[Clinical significance of glycated albumin analysis in biochemical tests].
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Biomedical subjects
Publications and source records attributed to K Shima.
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Two cases of inflammatory pseudotumor of the lung were reported. Case 1. A 68 year-old man was referred to our hospital because of an abnormal shadow on chest X-ray. He had a history of pneumonia in the right upper lobe five months before. The chest X-ray film revealed a coin lesion in the right upper lung field (S1), the same segment as the previous pneumonia. Although RPF and INH were administered for three months, the shadow did not change, and cough and sputum continued. In order to confirm the diagnosis, open thoracotomy was performed and microscopic findings of the resected tumor showed inflammatory pseudotumor; proliferation of fibrous tissue with infiltration by inflammatory cells (plasma cells, lymphocytes and a few neutrophils). Case 2. A 35 year-old man was admitted to our hospital because of an abnormal shadow on chest X-ray, i.e. a coin lesion with vascular indentation in the left lower lung field (S8). A wedge resection including the mass was performed, and histopathologic examination revealed inflammatory pseudotumor, or plasma cell granuloma; proliferation of fibrous connective tissue with infiltration by predominantly mature plasma cells. Both patients have been doing well after the operation. We also reviewed 46 cases reported in the Japanese literature and discussed various aspects of this disease. Of 10 patients who had a history of previous respiratory tract infection, 8 had histopathologic features with various inflammatory cells, including many lymphocytes, as in our Case 1. Although the common etiology of inflammatory pseudotumor is obscure, we suppose that in some cases the lesion may be a result of post-inflammatory repair process.
The binding of human LH and human FSH to postmenopausal ovarian tissue from 21 patients with cervical carcinoma was analyzed. The binding sites for FSH and LH were demonstrated in postmenopausal ovarian tissue. The surface-binding sites for gonadotropins were localized in the cells of cortical stroma of the postmenopausal ovary. In addition, diffuse cytoplasmic staining of endogenous estrogen and 3 beta-hydroxysteroid dehydrogenase activity were detected immunohistochemically and histochemically in the cells of the cortical stroma. Electron microscopic study also suggested steroidogenic function in the cells of the cortical stroma. The results of the present study suggest that postmenopausal ovaries contain specific binding sites for pituitary gonadotropins and play a role in ovarian steroidogenesis.
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Usefulness of ceftazidime (CAZ) was studied in 56 cases of intractable respiratory tract infections. CAZ was administered at a daily dose of 2-4 g in 2 divided doses by intravenous drip infusion for 3-15 days. 1. Analysis was carried out in 38 cases and the following result was obtained. Efficacy rate was: 68% (17/25) in pneumonia, 60% (3/5) in chronic bronchitis and 67% (4/6) in secondary infections in chronic respiratory disease cases, and the overall efficacy rate was 63.2% (24/38). 2. In bacteriological study, 68.2% (15/22) of eradication rate was obtained. Against Staphylococcus aureus, eradication was obtained in all strains (4 strains). Against Pseudomonas aeruginosa, eradication occurred in 4 strains out of 10, and decrease in number in 2 strains. 3. As for adverse effects, mild hepatic disorder was observed in 2 cases (3.6%) out of 56. 4. From the above result, CAZ is considered to be very useful when used as monotherapy for aged patients and in the treatment of severe and intractable infections accompanied by underlying diseases.
The patient was a 61 year old woman of Japanese who was in good health until May 1983, when she came to our hospital because of the visual disturbance. The chest X-ray film showed bilateral hilar lymphadenopathy and a transbronchial lung biopsy revealed sarcoid granuloma. She received systemic steroids (10 to 40 mg/2 days of prednisolone) for visual disturbance from August 1983 to May 1986. Then steroid therapy was suspended temporarily. In August 1987, she was readmitted because of syncopal episodes. She was noted to have irregular bradycardia and the electrocardiogram revealed atrioventricular block and paroxysmal polymorphous ventricular tachycardia. Initially cardioversion to sinus rhythm was accomplished with direct current electric shock and temporary pacemaker was inserted and subsequently a permanent transvenous demand pacemaker implanted. The patient then became asymptomatic. Coronary arteriography revealed no significant organic stenosis and left ventriculogram showed a left ventricular aneurysm of the inferior wall of the left ventricle. A transvenous percutaneous right ventricular endomyocardial biopsy revealed non-specific myocardial degeneration with slight interstitial fibrosis. Thallium-201 myocardial perfusion scans revealed the inferior left ventricular defects. We conclude the syncopal episodes and electrocardiographic abnormalities of this case were due to massive myocardial sarcoidosis which caused left ventricular aneurysm.
The contiguous three lobe of the pituitary gland have different endocrine functions and vascular bed. This study was designed to investigate the effects of dehydration, which stimulates the secretion of vasopressin, on the pituitary microcirculation. Male Sprague-Dawley rats, weighing 300-380 g, were divided into two groups. Twenty three rats were allowed free access to food and water, and 24 rats had free access to food but were deprived of water for 5 days. Capillary solute transfer (K), plasma volume (Vp) and erythrocyte volume (Ve) in each pituitary lobe were determined for both control and dehydrated rats. Quantitative autoradiographic techniques were used to measure the K with 14C-alpha-aminoisobutyric acid (AIB, a small neutral amino acid), the Vp with 125I-albumin and the Ve with 51Cr-erythrocytes. Body weight was lower (-23%) and the arterial hematocrit was higher (+22%) in the dehydrated rats. In the lobes of the control pituitary gland, the order of K from the highest to the lowest was posterior much greater than anterior greater than intermediate lobe. K was increased by several folds only in the posterior lobe in dehydrated rats (p less than 0.05). Even under normal hydrated conditions, K for AIB in the posterior lobe was several hundreds times greater than in cerebral gray matter structures. The rank of Vp and Ve in each lobe of normal animals was about the same order and anterior greater than posterior much greater than intermediate. Normal microvascular Vp in the anterior and posterior lobes was 5-10 times larger than in cerebral gray matter.(ABSTRACT TRUNCATED AT 250 WORDS)
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A method for determination of serum glycated albumin by high-performance liquid chromatography is presented. The system involves anion exchange chromatography to separate albumin and consecutive boronate affinity chromatography to separate glycated and nonglycated albumin. The method is rapid (20 min), precise (coefficient of variation, 0.7-4.9%), requires only a small sample (5 microliters), and can be automated. Assay of glycated albumin by this method is not influenced by the protein concentration of the sample or the presence of glucose. The variation in glycated albumin values in consecutive samples obtained within a day from diabetic patients (coefficient of variation, 2.02 +/- 0.65%) was significantly smaller (p less than 0.001) than that of values for fructosamine (coefficient of variation, 4.33 +/- 2.0%). The values of glycated albumin in normal subjects (20.2 +/- 1.6%) were clearly less than those in diabetic patients [39.6 +/- 5.4% in 40 Type 1 (insulin-dependent) and 39.4 +/- 5.9% in 25 Type 2 (non-insulin-dependent) patients]. The serum glycated albumin level was well correlated with HbA1c in 65 diabetic patients (r = 0.60). Because the life span of albumin in the circulation is short, measurement of glycated albumin should be useful as a short-term index of glycaemic control.
A radioimmunoassay using antibody against glucitol-lysine was developed to quantitate glycated proteins in the lens of diabetic rats. The amount of glycated protein was expressed as molar equivalents of reduced glycated hippuryl lysine (GlcRED-Hip-Lysine). Significant differences (p less than 0.01) were found in the amounts of glycated protein in the lenses of rats with streptozotocin-induced diabetes (3.92 +/- 0.59 nmol/mg protein, n = 5), those with streptozotocin-induced diabetes treated with insulin (2.94 +/- 0.36 nmol/mg protein, n = 4) and normal rats (1.23 +/- 0.22 nmol/mg protein, n = 5). There was a significant correlation between the concentration of glycated protein in the lens and the HbA1c level at the end of the 12 week experiment (r = 0.957, p less than 0.001). These results indicate that glycation of lens protein is parallel with the severity of diabetes in rats.
Ontogenetic appearances of glucagon, insulin and tyrosine hydroxylase (TH) were immunohistochemically investigated on developing pancreatic islets of rats. Glucagon immunoreactivity appeared first in some epithelial cells (g-cells) of the dorsal anlage of the pancreas on day 11.5 of gestation. On day 12.5, g-cells increased in number manufacturing the primitive islets, in which some cells appeared to be immunoreactive for insulin (i-cells) and about 40% of g-cells indicated also a slight immunoreactivity for insulin (g/i-cells). Afterwards, all the islet cells, especially g-cells, increased in number, and almost half of g-cells were g/i-cells. After day 16.5 of gestation, numerical increase of the cells with insulin immunoreactivity exceeded that of the cells with glucagon immunoreactivity, and about one fifth of g-cells were g/i-cells. After 20.5 days, however, no g/i cells were found. On day 16.5 of gestation, the immunoreactivity for TH appeared in occasional cells of the islets, but the cells did not show immunoreactivity for glucagon or insulin. It is concluded that the progenitor cells of the pancreatic islets appear to synthesize both glucagon and insulin by day 20.5 of gestation, but differentiate giving rise to mature A and B cells of adult islets afterward.
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A man with diabetes mellitus, chronic hepatitis, chronic pancreatitis, and blind loop syndrome but without any previous thyroid disease developed three episodes of transient primary hypothyroidism associated with protein-calorie malnutrition (PCM). Clinical examinations suggested that this primary hypothyroidism was not caused by chronic thyroiditis, iodine deficiency, or iodine excess. Since the three times association of primary hypothyroidism with PCM suggested the possibility that the primary hypothyroidism was caused by PCM, we have tried to clarify its mechanism. For this purpose we have investigated the change of thyroid functions during protein-calorie repletion and the effect of amino acid deficiency. Total parenteral nutrition with full supplementation of amino acids resulted in a rapid increase in serum thyroxine (T4), triiodothyronine (T3), free T4, and reverse T3, and subsequently, a rapid decrease in TSH in several days after the nutrition was begun. When amino acid solution was changed to that depleted of phenylalanine and tyrosine after the restoration of thyroid functions, serum T4 and T3 showed a gradual decrease, but serum free T4 and TSH remained within normal range. However, resupplementation of phenylalanine and tyrosine after 8 weeks of depletion gave a rapid increase in serum T4, T3, free T4, and reverse T3. These results suggested that the primary hypothyroidism was caused by an impaired T4 production and that the deficiency of amino acids in PCM partly contributed to the impairment of T4 production.
The insulinotropic actions of two forms of glucagon-like peptide 1 (GLP-1) containing 31 and 37 amino acid residues on perfused rat pancreas were compared with that of gastric inhibitory polypeptide (GIP), hitherto the most potent intestinal insulinotropic polypeptide known. The smaller form, C-terminally amidated GLP-1-(7-36), strongly enhanced insulin secretion stimulated by 11.1 mM D-glucose at a concentration as low as 0.1 nM. Comparable effects of GIP and GLP-1-(1-37) on insulin secretion were observed at concentrations of 1.0 nM and 10.0 nM, respectively. At the doses tested, neither GLP-1s nor GIP had any effect on insulin secretion induced by 3.3 mM D-glucose. At a concentration of 1.0 nM, GLP-1-(7-36 amide) also enhanced insulin secretion induced by 5 mM L-arginine whereas at concentrations of up to 10.0 nM, GLP-1-(1-37) did not. The results show that the smaller form of GLP-1 is more strongly insulinotropic than GIP. These findings suggest that the smaller GLP-1 may have a physiologically more important role as a modulator of insulin release.
The pharmacokinetics of glucagon-like peptide-1 (GLP-1) in vivo after bolus and continuous i.v. administrations of the peptide were compared with those of glucagon in rats. The half-disappearance time (t1/2) distribution volume (Vd) and metabolic clearance rate (MCR) of GLP-1 given as a bolus injection and by constant infusion, were, respectively, as follows: t1/2 (min), 47.7 +/- 14.5 and 39.5 +/- 15.5 (mean +/- S.D.); Vd (ml), 903.8 +/- 62.4 and 516.3 +/- 92.1 and MCR (ml kg-1 min-1), 27.4 +/- 10.8 and 18.6 +/- 8.6. These values differed significantly from the respective values for glucagon (t1/2, 3.3 +/- 0.6 and 5.8 +/- 1.0; Vd, 206.5 +/- 25.9 and 240.0 +/- 76.1; and MCR, 83.1 +/- 8.2 and 46.7 +/- 13.3). These findings demonstrate that GLP-1 is degraded more slowly than glucagon in vivo.
A series of ellipticine glycosides [2-N-glycosyl quaternary pyridinium salts of three ellipticines: ellipticine (1), 9-methoxyellipticine (2), and 9-hydroxyellipticine (4)] were stereoselectively synthesized in good yields by an improved condensation reaction between ellipticines [1, 2, and 9-acetoxyellipticine (3)] and protected (peracylated and perbenzylated) glycosyl halides with cadmium carbonate, followed by deprotection. These glycosides were preliminarily evaluated for their antitumor activity in the L1210 leukemia system. Twenty-six (53%) of the 49 glycosides tested were curative, and five [9-hydroxyellipticine L-arabinopyranoside (41b), D-lyxofuranoside (43a), L-lyxopyranoside (44b), D-xylofuranoside (49a), and L-rhamnopyranoside (56)] were selected for extended evaluation on the basis of their high levels of activity. The structure-activity relationships are discussed. The selected glycosides showed remarkable activity in six different murine tumor systems with excellent therapeutic ratios; their efficacy surpassed that of doxorubicin against three of these systems. On the basis of these results and ease of formulation, the two glycosides 41b (SUN4599) and 49a (SUN5073) were selected for further preclinical evaluation and possible clinical development.
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1. The spontaneous activity of hippocampal theta cells in head-restrained cats was recorded during slow-wave sleep (SWS), paradoxical sleep (PS), and the attentive state of bird watching (BW). We also recorded theta cell activity during a state of insomnia with pontogeniculoocipital (PGO) waves, which was induced by the administration of p-chlorophenylalanine (PCPA), a selective inhibitor of serotonin synthesis. 2. The time-dependent structure of fluctuations in theta cell activity was evaluated by power spectral analysis and Markovian analysis. The coefficient of variation for these time series was used as a measure of the variability of theta cell activity, which indicates the relative amplitude of fluctuations. 3. During SWS, theta cell activity showed a larger variability and a flat spectrum, i.e., low Markovian properties. During PS, this activity exhibited smaller variability and high spectral density in a low-frequency band (0.01-1.0 Hz), i.e., high Markovian properties. During BW, variability, spectral and Markovian properties were intermediate. 4. The firing pattern of theta cells during PCPA-induced insomnia was similar to that during PS. However, after the administration of either a serotonin agonist, 5-Methoxy-N,N-dimethyltryptamine, or a choline antagonist, atropine sulfate, theta cell activity no longer exhibited PS-like fluctuations, revealing instead a firing pattern similar to that during SWS. 5. During PS and PCPA-induced insomnia, not only the unit activity of theta cells, but PGO activity and theta wave frequency exhibited slow fluctuations, i.e., the high spectral density in the low-frequency band (0.01-1.0 Hz). 6. Cross-correlation analyses were performed between the fluctuations in theta cell activity, theta wave frequency, and PGO activity. These fluctuations correlated with each other during both PS and PCPA-induced insomnia. Bursts of PGO waves especially contributed to these cross-correlations. 7. These results suggest, first, that the slow fluctuations of the theta cell activity during PS and PCPA-induced insomnia is the physiological expression of the removal of aminergic influences and, secondly, that they are dependent on cholinergic mechanisms, including PGO generators.