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Biomedical subjects

K Ikekubo

Publications and source records attributed to K Ikekubo.

At least 37 records · Page 2Linked to original sources

[Detection of neural crest tumors by 123I-MIBG scintigraphy].

From January 1993 to January 1994, scintigraphy with 123I-MIBG and/or 131I-MIBG were performed in 22 patients and their scintigraphic usefulness was evaluated. Iodine-123 MIBG and 131I-MIBG scintigrams were obtained 24 hours after injection of 222 MBq of 123I-MIBG and 48 hours after injection of 20 MBq of 131I-MIBG, respectively. In two patients with pheochromocytoma, the 123I-MIBG and 131I-MIBG scans were performed and both images were compared. In a patient with single intraadrenal pheochromocytoma, the lesion not detected with 131I-MIBG was clearly visualized with 123I-MIBG. In the other patient with multiple metastatic pheochromocytoma, much more lesions were distinctly demonstrated on the 123I-MIBG images than on the 131I-MIBG images. All of the lesions were detected with 123I-MIBG in a patient with pheochromocytoma, 3 patients with neuroblastoma and a patient with medullary thyroid cancer. Most of the normal adrenal glands (86%) were visualized on the 123I-MIBG scintigrams, in 7 patients without neural crest tumor and adrenal diseases, while 131I-MIBG scintigraphy failed to visualize normal adrenal glands in 2 hypertensive patients. The main reason for the superiority of 123I-MIBG to 131I-MIBG is considered to be as follows: 1) higher specific activity of 123I-MIBG. 2) the larger amount of 123I-MIBG used. 3) gamma ray energy of 123I is ideal for gamma camera. In conclusion, 123I-MIBG appears to be a more suitable imaging agent than 131I-MIBG in depicting neural crest tumors.

3-Iodobenzylguanidine↗

[Phase 3 clinical study of 99mTc-MAG3 injectable, a dynamic renal imaging agent--comparison with 123I-OIH and 99mTc-DTPA].

A Phase 3 clinical study of 99mTc-mercaptoacetyl glycylglycylglycine (99mTc-MAG3) injectable was performed in 506 patients with renal and/or urinary disorders. The scintigraphic findings and renogram patterns of 99mTc-MAG3 were similar to those of 123I-OIH, and Tmax and T1/2 of the 99mTc-MAG3 renogram correlated with those of 123I-OIH (r = 0.62 and r = 0.74, respectively). The clinical efficacy of 99mTc-MAG3, evaluated by the investigators in the same patients, was superior to the efficacy of 123I-OIH and 99mTc-DTPA in 93 of 150 patients (62.0%) and 68 of 151 patients (45%), respectively. The image quality and the reliability of the scintigraphic findings with 99mTc-MAG3 were superior to those with 123I-OIH and 99mTc-DTPA, which reflect the more abundant photons of 99mTc-MAG3 than those of 123I-OIH and higher renal extraction of 99mTc-MAG3 than those of 99mTc-DTPA, respectively. Neither adverse reactions nor abnormal laboratory findings due to 99mTc-MAG3 administration were observed. These results suggest that 99mTc-MAG3 injectable is safe and a useful radiopharmaceutical for diagnosis of renal and urinary disorders.

Adult↗

[Measurement of serum free thyroxine concentrations using anti-T4 monoclonal antibody].

A new one-step radiolabeled antibody radioassay for measuring free T4 (FT4) in serum (Amerlex-MAB FT4) was evaluated in comparison with an analog tracer RIA of FT4 (Amerlex-M FT4). In this new method, 125I-labeled anti-T4 monoclonal antibody which has cross-reactivity with T3 is used as a tracer. When incubated with serum sample, the tracer binds to FT4 and the remaining tracer binds to a T3 coated particle (Amerlex MAB). The radioactivity bound to Amerlex MAB is measured. Counts of 125I bound to the T3 coated particle were inversely proportional to sample FT4 concentrations. The assay procedure is as follows. Fifty microliter of patient's serum or standard FT4, 500 microliters of Amerlex MAB and tracer is incubated at 37 degrees C for 30 minutes and centrifuged. Then the radioactivity of Amerlex MAB is measured using an autowell gamma counter. The intra-and interassay coefficients of variation were 1.6-2.7% and 2.6-8.0%, respectively. Although Amerlex-M FT4 values were significantly increased by adding human albumin to the serum, Amerlex-MAB FT4 values were not effected by the change of albumin concentrations. In nonthyroidal illness patients, Amerlex-MAB FT4 values were not affected by the concentrations of albumin, TBG and NEFA. The euthyroid central 95% reference range for FT4 determined by Amerlex-MAB FT4 was 0.99 to 1.54 ng/dl. The FT4 levels correlated well with the metabolic status. Although Amerlex-M FT4 values were spuriously increased in patients with anti-T4 autoantibodies, Amerlex-MAB FT4 values were not affected by the autoantibodies. Amerlex-MAB FT4 values of normal pregnant women were slightly lower in the second and third trimesters than in the first trimester. These lower FT4 concentrations in late pregnancy were considered likely not to be artefact by low serum albumin or high serum TBG but to be a physiological event. Amerlex-MAB FT4 values correlated well with FT4 indices and inversely correlated with TSH levels. A significant correlation (n = 401, r = 0.86, p = 0.0001) was observed between Amerlex-MAB FT4 and Amerlex-M FT4 values in various thyroid conditions without antithyroid autoantibodies. In summary, this new assay for FT4 is simple, rapid and reproducible. The measurement is useful for the evaluation of physiological thyroid function and helpful in the management of patients with thyroid diseases.

Adult↗

Measurement of functioning hepatocyte mass via [99mTc]galactosyl-neoglycoalbumin.

Technetium-99m-galactosyl-neoglycoalbumin (TcNGA) is a synthetic radiolabeled ligand specific for hepatic binding protein (HBP), a receptor that resides exclusively on hepatocytes. In vivo measurement of receptor concentration was obtained via kinetic analysis of liver and blood time-activity data obtained during the hepatic clearance of intravenously administered TcNGA. The purpose of this study was to assess receptor concentration as a measure of the functioning hepatocyte mass. Therefore, TcNGA and dual-injection indocyanine green maximal removal rate (ICG Rmax) studies were performed on nine patients with hepatic cirrhosis associated or not with hepatocellular carcinoma. Receptor concentration was compared with ICG Rmax, which is a validated method for the estimation of the functioning hepatocyte mass. The correlation coefficient was 0.76 (P = 0.017). It is concluded that HBP concentration ([HPB]o) as measured by functional imaging is a measure of functioning hepatocyte mass. This implies that measurement of an individual's receptor concentration by using nuclear medicine techniques provides an objective index of hepatic functional mass and supports attempts to rigorously evaluate [HBP]o for its clinical efficacy.

Aged↗

Growth hormone (GH) secretion from human lymphocytes is up-regulated by GH, but not affected by insulin-like growth factor-I.

Regulation of GH secretion from phytohemagglutinin (PHA)-stimulated lymphocytes was investigated in six normal subjects. Peripheral blood mononuclear cells were incubated with PHA (10 micrograms/mL) in the presence of various amounts of recombinant human GH (0-100 ng/L) and/or recombinant human insulin-like growth factor-I (0-1000 micrograms/L), and the secreted GH was measured by a highly sensitive enzyme immunoassay. PHA-stimulated lymphocytes secreted immunoreactive GH in all subjects (13.6 +/- 2.4 ng/L). Exogenous GH up-regulated the GH secretion in a dose-dependent manner, while IGF-I did not affect either basal GH secretion or the up-regulation by exogenous GH. These findings suggest a difference in the regulation of GH secretion between endocrine and immune systems.

Adult↗

A case of late-onset congenital adrenal hyperplasia due to partial 3 beta-hydroxysteroid dehydrogenase deficiency.

Late-onset congenital adrenal hyperplasia due to 3 beta-hydroxysteroid dehydrogenase deficiency has been reported with increasing frequency, but only a few adult women have been found to have this disorder in Japan. We report a 26-year-old Japanese hirsute woman with partial 3 beta-hydroxysteroid dehydrogenase deficiency. The diagnosis was based on significantly increased ratios of 17-hydroxypregnenolone to 17-hydroxyprogesterone and of dehydroepiandrosterone to androstenedione after administration of ACTH. Hirsutism improved with the administration of dexamethasone (0.5 mg) every evening. Since routine assay of delta 5-steroid metabolites has become available, the incidence of this disorder will increase. Diagnostic effort should be attempted since the disorder is treatable with low-dose dexamethasone.

3-Hydroxysteroid Dehydrogenases↗

Superior vena cava syndrome due to Graves' disease.

We encountered a patient with Graves' disease showing superior vena cava (SVC) syndrome. The patient was a 72-year-old woman with diffuse nontoxic goiter (diagnosed as chronic thyroiditis); she developed Graves' disease during L-T4 administration. Radioiodine-131 therapy failed to give sufficient effect, and the intrathoracic goiter became enlarged in association with increases in thyroid stimulating antibody activities, followed by the development of SVC syndrome. The surgically excised thyroid gland was diffuse without any nodules. Microscopic findings revealed adenomatous hyperplasia. The present case, though extremely rare, seems important for the understanding of the mechanism of onset of SVC syndrome in relation to thyroid gland enlargement.

Aged↗

[A phase 2 clinical study of 99mTc-MAG3 injectable a dynamic renal imaging agent--evaluation of its safety, effectiveness and optimal dose].

A phase 2 clinical study of 99mTc-mercapto acetyl glycylglycylglycine (99mTc-MAG3) injectable, a new dynamic renal imaging agent, was performed in 110 patients with renal and/or urinary disorders to evaluate the safety, efficacy and optimal dose of this agent. Neither adverse reactions nor abnormal laboratory findings due to intravenous administration of 99mTc-MAG3 were observed. The investigators evaluated the clinical efficacy of 99mTc-MAG3 was to be effective in 96 of 97 cases. Among the doses of 92.5 MBq, 185 MBq, 370 MBq and 555 MBq, the dose of 92.5 MBq was not large enough to provide adequate-quality blood flow images or reliable information for evaluation of the renal blood flow. It was concluded that the optimal dose range of 99mTc-MAG3 was 185-555 MBq with 370 MBq as the standard dose. Also, we surmise that 555 MBq is especially recommendable when detailed blood flow information is required. These results indicate that 99mTc-MAG3 injectable is useful for the diagnosis of renal and urinary disorders.

Adolescent↗

[The phase I study of 99mTc-MAG3 injection, a dynamic renal imaging agent--evaluation of its safety and biodistribution in normal volunteers].

The phase I study of 99mTc-mercaptoacetylglycylglycylglycine (99mTc-MAG3) injection, which was developed as a radiopharmaceutical for dynamic renal scintigraphy, was performed in three normal volunteers. After intravenous administration of 370 MBq of 99mTc-MAG3 injection, its safety and biodistribution were evaluated. Neither adverse reaction nor abnormal clinical laboratory findings due to 99mTc-MAG3 administration were recognized. Immediately after injection, 99mTc-MAG3 was rapidly accumulated to the kidney and excreted to urine. The liver, gallbladder and intestine were visualized in the whole body images, but each of the percent injected dose in these organs was less than 2%. Excellent renal scintigrams and renograms with high kidney-to-background ratios were obtained. The estimated absorption doses from 99mTc-MAG3 injection were lower than those from 123I-ortho iodo hippurate (123I-OIH) and 99mTc-diethylene triamine penta-acetic acid (99mTc-DTPA). The results suggest that 99mTc-MAG3 injection is useful to evaluate renal functions because of the pharmacokinetic property suitable for renal dynamic scintigraphy.

Adult↗

Quantitative assessment of hepatocellular function through in vivo radioreceptor imaging with technetium 99m galactosyl human serum albumin.

Technetium 99m diethylenetriaminepentaacetic acid-galactosyl human serum albumin is a newly developed analog ligand to asialoglycoprotein receptor, which is a hepatic cell surface receptor specific for galactose-terminated glycoproteins. Hepatic functional imaging, which yields estimates of asialoglycoprotein receptor concentration, was performed after intravenous injection of 3 mg technetium 99m diethylenetriaminepentaacetic acid-galactosyl human serum albumin. A total of 75 human subjects were studied: 6 controls without liver diseases, 51 patients with chronic liver diseases and 18 patients with acute liver diseases. In chronic liver disease the asialoglycoprotein receptor concentration significantly correlated with the clinical severity based on the criteria of the Liver Cancer Study Group of Japan (rs = -0.890, p = 0.0001). Good correlations between the asialoglycoprotein receptor concentration and conventional liver function tests were also observed. In acute liver disease the asialoglycoprotein receptor concentration correlated well with the normotest (r = 0.796, p = 0.0001), prothrombin time (r = 0.701, p = 0.0002) and total serum bilirubin (r = -0.642, p = 0.0007). We conclude that the parameter, asialoglycoprotein receptor concentration, obtained from the kinetic analysis of technetium 99m diethylenetriaminepentaacetic acid-galactosyl human serum albumin time-activity data, is a sensitive measure of functioning hepatocyte mass in acute and chronic liver disease.

Acute Disease↗

Serum growth hormone-binding protein, insulin-like growth factor-I, and growth hormone in patients with liver cirrhosis.

We determined serum growth hormone-binding protein (GHBP), insulin-like growth factor-I (IGF-I), and growth hormone (GH) levels in patients with cirrhosis and in age-matched control subjects, and investigated their relationships. Serum GHBP levels in cirrhotic patients (14.6% +/- 3.9%) (means +/- SD) were significantly lower than those in normal subjects (20.4% +/- 4.7%). GHBP levels had positive correlations with cholinesterase (r = .58, P less than .001) and Normotest (r = .66, P less than .001), both of which represent liver function in cirrhotic patients. Basal GH levels in cirrhotic patients (range, 0.35 to 13.0 micrograms/L; median, 3.9 micrograms/L) were significantly higher than those in normal subjects (0.015 to 6.0 micrograms/L; 0.19 microgram/L). GHBP levels in cirrhotic patients correlated positively with IGF-I levels (r = .39, P less than .01), and negatively with GH levels (r = -.33, P less than .01). These results may indicate that the serum GHBP level reflects the number of hepatic GH receptors, and that the high basal GH level observed in cirrhotic patients is, at least in part, attributable to decreased clearance of GH by these receptors.

Bilirubin↗

Growth hormone binding protein in Werner's syndrome.

OBJECTIVE: GH and growth hormone binding protein in Werner's syndrome were investigated to elucidate their relation to the short stature. DESIGN: The levels of GH binding protein and GH response to insulin-induced hypoglycaemia were determined. GH binding protein levels and its Scatchard analysis in Werner's syndrome were compared with those in normal subjects. PATIENTS: Three patients with Werner's syndrome (one man aged 45 years and two women aged 39 and 38 years) and 41 normal subjects (18 men and 23 women aged 39.3 +/- 5.5 years, mean +/- SD) were studied. MEASUREMENTS: GH binding protein levels were determined using an Ultrogel AcA44 minicolumn and GH levels were measured by a highly sensitive enzyme immunoassay. RESULTS: Two out of three patients with Werner's syndrome had GH binding protein levels above the mean +/- 2SD value in normal subjects. GH secretion was impaired in Werner's syndrome as judged by the low GH response to insulin-induced hypoglycaemia. CONCLUSIONS: Elevated GH binding protein levels may lead to an increase in the bound form of GH, which is probably less bioactive, resulting in growth failure in association with the impaired GH secretion in Werner's syndrome.

Adult↗

Autoantibody to human prolactin in patients with idiopathic hyperprolactinemia.

We have demonstrated the presence of anti-PRL autoantibody in 5 patients with idiopathic hyperprolactinemia. The clinical features were suggestive of a weak biological activity of PRL, such as regular menses and no galactorrhea. Total PRL levels were markedly elevated (685 +/- 386 micrograms/L) (mean +/- SD) and the proportion of the bound form was 90.7 +/- 7.1%. Scatchard analysis revealed a low-affinity, high-capacity antibody: the association constant was 0.73 +/- 0.56 x 10(7) mol-1 and the maximal binding capacity was 2139 +/- 1792 micrograms/L. Gel filtration study showed that a substantial amount of PRL (64.6 +/- 19.5%) was eluted at the position of 150,000-170,000 mol wt PRL (big-big PRL). Immunoprecipitation study using the chain-specific antibodies showed that the anti-PRL autoantibody belonged to kappa-type immunoglobulin G. These results may indicate that there exists autoantibody-related hyperprolactinemia, especially in those with particularly high serum PRL levels, who had previously been diagnosed as "idiopathic" hyperprolactinemia.

Adult↗

A normal ovulatory woman with hyperprolactinemia: presence of anti-prolactin autoantibody and the regulation of prolactin secretion.

We present the case of a normal ovulatory woman with marked hyperprolactinemia and no evidence of a pituitary adenoma on CT and MRI. Gel filtration studies showed that most immunoreactive PRL was eluted as 150K-170K macroprolactin. Anti-PRL autoantibody was detected and Scatchard analysis revealed a low-affinity (the association constant: 1.29 x 10(7) l/mol), high-capacity (the maximal binding capacity: 1174 micrograms/l) antibody. Dopamine had little suppressive effect on PRL levels and an antidopaminergic agent elicited an augmented response of PRL secretion. These results suggest that the presence of anti-PRL autoantibody may delay the clearance of PRL and/or may alter the central regulation of PRL secretion.

Adult↗

Hypokalemic paralysis associated with distal renal tubular acidosis.

A 68-year-old man had hydronephrosis due to ureteral stones for two months earlier and then increasing muscle weakness developed. A 30-year-old woman had rapidly progressive quadriparesis. In both cases, severe hypokalemia with metabolic acidosis was observed and the diagnosis of distal renal tubular acidosis was made. The former was considered to be an idiopathic incomplete form and the latter was a secondary complete form associated with Sjögren syndrome. Hypokalemic paralysis may occur as a complication of distal renal tubular acidosis.

Acidosis, Renal Tubular↗

[Metabolite of 15-p-iodophenyl-3(R,S)-pentadecanoic acid (123I) in blood and urine].

We analyzed metabolites of 123I-BMIPP in blood and urine using rats, rabbits and human, while human samples were obtained from normal volunteers of Phase I clinical study. We estimated metabolic pathway of 123I-BMIPP as a myocardial metabolic imaging agent. Radioactivity accumulated in heart after administration gradually decreased and was mainly excreted to bladder via kidneys. The main radioactive component in blood was 123I-PIPA for any species and the urinary components were metabolic conjugates of 123I-PIPA. As results of these studies, we considered that 123I-BMIPP was metabolized to 123I-PIPA by alpha-oxidation process for the first step, follow by beta-oxidation process, then 123I-PIPA was released to blood from tissues. Moreover, 123I-PIPA in blood was conjugated with other compounds and excreted to the bladder.

Animals↗

[Clinical utility of receptor imaging in the assessment of liver function].

Technetium-99m diethylene triamine pentaacetic acid-galactosyl human serum albumin (TcGSA) is a newly developed receptor-binding radiopharmaceutical, specific for the asialoglycoprotein receptor, which resides exclusively on the plasma membrane of hepatocytes. Clinical utility of TcGSA was evaluated in 3 control subjects with normal livers and in 54 patients with various liver diseases. The parameter, Receptor Index, was derived from liver and heart time-activity data and is the ratio of radioactivity of the liver over the radioactivity of the liver plus heart at 15 min after the intravenous injection of 3 mg of TcGSA. Receptor concentration ([R]o) was obtained by kinetic analysis of liver and heart time-activity data using pharmacokinetic nonlinear modeling. Values for the Receptor Index and [R]o was statistically different in the control subjects and in patients with mild, moderate, and severe liver diseases. Good correlations were obtained between the Receptor Index, [R]o and conventional liver function tests, such as Child-Turcotte criteria score, prothrombin time, and indocyanine green test. Receptor Index and [R]o were properly estimated even in patients with obstructive jaundice or remarkable portocaval shunt. These data suggest that the receptor imaging as well as its parameters, Receptor Index and [R]o, is a potentially practical and reliable diagnostic method for estimating the functioning hepatocyte mass and for assessing liver function.

Adult↗

Regional metabolic abnormality in relation to perfusion and wall motion in patients with myocardial infarction: assessment with emission tomography using an iodinated branched fatty acid analog.

The clinical usefulness of single-photon tomography using both a beta-methyl-branched fatty acid analog, 123I-15-(p-iodophenyl)-3-methyl pentadecanoic acid (BMIPP) and 201TI was assessed in 4 normal subjects and 28 patients with myocardial infarction. A homogeneous distribution of the tracer in the left ventricular myocardium was observed in each normal subject. BMIPP uptake was decreased compared to 201TI (discordant) in 17/28 patients (61%) and in 49/196 myocardial segments (25%). Such discordant BMIPP uptake was observed more often in areas of acute myocardial infarction (59% at less than or equal to 4 wk versus 31% at greater than 4 wk after onset) (p less than 0.01) and areas supplied with revascularized arteries (74% for revascularized versus 28% for nonrevascularized areas) (p less than 0.01). In addition, the discordant BMIPP uptake was seen more often in the segments exhibiting a wall motion score lower than the perfusion score (46%) in comparison to segments showing a similar decrease in both the wall motion and perfusion scores (12%) (p less than 0.01). Thus, BMIPP imaging may play a major role in increasing our understanding of the relationship between perfusion and wall motion, particularly in patients with acute myocardial infarction and those who received revascularization therapy.

Fatty Acids↗