Immunohistochemical study on tissue transglutaminase and copper-zinc superoxide dismutase in human myocardium: Its relevance to apoptosis detected by the nick end labelling method

The influence of free radicals on apoptosis was studied in the human heart; 45 autopsy cases were examined by the nick end labelling method (NELM) that detects DNA fragmentation. Immunostaining for copper-zinc superoxide dismutase (CuZn-SOD) and tissue transglutaminase (tTG) induced frequently during apoptosis were also studied. Positive immunoreaction for tTG was detected in mucinous degeneration of myocardial cells; these same cells were also positive for CuZn-SOD but negative for NELM. Myocardial cells showing basophilic alterations after haematoxylin and eosin staining were also positive for CuZn-SOD but negative for the other markers examined. Positive nuclear reaction by NELM was only observed in myocardial cells showing contraction band necrosis or irregularly shaped nuclei surrounding recent or long-standing infarcted foci. In these the other two markers were negative. Since mucinous degeneration lacks the distinguishing morphological features of apoptosis, immunoreactive tTG in this lesion may not imply that the cells are undergoing apoptosis. tTG can be induced in non-apoptotic conditions and may not be involved in apoptosis induced by infarction. Histological disassociation between CuZn-SOD expression and apoptosis suggests the possibility of a cytoprotective role played by endogenous CuZn-SOD against free radical generation in the human heart.     

Effects of L-DOPA and L-5-HTP on the visual evoked response

Small doses (10 and 20 mg/kg) of L-DOPA inhibited the amplitude of the visual evoked response (VER), while large doses (40 and 80 mg/kg) enhanced it. Though low doses (12.5 and 25 mg/kg) of L-5-HTP caused a slight increase in amplitude of the VER, the simultaneous administration of 12.5 mg/kg of L-5-HTP and 10 mg/kg of L-DOPA produced a marked enhancement. The peak latency was prolonged after the injection of any doses of L-DOPA, L-5-HTP, or both.     

IMMUNOELECTRON MICROSCOPIC LOCALIZATION OF THYROGLOBULIN IN HUMAN FOLLICULAR ADENOMA

An electron microscopic immunohistochemical localization of thyroglobulin (TG) using PAP methods has been made in 15 cases of cold follicular adenoma. All cases of follicular adenoma showed organ specific functions such as synthesis, storage, reabsorption, and hydrolysis of thyroglobulin except for an area composed of follicular cells with trabecular arrangement. Immuno-reaction product for TG was precisely demonstrated in follicular lumina, subapical vesicles and reabsorbed colloid droplets. The reaction product observed in the follicular lumen was clearly demarcated from the cytoplasm of the follicular cells by the apical plasma membrane. The subapical vesicles ranging approximately from 50 mμ to 300 mμ in diameter were rarely observed in follicular adenoma and some of them fused with the reabsorbed colloid droplets. The reabsorbed colloid droplets usually had the intense reaction product and hydrolyzed colloid droplets had a vacuole containing floccular low electron dense materials. There is no reaction product in rough endoplasmic reticulum and Golgi complexes.     

Peripheral lung carcinomas associated with central fibrosis and mixed small cell and other histologic components

Three cases of peripheral small cell lung carcinoma (SCLC) with central fibrosis are presented. Central fibrosis is usually present in adenocarcinomas. Cases 1 and 2 are combined SCLCs with components of papillary adenocar-cinoma, and case 3 is a mixed SCLC with a large cell component. Small cell Components showed intermediate cell type in ail cases. In cases 1 and 2, there was a gradual transition between small cell carcinoma and papillary ade-nocarcinoma. Small cell components showed Grimelius argyrophilia, but other neuroendocrine markers such as neuronspecific enorase, chromogranin A, Leu-7 and syn-aptophysln were negative. The chest X-ray examination of case 1 demonstrated rapid enlargement of a tumor shadow, which was present two years before, for a recent year. Central fibrosis, coexistence of small cell carcinoma and papillary adenocarcinoma, and a change of growth rate in the chest x-ray may suggest that some SCLC derive from papillary adenocarcinomas.     

The Serum Factor from Patients with Ulcerative Colitis that Induces T Cell Proliferation in the Mouse Thymus Is Interleukin-7

The disturbance of immune regulatory T cells is related to the pathogenesis of ulcerative colitis. Here we demonstrated and characterized the serum factor from ulcerative colitis patients that induced proliferation of intrathymic T cells. The factor isolated from the patient sera by a combination of gel filtration and anion-exchange chromatography induced proliferation of CD4⁺CD8^– intrathymic T cells in the organ-cultured embryonic mouse thymus. Purification and amino acid sequence analysis of the serum factor demonstrated that the N-terminal 12 sequence was homologous to that of interleukin-7. SDS-PAGE and Western blot confirmed that purified serum factor was interleukin-7. Enzyme immunoassay demonstrated that the serum interleukin-7 concentration was significantly increased in the patients. PCR and Southern blot hybridization demonstrated that interleukin-7 mRNA expression was increased in the thymus tissues from patients but decreased in the colonic mucosa. Since interleukin-7 is a crucial cytokine for proliferation and differentiation of T cells in the thymus, the present study indicates that interleukin-7 may contribute to the disturbance of immune regulatory T cells in ulcerative colitis.     

Non-invasive fibrosis assessments of non-alcoholic fatty liver disease associated with low estimated glomerular filtration rate among CKD patients: the Fukuoka Kidney disease Registry Study

Clinical and Experimental Nephrology - A growing body of evidence has shown that non-alcoholic fatty liver disease (NAFLD) is associated with chronic kidney disease (CKD). Non-invasive fibrosis...     

Accumulation of L-[2-(F-18)]fluorophenylalanine in peri-infarct area in a patient with acute cerebral infarction

We studied the brain uptake of amino acid in a patient with acute cerebral infarction with L-[2-(F-18)] fluorophenylalanine and positron emission tomography. The increased accumulation of the ligand was specifically found in the peri-infarct area where oxygen metabolism was still maintained but decreased later in the 72-day follow-up period. The kinetic analysis revealed that increased accumulation was not due to increased transport from the blood to the brain but to delayed washout from the brain to the blood. Although the mechanism is still unknown, abnormally high accumulation of L-[F-18]fluorophenylalanine may predict delayed neuronal changes after ischemic insults of the brain.     

Effects of activation of renal adenosine A2 receptor on renal function and renin release in dogs.

Direct effects of adenosine A2 receptor activation on renal function were examined in dogs. When renal perfusion pressure was maintained constant at 100 mmHg, renal administration of a selective A2 receptor agonist, CGS 21680C (sodium salt of CGS 21680, 2-[p-(2-carboxyethyl) phenethylamino]-5'-N-ethylcarboxamido adenosine) (1 microg x kg(-) x min (-1)), although it decreased blood pressure by 20 mmHg, increased renal blood flow and renin release, whereas glomerular filtration rate and urine flow were unaffected. These results suggest that stimulation of renal A2 receptor led to both afferent and efferent arteriolar dilatation, whereas renal A2 receptor plays a minor role in urine formation. CGS 21680C induced renin release and tachycardia that were blocked by propranolol, indicating these effects of A2 receptor stimulation appeared to be indirect.     

Role of Ca2+-activated K+ channels in acetylcholine-induced dilatation of the basilar artery in vivo

1. We tested the hypothesis that activation of large conductance calcium-activated potassium channels is involved in dilator responses of the basilar artery to acetylcholine in vivo. Using a cranial window in anaesthetized rats, we examined responses of the basilar artery to acetylcholine.
2. Topical application of acetylcholine (10⁻⁶ and 10⁻⁵ M) increased diameter of the basilar artery from 238±7 μm to 268±7 and 288±7 μm, respectively (P<0.05 vs. baseline diameter). Iberiotoxin (10⁻⁸ M), an inhibitor of large conductance calcium-activated potassium channels, did not affect baseline diameter of the basilar artery. In the presence of 10⁻⁸ M iberiotoxin, 10⁻⁶ and 10⁻⁵ M acetylcholine increased diameter of the basilar artery from 239±7 μm to 246±7 and 261±7 μm, respectively. Thus, iberiotoxin attenuated acetylcholine-induced dilatation of the basilar artery (P<0.05).
3. Sodium nitroprusside (10⁻⁷ and 10⁻⁶ M) increased diameter of the basilar artery from 242±9 μm to 310±12 and 374±13 μm, respectively (P<0.05 vs. baseline diameter). In the presence of iberiotoxin (10⁻⁸ M), sodium nitroprusside (10⁻⁷ and 10⁻⁶ M) increased diameter of the basilar artery from 243±6 μm to 259±9 and 311±12 μm, respectively. Thus, iberiotoxin attenuated dilator responses of the basilar artery to sodium nitroprusside (P<0.05).
4. Iberiotoxin partly inhibited dilator responses of the basilar artery to forskolin, a direct activator of adenylate cyclase, but did not affect vasodilatation produced by levcromakalim, a potassium channel opener.
5. These results suggest that dilator responses of the basilar artery to acetylcholine and sodium nitroprusside are mediated, in part, by activation of large conductance calcium-activated potassium channels. Because both acetylcholine and sodium nitroprusside have been shown to activate guanylate cyclase via nitric oxide, activation of large conductance calcium-activated potassium channels may be one of the major mechanisms by which cyclic GMP causes dilatation of the basilar artery in vivo.