[A case of Cushing's syndrome with diabetes, hypertension and ocular hemorrhage followed by secondary adrenal gland hypofunction].
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Adrenal Cortex Function Tests↗
Biomedical subjects
R Demura
Publications and source records attributed to R Demura.
Falsely elevated serum parathyroid hormone levels due to immunoglobulin G in a patient with idiopathic hypoparathyroidism.
A 73-yr-old patient with idiopathic hypoparathyroidism was admitted to our hospital in May 1981. The immunoreactive PTH (iPTH) level determined by RIA using antiserum specific for the C-terminal region of PTH-(65-69) was in the upper normal range (0.6 ng/mL) and over the next 7 yr increased gradually to 6 ng/mL. Since iPTH levels determined using other commercial RIA kits remained constantly decreased or in the undetectable range, we studied the mechanism of false elevation of iPTH in this patient. The patient's serum contained no binding protein to the tracer ([125I]) [Tyr45] human PTH-(46-84)), nor was any heterophilic antibody to the first [guinea pig immunoglobulin G (IgG)] or the second antibody (goat IgG) detected. Consistent with these findings, the dilution curve of the serum was parallel with that of standard bovine PTH-(1-84). Gel filtration analysis revealed that the iPTH-like substance was eluted in the void volume (apparent mol wt, greater than 70,000). Almost all of the iPTH-like substance was adsorbod by a protein-A-Sepharose column. When the IgG fraction purified by protein-A-Sepharose affinity chromatography was applied to an antihuman IgG lambda-Sepharose column, 72% of the iPTH-like substance was detected in the IgG lambda. These results suggest that the falsely elevated iPTH in the patient's serum was due to IgGs (mainly IgG lambda), which were cross-reactive with the antiserum highly specific for the C-terminal region of human PTH-(65-69).
Aged↗
Mutagenic activity of pyrolysates of cyanocobalamin and some other water-soluble vitamins in the model system with the Salmonella/mammalian microsomes.
Pyrolysates of cyanocobalamin, thiamine hydrochloride, riboflavin, pyridoxine hydrochloride, and ascorbic acid were tested for mutagenicity in the histidine-requiring mutants Salmonella typhimurium TA98 and TA100. Each vitamin was sealed in a glass tube and heated at 100-600 degrees C in a muffle furnace. Methanol-chloroform extracts of the pyrolysate of each vitamin tested did not show any mutagenicity in either TA98 or TA100 without rat liver 9000 x g supernatant fraction (S9) added. In the presence of S9, the B-group vitamins (cyanocobalamin, thiamine hydrochloride, riboflavin, and pyridoxine hydrochloride) were all mutagenic in TA98 and TA100, with the highest activity among the vitamins tested found in the pyrolysate of cyanocobalamin. The pyrolysate of 0.25 mumole cyanocobalamin produced 3200 revertants, while the pyrolysates of 0.25 mumole thiamine hydrochloride and riboflavin produced only 910 revertants, and the pyrolysate of pyridoxine hydrochloride did not show any mutagenicity at that amount. The mutagenicity was generally more active to TA98 than to TA100, indicating that frameshift-type mutagens were contained in the pyrolysates. The pyrolysate of ascorbic acid did not show any mutagenic activity in either TA98 or TA100 under the present experimental conditions.
Animals↗
[A clinical evaluation of the CA 72-4 serum level as a possible tumor marker].
The level of CA 72-4 in serum has been measured in various diseases by an immunoradiometric assay using CA 72-4 RIA Kit for an evaluation of its clinical significance as a possible tumor marker. CA 72-4 showed a high positive rate in patients with ovarian and bile duct cancers. In contrast, the false positive rate was low in benign gynecological and digestive diseases. Serum CA 72-4 was found to be increased in patients with a mucinous cystadenocarcinoma and in other histological types in the early stages of an ovarian cancer. Further, the serum CA 72-4 level changed in parallel with the clinical course of the ovarian cancer. Therefore, our results suggest that measurement of CA 72-4 be combined with measurement of CA 125, so as to provide a better sensitivity and specificity in monitoring an ovarian cancer.
Antigens, Tumor-Associated, Carbohydrate↗
[Long-term follow-up study of I-131 therapy for Graves' disease--index associated with late-onset hypothyroidism].
We have studied the follow-up of thyroid function in the patients with late-onset hypothyroidism and euthyroidism after I-131 therapy of hyperthyroidism. Thirty three patients who did not need the thyroid treatment until ten years after I-131 therapy were classified as euthyroid group. And eleven patients who needed the thyroid supplement of thyroid hormone for late-onset hypothyroidism were classified as hypothyroid group. Patients in both groups who required only a single dose of I-131 for successful treatment of hyperthyroidism had similar age, gland size, 24 hour I-131 uptake, pretreatment serum T3 uptake level and T4 concentration, and I-131 treatment dose. Subclinical hypothyroidism occurred in 28.6% of euthyroid group and 66.7% of hypothyroid group four months after I-131 therapy. The levels of T3 were recovered to higher than normal range at 6 months in euthyroid group, while the levels of T3 were kept within the normal range in the seventy percent of hypothyroid group. Patients who were still lower in the level of T3 uptake than normal range at 6 months had a higher incidence of late-onset hypothyroidism. Our observation showed no significant difference in the course of follow-up studies after I-131 therapy between the patients with late-onset hypothyroidism and euthyroidism.
Adult↗
[The effects of diclofenac sodium on thyroid function tests in vivo and in vitro].
In order to investigate the effects of the non-steroidal antiinflammatory drug, diclofenac sodium on thyroid function, 8 male and 2 female volunteers were given single dose of 50 mg diclofenac sodium. Ninety minutes after the administration of the drug, the concentrations of total T 3, total T 4 and free T 4 were decreased significantly, but the concentrations of free T 3 and the levels of T 3 uptake, % free T 3 and % free T 4 were increased. When diclofenac sodium was added to serum in vitro, the levels of free T 3, free T 4 and T 3 uptake were increased. These results showed that diclofenac sodium inhibited the binding of T 3 and T 4 competitively to the binding protein. The apparent decline in the concentrations of total T 3 and total T 4 after diclofenac sodium administration suggested that the drug altered distribution and metabolism of T 3 and T 4 mainly by increasing their free forms.
Anti-Inflammatory Agents, Non-Steroidal↗
Determination of metal content in three types of human gallstone.
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Cholelithiasis↗
Measurement of plasma free and total growth hormone concentrations in patients with growth hormone antibodies developed in response to therapy.
Recombinant human growth hormone is more antigenic than pituitary preparations. Since GH antibodies interfere with radioimmunoassay of GH, we measured plasma free and total GH in patients with pituitary dwarfism with GH antibodies during treatment with a recombinant methionyl GH preparation. Plasma free GH was measured in the supernatant after polyethylene glycol precipitation. Total GH was measured after extracting plasma with acid-ethanol. In normal subjects, both free and total GH levels were similar to those measured in plasma by a direct conventional RIA. Peak free GH levels after administration of 4 IU methionyl GH to 3 normal subjects were 38.0, 30.7 and 13.2 micrograms/1, values similar to those measured in most of the patients with GH antibodies. All values were undetectable in one patient with a very high antibody titre. Total GH levels were similar to free GH levels in normal subjects. In patients with GH antibodies, total GH levels were high compared with their free levels, but similar to those assayed by conventional RIA. The patient with the highest antibody titre had total GH levels which were the lowest of those observed in the patients with GH antibodies in spite of having the highest GH levels measured by conventional RIA. The antibody in this particular case may have a high capacity and a high affinity. A relatively poor growth rate in this patient may be associated with the finding of undetectable free GH levels. Measurement of plasma free and total GH may be of value in examining GH dynamics and their relation to the clinical effectiveness of GH treatment in patients with GH antibodies.
Adolescent↗
[Basic and clinical studies on the simultaneous measurement of serum and red blood cell folate and vitamin B12 concentrations using Baxter Travenol [57Co]vitamin B12/[125I]folate radioassay kit].
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Binding, Competitive↗
[Clinical evaluation of various tumor markers in pleural effusion and in the serum].
Various tumor markers and enzymes in the pleural effusion and serum have been measured in 47 patients with carcinoma and in 43 patients with benign disease, by means of a radioimmunoassay and biochemical methods. CEA in the pleural effusion showed a high specificity and sensitivity for the detection of the malignancy. In patients with a lung cancer, measurement of the NSE in the serum was more useful than in the pleural effusion. Further, both CA19-9 and SCC in the pleural effusion showed a high specificity in a differential diagnosis of cancer and benign diseases. On the other hand, CA 125, TPA and IAP in the pleural effusion and in the serum showed a high sensitivity, but a low specificity for diagnosing the malignancy. The levels of ADA were significantly higher in tuberculous pleural effusions than in carcinomatous effusions. Therefore, this suggests that measurement of the various tumor markers in both the pleural effusion and in the serum is useful in achieving a differential diagnosis of malignant and benign diseases.
Adenosine Deaminase↗
[Ovarian inhibin activity in rats with persistent estrus].
To investigate the significance of changes in ovarian inhibin in gonadal dysfunction with persistent estrus, female rats with persistent estrus were studied as animal model for polycystic ovaries (PCO). Newborn female Wistar rats treated with testosterone propionate s. c. (TP) and female rats raised under continuous light (LL) started at 9 weeks of age entered into continuous estrus 5 and 2 or 3 weeks after the treatment, respectively. Ovaries in both groups had many polycystic follicles Normal adult female rats with 4 day cycles were served as control. Ovarian inhibin content was measured by FSH suppressing activity of charcoal-treated ovarian homogenates using a rat anterior pituitary cell culture system. Blood samples were obtained at 11:00 a. m. and plasma levels of LH, FSH, PRL, estradiol (E2), progesterone (P) and testosterone were measured by RIA. Comparisons were made statistically between each experimental group and normal proestrus (PE). Both LH and FSH were similar to normal PE in TP LL, suggesting a lack of LH and FSH surges probably through hypothalamic dysfunction in TP and LL. Plasma PRL levels were variably elevated in both groups. Ovarian inhibin contents were comparably high to PE in both groups with parallel increases in plasma E2 and P. Plasma testosterone was elevated only in TP. In conclusion, female rats with persistent estrus induced by TP or LL exhibited polycystic ovarian changes similar to PCO. Increased inhibin content in TP and LL may reflect persistent follicular activity.
Animals↗
[Biochemical diagnosis of pheochromocytoma by determining normetanephrine and metanephrine concentrations in single voided urine].
Diagnosis of pheochromocytoma has been made by the determination of urinary noradrenaline and adrenaline excretion for 24 hours. The assay procedure and the collection of urine for 24 hrs. are intricate. In the present study, we have ascertained the clinical significance of urinary normetanephrine (NM) and metanephrine (M), chemically stable metabolites of catecholamines, in single voided urine for a diagnosis of pheochromocytoma. Urine and plasma samples were collected from 361 normal subjects, 59 patients with essential hypertension, 22 patients with chronic renal failure and 22 patients with pheochromocytoma. Urinary NM and M concentrations were determined by radioimmunoassay with prior hydrolysis by acidification with 1N HCl. Plasma NM and M concentrations in normal subjects were 71.8 +/- 30.7 pg/ml and 41.5 +/- 8.61 pg/ml, respectively. Plasma NM was increased in 8 and plasma M was increased in 20 of 21 patients with pheochromocytoma, although many of these overlapped with those patients with chronic renal failure (NM, 285.9 +/- 175.1 pg/ml; M, 206.3 +/- 186.7 pg/ml) and essential hypertension (NM, 107.7 +/- 90.7 pg/ml; M, 46.7 +/- 20.2 pg/ml). Urinary NM and M concentrations did not show specific diurnal variation and there was significant correlations between the values in single voided urine and those in the 24 hour urine. Urinary NM and M concentrations in normal controls were 197.5 +/- 46.7 ng/mg Cr. and 125.3 +/- 37.1 ng/mg Cr., respectively. Urinary NM concentration was increased in 14 and urinary M concentration was increased in all of 17 patients with pheochromocytoma. In addition, urinary M concentration was higher in most of the 17 patients with pheochromocytoma than that in the patients with chronic renal failure and essential hypertension. However, the values in three patients with Sipple's syndrome with a small adrenal tumor or recurrent cases overlapped with those in other diseases. Relationships between urinary concentrations of NM and/or M and tumor size showed positive correlations. Urinary NM and M concentrations showed significant decreases after surgical removal of the tumors. These results suggest that NM and/or M concentrations in single voided urine could be a sensitive and specific diagnostic tool for pheochromocytoma.
Adrenal Gland Neoplasms↗
Testosterone restores testicular inhibin content in cryptorchid rats.
The effects of testosterone administration on testicular inhibin content and histology were studied in bilaterally cryptorchid rats, in which a marked decrease in testicular inhibin content had been observed. Mature male Wistar rats weighing approximately 300 g were made bilaterally cryptorchid by placing the testes in the abdominal cavity. Testosterone in oil, 0.1, 1.0 or 10 mg, was given i.m. each week. Testicular inhibin and testosterone content, histology and plasma LH, FSH and testosterone were studied 2 weeks later. Abnormally decreased testicular inhibin in cryptorchidism was restored toward normal by testosterone in a dose dependent manner in 2 weeks after surgery. Sertoli cell structure also recovered toward normal with increasing amount of testosterone. Decreased testicular testosterone content and Leydig cell atrophy were observed with suppressed plasma LH and FSH after testosterone. These results showed that the increased plasma concentration of testosterone had a stimulatory effect on the Sertoli cell function in cryptorchidism, in which compensated Leydig cell failure was demonstrated.
Animals↗
Studies on pituitary-gonadal function in patients with Cushing's syndrome.
Basal levels of sex steroids, and the responses of LH and FSH to LH-RH were studied in twenty-five female patients with Cushing's syndrome (17 Cushing's disease and 8 adrenocortical adenoma). Only two patients had a regular menstrual cycle. Amenorrhea or oligomenorrhea had been of long duration in the other cases except for three postmenopausal patients. In patients with Cushing's disease, basal estradiol was low or below normal in 86%. Progesterone was normal in 83%, but testosterone was high in half of the cases. The response of LH to LH-RH in patients with Cushing's disease was normal in 35%, low in 35% and high in 29% of the cases. FSH response to LH-RH was normal in 23.5%, low in 23.5% and high in 53%. In patients with adrenocortical adenoma, basal of estradiol was low or below normal, but progesterone and testosterone were normal in all cases. The response of LH and FSH to LH-RH in all patients with adrenocortical adenoma was higher than normal. In three postmenopausal women, a higher response of LH and FSH to LH-RH was seen in two cases and suppressed in one case. These data suggest that the main site of suppression of the gonadal axis in patients with adrenocortical adenoma is the gonad rather than the pituitary gland or hypothalamus, though the mechanism of hypogonadism in patients with Cushing's disease is heterogeneous.
Adolescent↗
Hypercortisolism and the resistance to dexamethasone suppression during gestation.
Maternal adrenocortical function was studied by measuring plasma cortisol and urinary free cortisol during gestation. Changes in suppressibility of pituitary-adrenocortical function were determined by dexamethasone administration. Urinary free cortisol as well as plasma cortisol increased during the course of gestation. The suppressibility by dexamethasone became less effective as pregnancy advanced. These results suggest that pregnant women have pituitary-adrenocortical hyperfunction and tissue refractoriness to glucocorticoid which increases during the course of gestation.
Adrenal Cortex↗
The changes in plasma cortisol and urinary free cortisol by an overnight dexamethasone suppression test in patients with Cushing's disease.
We studied the suppressibility of cortisol secretion in 15 patients with Cushing's disease by measuring morning plasma cortisol level as well as the 24-hour urinary free corisol (UFC) excretion following single doses of increasing amounts of dexamethasone (ranging from 0.5 to 32 mg) given at 11 p.m. The mean plasma cortisol level in patients with Cushing's disease was twice as high as in normal subjects, whereas the mean UFC in these patients was 6 times as high. Plasma cortisol in seven patients were suppressed by less than 4 mg of dexamethasone (in 2 cases, less than 0.5 mg; in 3 cases, less than 2 mg; and in 2 cases less than 4 mg). In these cases, basal plasma cortisol and UFC were less than 25 micrograms/dl and 350 micrograms/day, respectively. Among the other eight patients, plasma cortisol was partially suppressed in 5 cases and not suppressed in 3 cases by high doses of dexamethasone (16-32 mg). In these cases the basal plasma cortisol and UFC were more than 25 micrograms/dl and 350 micrograms/day, respectively. There was a significant correlation between the basal plasma cortisol and UFC (r = 0.687, p less than 0.01). These data suggest that the suppression by increasing amounts of dexamethasone in most cases with Cushing's disease was related to the severity of hypercortisolism.
Cushing Syndrome↗
Effect of porcine follicular fluid on LH and FSH secretion in rats.
To investigate a mode and a site of action of inhibin on FSH and LH secretion, in vivo and in vitro effects of porcine follicular fluid (PFF) on FSH and LH secretion were studied in male rats. PFF administered i.v. suppressed basal FSH levels for 1-8 hr, but did not alter LH levels. On the contrary, PFF given either 1 or 6 hr in advance, suppressed LH-RH stimulated LH responses as well as LH-RH induced FSH responses. In cultured pituitary cells PFF exerted a partial suppressive effect on LH release. PFF suppressed LH release only under the maximal stimulation with 10(-10) M LH-RH and 0.1 mM 3-isobutyl-1-metylxanthine (IBMX) to a lesser degree compared with uniform and greater suppression on FSH release regardless of the experimental conditions. Above results showed a selective suppressive effect of PFF on FSH release and synthesis with a less inhibitory effect on LH release mainly at the pituitary level.
Animals↗
[A study of the clinical usefulness of the CA15-3 radioimmunoassay kit].
We have studied the clinical usefulness of the CA15-3 radioimmunoassay (RIA) kit that has been developed with two monoclonal antibodies (115D 8 and DF 3). Serum levels of CA15-3 exceeding the normal level were found in a high percentage of patients with ovarian cancer (80%), lung cancer (62.5%) and breast cancer (29.3%). In patients with breast cancer, the mean concentrations of CA15-3 before operation were higher than those after operation. Further, the levels of CA15-3 showed a good correlation with the extent and the stage of the breast cancer. These results suggest that CA15-3 levels can provide monitoring information in the follow-up management of patients with breast cancer.
Antigens, Tumor-Associated, Carbohydrate↗