Biomedical subjects

K Moridera

Publications and source records attributed to K Moridera.

At least 19 recordsLinked to original sources

PubMed2001

[Fundamental study of combination chemotherapy with THP, 5-FU and CDDP for human KB carcinoma cell line and its multidrug resistant cell line KB-C1--usefulness of treatment with 5-FU preceding CDDP].

This study was designed to investigate the usefulness of treatment with 5-FU preceding CDDP in combination chemotherapy with THP, 5-FU and CDDP. Using the human KB carcinoma cell line and its multidrug resistant cell line KB-C1, the difference in the antitumor effect due to the sequence of administration of CDDP and 5-FU (TCF or TFC) was examined on cultured cells and nude mouse tumor xenografts. When KB and KB-C1 were treated with THP (0.01 microgram/ml) on day 1, CDDP (0.05 microgram/ml) on day 2 or day 4 and 5-FU (0.25 microgram/ml) on day 3 and 4 or day 2 and 3, TFC suppressed the cell proliferation more strongly than TCF (p < 0.05), though there was no difference between KB and KB-C1. In nude mouse xenografts, intraperitoneal administrations of THP (0.5 mg/kg) on day 1, CDDP (2 mg/kg) on day 2 or day 5, and 5-FU (10 mg/kg) on day 3-5 or day 2-4 inhibited tumor growth more effectively in KB than in KB-C1. At three weeks postadministration, growth inhibition by TCF and TFC was 29.9% and 57.4% in KB and 25.2% and 49.8% in KB-C1, respectively. These results indicate that TFC was superior to TCF in cytocidal and antitumor effects for KB and KB-C1.

Animals↗

PubMed1998

Thyroxine (T4) metabolism in an athyreotic patient who had taken a large amount of T4 at one time.

As we had an opportunity to take blood samples from a totally thyroidectomized patient who had attempted suicide by taking 2,000 microg of Levothyroxine (L-T4), the serum levels of thyroid hormones were sequentially measured to investigate the metabolism of circulating thyroid hormones in an athyreotic human. The serum concentrations of most thyroid hormones reached a peak on the second day, but the serum T3 level showed a peak one day later. The maximum concentrations of T4 (315 microg/l), FT4 (48.8 ng/l) and rT3 (0.80 microg/l) were very high, while the peak T3 level (1.92 microg/l) did not exceed the upper limit of the normal range. The serum T4 and rT3 levels returned to their normal range 13-17 days after the suicide attempt. The TSH level was suppressed rapidly and reached its nadir (0.044 mU/l) on the 6th day. During this period, the T1/2 and MCR of serum T4 were 10.4 days and 0.64 l/day, respectively, which values were almost equivalent to those observed during 15 days after discontinuation of the maintenance L-T4 therapy. In summary, the oral intake of a large amount of L-T4 at one time does not induce a proportional increase in the T3 level in an athyreotic person. The MCR of serum T4 is decreased and the T1/2 of serum T4 is prolonged, probably due to the lack of intrathyroidal deiodination. These findings support the conclusion that the D1 activity in the thyroid is one of the major determinants in the metabolic clearance of serum T4.

Adult↗

PubMed1996

Long-term clinical course of two cases of lymphocytic adenohypophysitis.

In two patients with lymphocytic adenohypophysitis, images of the pituitary gland were serially observed by MRI. In both cases, the pituitary gland had swollen during the late stage of the first pregnancy. In case 1, MRI findings were representative of lymphocytic adenohypophysitis. After delivery, plasma levels of PRL, ACTH and cortisol decreased markedly. The height of the pituitary gland gradually decreased from 22 mm (14 days after delivery) to 13 mm (73 days) and became rapidly smaller (4.9 mm, 115 days) following administration of massive doses of hydrocortisone for the treatment of acute adrenal insufficiency induced by painless thyroiditis. Six years later, the height was 2.5 mm. Low plasma levels of PRL and cortisol persisted. Diabetes insipidus did not develop. In case 2, MRI revealed a pituitary mass accompanied by a cystic change. Lymphocytic adenohypophysitis was confirmed by histological examination. Because pituitary function tests indicated that ACTH, PRL, GH and TSH were of low levels, hydrocortisone and L-thyroxine were orally administered. No diabetes insipidus was demonstrated. MRI disclosed that the height of the pituitary gland was 23 mm (17 days after delivery) but decreased to 17 and 5.5 mm after 44 and 128 days, respectively. Four years later immediately after the second delivery, it was 1 mm, and the patient was diagnosed as having empty sella. Long-term observation of lymphocytic adenohypophysitis demonstrated that the pituitary gland was markedly atrophied, leading to empty sella. It is believed that some of the classic cases of Sheehan's syndrome associated with empty sella may include lymphocytic adenohypophysitis.

Adrenocorticotropic Hormone↗

PubMed1995

[Three thyroid patients showing fluctuation of thyroid hormone autoantibody titers during long-term treatment].

Development and fluctuation of thyroid hormone autoantibody (THAA) titers were observed during long-term treatment of thyroid diseases in three patients. The presence of THAA was noticed by spuriously high serum free thyroid hormone levels measured with an analog tracer RIA (Amerlex-M FT3, FT4) in all three patients. Amerlex-M FT3 or FT4 levels gradually decreased to appropriate values for the clinical status according to the decreasing titers of THAA. Free thyroid hormone levels with radiolabeled antibody radioassay (Amerlex-MAB FT3, FT4) were not affected by the THAA and always reflected actual thyroid function. Case 1 was a 46-year-old man with untreated primary hypothyroidism. Auti-T4 autoantibody was detected in his serum. The 125I-T4 analog binding to the autoantibody (125I-T4 analog binding ratio) gradually declined after L-T4 therapy and finally almost disappeared two years and four months later. Amerlex-MAB FT4 level rose to the normal range two months after T4 therapy, but TSH level remained slightly elevated (5.4-13 microU/ml) for five months during T4 therapy. The 125I-T4 analog binding ratio and anti-Tg autoantibody (TgAb) titer were inversely correlated. Case 2 was a 72-year-old woman had received desiccated thyroid for a long time. Sequential changes of 125I-T4 analog binding ratio were very similar to those of TgAb titer. Case 3 was a 74-year-old woman with Graves' disease. She had been treated with methimazole (MMI) and desiccated thyroid for three years and five months. Ten months after stopping both drugs, anti-T3 autoantibody was detected. The 125I-T3 analog binding ratio was transiently elevated and gradually declined to reference range for four years during L-T4 therapy. 125I-T3 analog binding ratio and TgAb titer changed in a similar way. These results suggest that desiccated thyroid hormone therapy and TgAb formation are related to the development of THAA and that L-T4 therapy reduces the THAA titer.

Aged↗

PubMed1995

Immunoglobulin G can cross-react with glucagon antisera and cause a spuriously high plasma immunoreactive glucagon level.

We had a patient with asymptomatic hyper-immunoreactive glucagonemia and with no evidence of pancreatic tumor detected by radiological examinations. The glucagon level was not decreased by the administration of glucose or somatosatin analogue (SMS 201-995). Gel filtration studies revealed that most glucagon immunoreactivity was eluted at the position of 150,000 daltons [big plasma glucagon (BPG)]. Binding studies with 125I-glucagon showed that glucagon autoantibody was negative. Acid treatment of plasma and reduction of immunoglobulin G (IgG) did not result in a shift of BPG to normal glucagon (3485 daltons). Glucagon immunoreactivity determined with anti-glucagon antiserum OAL 123 (C-terminal specific antiserum used in the present radioimmunoassay kit) did not dilute out in parallel to normal glucagon (3485 daltons), and the plasma glucagon level was normal with Unger's 30K (anther C-terminal specific antiserum) and OAL 196 (N-terminal specific antiserum). The patient's IgG dose-dependently reduced the binding of 125I-glucagon to anti-glucagon antiserum OAL-123. Glucagon degrading activity (GDA) was negative in the patient's plasma. These results suggest that the patient's IgG cross-reacted with the present anti-glucagon antiserum OAL 123, and caused a spuriously high plasma immunoreactive glucagon level.

Adult↗

PubMed1994

Spontaneous growth hormone (GH) secretion by unstimulated human lymphocytes and the effects of GH-releasing hormone and somatostatin.

We investigated in five normal subjects whether the secretion of GH from lymphocytes would occur spontaneously without mitogens and be regulated by GHRH and somatostatin as in the endocrine system. Peripheral blood mononuclear cells were isolated from heparinized blood by the standard Ficoll-Hypaque gradient centrifugation method, and incubated for up to 7 days with or without GHRH, somatostatin analog (SMS 201-995), cycloheximide, or actinomycin D. GH levels in the lyophilized samples were measured by a highly sensitive enzyme immunoassay. GH concentration in culture medium (5 x 10(5) cells/mL) time dependently increased in all subjects, reaching 0.47 +/- 0.18 ng/L at day 7. A protein synthesis inhibitor (cycloheximide) and RNA synthesis inhibitor (actinomycin D) completely blocked GH secretion from lymphocytes. Immunoreactive GH secreted by unstimulated human lymphocytes was similar to pituitary GH in terms of antigenicity and molecular weight. Physiological concentrations of GHRH (10(-10)-10(-8) mol/L) and SMS 201-995 (10(-8)-10(-6) mol/L) had no effects on the spontaneous secretion of GH from human lymphocytes. These results indicate that GH is spontaneously synthesized de novo and secreted from unstimulated human lymphocytes, and that the regulation of GH in the immune system differs from that in the endocrine system.

Adult↗

PubMed1994

Effects of anti-prolactin autoantibodies on serum prolactin measurements.

The influence of anti-PRL autoantibodies on PRL measurements determined by immunoassays was investigated in 10 patients with anti-PRL autoantibodies. Four different immunoassay systems (two double-antibody radioimmunoassays (RIAs), a single-antibody RIA and an immunoradiometric assay (IRMA)) were examined. Total and free PRL were extracted from sera by precipitating gamma-globulin with polyethylene glycol with and without acidification, respectively. PRL values determined by direct measurement were compared with total PRL values. The proportion of free to total PRL levels determined by each immunoassay in sera with anti-PRL autoantibodies was significantly lower than in control sera. Values obtained by direct measurement of PRL (a routine assay procedure) in control sera were similar to total PRL values, whereas in sera with anti-PRL (a routine assay procedure) in control sera were similar to total PRL values, whereas in sera with anti-PRL autoantibodies the values varied from one immunoassay to the other. In sera with anti-PRL autoantibodies, double-antibody RIA 1, RIA 2 and single-antibody RIA 3 yielded values lower for PRL than for total PRL (52 +/- 15% in RIA 1, 40 +/- 8.8% in RIA 2, 40 +/- 14% in RIA 3), while PRL levels determined by IRMA were not significantly different (112 +/- 14%). Immunoglobulin G purified from serum with anti-PRL autoantibodies dose-dependently decreased the recovery of PRL assayed by the double-antibody technique, while it did not affect that by IRMA. These data suggest that the presence of anti-PRL autoantibodies gives variable results depending on the immunoassays used.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies↗

PubMed1994

Correlation of the antibody titers with serum prolactin levels and their clinical course in patients with anti-prolactin autoantibody.

Patients with anti-prolactin (PRL) autoantibody were surveyed among 208 patients with hyperprolactinemia (PRL > or = 30 micrograms/l) and 228 subjects with normal PRL levels, and the relationship of the antibody titers with serum PRL levels and their clinical course were studied. Diagnosis of possessing the anti-PRL autoantibody was based on the polyethylene glycol method, displacement of the binding of [125I]PRL with the serum by unlabeled PRL and the binding of PRL to protein G, the affinity gel for immunoglobulin G. Prolactin was measured by an immunoradiometric assay that we found was not affected by the anti-PRL autoantibody. A significantly high frequency of anti-PRL autoantibody in patients with idiopathic hyperprolactinemia (16%) and a positive correlation between titers of the autoantibody and serum PRL levels (r = 0.74, p < 0.01) may indicate that the anti-PRL autoantibody itself is another cause of hyperprolactinemia, probably owing to the delayed clearance of PRL. Most patients with anti-PRL autoantibody lacked the clinical symptoms of hyperprolactinemia, such as amenorrhea and galactorrhea, and spontaneous pregnancy occurred despite the marked hyperprolactinemic state, indicating that the biological activity of PRL was attenuated by the autoantibody. In addition, PRL levels and the titers of anti-PRL autoantibody were not changed significantly during the observation period of up to 5 years without any medical intervention. These results suggest that the anti-PRL autoantibody itself is one of the causes of hyperprolactinemia and that medical intervention is unnecessary for this type of hyperprolactinemia.

Adolescent↗

PubMed1994

Insulinoma with normal plasma insulin concentrations and insulin/glucose ratios during hypoglycemic episodes.

A patient with insulinoma had frequent hypoglycemic episodes with normal plasma insulin levels and insulin/glucose ratios. When immunoreactive insulin (IRI) concentrations in this patient were compared among plasma samples with the same C-peptide immunoreactivity (CPR) levels, the concentrations were significantly lower than in control patients with insulinoma and equal to or lower than those of normal subjects. In hepatic venous samples, CPR levels were significantly higher and the IRI/CPR molar ratios were lower than those in a control subject. These results may indicate that normoinsulinemia in this patient could be explained by increased hepatic extraction of insulin.

Adolescent↗

PubMed1994

[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↗

PubMed1993

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↗

PubMed1993

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↗

PubMed1993

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↗

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↗