Changes in ultrastructure of hepatocytes and liver test results before,during, and after treatment with interferon-β in patients with HBeAg-positive chronic active hepatitis

We studied the histological and ultrastructural changes in the liver and alterations in the liver test results before, during, and after treatment with human interferon-content/n2p4756502774qr7/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0"> from five patients with hepatitis B e antigen-positive chronic active hepatitis. A daily dose of 3×10⁶ to 6×10⁶ units of interferon-content/n2p4756502774qr7/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0"> was given intravenously for four weeks. The total index of periportal and portal inflammation, intralobular degeneration, and focal necrosis before treatment was decreased significantly six months after treatment (P<0.05). Ultrastructurally, the structure of endoplasmic reticulum was irregularly shaped or fragmentally decreased during treatment, but these disappeared six or 12 months after treatment. Glycogen particles diminished greatly during treatment. The alanine aminotransferase concentrations in these patients increased during treatment. Serum albumin and cholinesterase levels decreased significantly at the fourth week of treatment (P<0.01) and at the third day (P<0.01) to the second week (P<0.05) of treatment, respectively. These results suggest that interferon-content/n2p4756502774qr7/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0"> injures endoplasmic reticulum and glycogen areas and damages the cholinesterase activity in the early stage of treatment and protein synthesis in patients with hepatitis B e antigen-positive chronic active hepatitis.     

Histochemical study of pituitary adenomas with Ki-67 and anti-DNA polymerase α monoclonal antibodies,bromodeoxyuridine labeling,and nucleolar organizer region counts

Summary The growth potential of 65 pituitary adenomas was determined by histochemical analysis with Ki-67 and anti-DNA polymerase content/v5240658vrn8m001/xxlarge945.gif" alt="agr" align="BASELINE" BORDER="0"> monoclonal antibodies, bromodeoxyuridine (BrdUdR) labeling, and counts of argyrophilic nucleolar organizer regions (Ag-NORs). The mean proliferating cell indices (PCIs) determined by Ki-67 and anti-DNA polymerase content/v5240658vrn8m001/xxlarge945.gif" alt="agr" align="BASELINE" BORDER="0"> and the BrdUdR labeling index (LI) were generally very low [1.0±0.2%, 1.1±0.2%, and 0.5±0.1% (±SE), respectively]. Apart from adrenocorticotropic hormone-positive adenomas, which had significantly higher indices, there were no statistically significant differences in the indices among the other subtypes of pituitary adenomas. Recurrent tumors had higher Ki-67 and DNA polymerase content/v5240658vrn8m001/xxlarge945.gif" alt="agr" align="BASELINE" BORDER="0"> PCIs and BrdUdR LIs (3.6%, 4.2%, 1.4%) than primary tumors (0.8%, 0.8%, 0.3%; P<0.005). The number of Ag-NORs did not correlated significantly with any of the three indices. The mean number of Ag-NORs was higher in nonfunctioning adenomas than in functioning adenomas (2.04 vs 1.66, P<0.005); among prolactin-positive adenomas, those treated preoperatively with bromocriptine had more Ag-NORs than untreated tumors (1.75 vs 1.57, P<0.005). These results suggest that the Ki-67 and DNA polymerase content/v5240658vrn8m001/xxlarge945.gif" alt="agr" align="BASELINE" BORDER="0"> PCIs and the BrdUdR LI predict the growth potential of individual pituitary adenomas, whereas the number of Ag-NORs appears to correlate with hormone production rather than with the proliferative potential.Supported by grants CA-13525 and CA-50210 from the National Cancer Institute, by a grant from the Phi Beta Psi Sorority, and by Grant-in-Aid A 63771083 from the Ministry of Education, Science, and Culture of Japan     

Regional brain kinetics of 6-fluoro-(β-11C)-L-dopa and (β-11C)-L-dopa following COMT inhibition. A study in vivo using positron emission tomography

Summary The regional brain kinetics of (content/r45512403483pk3m/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">-11C)-L-dopa and 6-fluoro-(content/r45512403483pk3m/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">-11C)-L-dopa was measured in six Rhesus monkeys using positron emission tomography (PET). Radioactivity accumulated specifically in the striatal region and the increase in L-dopa-derived radioactivity utilization with time was calculated using surrounding brain as a reference area, this being devoid of dopaminergic activity. The rate constant for selective striatal utilization i.e. grossly decarboxylation was 0.0110 ± 0.0007 (S.D) and 0.0057 ± 0.0006 min1 for (content/r45512403483pk3m/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">-11C)-L-dopa and 6-fluoro-(content/r45512403483pk3m/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">-11C)-L-dopa, respectively. After pre-treatment of the monkeys with the peripherally and centrally active catecholamine-O-methyl transferase (COMT) inhibitor Ro 40-7592 10 mg/kg, the decarboxylation rate remained unchanged (0.0112 ± 0.0015 min-1) for (content/r45512403483pk3m/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">11C)-L-dopa, whereas an increase in rate was measured for 6-fluoro-(content/r45512403483pk3m/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">-11C)L-dopa (0.0092 ± 0.0015 min–1). Differences in the distribution of radiolabelled metabolites i.e. the corresponding O-methyl-L-dopa in the reference area is most probably the reason for the difference in calculated decarboxylation rate seen between the radiotracers. The higher decarboxylation rate measured for 6-fluoro-(content/r45512403483pk3m/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">-11C)-L-dopa after blockade of COMT shows that the radiolabelled metabolites i.e. 6-fluoro-O-methyl-(content/r45512403483pk3m/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">-11C)-L-dopa significantly contributes to background radioactivity.     

Plasminogen activation in plasma of patients with systemic lupus erythematosus

Summary We measured content/u82776564551531p/xxlarge945.gif" alt="agr" align="BASELINE" BORDER="0">₂-plasmin inhibitor-plasmin complexes (PI-PC) in plasma of patients with systemic lupus erythematosus (SLE) to examine the plasminogen activation in SLE. The plasma PI-PC level in 23 patients with SLE was significantly higher than that in 18 normal subjects (P<0.001) and the SLE patients with nephrotic syndrome had higher plasma PI-PC levels than those without nephrotic syndrome (P<0.01). In addition, the plasma PI-PC level was significantly correlated with the level of plasma C3 breakdown products (iC3b/C3dg) in the patients with SLE (r=0.53, P<0.01). These results suggest that plasminogen is activated in plasma of patients with SLE and that the plasminogen activation may be associated with the activation of complement in SLE.     

The regional distribution of adenosine-regulating enzymes in the left and right ventricle walls of control and hypertrophic heart

Summary The transmural distribution of the adenosine-generating enzyme 5content/m36421tq26286362/xxlarge8242.gif" alt="prime" align="BASELINE" BORDER="0">-nucleotidase (5content/m36421tq26286362/xxlarge8242.gif" alt="prime" align="BASELINE" BORDER="0">N) and of the adenosine-degrading enzymes adenosine deaminase (ADA), AMP deaminase (AMP-D) and adenosine kinase (Ado-K) were determined across the walls of left and right ventricles of control and hypertrophic rat hearts.The enzyme distribution across the left ventricle wall (but not across the right wall) of normal hearts was not uniform: 5content/m36421tq26286362/xxlarge8242.gif" alt="prime" align="BASELINE" BORDER="0">N activity shows its highest levels in the subepicardial and in the subendocardial regions, whereas all the other enzyme activities show their lowest levels. A similar pattern of transmural distribution was also detected in other mammalian species (ox and pig).In the experimental cardiac hypertrophy, caused by two different types of chronic cardiac overload, the levels and the profiles of transmural distribution of 5content/m36421tq26286362/xxlarge8242.gif" alt="prime" align="BASELINE" BORDER="0">N and ADA enzyme activities may significantly change across the rat left ventricle wall.     

Spectrum of morphological appearance of amyloid deposits in Alzheimer's disease

Summary Immunocytochemical staining with monoclonal antibodies to the content/w0163080366r561t/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">-protein on tissue sections which have been pretreated with formic acid is not only a very specific but also a highly sensitive method for the detection of amyloid deposits in the brains of Alzheimer's disease victims. We report here a spectrum of morphological appearance of the brain amyloid deposits which are one of the main histopathological correlates of this disorder. Deposits of the content/w0163080366r561t/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">-protein are not only found in the well-known lesions [congophilic angiopathy and senile (neuritic) plaques] but are also seen under various morphological forms for which the word content/w0163080366r561t/xxlarge8220.gif" alt="ldquo" align="MIDDLE" BORDER="0">plaquescontent/w0163080366r561t/xxlarge8221.gif" alt="rdquo" align="MIDDLE" BORDER="0"> does not appear an appropriate term: amyloid fibrils are found as large areas of diffuse infiltration of the neuropil, as ribbon-like infiltration in the subpial layer of the cerebral cortex, as granular deposits in the white matter, as diffuse deposits in the molecular layer of the cerebellum and the basal ganglia and as star-shaped deposits in the cerebellar Purkinje cell layer. The morphology of these deposits seems to depend on the cyto-and fibroarchitectonics of the brain region in which they are found, on the amount of amyloid deposited, and also on the type of staining technique used. It is only under specific circumstances that the deposition of amyloid in the neuropil is accompanied by the formation of paired helical filaments in nerve cell processes and their parent perikarya. In conclusion, our studies suggest that the extent of brain amyloidosis in Alzheimer's disease is much wider than so far appreciated.Supported in part by grants 5-AGO-4220-05 and 5-HD-22634-02 from the National Institutes of Heath     

Neuropathy in igMλ paraproteinemia

Summary In axonal neuropathies associated with IgM paraproteinemia, reports of antigen specificity of the M-protein are few. A patient with IgM paraproteinemia presented with progressive mononeuritis multiplex. IgM was found deposited in striking amounts in endoneurium and shown to bind specifically to neural proteins and chondroitin sulfates. Direct immune mechanisms, as well as the physical effects of IgM deposition, likely contributed to the development of the neuropathy.     

Diffuse type of senile plaques in the cerebellum of Alzheimer-type dementia demonstrated byβ protein immunostain

Summary We studied senile plaques (SP) in the cerebella of six autopsied subjects with Alzheimer-type dementia (ATD) and ten non-ATD autopsied subjects between the ages of 78 and 90. Neither SP nor amyloid angiopathy (AA) was observed in any of the non-ATD subjects. In the four of the six ATD subjects, diffuse plaques in the molecular layer were seen as ill-defined areas of fine fibrillar materials by content/xq44h662p9k23kp5/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0"> protein immunostaining with formic acid pretreatment, the modified Bielschowsky stain, and periodic acid-methenamine silver (PAM) stain. The plaques were not visible with Bodian, Congo red, or periodic acid-Schiff stains. Compact plaques in the Purkinje cell or in the granular cell layers were found in three of the six subjects. Their amyloid core was often surrounded by areolar amyloid deposits. AA was observed in three of the six subjects. The argyrophilia of the diffuse and compact plaques, demonstrated by the modified Bielschowsky and PAM stains, became undetectable when the sections were first treated with formic acid. Such treatment made the plaques immunoreactive with content/xq44h662p9k23kp5/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0"> protein antiserum. The findings suggested that cerebellar diffuse plaques and compact plaques consist mainly of an amyloid component, and are characteristic of ATD.     

The sodium channels of the neuroblastoma x glioma 108 CC 15 hybrid cell change their sensitivity for volatile and local anesthetics upon continuous passage

Summary We have studied the ion flux through the sodium channels of low passage number (<50p.) and high passage number (>150p.) neuroblastoma x glioma hybrid cells using [¹⁴C] guanidinium and specific neurotoxins to induce channel opening and closing. The sodium channels of low passage number hybrid cells could be opened by veratridine alone, suggesting the presence of voltage dependent channels in agreement with electrophysiological studies reported in the literature. The sodium channels of the high passage number hybrid cells, however, needed the synergistic action of veratridine and scorpion toxin for activation suggesting that these channels are content/tjgp7t4842138024/xxlarge8220.gif" alt="ldquo" align="MIDDLE" BORDER="0">silentcontent/tjgp7t4842138024/xxlarge8221.gif" alt="rdquo" align="MIDDLE" BORDER="0">. The [¹⁴C] guanidinium ion flux through the sodium channels of the high passage number hybrid cells was inhibited by significantly lower concentrations of the volatile anesthetics (halothane, isoflurane and enflurane) and the lcoal anesthetics (tetracaine and bupivacaine) than the comparable flux through the sodium channels of the low passage number hybrid cells.Dedicated to Prof. Dr. E. Wecker on the occasion of his 65th birthday.