diploidy (P < 0.01). Anaplastic transformation was observed in 3 patients in the DNA-aneuploid group but in none of the patients in the DNA-diploid group. CONCLUSION: High 201TI uptake indicates greater incidence of abnormal DNA content with aggressive clinical behavior of metastatic tumors. Thus, 201TI scintigraphy may be useful in characterizing metastatic thyroid carcinoma and in identifying those patients with poorer prognoses.

Adenocarcinoma, Follicular↗

Pharmacokinetics of bisoprolol and its effect on dialysis refractory hypertension.

The efficacy, safety, and pharmacokinetics of bisoprolol were investigated following oral administration once daily for 12 weeks in hyperreninemic patients with dialysis-refractory hypertension. Mean blood pressure rapidly fell from 132 to 112 mmHg in the 5.0-mg/day (n = 6) and from 142 to 128 mmHg in the 2.5-mg/day patients (n = 5), which were accompanied by a fall in plasma renin activity. On nondialysis days, Cmax and T1/2 were significantly higher in patients than in healthy control subjects. However, Cmax in the 2.5-mg/day patients was almost equal to that in healthy control subjects receiving 5.0 mg/day of bisoprolol. Plasma bisoprolol was dialyzable. During the course of the study, dialysis hypotension and bradycardia occurred in two patients receiving 5.0 mg/day of bisoprolol. In conclusion, a daily dose of 2.5 mg bisoprolol seems to be an adequate and relatively effective dose in our patients with dialysis-refractory hypertension.

Administration, Oral↗

Accumulation of iodine-131-iodocholesterol in renal cell carcinoma adrenal metastases.

Adrenocortical scintigraphy is a useful technique for differentiating between types of nonhyperfunctioning adrenal masses. Metastatic tumors do not normally accumulate radioiodocholesterol and show discordant uptake on scintigrams. We present two patients who showed accumulation of 131I-6beta-iodomethyl-19-norcholesterol (NP59) in the adrenal metastases from renal cell carcinoma. In one patient with bilateral adrenal metastases, accumulation in the primary tumor as well as adrenal metastases was demonstrated. The adrenal metastases in both patients were resected and were histologically proven to be metastases from clear-cell renal carcinoma. Accumulation of NP59 in metastatic adrenal tumors, although a very rare finding, suggests a pitfall in the differential diagnosis of adrenal cortical tumors.

19-Iodocholesterol↗

Thallium-201 scintigraphy to predict therapeutic outcome of iodine-131 therapy of metastatic thyroid carcinoma.

UNLABELLED: We studied the relationship between 201Tl uptake and the efficacy of radioiodine therapy in thyroid carcinoma. METHODS: Forty-four patients with metastases of well-differentiated thyroid carcinoma received 201Tl scintigraphy within the 2 mo before their initial 131I therapy. Patients were classified into two groups according to the tumor-to-background (T/B) ratio on the late 201Tl scan: high 201Tl uptake (T/B > or = 2.1) and low 201Tl uptake (T/B < 2.1). The therapeutic outcome was judged by the percent reduction in the tumor diameter at 6 mo after the treatment. The treatment was defined as effective when the tumor showed more than 50% reduction in the tumor diameter. The patients in whom radioiodine was ineffective were followed up to determine if the tumor showed further growth. RESULTS: Of the 44 patients, 25 had high 201Tl uptake and 19 had low 201Tl uptake. The therapy was effective in 15 patients and was ineffective in 29. All the patients in whom radioiodine was effective had low 201Tl uptake. On the other hand, 25 of 29 patients in whom radioiodine was ineffective had high 201Tl uptake. Eight patients, in whom radioiodine was ineffective despite good 131I uptake, had high 201Tl uptake. There were no significant differences in the positive predictive value and the negative predictive value for effective treatment between 201Tl scintigraphy and therapeutic dose 131I scintigraphy. Among the 25 patients in whom radioiodine was ineffective and who had high 201Tl uptake, the tumor diameter increased in 7 (28%). However, none of the tumors with low 201Tl uptake increased in size during the follow-up period. CONCLUSION: Thallium-201 scintigraphy has a high predictive value for the efficacy of radioiodine therapy in metastatic thyroid carcinoma. Thus, it is helpful in determining the indication for radioiodine therapy and it seems to be an adjunct to tracer dose 131I scintigraphy.

Adenocarcinoma, Follicular↗

[Comparison of single sample methods for determination of plasma clearance using 99mTc-MAG3].

We compared relationship among three single blood sampling methods which have been proposed for determination of plasma clearance with 99mTc-MAG3. Russell's and Bubeck's algorithms were employed for 48 adults (average age: 53 years) and Bubeck's and Piepsz's algorithms were used in 9 children (average age: 5.8 years). Three methods showed very high correlation among them. However, Russell's and Piepsz's methods were about 1.4 times higher than Bubeck's method in calculating plasma clearance of 99mTc-MAG3. The present study indicates that three methods discussed here are useful for the determination of plasma clearance with 99mTc-MAG3. In addition, Bubeck's method may be preferable as a reference for single plasma sampling method because of common application to adults and children.

Adolescent↗

Thallium-201 single photon emission computed tomography as an indicator of prognosis for patients with lung carcinoma.

BACKGROUND: The uptake of thallium-201 (T1-201) in malignant tumors is associated with malignant potential (metastatic potential and proliferative activity). The grade of accumulation of T1-201 in malignant tumors may provide information regarding prognosis. METHODS: A T1-201 single photon emission computed tomography was conducted 120 minutes after intravenous injection of 111 megabecquerel of T1-201 chloride. The authors calculated the uptake ratio to evaluate the degree of T1-201 uptake in the primary tumor. This ratio was compared with survival time and other prognostic factors. RESULTS: The authors studied 152 patients (125 men and 27 women). The group of patients with the low T1-201 uptake ratio survived longer than the group of patients with the high T1-201 uptake ratio (median survival, 58 weeks vs. 33 weeks; P = 0.0138 by the log rank test). The multivariate analysis confirmed that the T1-201 uptake ratio was an independent prognostic factor for survival. CONCLUSIONS: These results suggest that the T1-201 uptake ratio provides independent and objective prognostic information for patients with lung carcinoma.

Adult↗

Sequential change of BMIPP uptake with age in spontaneously hypertensive rat model.

UNLABELLED: Changes in myocardial perfusion and metabolism are often associated with myocardial hypertrophy, but there are few reports describing the serial assessment of fatty acid metabolism in hypertrophic myocardium. The aim of this study is to assess fatty acid metabolism serially in hypertrophic myocardium in spontaneously hypertensive rats (SHR) with 125I-BMIPP, a branched fatty acid analog. METHODS: SHR and Wistar-Kyoto rats (WKY) as the control were divided into 4 groups (12, 15, 18 and 51 weeks after birth). The heart was extracted 10 minutes after intravenous injection of 125I-BMIPP and 201Tl at the same time. The accumulation of each radiotracer in the myocardium was counted with a well gamma counter. In addition, 125I-BMIPP uptake was corrected by 201Tl uptake (B/T). RESULTS: The heart weight/body weight ratio was significantly higher in SHR than that in WKY (p < 0.001). In SHR, this ratio increased up to 18 weeks (12 weeks; 0.266 +/- 0.005, 18 weeks; 0.281 +/- 0.006: mean +/- SE, p < 0.05). The 125I-BMIPP uptake tended to be significantly reduced in SHR (12 weeks; 2.373 +/- 0.212, 18 weeks; 1.380 +/- 0.047; mean +/- SE, p < 0.05). Such a difference in BMIPP uptake was more evident when BMIPP uptake was corrected by Tl uptake (B/T), but no regional difference or heterogeneity of BMIPP distribution was observed in the hypertrophic myocardium in SHR. CONCLUSION: A change in fatty acid metabolism with age was observed in association with myocardial hypetrophy in this hypertensive rat model, which was well demonstrated with 125I-BMIPP and 201Tl.

Aging↗

Incidence and clinical significance of linear defects ascribed to interrenuncular septa on 99Tcm-DMSA SPET.

99Tcm-dimercaptosuccinic acid (99Tcm-DMSA) planar and single photon emission tomographic images from 100 children were reviewed to analyse whether linear defects corresponding to anatomical characteristics of interrenuncular septum (IRS) could be seen. Thirty sites in 30 kidneys (20 right, 10 left) from 27 patients were determined as showing IRS. They were seen less frequently in patients less than 7 years of age. The prevalence of IRS in the patients with vesico-ureteric reflux (VUR) was not significantly different from that in the patients without VUR. The interrenuncular septum was never seen on planar images and was most clearly demonstrated on conventional coronal tomographic images. The linear defects ascribed to IRS on 99Tcm-DMSA scintigrams were of a similar incidence to that reported previously. However, IRS is still an unestablished structure, and there is no evidence that these linear defects actually correspond to the structure described as the interrenuncular septum.

Child↗

Visualization of lung cancer with 99Tcm-tetrofosmin imaging: a comparison with 201T1.

We evaluated the usefulness of 99Tcm-tetrofosmin imaging in lung cancer. The study sample comprised 46 patients with lung cancer. Single photon emission tomography was conducted after the intravenous injection of 740 MBq 99Tcm-tetrofosmin and 111 MBq 201T1-chloride. We obtained an uptake ratio (counts per pixel in the lesion/counts per pixel in contralateral normal lung) for each scan to evaluate the degree of uptake in the tumour. Our results demonstrate that 89.1% of the primary lung cancers were visualized by 99Tcm-tetrofosmin and 95.7% by 201T1. The difference between the 201T1 uptake ratio and the 99Tcm-tetrofosmin uptake ratio was significantly greater in squamous cell carcinomas than small cell carcinomas (P < 0.01) and tended to be greater in squamous cell carcinomas than adenocarcinomas (P = 0.093). This study has indicated that 99Tcm-tetrofosmin, like 201T1, is a highly effective agent in the delineation of lung cancer. The difference between the 99Tcm-tetrofosmin and 201T1 uptake ratios might provide further information regarding the histological type of lung cancer.

Adenocarcinoma↗

Early massive accumulation of In-111 pentetreotide in a metastatic liver tumor of islet cell carcinoma.

A 62-year-old woman was examined with In-111 pentetreotide and Ga-67 citrate. She had undergone an operation to resect a neuroendocrine tumor of the pancreas and still had masses in the liver. One of her hepatic lesions had been biopsied and acinar cell carcinoma was suspected. Fluid in the cyst of the tumor, however, contained a high concentration of gastrin and the tumor was strongly suspected of being a metastasis from the neuroendocrine tumor of the pancreas. The hepatic tumors quickly accumulated In-111 pentetreotide immediately after the injection, but there was no Ga-67 citrate uptake in the tumor. Five months after pentetreotide scintigraphy, her hepatic tumors were resected and histologically proven to be metastasis of islet cell carcinoma. In-111 pentetreotide provides information of the somatostatin-receptor status on the tumor and supports the diagnosis made by hormonal survey.

Biopsy↗