Hyperplasia and tumors of the parathyroid glands

Zusammenfassung Die verschiedenen Formen des Hyperparathyreoidismus werden überwiegend von Hyperplasien und Adenomen der Nebenschilddrüsen verursacht. Während früher die Diagnose des Pathologen (meist schon im intraoperativen Gefrierschnitt) für das chirurgische Vorgehen maßgebend war, wird das Operationsausmaß heute überwiegend durch die wesentlich verbesserte präoperative Diagnostik bestimmt (bildgebende Verfahren) und durch den nach der Entfernung der vergrößerten Nebenschilddrüse(n) intraoperativ gemessenen Abfall des Parathormons kontrolliert. Nichtsdestotrotz sollte dem Pathologen die morphologische Differenzialdiagnose der Hyperplasie, des Adenoms und Karzinoms der Nebenschilddrüsen geläufig sein.

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Status of hepatitis B virus DNA in hepatocellular carcinoma: a study based on paired tumor and nontumor liver tissues

To investigate the hepatitis B virus (HBV) DNA status in the liver when hepatocellular carcinoma (HCC) has developed, 35 paired nontumorous and tumorous liver tissues from 27 hepatitis B surface antigen (HBsAg)-seropositive and 8 HBsAg-negative patients with HCC were studied by Southern blot analysis. The hybridization patterns of HBV DNA were different in the nontumor and tumor parts in 26 (96.3%) of the 27 HBsAg-positive patients. In the nontumor parts, integration of HBV DNA into the host genome was significantly less when compared to the tumor parts (15/27 vs. 25/27, P less than 0.05), whereas free replicative viral forms were significantly more frequent (17/27 vs. 7/27). The integrated HBV DNA in the nontumor parts showed discrete band patterns in the majority of cases (13/15). Hepatitis B e antigen (HBeAg) was significantly associated with the expression of free replicative forms of HBV DNA in the tumor tissues. An integrated HBV DNA sequence was detected in the tumor part of one HBsAg-negative patient, but not in her nontumor counterpart. Our observation that discrete integrated HBV DNAs are present in the nontumor part, representing subclinical clonal expansion that precedes the development of HCC, suggests the risk of future new tumor growth from these cell clones.     

Novel neuritic clusters with accumulations of amyloid precursor protein and amyloid precursor-like protein 2 immunoreactivity in brain regions damaged by thiamine deficiency.

Experimental thiamine deficiency (TD) is a classical model of a nutritional deficit associated with a generalized impairment of oxidative metabolism and selective cell loss in the brain. In rats, TD-induced cell degeneration is accompanied by an accumulation of amyloid precursor protein (APP)/amyloid precursor-like protein 2 (APLP2) immunoreactivity in abnormal neurites and perikarya along the periphery of, or scattered within, the lesion. Prompted by these data and our previous findings of a genetic variation in the development of TD symptoms, we extended our studies to mice. C57BL/6, ApoE knockout, and APP YAC transgenic mice received thiamine-deficient diet and pyrithiamine injections. Unlike rats, APP/APLP2-immunoreactive neurites in all strains of mice were sparsely scattered within damaged areas and did not delimit the thalamic lesion. In addition, abnormal clusters of intensely immunoreactive neurites occurred only in areas of damage including the thalamus, mammillary body, and inferior colliculus. The clusters appeared as either irregular clumps or round or oval rosettes that strikingly resembled the neuritic component of Alzheimer amyloid plaques. However, immunostaining using various antisera to synthetic amyloid beta-protein (A beta 1-40) and thioflavine S histochemistry failed to show evidence of a component of A beta Neither APP/APLP2-immunoreactive clusters nor amyloid plaques were observed in the brain from patients with Wernicke-Korsakoff syndrome, the clinical manifestation of TD in man. Our results demonstrate species (i.e., genetic) differences in the response to TD-induced damage and support a role for APP and APLP2 in the response to brain injury. This is the first report that chronic oxidative deficits can lead to this novel pathology.     

Recombinant hepatitis delta antigen from E. coli promotes hepatitis delta virus RNA replication only from the genomic strand but not the antigenomic strand

Hepatitis delta antigen (HDAg) of hepatitis delta virus (HDV) typically consists of two related protein species. The small HDAg (S-HDAg) is a 24-kDa protein of 195 amino acids and the large HDAg (L-HDAg) is a 27-kDa protein with an additional 19 amino acids at its C-terminus. These two proteins have distinct functions in the HDV life cycle. We have developed conditions for expressing S-HDAg and L-HDAg in E. coli as soluble proteins to facilitate large-scale purification. These proteins were purified to homogeneity and shown to be biologically active. Transfection of the purified recombinant S-HDAg together with HDV genomic RNA resulted in viral RNA replication. Surprisingly, the purified S-HDAg could not initiate replication from the antigenomic-sense HDV RNA, even though the latter led to RNA replication when transfected with an mRNA encoding the S-HDAg. These results suggest that initiation of HDV RNA synthesis from the antigenomic RNA may require a form of HDAg that is modified in mammalian cells; in contrast, RNA synthesis from the genomic RNA could be initiated by the recombinant S-HDAg from E. coli. Interestingly, the purified L-HDAg appeared as multiple protein species, including one corresponding to S-HDAg, probably as a result of degradation. The partially proteolyzed L-HDAg also initiated HDV RNA replication under the same conditions. These results add to the mounting evidence that genomic- and antigenomic-strand HDV RNA syntheses are carried out by different mechanisms.     

Selective decline in protein F1 phosphorylation in hippocampus of senescent rats

Certain forms of neuronal plasticity have been found to be expressed through alterations in brain protein phosphorylation, and its regulation by protein kinase activity. Of interest in this regard is the possibility that the decline in neuronal plasticity and cognitive function that occurs in advanced age may result in part from altered phosphorylation of specific proteins. As a first attempt to identify age-related changes in phosphoproteins, we assayed in vitro phosphorylation of proteins in hippocampus, cerebellum, entorhinal cortex, and frontal cortex from Fischer-344 rats of 5 months, 11 months, and 25 months of age. Compared to the middle-aged animals, the aged rats showed a selective 46% decline in phosphorylation of the 47 kDa protein (F1) in hippocampus, with no change in the phosphorylation of other proteins measured in this structure. Aged animals also showed decreased phosphorylation relative to young animals. No age-related change was observed in any protein band for the other brain areas examined. Since protein F1 is phosphorylated by protein kinase C (PKC), the cytosolic and membrane distribution of this enzyme was compared across age groups. The activity of PKC in hippocampus did not change across age. The explanation of this age-related decline in protein F1 phosphorylation is likely to be a decline in the substrate protein itself. The results are discussed in terms of protein F1's possible role in age-related decline of hippocampal synaptic plasticity.     

A comparative study on commercial samples of phellodendri cortex

A total of 31 commercial samples of Phellodendri cortex (Rutaceous plant) which originated from PHELLODENDRON AMURENSE Ruprecht, P. CHINENSE Schneid, P. WILSONII Hayata et Kanehira, and P. AMURENSE Rupr. var. SACHALINENSE Fr. Schm., respectively, were collected from the Taiwan and Japan herbal markets. The contents of five quaternary alkaloids (berberine, palmatine, jatrorrhizine, phellodendrine and magnoflorine) in these samples were determined by capillary electrophoresis. It was found that P. WILSONII (4.10 +/- 0.78%) and P. AMURENSE var. SACHALINENSE (4.18 +/- 1.03%) were superior to P. AMURENSE (1.55 +/- 0.72%) and P. CHINENSE (1.54 +/- 0.60%). Berberine was the major alkaloid in almost all samples. In comprised about 80% of the total alkaloids in the first two of the four herbs named above, but only about 40% in the latter two. From the data on the chemical analysis of the herb's constituents, as well as the herb's texture and color, we can postulate the origin and quality of a herb drug.     

46,XY gonadal dysgenesis associated with congenital nephrotic syndrome and sepsis

The occurrence of nephrosis in the first 3 months of life is rare and is termed ’congenital nephrotic syndrome.’ The congenital nephrotic syndrome is a group of heterogeneous diseases with a clinical course that differs markedly from the childhood nephrotic syndrome. The coexistence of a congenital nephrotic syndrome and gonadal dysgenesis in a 46,XY karyotype with normal female external genitalia is extremely rare. Frequent severe infections are often seen in the Finnish type, but sepsis leading to death is rare in the neonatal onset of gonadal dysgenesis. This report describes an unusual case of complete XY gonadal dysgenesis in a 46,XY female neonate with the congenital nephrotic syndrome and overwhelming sepsis. Received: 4 January 1999 / Revised: 24 May 1999 / Accepted: 25 May 1999     

A DLST genotype associated with reduced risk for Alzheimer's disease

Recent studies suggest that variants of the DLST gene alter the risk of AD. DLST encodes the core subunit of the mitochondrial alpha-ketoglutarate dehydrogenase complex, which is deficient in AD. The authors report that in 247 US white subjects, homozygosity for DLST A19,117, T19,183 was associated with a reduced risk of AD (odds ratio [OR] = 0.35, p = 0.018). The reduced risk was marked in subjects who did not carry the apolipoprotein (APOE)-4 allele (OR = 0.16, p = 0.014). Further study of DLST in AD appears warranted.     

Higher gastric cycloxygenase-2 expression and precancerous change in Helicobacter pylori-infected relatives of gastric cancer patients.

PURPOSE: This study was conducted to determine whether relatives of gastric cancer patients (GCF) showed greater gastric cycloxygenase-2 (COX-2) expression or a greater incidence of precancerous lesions after Helicobacter pylori infection and whether H. pylori eradication could reduce COX-2 expression. EXPERIMENTAL DESIGN: Three hundred subjects were enrolled in this study: half were relatives of 50 H. pylori-infected gastric cancer patients, and half were relatives of 50 H. pylori-infected duodenal ulcer (DU) patients (controls). Each relative underwent endoscopy to detect H. pylori infection and related gastric histology. One hundred and twenty GCFs were found to have H. pylori infection. After H. pylori eradication, 90 of the 120 GCFs were followed up with annual endoscopy examinations over the next 2 years. Gastric COX-2 intensity in all of the specimens collected from these patients was immunochemically stained and graded from 0 to 4. RESULTS: H. pylori infection, gastric atrophy, and intestinal metaplasia (IM) were more prevalent in GCFs than in relatives of H. pylori-infected patients with DUs (P < 0.05). H. pylori-infected GCFs also showed a greater COX-2 intensity than H. pylori-infected relatives of patients with DUs (89.1% versus 62.7%, P < 0.001; relative risk: 4.9; 95% confidence interval: approximately 2.34-10.29). Among the H. pylori-infected GCFs, COX-2 intensity correlated with atrophy and IM (P < 0.001). After H. pylori eradication, gastric COX-2 expression disappeared only in those relatives without IM (P < 0.001). CONCLUSIONS: GCFs are more likely to show greater gastric COX-2 expression and a higher incidence of precancerous lesions after H. pylori infection than the relatives of H. pylori-infected patients with only DUs. H. pylori eradication can reverse gastric COX-2 expression in patients without IM but not in patients with IM.     

The influence of hypotonicity on large-conductance calcium-activated potassium channels in human retinal pigment epithelial cells.

The aim of this study was to characterize the effects of hypotonicity on the activity of large-conductance Ca(2+)-activated K+ (BK(Ca)) channels in human retinal pigment epithelial (RPE R-50) cells. Effects of hypotonicity on ion currents were investigated with the aid of the patch-clamp technique. A regulatory volume decrease in response to a hypotonic solution (200 mOsm/L) was observed that could be blunted by paxilline. In whole-cell current recordings, a hypotonic solution (200 mOsm/L) reversibly increased the amplitude of K+ outward currents (I(K)). The increase of I(K) could be reversed by iberiotoxin (200 nM), paxilline (1 microM), or tetrandrine (5 microM), but not by glibenclamide (10 microM), disulphonic acid (DIDS) (100 microM), or dequalinium dichloride (10 microM). In RPE R-50 cells pretreated with thapsigargin, aristolochic acid, or pertussis toxin, the increased amplitude of I(K) in response to hypotonicity was unaltered. In cell-attached patches, an increase in BK(Ca)-channel activity was observed during hypotonicity-induced cell swelling. The enhanced channel activity elicited under this condition was mainly mediated by an increase in the number of long-lived openings. These findings support the evidence for the coupling of volume swelling to the functional activity of BK(Ca) channels.