Gene Literature Dashboard

Evaluation of estrogen receptors (ERs) is essential for the treatment and prognosis of human breast cancer. The authors have undertaken a study of 225 primary breast cancers to compare the receptor values using immunohistochemistry and enzyme immunoassay (EIA) techniques. The results are compared with the biochemical assay with the use of the dextran-coated charcoal (DCC) method done on the same specimens. The overall concordance between ER-ICA and DCC was 77%. Ninety-seven percent concordance was observed for specimens with a positive ER-ICA score (greater than 70 and the DCC more than 10 fmol/mg protein). Ninety-two percent of tumors had negative results by ER-ICA when the DCC was less than 10 fmol/mg protein. When the ER-ICA score was plotted against the DCC or EIA value, a significant correlation was obtained with a P value of less than 0.001. The correlation between the ER-ICA score and the total ER content (cytosol and nuclear) assayed by EIA was similar to comparison with cytosol alone. The authors conclude that the ER-ICA can be useful in assessing ERs in breast especially in hypocellular or small tumors and in assessing the degree of heterogeneity in a given tumor. The immunohistochemical and biochemical assay methods are complementary and provide greatly needed information for the management of breast cancer.

Serum levels of 4 protease inhibitors, alpha-1-antitrypsin, C1-inactivator, alpha-2-macroglobulin and antithrombin-III were measured in 11 patients with amyotrophic lateral sclerosis (6 males and 5 females) and a control group without neurologic disease. Our results indicated no significant differences in the level of serum alpha-2-macroglobulin between the 2 groups. We found slight but significantly lower levels of serum antithrombin-III in ALS. The possibility of the participation of proteases or protease inhibitors in the pathogenesis of ALS is discussed.

The development and long-term performance of a radioimmunoassay method for cardionatrin (C I = ANF 99-126) is described. The method was evaluated for accuracy, specificity and precision using different protocols and in various species. The antiserum raised against C I cross-reacts 100% with both human and rat C I and 122% with cardionatrin IV (C IV = ANF 1-126). Dextran-coated charcoal (DCC) and double antibody (DA) disequilibrium protocols were used for the separation of free from antibody-bound radioactivity. The sensitivity, coefficient of variation within assay and between assay for DCC was 4.6 pg/tube, 3.1% and 13.8% respectively, and 1.5 pg/tube, 3.8% and 9.1% for the DA. The mean normal plasma C I levels in human, rat and dog after plasma acidification and extraction using the DA method was 49.7 +/- 4.0; 253.6 +/- 19.6 and 59.9 +/- 3.4 pg/mL respectively.

In a prospective study with cross-over design 20 patients with insulin-dependent diabetes mellitus of more than 2 years duration were treated for 6 months with continuous subcutaneous insulin infusion (CSII) and multiple insulin injections (MII). Metabolic control, platelet aggregability, thromboxane B2 levels in serum and plasma as well as antithrombin III (ATIII) activity and von Willebrand factor antigen were evaluated. A good metabolic control was obtained by both intensified regimens. No difference could be demonstrated between either platelet function tests or serum level of von Willebrand factor antigen during treatment with CSII and MII. However, the plasma level of ATIII activity was significantly higher (P less than 0.01) during MII treatment as compared to CSII treatment. There was no correlation between ATIII activity and daily insulin requirement or serum fructosamine. In conclusion, long-term metabolic control with MII has a favourable effect on ATIII activity in plasma. This may be important for a delay in onset and progression of diabetic vascular complications.

In order to carry out a multicenter study aimed at understanding the association of hemostatic factors with atherosclerotic vascular disorders for the Atherosclerosis Risk In Communities (ARIC) Study, we compared a blood collection and processing system developed in our laboratory with the state-of-the-art-procedures. The salient features of our system included the use of a new phlebotomy set for venipuncture, the use of Millipore filters for removing platelet residues in the plasma and the use of a mixture of anticoagulants and antiplatelet agents for inhibiting the in vitro activation of platelets, coagulation and fibrinolytic system. The results derived from systematic evaluations indicate that this newly developed system yields the lowest values of plasma beta TG, PF 4 and FPA when compared with the reported values. The technique also gave reliable values of representative hemostatic measurements such as fibrinogen, factor VII, factor VIII, von Willebrand factor, antithrombin-III, protein C, tissue-type plasminogen activator, and serum thromboxane B2. Further experiments revealed that the samples withstood temporary storage at -70 degrees C and overnight "shipping" manipulations without significant changes in the hemostatic values. We conclude that the described blood collection and processing system may be a valuable asset for conducting multicenter cooperative clinical trials and epidemiologic studies involving blood collection by multiple field centers or clinics.

Both congenital and acquired antithrombin-III (AT-III) deficiencies are amenable to replacement therapy. We describe two antithrombins produced by recombinant DNA techniques from human alpha 1-antitrypsin (alpha 1AT) cDNA in yeast. Alteration of the alpha 1AT active site, replacing methionine 358 with arginine, results in a thrombin inhibition rate similar to that of heparin-activated AT-III. Alteration of two further residues, to give a five-residue sequence identical to AT-III, does not increase this rate further. Neither antithrombin is activated by heparin; both are unglycosylated and have shorter in vivo half-lives (t1/2) than human alpha 1AT. These antithrombins should be suitable for therapeutic replacement of AT-III in cases of congenital deficiency and in conditions associated with acquired AT-III deficiency, such as disseminated intravascular coagulation.

Today, the immuncytochemical demonstration of estrogen receptors can be regarded as established. Recently, a monoclonal antibody (mab) against the progesterone receptor-complex became commercially available. The antibody Mi 60-10, developed by Milgrom and co-workers, is murine and principally directed against the progesterone receptor of the rabbit, but it also attacks an "epitop" of the human receptor. The Western-Blot analysis shows the antibody having several specific bands against T-47-D cells in the region of 110,000 dalton. To estimate the practical performance of this antibody, 73 primary breastcarcinomas were incubated with both the ER-ICA-Kit and the new "mab". The PAP method was used for visualisation. In a frozen section the mab Mi 60-10 proved as successful as the ER-ICA-Kit. However, in contrast to the ER-ICA-Kit, the mab Mi 60-10 is also successful in locating the receptor, also in formalin-fixed samples embedded in paraffin. This is also the case with blocks, which were stored for several years. In aspirated cytological samples the immunocytochemical demonstration of progesterone was just as successful as that of estrogen and comparable with results on the histological section. A satisfactory validity can be obtained today through the development of highly specific monoclonal antibodies against the progesterone receptor complex, with the complete receptor diagnosis of mammary carcinoma both immunocytochemically in frozen sections and additionally, of progesterone receptors in paraffin wax sections. The only current problems involve the exact quantification of the immunocytochemical results. It is predictable today, that the DCC-method, when compared to the immunocytochemical receptor analysis, will reduce in significance.

DNase I footprints and affinity measurements showed that the C-terminal arm of Xenopus transcription factor IIIA interacts differently with different Xenopus 5S DNAs, forming three distinct types of transcription factor IIIA-5S DNA complexes: a somatic type, a major-oocyte (and pseudogene) type, and a trace-oocyte type. Site-directed mutagenesis on the major-oocyte 5S gene revealed that somatic-type changes at positions 53, 55, and 56 changed the structure of the transcription factor IIIA-5S DNA complex from major-oocyte to somatic, and a single trace-oocyte change at position 56 caused the change from major-oocyte to trace-oocyte complex. We further show that the somatic-type changes are accompanied by a marked enhancement in the rate of 5S RNA transcription, and we discuss the possible biological relevance of these findings.

Changes in intraoperative coagulation and fibrinolysis during pulmonary surgery were studied using mongrel dogs. Twenty dogs were divided into two groups; dogs in group I (N = 10) received physical manipulation, "massage" of the left lung under thoracotomy, while dogs in group II (N = 10) underwent thoracotomy with no mechanical manipulation. In comparison with group II, subjects in group I showed significant decrease antithrombin III (ATIII) and alpha 2-plasmin inhibitor (alpha 2-PI) in blood of the pulmonary vein, pulmonary artery and peripheral vein for four hours after the initiation of the experiment. This finding suggested that both coagulation and fibrinolytic activity increased in lung tissue and circulating blood thoracotomy and pulmonary manipulation for more than four hours. Changes in postoperative coagulation and fibrinolysis were studied in 57 patients in whom pulmonary surgical procedures (pneumonectomy in 4 cases, lobectomy in 27, partial resection in 7, bullectomy in 16 and exploratory thoracotomy in 3 cases) were performed at Toho University Hospital from January, 1986 to June, 1987. Both protein C and ATIII, which are coagulation inhibiting factors, showed the lowest levels from the first to third postoperative day which suggested that coagulation activity was accelerated in that period, with a return to preoperative values being observed on the seventh postoperative day.

An anomaly of the iron-loading disorder hereditary hemochromatosis is that bone marrow iron stores remain low until later stages of the disease. The possibility that this may be related to a disorder of reticuloendothelial ferritin metabolism was examined by studying ferritin release from mononuclear cells. Ferritin release was measured in peripheral blood mononuclear cells from four patients with hemochromatosis who had not received treatment, from six patients with hemochromatosis who had received treatment, and from 10 age- and gender-matched controls by using a modified hemolytic plaque assay. Ferritin release from the hemochromatotic cells was enhanced when compared with that of controls, and added iron stimulated ferritin release to a comparable degree in both groups. Enhanced ferritin release above matched control values was found both in cells from patients with hemochromatosis with partial phlebotomy who had high serum ferritin values and in cells from patients with hemochromatosis with full phlebotomy who had normal serum ferritin values. The increased ferritin release observed in these studies may signify abnormal reticuloendothelial iron metabolism in hemochromatosis.

With regard to disturbances of the iron metabolism, porphyria cutanea tarda (PCT) is most frequently accompanied by liver siderosis. In 74 out of 88 patients suffering from PCT (84%), we found histochemical evidence of liver siderosis. These patients showed a significantly higher incidence of HLA A3--which has been proved to be associated with hemochromatosis--than those without liver siderosis (39.2% vs. 7.1%). With part of the PCT patients, disorders of the iron metabolism related to the HLA system (A3) might contribute to the manifestation of the disease. We discuss PCT as the result of the combined action of several predisposing genetic markers and exogenic factors.

Sixteen patients with mesenteric venous thrombosis were reviewed retrospectively during a period from 1983 to 1987. Twelve patients had progressive abdominal pain, three had gastrointestinal bleeding, and one had general malaise. Seven of these 16 patients had previous deep-vein thrombosis. After negative routine gastrointestinal and hepatobiliary evaluation, 11 patients underwent an infusion computerized tomographic scan. Of these, 10 had superior mesenteric vein thrombosis; three of these 10 patients had portal vein thrombosis. Selective arteriography was done in two patients because of gastrointestinal bleeding, and a diagnosis of mesenteric vein thrombosis was made on the venous phase of the examination. The remaining four patients developed acute abdominal symptoms requiring surgical exploration, at which time mesenteric venous thrombosis was discovered. An identifiable coagulopathy was detected in nine patients (protein C deficiency in six, protein S deficiency in two, and factor IX deficiency treated with factor IX concentrate in one). No case of congenital antithrombin-III deficiency was identified. Six of these nine patients had a past history of deep venous thrombosis. Of five patients who underwent surgical exploration, all required bowel resection. In follow-up, two patients died of intestinal necrosis and a third died of associated pancreatic cancer. Thirteen patients were discharged from the hospital. Treatment of coagulopathy was by heparin in three patients and sodium warfarin (Coumadin) in four patients. Long-term anticoagulation was not instituted because of gastrointestinal bleeding in three and cirrhosis in three patients. Mesenteric venous thrombosis can occur without gangrenous bowel. Diagnosis should be suspected when acute abdominal symptoms develop in patients with prior thrombotic episodes and a coagulopathy.(ABSTRACT TRUNCATED AT 250 WORDS)