Biomedical subjects

K Ikekubo

Publications and source records attributed to K Ikekubo.

At least 19 recordsLinked to original sources

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

[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↗

PubMed1992

[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↗

PubMed1992

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↗

PubMed1992

[Hepatic receptor imaging with Tc-99m GSA: estimates of liver function in acute liver disease].

Technetium-99m galactosyl human serum albumin (TcGSA) is a synthesized radiolabeled analog ligand to asialoglycoprotein receptor, which resides only at a mammalian hepatocyte. TcGSA studies were performed on 16 patients with various acute liver disease and 3 controls with normal livers. Dynamic data were obtained by a gamma camera during 35 minutes after an intravenous injection of 3 mg (185 MBq) of TcGSA. The parameters of TcGSA time activity curves were obtained by dividing radioactivity of the liver by that of the liver plus heart at 15 min (Receptor Index), and by dividing radioactivity of the liver at 15 min by that at 3 min post injection (Clearance Index). The two parameters correlated well with prothrombin time, clinically estimated staging, and severity of acute liver disease. We have concluded that liver function study by the newly developed receptor imaging with TcGSA can be a sensitive and promising tool in estimating the severity and prognosis of acute liver disease.

Acute Disease↗

PubMed1992

[Phase II clinical study on 99mTc-GSA, a new agent for functional imaging of the liver].

Phase II study of 99mTc-DTPA-galactosyl human serum albumin (99mTc-GSA), a new radiopharmaceutical which binds to the asialoglycoprotein receptors on the hepatocytes, was performed in 81 patients with liver diseases to validate its safety and possibility for the evaluation of hepatic function. None of adverse reactions, abnormal clinical laboratory findings and anti-99mTc-GSA antibody production due to 99mTc-GSA was recognized. Immediately after the injection of 99mTc-GSA, the dynamic data and serial hepatic images were obtained for 60 min. The indices for blood clearance and liver accumulation were calculated based on the counts in the regions of interest on the hearts and livers. In 54 patients with chronic hepatic disorders such as liver cirrhosis, the blood clearance and liver accumulation of 99mTc-GSA were retarded according to the progress of the hepatic disorders. The findings of 99mTc-GSA scintigraphy also reflected the hepatic functions of the patients with large hepatic tumors, obstructive jaundice and acute hepatitis. These results suggest that 99mTc-GSA has the clinical potentials to evaluate the liver functions in the patients with hepatic disorders.

Adult↗

PubMed1992

Receptor index via hepatic asialoglycoprotein receptor imaging: correlation with chronic hepatocellular damage.

Galactosyl human serum albumin is a newly developed receptor-binding agent, specific for the asialoglycoprotein receptor, which resides exclusively on the plasma membrane of mammalian hepatocytes. The receptor-binding agent was synthesized by the covalent coupling of carbohydrate units to human serum albumin. The clinical utility of technetium-99m-labeled galactosyl human serum albumin was evaluated in six control subjects with normal livers and in 50 patients with chronic liver disease. 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 the heart at 15 min after the intravenous injection of 3 mg of labeled ligand. Values for the receptor index in the control subjects and in patients with mild, moderate, and severe liver disease were 0.936 +/- 0.015, 0.909 +/- 0.034, 0.848 +/- 0.070, and 0.669 +/- 0.085, respectively. Good correlations were obtained between the receptor index and conventional liver function tests, such as the Child-Turcotte criteria score (rs = -0.776, p = 0.0001), prothrombin time (r = 0.736, p = 0.0001), and the plasma disappearance rate of indocyanine green (r = 0.805, p = 0.0001). These significantly high correlations of the receptor index with classical indicators of hepatic functional reserve suggest that the receptor index is a potentially practical and reliable diagnostic method for estimating the functioning hepatocyte mass and for assessing liver function.

Adult↗

PubMed1991

[Clinical application of asialoglycoprotein receptor-mediated liver scintigraphy using 99mTc-DTPA-galactosyl-human serum albumin].

Technetium-99m-diethylenetriaminepentaacetic acid-galactosyl-human serum albumin (99mTc-GSA) is a new liver scintigraphy agent which binds to asialoglycoprotein receptors on the hepatocytes. Studies were performed in three normal volunteers and 19 patients with chronic liver diseases. Serial scintigrams and time-activity curves of heart and lever were obtained for 60 min following a single intravenous injection of 99mTc-GSA (1 mg/185 MBq). % Injected dose (%ID) in the blood at 60 min after injection and that in the liver were determined. Excellent hepatic images were obtained for 60 min in normal subjects, and neither blood pool image nor extrahepatic uptake was recognized. In the studies of patients, however, blood pools were also visualized in various degrees suggesting altered receptor quantity, although the livers were visualized clearly. The %ID in the blood at 60 min after the injection showed significant correlations with serum albumin levels (r = -0.741, p less than 0.0001), retention rates of ICG at 15 min (r = 0.855, p less than 0.0001), plasma disappearance rates of ICG (r = -0.760, p less than 0.0005), prothrombin times (r = -0.696, p less than 0.002), hepaplastin tests (r = -0.575, p less than 0.05), total bilirubin levels (r = 0.689, p less than 0.001) and Child Turcotte scores (r = 0.769, p less than 0.0001). Significant differences of %ID in both blood and liver were observed between normal subjects and patients in accordance with severities of the hepatic disorders. These results suggest that 99mTc-GSA liver scintigraphy is useful in evaluating the liver function.

Adult↗

PubMed1991

[A case of pregnancy-induced lymphocytic adenohypophysitis complicated by postpartum painless thyroiditis].

We report a patient with pregnancy-induced lymphocytic adenohypophysitis complicated by postpartum painless thyroiditis. A 27-year-old female noticed visual field defect in the 36th week of pregnancy. After delivery in the 39th week by cesarean section, she was admitted for close examination. Goiter was not palpable, and postpartum galactorrhea was not observed. Routine examination revealed no abnormal findings. On October 8, 1989, magnetic resonance imaging (MRI) revealed a tumor image (height 22.4mm) from the sella turcia to suprasellar cistern with a lower signal intensity than that of the white matter on T1 weighted images and a high signal intensity on T2 weighted images. Gd-DTPA contrast images showed a symmetrical and homogeneous tumor image at the same site. However, the posterior lobe of the pituitary gland appeared normal. These findings suggested lymphocytic adenohypophysitis. The LH was less than 0.3mIU/ml. The FSH (7.8mIU/ml), PRL (12ng/ml), GH (1.6ng/ml) and cortisol (10 micrograms/dl) levels were normal. T4 was 5.3 micrograms/dl, T3 67ng/dl, fT4 0.53ng/dl, which indicated mild hypothyroidism, but the TSH was normal. TRH test showed a slight increase in TSH and no response of PRL. Insulin tolerance test showed delayed response of GH and normal response of cortisol. LHRH test revealed no response of LH and delayed response of FSH. Anti-GH3 cell antibody and anti-thyroglobulin antibody were positive, but the anti-AtT20 cell antibody was negative. Since visual disturbance improved, and slight reduction in the mass (height 20.1mm) was confirmed by MRI after delivery on October 21, her course was observed without treatment. After 1 month, the LH became detectable, but the PRL and cortisol decreased to 2.5ng/ml and 6.0 micrograms/dl, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Functional hepatic imaging with receptor-binding radiopharmaceutical: clinical potential as a measure of functioning hepatocyte mass.

Asialoglycoprotein receptor (ASGP-R) is a hepatic cell surface receptor specific for galactose-terminated glycoproteins. Technetium-99m diethylenetriaminepentaacetic acid-galactosyl human serum albumin (TcGSA) is a newly developed analog ligand to ASGP-R. Fourteen human subjects were studied: three normal volunteers, one with chronic hepatitis, 6 with liver cirrhosis, and 4 with hepatocellular carcinoma associated with liver cirrhosis. The receptor index parameter (LHL15), was obtained from the liver and heart time-activity data as the ratio of radioactivity of the liver over that of the liver plus heart at 15 min after intravenous injection of 1 mg of TcGSA. Means +/- standard deviations of LHL15 in normal volunteers (3 cases), patients with mild (4 cases), moderate (2 cases), and severe liver damage (5 cases) were 0.933 +/- 0.006, 0.789 +/- 0.045, 0.723 +/- 0.033, and 0.488 +/- 0.094, respectively. The difference between the mean values of each group was statistically significant (P less than 0.05). LHL15 correlated well with classical indicators for hepatic functional capacity such as serum albumin level, serum bilirubin level, prothrombin time, ICG R15 or Child-Turcotte criteria score. Our preliminary experiences of high correlations of TcGSA functional imaging data with clinical data suggest that the dynamic data using this receptor-binding radiopharmaceutical provides invaluable information with regard to liver function, and thus, the TcGSA study is potentially a noninvasive practical tool to measure functioning hepatocyte mass.

Asialoglycoprotein Receptor↗

PubMed1991

Effects of sex and age on serum GH binding protein levels in normal adults.

OBJECTIVE: The effects of sex and age on serum growth hormone binding protein (GHBP) levels during adulthood were investigated. DESIGN: The levels of GHBP, insulin-like growth factor-I (IGF-I), and growth hormone (GH) were determined and analysed as a function of sex and age. PATIENTS: We studied 101 normal adults (45 men, aged 20-77 years; 56 women, aged 20-80 years). MEASUREMENTS: GHBP levels were determined using an Ultrogel AcA 44 minicolumn. RESULTS: During the second and third decade, GHBP levels were not different between men (22.8 +/- 1.1%) (mean +/- SE) and women (23.2 +/- 0.8%). After the age of 40 years, however, GHBP levels in men were significantly decreased (19.1 +/- 0.7%), and were lower than those in women (22.7 +/- 0.9%). IGF-I levels correlated positively with GHBP levels in men (r = 0.51, P less than 0.01) but not in women (r = 0.16, NS). CONCLUSIONS: These results indicate that both sex and age may have some effects on the GH-GH receptor-IGF-I axis.

Adult↗

PubMed1991

LH- and FSH-secreting pituitary adenoma in a postmenopausal woman.

Gonadotropin secreting pituitary adenomas have been reported with increasing frequency in men, but they are still rarely recognized in women. We report a 52-year-old postmenopausal woman with LH- and FSH-secreting pituitary adenoma. She had increased LH (37.0 +/- 13.7 IU/l) (mean +/- SD) and FSH (109.9 +/- 26.7 IU/l) but these concentrations were within normal ranges in 80 postmenopausal women (LH: 29.7 +/- 18.3 IU/l, FSH: 104.0 +/- 43.9 IU/l). The administration of GnRH and conjugated estrogen resulted in normal response of LH and FSH. No abnormal response of gonadotropin to TRH and bromocriptine was observed. After transsphenoidal adenomectomy both LH and FSH decreased (LH: 11.1 +/- 4.2 IU/l, FSH: 37.0 +/- 9.6 IU/l). An immunocytochemical study revealed that the adenoma cells synthesize both LH and FSH. The rarity of gonadotropin secreting pituitary adenomas in women could be the result of greater difficulty in recognition due to an increase in serum gonadotropin in postmenopausal women.

Adenoma↗

PubMed1991

[Phase I clinical study on 99mTc-GSA, a new agent for functional imaging of the liver].

Technetium-99m-DTPA-galactosyl human serum albumin (99mTc-GSA) is a new radiopharmaceutical which binds to the asialoglycoprotein receptors located specifically on the hepatocytes. Phase I study of 99mTc-GSA was performed on seven normal volunteers, who were intravenously injected with 185 MBq (5 mCi) and 1-10 mg of 99mTc-GSA. None of adverse reactions, abnormal findings of laboratory test and anti-99mTc-GSA antibody production was recognized. The livers were clearly visualized in all subjects. In the pharmacokinetic analyses on five subjects, 99mTc-GSA was rapidly taken up by the livers immediately after the injection and was slowly excreted through the biliary tracts and the urinary tracts. Dose-dependency which is a specific feature for the receptor-mediated agents was observed; the blood clearances of 99mTc-GSA were prolonged in proportion to the injected ligand doses. These results suggest that 99mTc-GSA may be a potential agent for evaluating hepatic functions based on the hepatic receptor quantities.

Adult↗

PubMed1991

[Value of fatty acid imaging using 123I-beta-methyl iodophenyl pentadecanoic acid (BMIPP) to assess viability of infarcted myocardium].

To evaluate clinical value of a new fatty acid imaging tracer, 123I-beta-methyl iodophenyl pentadecanoic acid (BMIPP), 27 patients with myocardial infarction (MI) underwent BMIPP imaging at rest. The results were compared with those of thallium-201 imaging and contrast ventriculography. Of 100 hypoperfused segments on thallium-201 imaging, 34 segments (34%) showed lower BMIPP uptake than thallium-201, and remaining 66 segments showed similar distribution of those tracers. This discrepancy was more often observed in a patients with acute or subacute stages of MI (less than 4 weeks from onset) than those with chronic stage of MI (greater than 4 weeks) (75% vs. 47%; p less than 0.005). In addition, in the patients with chronic stage of MI, the regional wall motion abnormality was less severe in those showing discrepant BMIPP uptake than those showing concordant distribution (the wall motion score: 1.33 +/- 0.62 vs. 0.63 +/- 0.99; p less than 0.05). Furthermore, redistribution on stress thallium-201 imaging was more often observed in than those showing concordant distribution (12%) than those showing concordant distribution (12%) (p less than 0.005). These preliminary study indicates that discrepant distribution of BMIPP and thallium-201 may be often observed, particularly in recent MI and those showing less wall motion abnormality and redistribution on stress thallium-201 imaging. Thus, the combined study of BMIPP and thallium-201 has a potential for assessing tissue viability in patients with MI.

Adult↗