Biomedical subjects
Publications and source records attributed to A Cohen.
The complement fixing antigens of rubella virus have been found to contain virion envelope but little nucleocapsid polypeptides. They are also shown to be associated with two additional polypeptides of host origin. Evidence is presented to suggest that the complement fixing antigens are structural components of the plasma membrane of virus infected cells.
Pulmonary function tests were performed on 19 patients with homozygous beta-thalassemia ranging in age from 10 to 29 years. These included patients who had and had not received transfusions. None of the 19 subjects had completely normal pulmonary function. Residual volume (in 16 of 19 patients), ratio of residual volume to total lung capacity (12 of 19), and airway resistance (16 of 19) were abnormally increased; maximum expiratory flow (15 of 19) and peak flow (10 of 19) were abnormally reduced. Single-breath carbon monoxide diffusion was normal in 16 of 19. These results indicate that mild to moderate small airway obstruction and hyperinflation are common in thalassemia and that patient age, transfusion history, and iron accumulation are not important factors in the genesis of these pulmonary abnormalities.
Stridor and snoring are common signs of upper airway obstruction. The nature and characteristics of the stridor and snoring depend upon the site of obstruction. Sophisticated analysis of these sounds may provide important information concerning the source of the sound helping to assess the patient more objectively. The preliminary results of computerized digital analysis of stridor and snoring sounds are presented in 5 children. Two main programs were applied to analyse the signal: the Power Spectral Density (PSD) function and the Estimated Cross-sectional Area (ECSA). A consistent pattern according to the site of the produced sound was seen. Further acoustical analyses are needed to standardize this method and to program the computer to indicate the various sites of lesions.
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The effect of recombinant interferon-alpha 2 (IFN-alpha 2) (50 U/ml) on the cell cycle, nucleotide metabolism, and protein and nucleic acid synthesis was studied in human B-lymphoblastoid (Daudi) cells. Cell cycle analysis showed that IFN treatment resulted in G0/G1 arrest (69%) as compared to control cells (42% at G0/G1). IFN inhibited the incorporation of radioactive thymidine and uridine into DNA and RNA, respectively, but had only slight effect on incorporation of radioactive threonine, leucine, or valine into proteins. IFN inhibited ribonucleotide biosynthesis by de novo and salvage pathways and decreased level of the P-ribose-PP. Both pathways of deoxyribonucleotide biosynthesis, ribonucleotide reduction and deoxyribonucleoside salvage, were also markedly inhibited by IFN., In contrast, ribonucleotide catabolism was significantly increased in the presence of IFN. No changes in ribonucleotide interconversion were found. Intracellular concentrations of both ribonucleotides and deoxyribonucleotides were markedly diminished by IFN. These results suggest that inhibition of both ribonucleotide and deoxyribonucleotide biosynthesis, together with increased rate of nucleotide catabolism, may significantly decrease intracellular nucleotide availability. Decrease of the supply of nucleic acid precursors, as well as limitation of nucleotides for energy metabolism and other processes, may result in the inhibition of cell multiplications.
The activity of O6-methylguanine-DNA methyltransferase (MT) was assayed in various human lymphoid cell populations. It was found that during T-cell differentiation the activity of MT increased from 7000 MT molecules in thymocytes to 31,000 MT molecules in mature T-lymphocytes. The number of MT molecules also increased 2- to 3-fold in the course of the cell division cycle but the specific activity of MT did not change significantly. T-cell tumors and T-cell lines contained a higher number of MT molecules (70,000-125,000 molecules/cell) compared to normal T-lymphocytes. The sensitivities of various lymphoid cells to the DNA methylating agent N-methyl-N'-nitro-N-nitrosoguanidine correlated well with MT activities observed in cell extracts.
The immunological events mediated by, and antigen specificity of, allograft-bound lymphocytes (ABLs) are poorly understood. To further define the role of antibody-mediated rejection, a rejected allograft from a patient with primary anti-TBM disease was sterilely minced and pressed through a microscreen. The ABLs were isolated by density gradient centrifugation. Using this technique, 8.5 X 10(6) ABLs were isolated. Then 1 X 10(6) washed ABLs/ml were suspended in RPMI 1640 with 20% fetal calf serum and cultured in microtiter plates with media only, or with pokeweed mitogen (PWM) (100 micrograms/culture). The cells were incubated for 7 days and supernatants were collected and assayed for total IgG and IgM by a solid-phase enzyme immunoassay (EIA) and reactivity with normal human kidney targets by indirect immunofluorescence (IF) and immunoperoxidase (IP) techniques. Total IgG production was 500 ng/ml for both spontaneous and PWM stimulated cells. No IgM production was detected. IF and IP studies demonstrated IgG-anti-TBM antibodies in the spontaneous supernatants only. IgG antibodies reactive with peritubular capillaries (anti-PTC) were also noted. IgG-anti-TBM anti-bodies and antibodies reactive with arterioles were subsequently demonstrated by direct immunofluorescence techniques in the rejected allograft. Analysis of serum samples obtained at the time of allograft rejection showed no IF or IP reactivity with the kidney targets. Subsequent analysis of anti-TBM production by the patient's peripheral blood mononuclear cells (PBMs) showed IgM-anti-TBM only. These studies suggest that the IgG-anti-TBM and IgG-anti-PTC antibodies reactive with the allograft resulted from in situ antibody production by ABLs; the role of anti-TBM antibodies in mediating the AR is unclear, but their presence suggests recurrence of the original disease in the allograft. Anti-PTC antibodies could be important in mediation of the vascular AR.
The cause of an enterocutaneous fistula following an abdominal operation, in the absence of inflammatory bowel disease or irradiation damage, is often obscure. In this study, it is postulated that distal obstruction, associated with peritoneal adhesions or abscess, is the critical determinant of fistula persistence. The 'venting' effect of the fistula, and the presence of obstruction which is frequently partial, makes recognition of the obstructive element difficult. It is suggested that operations to cure postoperative fistula should be based on the assumption that distal obstruction is always present, and should include a complete lysis of adhesions involving the small and large bowel. A postoperative fistula was cured in 21 out of 23 patients treated on this basis.
Splenectomy produces significant immediate and long-term risks for the patient, and there is general agreement that it should be reserved for clear-cut unavoidable indications. However, accidental injury to the spleen in the course of another operation (incidental splenectomy,) accounts for almost 40% of splenectomies in some series. Incidental splenectomy is most likely to occur in left upper quadrant operations such as proximal gastric vagotomy, or in colonic operations involving mobilization of the splenic flexure. Incidental splenectomy rates of between 2% and 9% have been reported in association with these procedures. The results of an operative strategy of specific protection of the spleen as the first step in a left upper quadrant operation ('defusing' the spleen) are reported. It was not necessary to remove the spleen because of accidental injury in 417 consecutive operations over a 5 year period after implementation of this policy. There were several minor splenic capsular tears which were controlled by intraoperative haemostatic measures. There were no cases of postoperative splenic bleeding. 'Defusing' the spleen is an effective step in preventing splenic injury in left upper quadrant operations.
Linear plasmid multimers were identified in extracts of recB21 recC22 strains containing derivatives of the ColE1-type plasmids pACYC184 and pBR322. A mutation in sbcB increases the proportion of plasmid DNA as linear multimers. A model to explain this is based on proposed roles of RecBC enzyme and SbcB enzyme (DNA exonuclease I) in preventing two types of rolling-circle DNA synthesis. Support for this hypothesis was obtained by derepressing synthesis of an inhibitor of RecBC enzyme and observing a difference in control of linear multimer synthesis and monomer circle replication. Reinitiation of rolling-circle DNA synthesis was proposed to occur by recA+-dependent and recA+-independent recombination events involving linear multimers. The presence of linear plasmid multimers in recB and recC mutants sheds new light on plasmid recombination frequencies in various mutant strains.
Alkalinization of intracellular pH (pHi) causes an increase in UV resistance in wild-type and pH-sensitive mutant (DZ3) cells of Escherichia coli. Utilizing cells transformed with a plasmid (pA7) which bears the uvrA promoter fused to galK galactokinase structural gene, it was shown that alkaline pHi leads to an increase in the specific activity of galactokinase. This effect was not displayed in a mutant bearing a recA-insensitive lexA gene, nor in cells harboring a plasmid (pA8) in which the galK is fused to a lexA-insensitive uvrA promoter. Hence, the effects of pHi on cells functions may involve the lexA product of the SOS system.
Glucose and nucleoside uptake into human red cells occurs through protein(s) which copurify in a complex, known as band 4.5 of relative mass (Mr) 66,000 to 50,000. The specific inhibitor of glucose transport, [3H]cytochalasin B, and the specific inhibitor of nucleoside transport, [3H]nitrobenzylthioribofuranosylpurine ([3H]NBMPR), incorporate covalently into component(s) of band 4.5 upon irradiation with ultraviolet light. Both photolabelled components are shown to be glycoproteins, since their migration in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) is increased after treatment of photolabelled band 4.5 with endoglycosidase F. Peptide maps of the photolabelled components were compared. Red cell membranes were photolabelled with either [3H]cytochalasin B or [3H]NBMPR and subjected to SDS-PAGE. The region containing band 4.5 was cut and transferred to a second SDS-PAGE system and exposed to either papain or Staphylococcus aureus V8 protease. Papain (5 micrograms) completely cleaved band 4.5 and produced fragments of Mr 33,000, 26,000, 21,000, 15,000, and 12,500. Of these, the 21,000 fragment was the most conspicuous and it retained the label of [3H]cytochalasin B; the 33,000 fragment retained the label of [3H]NBMPR. The V8 protease (0.75 microgram) completely cleaved band 4.5 and produced fragments of Mr 35,000, 28,000, 22,000, 16,000, 13,500, and 9,000. The 28,000 fragment retained the label of [3H]cytochalasin B. The label of [3H]NBMPR was distributed along the gel in several regions comprising the 35,000, 28,000, and 16,000 fragments. Longer treatment with the V8 protease did not alter the position of the 28,000 [3H]cytochalasin B labelled peak, but completely abolished the [3H]NBMPR labelled peaks. Genetic segregation of the glucose and nucleoside transporters was determined in a lymphoma cell line. A mutant (14T- g) of S49 cells was selected which had lost the capacity to transport thymidine or to bind NBMPR. Uptake of either 2-deoxyglucose or 3-O-methylglucose, inhibitable by cytochalasin B, was not impaired in this mutant. It is concluded that the nucleoside and glucose transporters are glycoprotein components of band 4.5, which are differentiated by peptide map analysis. Further, a lymphoblast mutant was isolated which had lost the nucleoside transport function but retained the glucose transport function.
Previous studies on the determinants of locus of perception of stimuli on the body have suggested that the position of the stimulus has a significant effect whether a subject perceives a tactile pattern as seen from inside or outside the body. However, it is possible that previous investigators confounded stimulus location--dorsal or frontal--and experimenter's position--behind or in front of the subject. Using 42 male subjects in a 2 X 2 design, the effects of experimenter's position and stimulus location were studied by a new technique for inferring locus of perception. Experimenter's position, rather than stimulus location, affects subjects' locus of perception. Perception of stimuli on the body involves three independent factors, the demand characteristics of the experiment, the manner in which an individual perceives the boundaries of his own body, and an individual's ability to adopt the experimenter's perceptual standpoint.
The underlying assumption of the paper is that the poor state of our understanding in the field of addiction stems, in part, from our failure to differentiate among different personality structures to be found in addicted people. To test this assumption, a typology was developed based on personal and psychological data of 663 drug addicts. Cluster analysis of these data, which did not include variables pertaining to drug abuse, resulted in nine types of addicts with different sociocultural backgrounds and psychological makeups. Treatment recommendations, including goals, techniques, staff, settings, and prognosis are offered for five types. The paper concludes that drug addicts are not a homogeneous group, but that there are different types of addicts with differing motives for drug use and differing psychological needs, and therefore drug addiction treatment should be matched with the specific needs of each type.
Attempts to classify drug abusers are divided into three main categories: psychiatric classifications, psychosocial classifications and classifications by pattern of abuse. The present article focuses on pattern of abuse classifications which are divided into two subcategories: by substance of abuse and by degree of involvement. The various groups of these classifications are reviewed and their potential uses are discussed. The review indicates that classifications by substance of abuse may be useful for administrative and theoretical purposes, while their clinical uses are limited to medical emergencies. On the other hand, classifications by degree of involvement are useful for initial treatment planning and for predicting treatment outcomes. The authors conclude that for a thorough treatment planning and for better understanding of the addiction process, psychosocial classifications may be the most useful approach.
Two variants of HL-60 promyelocytic leukemia cells (HSC, OCI) that were indistinguishable by morphology, cell surface markers, DNA histograms, and by their inability to reduce nitroblue tetrazolium, were induced to differentiate by retinoic acid (RA), 12-O-tetradecanoyl-phorbol-13-acetate (TPA), and by phytohemagglutinin-leucocyte conditioned medium (PHA-LCM). Only OCI cells were induced to differentiate to mature granulocytes by TPA. Both cell lines expressed, however, the monocytic associated cell surface antigen detected by MO1 monoclonal antibody in response to TPA. MO1 expression was detected as early as 32 hours after initiation of differentiation by TPA, whereas partial morphologic changes were apparent only after 72 hours. Induction of differentiation by retinoic acid led to a significant inhibition of colony formation in HSC variant (from 1522 +/- 60 to 523 +/- 20/10(4) cells plated) and in the OCI variant (from 628 +/- 20 to 185 +/- 33 colonies/10(4) cells plated). The addition of PHA-LCM further inhibited colony growth of both RA-induced cell lines (155 +/- 7/10(4) cells plated in HSC, and 59 +/- 4 in OCI). PHA-LCM by itself reduced HL-60 colony numbers in a dose-related manner, and also increased the expression of MO1 on noninduced HSC and OCI cells. These observations suggest that differentiation of HL-60 cells is not necessarily accompanied by concomitant change in morphology, cell surface characteristics, and proliferation potentials, and may be dependent on different degrees of cellular commitment. They also suggest a role for growth factors in the induction to maturation of leukemic cells.
Resting peripheral blood lymphocytes have a large number of single strand breaks and are especially sensitive to DNA damaging agents. Deoxyadenosine, an adenosine deaminase substrate, in combination with the adenosine deaminase inhibitor deoxycoformycin, causes accumulation of single strand breaks in resting peripheral blood lymphocytes. The induction of single strand breaks by deoxyadenosine is the result of the accumulation of large amounts of intracellular dATP, which creates imbalance in deoxynucleoside triphosphate levels. This imbalance in deoxynucleoside triphosphate levels interferes with the repair of single strand breaks in deoxyadenosine treated cells. Deoxyadenosine acts synergistically with N-methyl-N'-nitro-N-nitrosoguanidine, a DNA alkylating agent, by inhibiting the repair of N-methyl-N'-nitro-N-nitrosoguanidine-induced single strand breaks. We propose that the increased sensitivity of resting peripheral blood lymphocytes to deoxyadenosine and possibly to other DNA damaging agents may be associated with impaired DNA repair ability due to imbalance in intracellular levels of deoxynucleoside triphosphate.
The lungs of 139 deceased and 29 slaughtered calves were examined for Legionella by culture and by direct immunofluorescence (DIF) with fluorescein-conjugated antisera. About 17% of the cadaver lungs and 4% of lungs from slaughtered animals were positive by DIF, but only two L. pneumophila serogroup 1 strains were isolated from the lungs of two cadavers. In a prevalence study of antibodies to Legionella in domestic and wild animals of various species, titers of 1:64 were demonstrated by the indirect immunofluorescence technique in the sera of 10% of the dairy cattle, 5% of the beef cattle, 4% of the sheep, 22% of the antelopes, 35% of the horses, 36% of the water buffaloes and none of the laboratory rabbits. The isolation of Legionella from lung tissue is the strongest indication so far reported of the possible role of Legionella spp. in animal disease.