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A wide spectrum of liver disease is seen in general practice. For the most part, asymptomatic increases in transaminase may be followed for several months, but the treatable conditions described should be ruled out early on. It is essential do diagnose as promptly as possible Wilson's disease, hemochromatosis, autoimmune heaptitis, and hepatitis B. Drugs are a frequent cause of wild transaminitis. Heavy alcohol consumption as a cause of liver disease must always be suspected, but may be difficult to prove.

A detailed histopathologic analysis of 399 primary breast carcinomas was performed, and several morphologic features were correlated with the estrogen receptor (ER) status. In all cases ER status was determined immunocytochemically by estrogen receptor immunocytochemical assay (ER-ICA). In 359 carcinomas ER status was also biochemically determined. Invasive lobular, mucoid, and tubular carcinomas rather than ductal carcinomas were ER-positive more frequently in ER-ICA. Medullary and papillary carcinomas had corresponding lower or higher ER positivity, respectively, by both methods. The correlation of histologic grade and its single factors with ER status was statistically significant by both methods. Lymphocytic reaction to tumor showed a significant inverse relationship to ER status by both methods. A statistically significant higher number of ER-positive carcinomas in ER-ICA and dextran-coated charcoal assay (DCC) occurred when elastic tissue was present. Different associations were found between stromal content, tumor diameter, and ER status in DCC and ER-ICA, respectively.

This 26-month prospective study monitored 104 children from one day care center (DCC), and their families, for cytomegalovirus (CMV) infections. Among the children, 14 different strains of CMV were identified by restriction endonuclease analysis of the viral DNA of isolates. Three of these strains infected 44 DCC children and apparently were transmitted within the DCC environment. Only children younger than 3 years of age acquired the DCC-associated CMV strains. Of 75 seronegative children in this age group, 34 acquired DCC-associated CMV strains, and four were infected with unique strains. Among 23 children older than 3 years of age, none acquired the DCC-associated strains, although six were infected with unique strains. Of 18 seronegative mothers, six acquired CMV infections within 3 to 7 months after their children became infected; the strains were identical to those isolated from their children and were DCC associated. Four fathers, three seropositive mothers, and two caretakers also shed DCC-associated strains of CMV. None of the 31 mothers whose children were not infected shed CMV. There was no apparent CMV-associated morbidity. These results prove the frequent transmission of CMV within the DCC environment and from DCC children to their parents. They further suggest that caretakers do acquire CMV from DCC children.

Genomic DNA clones containing the human and murine genes coding for the 50-kDa T11 (CD2) T-cell surface glycoprotein were characterized. The human T11 gene is approximately equal to 12 kilobases long and comprised of five exons. A leader exon (L) contains the 5'-untranslated region and most of the nucleotides defining the signal peptide [amino acids (aa) -24 to -5]. Two exons encode the extracellular segment; exon Ex1 is 321 base pairs (bp) long and codes for four residues of the leader peptide and aa 1-103 of the mature protein, and exon Ex2 is 231 bp long and encodes aa 104-180. Exon TM is 123 bp long and codes for the single transmembrane region of the molecule (aa 181-221). Exon C is a large 765-bp exon encoding virtually the entire cytoplasmic domain (aa 222-327) and the 3'-untranslated region. The murine T11 gene has a similar organization with exon-intron boundaries essentially identical to the human gene. Substantial conservation of nucleotide sequences between species in both 5'- and 3'-gene flanking regions equivalent to that among homologous exons suggests that murine and human genes may be regulated in a similar fashion. The probable relationship of the individual T11 exons to functional and structural protein domains is discussed.

Bacterial Salmonella enteritidis var. Issatchenko in media without exogenic energy source uptakes K+ in one step with Km 2.1 mM and Vmax 0.08 mM min-1/10(12) cells. This K+ uptake does not depend on pH and osmotic shock and is not inhibited by DCC. Endogenic energy source (glucose) leads to K+ uptake with Km 2.8 mM and Vmax 0.10 mM min-1/10(12) cells, and secretion of H+. The ratio of the DCC-sensitive fluxes of H+ to K+ equals 2. Arsenate and protonophores depress the K+ uptake. Valinomycin decreases the rate of K+ uptake. It is assumed that K+ uptake takes place via the Trk-like system, which works as a separate system as supercomplex with the H+-ATPase complex.

Taking as a model the N-terminal folding of the cholecystokinin tyrosine-sulfated octapeptide [CCK-8; Asp-Tyr(SO3H)-Met-Gly-Trp-Met-Asp-Phe-NH2] deduced from conformational studies, two cyclic cholecystokinin (CCK) analogues were synthesized by conventional peptide synthesis: Boc-D-Asp-Tyr(SO3H)-Ahx-D-Lys-Trp-Ahx-Asp-Phe-NH2 [compound I (Ahx, 2-aminohexanoic acid)] and Boc-gamma-D-Glu-Tyr(SO3H)-Ahx-D-Lys-Trp-Ahx-Asp-Phe-NH2 (compound II). The binding characteristics of these peptides were investigated on brain cortex membranes and pancreatic acini of guinea pig. Compounds I and II were competitive inhibitors of [3H]Boc[Ahx28,31]CCK-(27-33) binding to central CCK receptors and showed a high degree of selectivity for these binding sites (compound I: Ki for pancreas/Ki for brain, 179; compound II: Ki for pancreas/Ki for brain, 1979). This high selectivity was associated with a high affinity for central CCK receptors (compound I: Ki, 5.1 nM; compound II: Ki, 0.49 nM). Similar affinities and selectivities were found when 125I Bolton-Hunter-labeled CCK-8 was used as a ligand. Moreover, these compounds were only weakly active in the stimulation of amylase release from guinea pig pancreatic acini (EC50 greater than 10,000 nM) and were unable to induce contractions in the guinea pig ileum (to 10(-6) M). The two cyclic CCK analogues, therefore, appear to be synthetic ligands exhibiting both high affinity and high selectivity for central CCK binding sites. These compounds could help clarify the respective role of central and peripheral receptors for various CCK-8-induced pharmacological effects.

Steroid hormone receptors were studied in 45 patients with primary, recurrent, or metastatic ovarian cancer in cryostat-frozen sections and imprint preparations. The ligands, 17 B-estradiol-6-carboxymethyloxine-bovine serum albumin fluorescein isothiocyanate (FITC-BSA estradiol) and hydroxyprogesteronehemisuccinate bovine serum albumin tetramethylrhodamine isothiocyanate (TMRITC-BSA progesterone) were used in the fluorescent cytochemical method. Results were compared with standard dextran-coated charcoal (DCC) biochemical assay. An overall significant correlation between biochemical values and cytochemical results was found. However, the imprint results were more sensitive and more specific than the frozen section results. A statistically significant difference (P less than 0.05) was observed between touch preparation material and frozen section specimens by the fluorescent method.

We have studied the merit of a new enzyme immunoassay (EIA) in relation to the results obtained with a conventional dextran-coated charcoal assay (DCC) of estrogen receptors (ER) in cytosols and nuclear extracts of human breast cancer tissue. The results of the two assays were related to cytosolic progesterone receptor content (PgR), semiquantified ER content in formalin-fixed paraffin embedded tissue specimens and tumor differentiation. The EIA was found stable at low cytosol protein concentrations (0.5 mg/ml). The EIA and DCC assays were highly correlated both in cytosols (r = 0.92, n = 57) and nuclear extracts (r = 0.82, n = 25), but the EIA slightly overestimated the ER values in both ER fractions. A significant correlation between ER in nuclear (ER(N] and cytosolic (ER(C] fractions was established with both assays (DCC: r = 0.90, n = 56; EIA: r = 0.83, n = 24). A qualitative relationship was established between PgR and ER fractions as determined with both assays, the best quantitative association was between PgR and ER(N(DCC] (r = 0.58, n = 34, P less than 0.001). A significant qualitative and quantitative relationship was found between semiquantified ER content in formalin-fixed, paraffin-embedded tissue and ER(C(DCC] (r = 0.88), ER(N(DCC] (r = 0.86], ER(C(EIA] (r = 0.60), ER(N(CIA] (r = 0.64) and PgR (r = 0.65). Finally, we found tumor differentiation to be significantly associated with ER content as determined with all assays except for ER(N(EIA]. We recommend the use of the DCC assay for routine analysis of ER until the clinical correlation of EIA results has been established.

Functional assays for heparin cofactor II (HC-II) are based on the inactivation of thrombin by HC-II in the presence of dermatan sulfate (DS). Residual thrombin is measured in a chromogenic assay. Interference by the antithrombin-III (AT-III)/heparin complex, which also rapidly inactivates thrombin, must be eliminated from the HC-II test system. Commercial DS is contaminated with heparin, while plasma specimens to be tested contain AT-III. After NaNO2/acetic acid treatment of DS (to inactivate heparin), there was enough residual heparin to cause AT-III interference. Treatment of plasma with commercially available anti-AT-III antiserum largely, but not completely, removed AT-III interference from the HC-II assay. With commercially available reagents, both NaNO2/acetic acid treatment of DS and anti-AT-III treatment of plasma were needed to eliminate heparin/AT-III interference. Protamine sulfate inactivated DS as well as heparin and could not be used to reduce AT-III/heparin interference with the HC-II assay.

Lysosomal structures in liver parenchymal cells of 3 patients with iron overload and of 3 subjects without iron-storage disorders were investigated. A combination of enzyme cytochemistry--with cerium as a captive ion to demonstrate lysosomal acid phosphatase activity--and electron probe X-ray microanalysis (EPMA) was used. We were able (1) to define and quantify lysosomal structures as lysosomes, siderosomes, or residual bodies, (2) to quantify the amount of iron and cerium simultaneously in these structures, and (3) to evaluate a possible relation between iron storage and enzyme activity. With histopathologically increased iron storage, the number of siderosomes had increased at the cost of lysosomes, with a corresponding increase in acid phosphatase activity in both organelles. In histopahtologically severe iron overload, however, acid phosphatase activity was low or not detectable and most of the iron was stored in residual bodies. After phlebotomy treatment, the number of siderosomes had decreased in favor of the lysosomes, approaching values obtained in control subjects, and acid phosphatase activity was present in all iron-containing structures. In this way a relationship between iron storage and enzyme activity was established. The iron content of the individual lysosomal structures per unit area had increased with histopathologically increased iron storage and had decreased after phlebotomy treatment. From this observation, it is concluded that the iron status of the patient is not only reflected by the amount of iron-containing hepatocytes but, as well, by the iron content lysosomal unit area.