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Estrogen receptor (ER) concentrations have been determined in 191 freshly prepared cytosols from breast cancer biopsies using both the monoclonal enzyme immunoassay (ER-EIA) and the dextran-coated charcoal (ER-DCC) methods in a single laboratory. The concentrations of the ER detected using the two methods are highly and significantly correlated (linear regression curve: ER-EIA = 15.5 + 0.82 ER-DCC; r = 0.97). Nevertheless, it may be most correct to interpret the data by resolving the correlation into two lines, one describing the fit for cytosols with low and intermediate concentrations (the first 75% of the distribution of ER values for all primary breast cancers; less than 217 fmol ER/mg cytosol protein) and one describing the fit for cytosols with the highest ER concentrations (i.e., greater than or equal to 217 fmol ER/mg cytosol protein). Using a cutoff limit of 10 fmol/mg cytosol protein to distinguish between ER positive and ER negative biopsies, discrepancies in the classification of ER status were found in only 6% (12 of 191) of the cases using the two different methods. In all 12 cases, the ER concentrations as determined by both methods were in the lower range of receptor concentrations (0-53 fmol/mg cytosol protein). Of the 12 discrepancies, 10 biopsies were classified as ER negative using the ER-DCC method but ER positive using the ER-EIA method. Additional available data for these 10 patients indicate that the ER-EIA assay yielded the more biologically "correct" result. All 10 of these biopsies were either progesterone receptor positive or had nuclear ER. By identifying the outliers of the linear regression curves (points exceeding the 80% confidence interval) of the logarithmically transformed ER concentrations, 9 of the 12 biopsies were identified. Thus, it is unlikely that the observed discrepancies are due to random events in most cases here. Since most of the few deviations observed appear to represent true differences in the sensitivities of the two methods, the ER-EIA method appears to be superior to the ER-DCC method in our hands. The concentration of ER in 47 cytosols stored at -70 degrees C for 3-6 yr was analyzed using the ER-EIA method, and results were compared to the concentration of ER found using the ER-DCC method on freshly prepared cytosols when the biopsies had been received at the laboratory. The linear regression curve of the correlation between ER concentrations determined using the two methods did not differ significantly from that found for the 191 freshly prepared cytosols.

2A new calcitonin analogue, model calcitonin III (MCt-III), has been synthesized, and its biological and physical characteristics have been studied. This analogue has an idealized alpha-helix from residue 8-22 with glutamate at position 15 interrupting an otherwise continuous surface of aliphatic side chains (those of leucine residues) on the hydrophobic face of the helix. MCt-III differs from a previous model, MCt-II, only by the substitution Leu15----Glu and is here compared with salmon calcitonin I (sCt-I) and MCt-II to elucidate further the role of the putative amphiphilic alpha-helix in determining biological and physical properties of the hormone. MCt-III shows physical properties intermediate between those of sCt-I and MCt-II, demonstrating the influence of appropriately positioned single residues on properties of amphiphilic structures. In our two biological assays, a brain-binding assay and an in vivo hypocalcemic assay, MCt-III reproduces the sigmoidal dose-response curves of sCt-I; this contrasts with the behavior of MCt-II, which demonstrated unusual dose-response curves in these two assays. MCt-III is almost three times more potent than sCt-I in our hypocalcemic assay; this activity groups MCt-III among the most potent known analogues of sCt-I.

Two hundred fifty pediatric (less than 18 years of age) patients underwent orthotopic liver transplantation because of end-stage liver disease and were given combination therapy with cyclosporine and prednisone. The most common indications for transplantation in decreasing order of frequency were biliary atresia, inborn errors of metabolism, and postnecrotic cirrhosis. The 5-year actuarial survival for the entire group was 69.2%. Age and diagnosis did not influence survival. Infections were the most common cause of death, followed by liver failure and cerebrovascular accident. The impact of retransplantation on survival depends on the indication. The survival is better when retransplantation is carried out after rejection than because of technical complications, and the latter has a better survival than does primary graft nonfunction. The difference in survival among these groups is statistically significant. The quality of life for 164 of 173 survivors is good to excellent; only nine children are currently experiencing medical problems. A persistent problem in pediatric transplantation is the scarcity of small donors.

We have adapted a commercially available enzyme immunoassay for ER (ER-EIA) for use with nuclear extracts of breast carcinoma specimens, and have examined the data obtained in relation to the results from cytosolic ER-EIA and radioligand (DCC) assays and from DCC assays for PgR. In a series of 139 carcinoma specimens, we observed a very significant correlation between the cytosolic ER concentration as measured by the EIA and DCC methods, and also between the log10 of the concentration of ER in the cytosolic and nuclear fractions assayed by the ER-EIA method. The correlation between nuclear ER and cytosolic PgR was also highly significant, but not as close as for cytosolic ER. If 130 fmol ER/mg DNA was used as a "cut-off" point to discriminate between specimens "positive" and "negative" for ERN, there was 87% concordance in receptor status between ERN and cytosolic ER, and 79% concordance between ERN and cytosolic PgR. Forty-one percent of specimens were positive or borderline for both ERN and cytosolic PgR, and it is suggested that this receptor combination may be a valuable predictive factor in prognosis and response to hormonal treatment.

The gene for Escherichia coli leucyl-tRNA synthetase leuS has been cloned by complementation of a leuS temperature sensitive mutant KL231 with an E.coli gene bank DNA. The resulting clones overexpress leucyl-tRNA synthetase (LeuRS) by a factor greater than 50. The DNA sequence of the complete coding regions was determined. The derived N-terminal protein sequence of LeuRS was confirmed by independent protein sequencing of the first 8 aminoacids. Sequence comparison of the LeuRS sequence with all aminoacyl-tRNA synthetase sequences available reveal a significant homology with the valyl-, isoleucyl- and methionyl-enzyme indicating that the genes of these enzymes could have derived from a common ancestor. Sequence comparison with the gene product of the yeast nuclear NAM2-1 suppressor allele curing mitochondrial RNA maturation deficiency reveals about 30% homology.

The expression of the pS2 gene, which is induced by estrogen in the breast cancer cell line MCF-7, has been investigated in breast cancers by using pS2 mRNA determination in tumor specimens and immunocytochemistry to identify pS2 protein in paraffin-embedded sections. Using these assays we show that determination of pS2 gene expression allows the definition of subclasses of estrogen-receptor-containing breast cancers that may be used to more precisely identify estrogen-dependent tumors. Tumor specimens have also been analyzed for the presence of mRNAs for the estrogen receptor and for the ERBB2 oncogene. No evidence for the presence of truncated forms of estrogen-receptor mRNA has been found, and overexpression of the ERBB2 oncogene did not correlate with the steroid receptor status or pS2 gene expression.

The authors studied 48 cases of well-differentiated lymphocytic neoplasms using a panel of monoclonal antibodies applied to frozen sections. Forty-seven tumors expressed monotypic immunoglobulin, one or more B-lineage antigens, and Ia (HLA-DR) antigen. Proliferation centers expressed the T9 antigen and increased numbers of Ki-67-positive cells. One tumor was of T-cell origin, had a cytotoxic/suppressor cell phenotype, and showed anomalous loss of Leu-1 antigen. Immunophenotypic findings were correlated to the clinical presentation and morphologic features of each neoplasm. Sixteen tumors were associated with peripheral lymphocytosis (greater than 4000/cu mm), 13 biopsies were obtained from extranodal sites, 16 tumors had proliferation centers, and 11 neoplasms had plasmacytoid features. The authors found no absolute and few statistically significant immunologic differences between the B-cell tumors according to their clinical presentation or morphologic features. Tumors associated with peripheral lymphocytosis more commonly expressed the Leu-1 antigen (P less than 0.01) and IgD (P less than 0.01) and less frequently were stained by BA-2 (P less than 0.05) and OKT9 (P less than 0.05). Plasmacytoid neoplasms more frequently expressed the Tac (P less than 0.01) and T9 antigens (P less than 0.05), and all expressed kappa light chain (P less than 0.05). Extranodal neoplasms more commonly expressed IgM (P less than 0.01). In contrast to the markedly different clinical presentation and morphologic appearance these tumors may have, the immunologic data suggest that B-cell small lymphocytic neoplasms are relatively homogeneous. For an individual case, immunophenotype does not predict clinical presentation or morphologic features.

The profile of urinary salicylate metabolites was determined after an oral administration of acetylsalicylic acid (ASA) to: 1, control rats; 2, rats treated with CCl4 and 3, rats intoxicated with CCl4 and also pretreated with colchicine for 7 days. The following enzymatic activities were determined: liver and plasma ASA-esterase, liver UDP-glucuronyltransferase and liver aniline hydroxylase. The time course of plasma concentration of salicylates in similar groups were followed after the intraperitoneal administration of acetylsalicylic acid (ASA), salicylic acid (SA) or gentisic acid (GA). The animals acutely intoxicated with CCl4 showed a reduction in urinary excretion of glucuronates and an increased urinary excretion of gentisic and salicylic acids. The activities of plasma and liver ASA-esterases were significantly increased in CCl4-treated rats while the aniline hydroxylase was reduced and the UDP-glucuronyltransferase remained unchanged. The plasma half lives of salicylates were reduced in CCl4-treated rats regardless of the administered parent compound. Colchicine pre-treatment completely prevented the alterations produced by acute intoxication with CCl4. The heterogeneity of liver metabolic dysfunctions present in acute liver damage was evidenced. It is emphasized that the pharmacokinetic alterations produced by acute liver injury can be the result of complex factors that may involve changes in circulation, hepatic binding protein and other routes of elimination.

In view of the possible introduction of screening programmes, this study compares oestrogen receptor (ER) levels in a series of women whose primary tumour was detected by screening and an age-matched consecutive series of women whose tumours were diagnosed after symptomatic presentation. Because of missing data and other statistical considerations, the comparison was made using T1 and T2 categories of tumour only. Some differences were found: the distribution of ER levels was significantly different in the two groups, with more extreme values in the symptomatic series; the screening series, however, had more moderate/rich ER levels than the symptomatic group. Tumours of special pathological type (for example, tubular, cribriform, lobular, medullary, and mucoid) were more likely to be ER-moderate or -rich, and there were more of these tumours in the screening series. The relationship of these findings to tumour growth rate is discussed. The study highlights the difficulty of obtaining sufficient tissue for conventional DCC biochemical assays from the small non-invasive tumours found by screening, and suggests that newer alternative methods employing monoclonal antibodies may be required for such types of tumour.

In spite of its unpredictable kinetics, heparin is still not generally monitored during peripheral vascular surgery. To evaluate heparin levels and neutralisation, plasma heparin concentrations were measured using a chromogenic substate method during 20 consecutive operations on the Abdominal Aorta. This was combined with measuring activated partial thromboplastin time (APTT), thrombin time (ThT), prothrombin time (PT), antithrombin-III (AT-III) and fibrinogen concentration. Heparin concentration 5 min after administration and the elimination rate showed a wide variation. Using a standard dosage for all patients resulted in plasma heparin levels that are potentially too low in some patients. The APTT and ThT were found to be unsuitable for an exact calculation of heparin levels. Protamine administration based on the surgeon's judgement of haemostasis was inadequate. Furthermore an intraoperative decrease of AT-III and fibrinogen was seen in eight patients. It is advisable and possible to have direct monitoring of heparin concentration during peripheral vascular surgery.

Nanostructural features in some ceramics have been discussed and reviewed. Based on our research results and recent published investigations, many topics, such as grain, grain boundary, interface film, grain boundary engineering, microcrack, microdomain, nanodomain, domain boundary, and phase transformation, etc., have been dealt with; and many materials, such as Si3N4, beta''-Al2O3, MgO, SiC, (Hg, Cd) Te, BNN, ZrO2, PLZT, CdSe, Ca10(PO4)6, (OH)2, etc., have been involved. The results are important to understand the relation between the structure and property of materials and to improve the materials' technology.

Over a 2-month period, 40 patients with untreated malignancy were studied for protein-C (PRC), antithrombin-III (AT-III), fibrinopeptide A (FPA), routine hemostatic screens, and presence of liver metastases to determine pretreatment changes of hemostasis and relate them to subsequent development of thrombotic or hemorrhagic complications. These patients were observed for a mean period of 18 months. There were 23 males and 17 females with a median age of 64 years. Nine patients had lung carcinoma, 8 colon carcinoma, 7 lymphoma, 5 breast carcinoma, 5 head and neck carcinoma, 2 acute leukemia, 2 prostate carcinoma, 1 adenocarcinoma of unknown primary, and 1 sarcoma. Eight patients had liver metastases. PRC was measured by ELISA, AT-III by radial immunodiffusion, and FPA by RIA. Four patients had decreased AT-III, 28 had decreased levels of PRC, and 39 had elevated levels of FPA. All patients with liver metastases had low PRC. Albumin levels were lower in patients with low PRC (mean 3.3 g/dL v 4.0 g/dL for others). Eight patients, five with liver metastases, developed thrombotic (4), hemorrhagic (3), or both (1) complications. Statistically significant associations were found between (1) presence of liver metastases and development of thrombotic and hemorrhagic complications (P less than .001), (2) presence of liver metastases and decreased PRC (P = .001), and (3) lower albumin levels and decreased PRC (P = .0001). Our study documents early changes of hemostasis in untreated malignancy. We extend previous observations that decreased PRC levels in malignancy may be due to poor synthetic functions of liver. Presence of liver metastases was the only factor associated with subsequent development of thrombotic and hemorrhagic complications. Biochemical markers of hemostatic abnormalities, even though encountered frequently at the time of presentation, are of little predictive value for development of thrombotic and hemorrhagic complications.