Distinction between endocervical and endometrial adenocarcinoma with immunoperoxidase staining of carcinoembryonic antigen in routine histological tissue specimens. The differential diagnosis of endocervical and endometrial adenocarcinomas can be improved by the demonstration of carcinoembryonic antigen (CEA) in tissue by means of immunoperoxidase staining. Tissue from 131 (80%) of 163 patients with endocervical adenocarcinoma but only 11 (8%) of 137 patients with endometrial adenocarcinoma was CEA-positive. The commonest exceptions were endocervical mesonephroid adenocarcinomas (which were CEA-negative) and endometrial adenosquamous carcinomas (which were CEA-positive). After exclusion of these on simple morphological criteria, 86 of 107 endocervical adenocarcinomas (80%) were CEA-positive, and all 122 endometrial adenocarcinomas were CEA-negative. The remarkable difference in the expression of CEA between endocervical and endometrial adenocarcinomas suggests a novel application of immunohistochemistry in routine clinical practice.


Is faecal alpha 1-antitrypsin excretion a reliable screening test for protein-losing enteropathy? Estimation of alpha 1-antitrypsin in random faecal samples has been suggested as a reliable index of intestinal protein loss. There was a poor correlation between faecal alpha 1-antitrypsin concentrations and simultaneously measured faecal loss of 51Cr-albumin in twenty adults with suspected protein-losing enteropathy. This indicates that faecal alpha 1-antitrypsin estimation may not be a valid screening test for protein-losing enteropathy.


Production of 6-oxo-PGF1 alpha by human lung in vivo. The production of 6-oxo-PGF1 alpha, a stable hydrolysis product of prostacyclin (PGI2), by human lung was demonstrated in five adults. The lowest increase in 6-oxo-PGF1 alpha on passage through the lung was noted in a woman on oral contraceptives.


Identification of site of urinary-tract infections by antibody-coated bacteria assay. Accurate identification of the site of urinary-tract infection (UTI) may be clinically and epidemiologically valuable. A review of the literature on the assessment of the antibody-coated bacteria (ACB) assay, a non-invasive technique introducted five years ago, shows that, compared with acceptable standards (bilateral ureteral catheterization or bladder washout), the overall sensitivity of the ACB assay is 83.1%, the specificity is 76.7%, the predictive value positive is 81.3%, and the predictive value negative is 78.8%. These findings suggest that the ACB assay has at present no role in the management of patients with UTI. Its usefulness as an epidemiological tool remains to be demonstrated.


Work-site treatment of hypertension by specially trained nurses. A controlled trial. The clinical efficacy of using specially trained nurses to treat hypertension at the patient's place of work was compared in a controlled trial with management by the patient's family doctor. The 457 study participants were selected from 21 906 volunteers in industry and government whose blood-pressure was screened. The nurses were allowed to prescribe and change drug therapy at the work site without prior physician approval. Patients randomly allocated to receive care at work were significantly more likely to be put on antihypertensive medications (94.7% vs 62.7%, to reach goal blood-pressure in the first six months (48.5% vs 27.5%), and to take the drugs prescribed (67.6% vs 49.1%). Only 6% of patients were dissatisfied with the care provided by the nurses. Thus provision of care at work by specially tranined nurses was well accepted and resulted in significantly improved blood-pressure control and medication compliance among employees with asymptomatic and uncomplicated hypertension.


Voice preservation in treatment of carcinoma of the pyriform sinus. A retrospective analysis of 175 patients having a histopathologic diagnosis of epidermoid carcinoma of the pyriform sinus presenting between January 1, 1964 and December 31, 1973 was undertaken to establish the effectiveness of  conservation surgery in preserving voice. Patients were treated by three separate methods: 1. preoperative radiation therapy, partial laryngopharyngectomy and radical neck dissection (PLP and RND) (N = 85); 2. preoperative radiation therapy, total laryngopharyngectomy and radical neck dissection (TLP and RND), (N = 57); and 3. palliation, which consisted of palliative radiation therapy alone or combinations of radiation therapy and chemotherapy or palliative surgery (N = 33). Of the 85 patients treated with the expectation of cancer cure and voice preservation (PLP and RND), 44 or 52% actually had their voice preserved. Of course, in none of the patients treated by TLP and RND was voice preserved, but 2 of the 33 patients treated palliatively retained ability to speak. Overall, 46 of 175 patients (26%) with carcinoma of the pyriform sinus were afforded voice preservation. The ability to preserve voice is correlated with stage and an analysis of operative complications is presented.


[Chemical composition of the cell wall of Streptomyces chrysomallus which produces the antibiotic aurantin]. The cell wall chemical composition of Streptomyces chrysomallus producing the antibiotic aurantin was studied. The cell wall represents 11--13% of the dry cell weight and contains three major polymers, namely, peptidoglycan, ribitol teichoic acid and a polysaccharide. Each muramic acid of peptidoglycan has a peptide subunit which consists of two alanine residues, glutamic acid and diaminopimelic acid residues. Peptide chains are connected with bridges consisting of one glycine residue. The poly(ribitol phosphate) chain contains glucosyl substituents and O-acetyl groups. The main monosaccharides of the polysaccharide are glucose and galactose; mannose, fucose and galactosamine are found in minor amounts. The composition of the cell wall changes during cell development and aging: the content of teichoic acid decreases while that of the polysaccharide increases. Possible factors causing these changes are discussed.


[Effect of protein synthesis inhibitors on the growth and biosynthetic activity of Trichothecium roseum]. The effect of inhibitors of protein synthesis on growth was studied with Trichothecium roseum producing thichothecin and fibrinolytic enzymes. Levomycetin, acridine orange and polymyxin inhibited the biomass accumulation, the growth rate, and the biosynthesis of fibrinolytic enzymes, particularly at the early stages of fungal growth. This effect was found either when the substances were added at the same time as the mycelium was inoculated, or when they were introduced 24 hours after the beginning of cultivation. The substances inhibited the differentiation of the substrate mycelium of T. roseum. Substrate conidia, budding and initial cells were formed by the mycelium only after 72--96 hours of growth.


[Enzymatic synthesis and characterization of DNA complementary to ceruloplasmin mRNA from rat liver]. Poly(A) containing rat liver 21S RNA homogeneous in polyacrylamide gel electrophoresis under denaturing conditions and stimulating the synthesis of ceruloplasmin in a cell-free proteinsynthesizing system, was used as a template for reverse transcription in the presence of T10 primer and highly purified reverse transcriptase from avian myeloblastosis virus. The cDNA made this way was characterized by means of hybridization kinetics with mRNA, by melting of the hybrids formed and by chain length measurements. To increase the degree of representativity, the ceruloplasmin mRNA was fragmented by mild alkaline treatment, enzymatically polyadenylated and transcribed. The cDNA made was fully characterized and the kinetic complexity measured by hybridization with the mRNA was found to be equal to 2300 nucleotides as compared with the value of 3000 nucleotides is expected from gel electrophoresis data. The observed difference may indicate the presence of repeated sequences in the given mRNA. The sufficient representativitness of the synthesized cDNA and its specificity with respect to ceruloplasmin mRNA allows to use it as a molecular probe to study the ceruloplasmin gene structure.


[Investigation of serological features and molecular heterogeneity of virion proteins of morphologically related phages]. Some interaction process peculiarites of morphologically related phate T4, DDVI and FI1 with the corresponding antiphageous sera in cross reactions of neutralisation have been investigated. Close serological relationship of phage T4 and DDVI was demonstrated. Inactivation of phage FI1 in these serological reactions showed anomalous nature and did not submit to the rules of the first step reaction. According to investigations of the protein component of virions of these phages by electrophoresis in polyacrylamide gel, phages T4 and DDVI contain twelve, FI1 and DDVI four, and T4 and FI1 two protein fractions common in molecular weight. The data obtained indicates that close serological relationship between phages T4 and DDVI is determined by the presence of common protein antigens in the absorptional apparatus of virions. Proteins of phage FI1, common with the proteins of T4 and DDVI, are obviously located in other structural components, and this determines the specific aggregation of virions in cross reactions of neutralization.


Development of new antiallergic drugs (cromolyn sodium, lodoxamide tromethamine). What is the role of cholinergic stimulation in the biphasic dose response? The antiallergy drugs, cromolyn sodium and lodoxamide tromethamine (U-42,585E) show in vitro dose responses which are bell-shaped or biphasic in mast cells. The nature of the biphasic dose response is poorly understood; however, through the use of specific antagonists, it has been possible to show that at the high concentrations of these drugs leading to enhanced histamine release or multiple high-dose tachyphylaxis, a cholinergic receptor is stimulated in the cell. This receptor is muscarinic in nature and can be blocked by atropine or quinuclidinyl benzilate (QNB). Prevention of multiple dose tachyphylaxis to either drug can be modulated by pretreatment with atropine or QNB. High concentrations of both drugs cause the cell accumulation of cyclic-guanosine monophosphate through stimulation of guanyl cyclase and prevention of cGMP breakdown by inhibition of the phosphodiesterase (PDE) for cGMP.


BL-5255, a tetrazolylpyrimidinone with potent oral antiallergy activity in animals. BL-5255, 2-(2-n-propoxyphenyl)-5-(5-1 H-tetrazolyl)pyrimidin-4 (3H)-one, effectively inhibited allergic reactions in sensitized rats or guinea pigs when administered by oral or intravenous routes as the water-soluble sodium or ethanolamine monohydrate salts. In the IgE-mediated rat PCA, BL-5255 was 50 times more potent than disodium cromoglycate by intravenous administration. When administered orally in this model, BL-5255 inhibited the PCA reaction by 50% at 0.1 mg/kg. At less than 0.1 mg/kg p.o., the compound protected conscious actively sensitized guinea pigs from aerosolized antigen-induced collapse. In N. brasiliensis-sensitized rats, BL-5255 administered at 0.1--10 mg/kg p.o. inhibited antigen-induced airway constriction in a dose-related manner. BL-5255 is not a histamine or serotonin antagonist but appears to exert its antiallergic effect by inhibiting the release of mediators.


Myosin isoenzyme redistribution in chronic heart overload. Since the first observation by Spann et al., it has become clear that in cardiac hypertrophy induced by a mechanical overloading, the velocity of shortening of the cardiac muscle (Vmax) is reduced (see ref. 2 for review). Most authors agree that this mechanical alteration is accompanied by a decrease in the Ca2+-dependent ATPase activity of myosin (see ref. 3 for review). The molecular basis of such changes was unknown because the structural modifications of the myosin molecule were ill-defined. Nevertheless, it has recently been shown that, like skeletal muscle myosin, cardiac myosin is composed of several polymorphic forms, comparable to isoenzymes. In the skeletal muscle, new functional requirements can induce changes in both contractile activity and type of myosin isoenzyme synthesised. We now report that an increase in cardiac work produced by mechanical overloading in rats induces the preferential synthesis of a cardiac myosin isoenzyme characterised by specific immunological and electrophoretic properties and exhibiting a lower ATPase activity. This adaptive change could account for the reduced shortening speed of this hypertrophied cardiac muscle.


Specificity of the antibody response of rabbits to a self-antigen. The demonstration that the antigenic determinants on rabbit cytochrome c that elicit antibodies in rabbits occur in regions of variability among mammalian cytochromes c suggests the existence of an evolutionary process which eliminates genetic specificities for self-determinants.


PGI2 enhanced cAMP content in bovine coronary arteries in the presence of isobutylmethylxanthine. Incubation of bovine coronary artery (BCA) rings with isobutylmethylxanthine (IBMX) resulted in a time-dependent increase of cAMP content. This effect was blocked, when the rings were preincubated with indomethacine or 15-hydroperoxy-arachidonic acid for 5 min, indicating that the IBMX-induced increase in cAMP content may depend on endogenous PGI2 formation. PGE2 did not increase the cAMP content in BCA rings. Dipyridamole did not effect cAMP content, when used as a substitute for IBMX. It is suggested that PGI2 stimulates cAMP formation in arterial walls, but that this effect only becomes visible in the presence of a phosphodiesterase inhibitor.


The action of lindane in accelerating the spontaneous release of transmitter at the frog neuromuscular junction. Lindane (5 x 10(-5) M) causes a progressive and marked rise in MEPP frequency at the frog neuromuscular junction. Concentrations over a range of 5 x 10(-6) M to 5 x 10(-4) M were tested. The results suggest that it has two actions in promoting this effect. Its major effect is probably to cause an increase in Ca2+-permeability and a rise in Ca2+ entry. Its second, smaller effect, which persists in the absence of extracellular Ca2+, is probably also because of a rise in [Ca2+]i. The ways in which these effects might be produced and the significance of these findings for explaining the known pharmacological actions of lindane are discussed.


[Blood-cerebrospinal fluid barrier and the local immune response in the course of meningitis in childhood]. The condition of the blood-CSF barrier can be evaluated by the simultaneous quantitation of marker proteins in serum and cerebrospinal fluid. The concentration ratios of albumin and alpha 2-macroglobulin, plotted versus the hydrodynamic radii are used as permeability parameter. There are wide ranging barrier disturbances during the early stages of meningitis. In mumps meningitis only slight disturbances were found, meanwhile in bacterial meningitis the barrier permeability was strongly increased. In both disease groups one may detect secretory fractions of both immunglobulins G and A. In some cases of mumps meningitis a prolonged humoral immune reaction was found.


[Ultrastructural cytochemistry of the mouse juxtaglomerular apparatus (author's transl)]. The ultrastructural cytochemistry of the mouse juxtaglomerular apparatus has been studied. The specific granules of the juxtaglomerular cells were found to be argentaphobic when ultrathin sections of araldite-embedded renal cortex were stained according to the periodic acid-thio-carbohydrazide-silver proteinate technique of Thiery. This technique revealed an abundant glycogen of type beta in the specific granules and in the cytosol of these cells. The rim of specific granules was positive when ultrathin sections of glutaraldehyde-fixed, glycol methacrylate-embedded kidneys were stained with phosphotungstic-hydrochloric acids at a low pH. A reaction was also shown by the cell coat, lysosomes, autophagolysosomes, residual bodies and part of the Golgi complex. These results indicate that the specific granules of the mouse juxtaglomerular apparatus contains glycoproteins that are glycosylated in the Golgi complex.


[Microscopic, immunochemical and ultrastructral study of livers histologically normal or subnormal in patients with hepatitis B surface antigen (HBs). Report of 18 cases (author's transl)]. Liver specimens obtained by biopsy in 18 patients with asymptomatic HBs Ag were studied with specific immunofluorescent technic for this antigen by light and electron microscopy. Only insignificant changes were disclosed by routine microscopy examination. Under light microscopy "ground glass" hepatocytes were found in eight cases. Specific immunofluorescence was found positive in nine cases and was closely correlated with the "ground glass" hepatocytes in eight of them. In one on the three cases studied by electron microscopy, only spherical and tubular formations, 20 to 30 nm in diameter found in the cisternae of the smooth endoplasma reticulum in a few hepatocytes, seem to be HBs Ag.


Binding of 125I-labeled proteinases to plasma proteins in cystic fibrosis. Samples of plasma or serum from 53 cystic fibrosis (CF) patients, 90 relatives of CF patients , and 159 controls have been incubated with porcine or bovine 125I-trypsin, electrophoresed on polyacrylamide gel, and autoradiographed. In these individuals, the main binding protein for 125I-trypsin has been shown to be alpha 2-macroglobulin (alpha 2M). Using this method of analysis, no difference in electrophoretic migration of 125I-trypsin-alpha 2M complexes has been observed between CF and control individuals. However, trypsin binding to IgG has been observed in 80% of CF patients, 30% of their mothers, 3% of controls, and in two patients affected with pancreatitis. These trypsin binding immunoglobulins are called TbIg, and specifically, Tb1gG when referring to the G class. Experimental evidence indicates that binding of trypsin to IgG occurs through the Fab portion of the molecule. Tb1gG must be antibodies most probably induced by the exogenous trypsin ingested daily by most CF patients (and by patients affected with chronic pancreatitis). Antibodies against porcine pancreatic elastase have been observed using the same analysis, but not as frequently as Tb1g.


X-ray induced DNA double strand break production and repair in mammalian cells as measured by neutral filter elution. This work presents a neutral filter elution method for detecting DNA double strand breaks in mouse L1210 cells after X-ray. The assay will detect the number of double strand breaks induced by as little as 1000 rad of X-ray. The rate of DNA elution through the filters under neutral conditions increases with X-ray dose. Certain conditions for deproteinization, pH, and filter type are shown to increase the assay's sensitivity. Hydrogen peroxide and Bleomycin also induce apparent DNA double strand breaks, although the ratios of double to single strand breaks vary from those produced by X-ray. The introduction of double strand cuts by HpA I restriction endonuclease in DNA lysed on filters results in a rapid rate of elution under neutral conditions, implying that the method can detect double strand breaks if they exist in the DNA. The eluted DNA bands with a double stranded DNA marker in cesium chloride. This evidence suggests that the assay detects DNA double strand breaks. L1210 cells are shown to rejoin most of the DNA double strand breaks induced by 5-10 krad of X-ray with a half-time of about 40 minutes.


Extensive sequence homology at the 3'-termini of the four RNAs of cucumber mosaic virus. The sequences of 270 residues from the 3'-termini of the four RNAs of cucumber mosaic virus have been determined by copying the in vitro polyadenylated RNAs with reverse transcriptase using d(pT8G) as primer and the 2',3'-dideoxynucleoside 5'-triphosphates as specific chain terminators. The terminal sequences of RNAs 3 and 4 were identical; this was expected since hybridization data has shown that the sequence of RNA 4 was present at the 3'-end of RNA 3 (Gould and Symons (1978) Eur. J. Biochem. 91, 269-278). The first 138 residues of RNAs 1 and 2 were identical to those of RNAs 3 and 4 except for one residue in RNA 1 and three residues in RNA 2. From residue 139 to 270 from the 3'-terminus, RNAs 1 and 2 showed, relative to RNAs 3 and 4, a non-homologous region of 33 residues, a homologous region of 40 residues, a partially homologous region of 14 residues which probably extended to about residue 300. There were 11 residues different between RNAs 1 and 2.


New procedure for the production of influenza virus-specific double-stranded DNA's. A novel technique is described for the production of pure, full-length influenza virus ds DNA's corresponding to each segment of the influenza virus genome, and suitable for molecular cloning and restriction endonuclease mapping. The method involves the synthesis of DNA complementary to both virion (negative strand) and messenger (positive strand) RNA, gel purification and annealing. By avoiding the use of SI nuclease, which often removes the terminal regions of DNA duplexes, the method allows transcription of the total sequence information of influenza virion and messenger RNA's into a ds DNA form.


Isolation and partial purification of the major abundant class rat seminal vesicle poly(A+)-messenger RNA. Total poly(A(+))-RNA (poly(A(+))-RNA(tot)) was isolated from rat seminal vesicle and its size distribution determined by 70% formamide 5-25% sucrose density analysis. One major peak was resolved in the 10-13 S region and accounted for approximately 35% of the total poly(A(+))-RNA applied. Preparative 1% SDS, 5-20% linear sucrose density gradients also resolved a single major peak in the 11S region (poly(A(+))(11S). Analysis of poly(A(+))-RNA(tot) and poly(A(+))-RNA(11S) under denaturing conditions on 2% agarose gel electrophoresis demonstrated two major components in both poly(A(+))-RNA populations. Size estimations for these components are 620 and 540 NT respectively. (3)H-cDNA was made to both poly(A(+))-RNA(tot) and poly(A(+))-RNA(11S). Back-hybridization of poly(A(+))-RNA(tot) and poly(A(+))-RNA(11S) to their respective (3)H-cDNA revealed a highly abundant class representing 41% and 85% of the sequences in their respective (3)H-cDNA's. The highly abundant class corresponded to 3-5 sequences present in 30,000-50,000 copies/cell. Invitro translation of poly(A(+))-RNA(11S) resulted in two major polypeptides coded for by the 620 NT long and 540 NT long poly(A(+))-RNA respectively.Images