Biomedical subjects
T Yamaji
Publications and source records attributed to T Yamaji.
Plasma endothelin-1 levels in patients with hyponatremia.
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Serum propeptide and intact molecular osteocalcin in normal children and children with growth hormone (GH) deficiency: a potential marker of bone growth and response to GH therapy.
To establish a sensitive marker for bone formation we have developed a sandwich enzyme-linked immunosorbent assay for intact osteocalcin (OC) and its propeptide. Serum levels of these peptides were studied in 185 normal children, aged 4-15 yr, and in 23 GH-deficient children treated with GH. The serum levels of the propeptide in normal prepubescent children were 1.43 +/- 0.23 (mean +/- SE) micrograms/L in boys and 1.53 +/- 0.23 micrograms/L in girls. The peak value occurred at the age of 13 yr in boys (2.91 +/- 0.42 micrograms/L) and 11 yr in girls (2.34 +/- 0.34 micrograms/L). The serum intact OC levels in prepubescent boys and girls were 18.8 +/- 2.1 and 20.7 +/- 2.1 micrograms/L, respectively, and these levels increased to 41.0 +/- 3.7 micrograms/L in boys aged 13 yr and to 27.0 +/- 2.5 micrograms/L in girls aged 11 yr. In the GH-deficient patients, a 2.3-fold increase in the propeptide level and a 1.7-fold increase in the intact OC level was observed after 1 month of GH therapy. Serum propeptide and intact OC levels after 1 month of GH therapy correlated with the growth response after 12 months of GH therapy (r = 0.660 and P < 0.01, for propeptide; r = 0.537 and P < 0.01 for intact OC). These results show that since both propeptide and intact OC in serum were increased when the growth rate was elevated, these peptides are sensitive markers of bone formation. Serum levels of these peptides, particularly propeptide, after 1 month of GH therapy might be a helpful predictor of the growth response to long term GH therapy.
Adrenal myelolipoma associated with congenital adrenal 21-hydroxylase deficiency.
The occurrence of adrenal myelolipomas is reported in an untreated patient with congenital adrenal 21-hydroxylase deficiency. Laparotomy demonstrated the presence of two lesions, a large tumor which arose from an ectopic adrenal cortex and a smaller tumor in the left adrenal gland. Six cases of adrenal myelolipomas and congenital adrenal hyperplasia have been reported in the literature. All patients were associated with excessive ACTH secretion for a long period of time. The relative frequency of this association, coupled with the observation by Selye and Stone (Am J Pathol 26:211, 1950) that anterior pituitary extracts cause myelolipomatous changes in rats, may indicate a possible role for ACTH in the development of myelolipomas.
Sandwich immunoassay for intact human osteocalcin.
To overcome the problems of limited-region specificity associated with conventional radioimmunoassay (RIA), we developed a sandwich enzyme immunoassay (EIA) for intact human osteocalcin (hOC). For this EIA we used antibodies to the N- and C-terminal regions of hOC that were raised against an N-terminal 20-residue peptide and a C-terminal 7-residue peptide, both synthetic. Immunoassay profiles of tryptic digests of hOC and serum from patients with renal failure, fractionated by reversed-phase HPLC, facilitated direct demonstration of the region specificity of this method. A preliminary study of serum osteocalcin concentrations in patients with renal failure further confirmed this specificity, showing lower positive rates obtained by this method than by conventional RIA. The cross-reactivity data of hOC with bovine and rat osteocalcins by the sandwich method indicated its species specificity. These studies demonstrate the superior specificity of this sandwich EIA compared with conventional RIA and thus confirm its potential diagnostic superiority.
[A case of Cushing's syndrome with diabetes, hypertension and ocular hemorrhage followed by secondary adrenal gland hypofunction].
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Plasma endothelin-1 levels in patients with disseminated intravascular coagulation.
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Distribution of atrial natriuretic peptide in the conduction system and ventricular muscles of the human heart.
Atrial natriuretic peptide (ANP), a cardiac hormone, is known to be located in the atrial specific granules, but its presence and localization in the ventricular muscle of the human heart has not been examined fully. Using a specific antibody to human ANP, we studied the conduction system and ventricular muscle with immunohistochemical and ultrastructural methods in 30 hearts obtained at autopsy. These included 12 normal and 18 diseased hearts. In the normal hearts, ANP-positive granules, which were regularly observed in the atrial myocytes, were found in small quantities in the cells of the penetrating and branching bundles in 4 of 12, and in the cells of the ventricular free walls in 2 of the 12 hearts. In the diseased hearts, the positivity increased significantly (P less than 0.05), being found in 13 of 18 (72.2%) conduction systems and 10 of 18 (55.6%) ventricular muscles. The granules were confirmed to be immunoreactive with ANP by ultrastructural examination. Furthermore, the presence of ANP mRNA in the conduction system as well as in the ventricular myocytes was demonstrated by Northern blot hybridization for which we used the complementary DNA of human ANP. Thus, a small quantity of ANP appears to be synthesized and stored in the conduction system and ventricles of some normal hearts. However, ANP was shown to be present in a larger percentage of the diseased hearts.
Thirst and plasma levels of vasopressin, angiotensin II and atrial natriuretic peptide in patients with non-insulin-dependent diabetes mellitus.
To clarify a possible mechanism whereby the perception of thirst may be associated with diabetes mellitus, we measured plasma levels of vasopressin (AVP), angiotensin II (ANG II), atrial natriuretic peptide (ANP) and plasma renin activity (PRA) in non-insulin-dependent (NIDDM) diabetic patients with or without thirst. Thirteen male NIDDM patients complaining of thirst had a significantly high blood hematocrit, plasma urea nitrogen and creatinine concentrations and plasma osmolality, indicating a reduction in plasma volume. In addition, the patients had a significantly high mean plasma concentrations of AVP (3.20 +/- 1.27 pmol/l) ANG II (33.8 +/- 31.4 pmol/l) and PRA, but a low mean plasma ANP concentration (8.9 +/- 4.5 pmol/l). After treatment with diet and/or sulfonylurea, plasma levels of AVP, ANG II and PRA decreased with a concomitant increase in plasma volume and disappearance of thirst. In contrast, 13 NIDDM patients (9 females and 4 males) without thirst had normal plasma urea nitrogen and creatinine concentrations, and the hematocrit did not change significantly after treatment. Plasma AVP (0.95 +/- 0.34 pmol/l), ANG II (14.7 +/- 8.8 pmol/l) and ANP (10.7 +/- 4.9 pmol/l) concentrations, and PRA were normal in this group of patients. There was no significant difference between the two groups of patients, however, in fasting glucose concentration and HbA1c. We conclude from these results that a reduction in plasma volume may be the major factor responsible for the induction of thirst sensation and for increased AVP secretion in NIDDM patients. The mechanism underlying a reduction in plasma volume remains unclear.
Anti-thyroid antibodies in patients with hyperprolactinemia.
To clarify the possible role of prolactin in the regulation of immune responses in man, we measured circulating anti-thyroid antibodies in 172 normal subjects, 84 patients with prolactinoma and 63 patients with acromegaly with normal thyroid and adrenocortical functions. Frequencies of positive thyroidal microsome and thyroglobulin antibodies were significantly (p < 0.05 and p < 0.01, respectively) higher in women with prolactinoma (20.6% and 20.6%) than in normal women (7.5% and 4.7%). Men with prolactinoma had a significantly (p < 0.05) higher frequency of positive thyroglobulin antibody (18.8%) than normal men (1.5%). When the subjects were divided by decade, women with prolactinoma in the 4th decade had significantly (p < 0.05) higher frequencies of positive thyroidal microsome and thyroglobulin antibodies (30.8% and 30.8%) than normal women of corresponding age (3.7% and 3.7%). In contrast, there was no significant difference in the frequencies of positive anti-thyroid antibodies in patients with acromegaly and in normal subjects. Analysis of the peripheral lymphocyte population revealed that patients with prolactinoma had a higher percentage of B cells than normal subjects, while there was no significant difference in the percentages of total T lymphocytes or in the helper and suppressor T cell ratios in the two groups of subjects. These results suggest that prolactin regulates humoral immune responses in man directly by stimulating B lymphocytes or indirectly by inhibiting suppressor T lymphocyte activity.
[A case of primary malignant lymphoma in transverse colon associated with macroglobulinemia].
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[A case of adenocarcinoma of the stomach associated with SIADH].
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Plasma endothelin-1 levels in patients with pregnancy-induced hypertension.
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Atrial natriuretic peptide and vasopressin during percutaneous transvenous mitral valvuloplasty and relation to renin-angiotensin-aldosterone system and renal function.
To study the relation between plasma atrial natriuretic peptide (ANP) and cardiac pressure, and to assess the pathophysiologic significance of ANP in water and electrolyte metabolism, the changes in plasma levels of ANP and arginine vasopressin (AVP) were examined in 11 patients with mitral stenosis who underwent percutaneous transvenous mitral valvuloplasty, and compared with the changes in the renin-angiotensin-aldosterone system and renal function. Immediately after valvuloplasty, plasma ANP levels decreased significantly with a concomitant decrease in mean pressures in the left atrium, the pulmonary artery and the right atrium. Plasma ANP levels decreased to the normal range in 4 of the 6 patients with normal sinus rhythm, while all 5 patients with atrial fibrillation had higher levels despite a similar degree of decrease in atrial pressure. There were significant positive correlations between plasma ANP levels and the mean left atrial pressure (r = 0.61, p less than 0.01), the mean pulmonary arterial pressure (r = 0.49, p less than 0.01) and the mean right atrial pressure (r = 0.54, p less than 0.01). The mean plasma AVP levels, on the other hand, showed a transient increase after valvuloplasty from 0.5 +/- 0.1 to 1.2 +/- 0.4 pg/ml (p less than 0.05). The mean plasma renin activity (1.3 +/- 0.3 vs 2.7 +/- 0.8 ng/ml/hr, p less than 0.05) and plasma aldosterone concentration (8.6 +/- 2.3 vs 17.2 +/- 5.2 ng/dl, p less than 0.05) also increased significantly 30 minutes after valvuloplasty.(ABSTRACT TRUNCATED AT 250 WORDS)
An immunomodulating protein, Ling Zhi-8 (LZ-8) prevents insulitis in non-obese diabetic mice.
Ling Zhi-8 (LZ-8), a novel and recently discovered immunomodulatory protein having in vivo immuno-suppressive activity, was tested for in vivo effect against Type 1 (insulin-dependent) diabetes mellitus in the nonobese diabetic mouse, the disease having immunologically mediated aetiology in this animal. LZ-8 had mitogenic activity in vitro towards spleen cells of the non-obese diabetic mice as previously shown towards those of DBA/2 mice. Intraperitoneal administration of LZ-8 twice weekly into the mice (10.3-12.6 mg/kg body weight) from 4 weeks of age prevented insulitis and an almost normal number of insulin producing cells were observed. Extreme insulitis and reduction of the number of insulin producing cells were observed in the pancreata of the untreated non-obese diabetic mouse. No cumulative incidence of diabetes mellitus was observed in the LZ-8 treated group, while cumulative incidences of 70% and 60% were observed in an untreated group followed up to 42 weeks of age when the incidence of diabetes was defined as a plasma glucose level of greater than 11 mmol/l and as a urine glucose level of greater than 2+, respectively. T cell subset population analysis was performed to further investigate the action of LZ-8 on the non-obese diabetic mouse which revealed that LZ-8 treatment increased in L3T4'/Lyt-2+ ratio.
Role of atrial natriuretic peptide in hemoconcentration during exercise.
Changes in plasma levels of atrial natriuretic peptide (ANP) and albumin, and blood hematocrit (Hct) during treadmill exercise were studied in 6 healthy men before and after beta-adrenergic blockade. Plasma ANP levels increased during exercise and then gradually decreased. There was a concomitant increase in both Hct and plasma albumin concentrations. Prior administration of a long-acting propranolol, 160 mg daily for 3 consecutive days, markedly elevated plasma ANP levels before, during and after exercise. In addition, the mean basal Hct increased significantly and further rose during exercise after propranolol administration. When increments in plasma ANP concentrations during exercise in individual subjects were compared with those in Hct, there was a significant positive correlation between the two variables before and after propranolol administration. The results indicate a close relationship between the changes in plasma ANP and those in Hct during exercise at different ANP levels, and suggest that ANP may be at least one of the factors involved in the hemoconcentration associated with exercise.
Endocrine and immunohistochemical studies on thyrotropin (TSH)-secreting pituitary adenomas: responses of TSH, alpha-subunit, and growth hormone to hypothalamic releasing hormones and their distribution in adenoma cells.
Endocrine and immunohistochemical studies were performed in two cases of TSH-secreting pituitary adenomas. The patients had elevated serum TSH and alpha-subunit concentrations despite high serum thyroid hormone levels. In addition, one patient (no. 1) had elevated serum GH levels with clinical evidence of acromegaly. GH-releasing hormone infusion increased serum levels of TSH, alpha-subunit and GH in the two patients. TRH injection increased serum TSH levels in both patients and, concomitantly, serum alpha-subunit and GH levels in patient 1. Basal TSH levels and their responses to TRH changed reciprocally to changes in serum thyroid hormone levels, although TRH-induced GH release did not. The administration of GnRH also increased serum TSH, alpha-subunit, and GH levels in patient 1. In accordance with these in vivo results, pituitary adenoma cells in culture obtained from patient 1 responded to GH-releasing hormone, TRH, or GnRH to secrete TSH, alpha-subunit, and GH. Incubation of cells with dexamethasone resulted in inhibition of TSH and stimulation of GH secretion without a significant change in alpha-subunit secretion. On the basis of light microscopic and electron microscopic double gold immunohistochemistry, the tumor from patient 1 was a bimorphous adenoma composed of two separate cell types: cells with TSH beta-subunit (TSH beta) and alpha-subunit, and those with GH and alpha-subunit. The remainder consisted mainly of cells with TSH beta and alpha-subunit. The coproduction of the unusual combination of two hormones such as GH and alpha-subunit in a single-type of adenoma cell and the coexistence of thyrotrophs and somatotrophs in one pituitary adenoma along with the aberrant responses of TSH beta, alpha-subunit, and GH to multiple hypothalamic hormones suggest the dedifferentiation of pituitary cells to multipotential progenitor cells by neoplastic transformation.
Endothelin family in human plasma and cerebrospinal fluid.
To clarify whether endothelin may be present in human cerebrospinal fluid (CSF) and, if it exists, to compare its molecular forms with those of endothelin in human plasma, we analyzed pooled human CSF and plasma by high performance liquid chromatography with specific enzyme immunoassays for each endothelin peptide. Of the four human endothelin peptides hitherto identified, big endothelin-1 was the major molecular form of endothelin present in human CSF. In addition, there was a small but significant amount of endothelin-1 and endothelin-3 in CSF, while endothelin-2 was not detectable. Similarly, big endothelin-1, endothelin-1, and endothelin-3 were identified in human plasma. Although big endothelin-1 was the most abundant, a substantial amount of endothelin-1 and endothelin-3 was found in plasma with a resultant lower molar ratio of big endothelin-1 to endothelin-1 than in CSF. In all CSF samples from 17 patients requiring diagnostic lumbar puncture or lumbar anesthesia, endothelin was detectable, with a preponderance of big endothelin-1 relative to endothelin-1 and endothelin-3. The mean concentrations of endothelin-1 and endothelin-3 in simultaneously collected plasma were significantly (P less than 0.01) higher than those in CSF, while there was no significant difference between the mean big endothelin-1 concentration in plasma and that in CSF. There was no significant correlation among concentrations of big endothelin-1, endothelin-1, and endothelin-3 in each paired sample. These results indicate that endothelin is present in human CSF that is differently processed from endothelin in vascular endothelial cells and suggest a possible role for endothelin as a modulator of neuronal functions.