Biomedical subjects
D Mann
Publications and source records attributed to D Mann.
Hereditary malignant melanoma is not linked to the HLA complex on chromosome 6.
Detailed HLA typing was performed in 11 families with hereditary cutaneous malignant melanoma (CMM) and dysplastic nevi to determine if the melanoma susceptibility locus was genetically linked to the major histocompatibility complex. Previously published data from 19 other families were re-analyzed in the same manner. When data from all 30 families were pooled and CMM was defined as the disease trait, the hypothesis of linkage was rejected for all values of recombination (theta) less than 40%. Data on family members' status regarding dysplastic nevi (DN), a well-characterized precursor of hereditary CMM, were available for our 11 families and 7 previously-reported families. Linkage analysis between the combined CMM/DN trait and HLA provided strong evidence against this hypothesis. Significant heterogeneity was observed when various sub-groups of families were compared; these data suggested that preferential reporting of positive linkage findings and misclassification of study subjects' CMM susceptibility status may have contributed to previous beliefs that the hereditary melanoma gene was linked to HLA. When our data are combined with previously-published information, we conclude that there is strong evidence against linkage of a CMM/DN gene with the major histocompatibility complex.
[Possibilities for trend registration of the behavior of extrasystoles in patients with coronary disease].
The ECG long-term registration as a method of controlling the action of the heart proves to be particularly evident above all when using it in patients with endangered coronaries. A partial achievement in this questioning can also be obtained by checking the behaviour of cardiac rhythm showing a tendency and disturbances of cardiac rhythm, respectively. Own investigations using a new combination of trend processing system and arrhythmia monitor BMT5111 of the combined works VEB Messgerätewerk Zwönitz show that particularly the signal parameters prematurity and breadth of QRS-basis are suitable for the differentiated registration and documentation of arrhythmic events. The continuous registration of disturbances of rhythm as well as the obtaining of informations on their short-term and long-term behaviour allow simultaneously a clinical valuation. With the help of an observation group of 67 patients and selected instances mode of action, indication area and effectiveness of the trend registration method are made clear.
VLA-1: a T cell surface antigen which defines a novel late stage of human T cell activation.
The VLA-1 protein complex defines a previously undescribed very late stage of activated T cell differentiation, following either alloantigen or mitogen activation. This protein appears after 2-3 weeks of activation, considerably later than the early T cell activation antigens such as the interleukin 2 (IL 2) receptor, transferrin receptor, 4F2 antigen, T10 and HLA-DR, and has therefore been termed very late antigen-1 (VLA-1). Unlike the IL 2 receptor, VLA-1 expression does not require restimulation with antigen, and in fact, VLA-1 expression was high on T cells that had lost their IL 2 receptors. Expression of VLA-1 was found on all or nearly all long-term-activated T cells including T4+ and T8+ clones, bulk cultures, long-term T cells from adults and newborns and long-term T cells maintained in pure or crude IL 2 preparations. VLA-1 was also found on HTLV-1 infected T cell populations. Immunoprecipitation experiments confirmed that the VLA-1 protein complex (210 000/130 000 Mr) can be co-expressed with another protein complex called VLA-2 (165 000/130 000 Mr) on the same T cell clones. However, co-expression was not obligatory because in some long-term cultures little or no VLA-2 was present relative to VLA-1. Because VLA-1 defines a novel late stage of T cell activation, being present on all or most all types of long-term activated T cells, and not on any other cell types in peripheral blood, it has unique potential as a marker for activated T cells in vivo and may provide a clue towards elucidating novel long-term T cell functions or growth requirements of this late stage of T cell differentiation.
Clonal selection of T lymphocytes infected by cell-free human T-cell leukemia/lymphoma virus type I: parameters of virus integration and expression.
We have successfully transmitted cell-free HTLV-I to normal cord blood and peripheral blood lymphocytes and have exploited this system to study the kinetics of infection and transformation of these cells. Transmission was successful in 4 out of 23 attempts. In all 4 cases, the infected cells progressed from an initial stage of polyclonality to predominantly monoclonal cells within 4-6 weeks. Both complete and defective proviruses were transmitted to the recipient cells initially, but cells with a complete provirus were preferentially maintained. The monoclonally infected cells have persisted in culture for more than 6 months and may be considered immortalized. Expression of core antigens as detected by immunoflourescence and the reverse transcriptase activity in the medium at least in one case was not observed until weeks after the cells had become monoclonal, suggesting that expression of virus or viral structural proteins is not necessary for selected growth of the infected cells in vitro.
Free perforation in Crohn's disease: I. A survey of 99 cases.
A review of more than 181 reported cases of free perforation in Crohn's disease yielded 84 cases that fulfilled rigorous criteria for classification as spontaneous free perforation with generalized peritonitis. An additional 15 cases from The Mount Sinai Hospital, derived from a population of 1010 patients with Crohn's disease, bring the total number to 99. Separately tabulated are 116 other cases either occurring in bypassed segments, developing after surgery, presenting with ruptured abscesses, or not definitively documented. Most reported perforations in the literature occurred in the distal small bowel. Among the Crohn's disease patients in our hospital, however, the incidence of colonic and small bowel perforation were 1.6 and 0.7%, respectively, with the highest frequency actually occurring in diseased segments of jejunum (2/50 = 4%). Free perforation was the presenting manifestation of the disease in 25 of the 84 reported cases. In our 15 patients, although perforation was never the presenting manifestation, it tended to occur early in the course of the disease (mean 3.5 years from onset of symptoms). Ninety-six of the 99 cases were operated on. The three patients treated without surgery all died. Mortality was most frequent following simple suture in the earliest reported case (39%), but considerably less frequent after resection and anastomosis (3.7%). All 18 patients treated by resection and diversion survived. Immediate surgery with resection and/or diversion therefore appears to be appropriate treatment for free perforation in Crohn's disease.
Intradermal testing of swine to monitor changes in delayed hypersensitivity response.
Pigs were tested (intradermal injection) on the abdomen with either phytohemagglutinin (PHA) or PHA and tuberculin. The response to PHA was consistent; double-skin thickness averaged 247% of the preinjection thickness during daily testing. Pigs that were primed with Freund's complete adjuvant had a mean double-skin thickness of 208% for tuberculin and 236% for PHA, indicating that the mitogen induced an antigen-like response. Unexpectedly, injections of dexamethasone (0.1 mg/kg of body weight on 2 days) increased the reactivity to both tuberculin and PHA, indicating that the lymphocyte and macrophage response to dexamethasone in swine may be slightly different than the response reported in other species.
Alteration of T-cell functions by infection with HTLV-I or HTLV-II.
Two functionally different types of human T-cell clones, one with helper function and two with specific activity, were infected with different isolates of HTLV-I and HLTV-II. Both types of human T cells showed alterations in specific function after infection with either of the HTLV subgroups. Before HTLV infection, the T-cell clone with helper function proliferates and provides help to B cells only in the presence of both a specific soluble antigen (keyhole limpet hemocyanin) and histocompatible antigen-presenting cells. After HTLV infection, these cells respond with increased proliferation and indiscriminant stimulation of polyclonal immunoglobulin production by B cells, regardless of the histocompatibility of the antigen-presenting cells or the presence of the soluble antigen. Infection of the normal cytotoxic T-cell clones led to a dimunition or loss of the cytotoxic function. The results of these studies suggest some possible mechanisms for induction of immune deficiency and of polyclonal B-cell activation by viruses of the HTLV family.
[Multicenter study of the results of the extraction of transvenously implanted heart-pacemaker electrodes using continuous traction].
The continuous traction of firmly grown-in collar electrodes from the right ventricle is a simple technique poor in complications with a high success rate, which can be recommended taking into consideration the indications in the failure of the immediate manual extraction and which can be performed in every centre for cardiac pacemakers. Apart from the consideration of adequate informations in literature this evidence above all depends on the evaluation of data of 29 cases from 10 centres for cardiac pacemakers.
Neurologic sequelae following transcatheter embolization to control massive perineal hemorrhage.
A case of exsanguinating perineal hemorrhage resulting from rupture of a pseudoaneurysm of the right internal pudendal artery is presented. Transcatheter embolization of Gelfoam and wire coils proved to be life saving, but subsequent neurologic sequelae developed, including loss of sensation over the right side of the scrotum, penis, and medial thigh. Urinary incontinence developed as well. Fortunately, the paresthesias were temporary.
Deficient DR antigen expression on human cord blood monocytes: reversal with lymphokines.
Expression of DR antigen on cord blood (neonatal) human monocytes using complement-mediated cytotoxicity with anti-DR alloantisera and fluorescent-activated cell sorting (FACS) utilizing a battery of anti-DR mouse monoclonal antibodies was assessed. Forty preparations of neonatal cord blood monocytes were purified by adherence and elution from plastic petri dishes: lymphocyte contamination was less than 5% as indicated by esterase and peroxidase stains and cell sizing. By cytotoxicity tests 22 +/- 5.5% (SD) of neonatal monocytes expressed DR compared to its expression on 78.6 +/- 3.1% of adult monocytes. By FACS analysis, the frequency of DR expression on neonatal monocytes was 19-33% compared to 71-82% for adult monocytes. Incubation of neonatal monocytes with concanavalin A (Con A) or phytohemagglutinin (PHA)-stimulated human peripheral blood mononuclear cell culture supernatants (lymphokine) or recombinant interferon-alpha (IFN-alpha) increased the expression of DR antigens in a dose- and time-dependent manner. A Con A-supplemented culture supernatant of unstimulated peripheral blood mononuclear cells had no effect on DR expression. Neonatal monocytes that were pretreated with anti-DR and complement in order to remove DR-positive cells were induced to express DR antigen after 2 days in culture with lymphokine. Thus DR-negative neonatal monocytes can be induced to express DR antigen. These results suggest a correctable maturational deficiency of neonatal monocytes. The inducibility of DR antigen expression by lymphokines and recombinant IFN-alpha suggests that they play an important role in the regulation of immune responses.
HTLV: epidemiology and relationship to disease.
With the discovery of the human retrovirus class, an important turning point in the understanding of the process by which cancer is caused and develops in humans has been achieved. As summarized here, clinical and epidemiologic studies have documented the close association of human T-cell leukemia virus (HTLV-I) to a particular form of T-cell malignancy, adult T-cell leukemia/lymphoma (ATL). Yet to be understood is the process involved in translating virus infection into malignant lymphoproliferation. Epidemiologic data suggest that this may involve a relatively long latent period between primary HTLV-I infection and subsequent malignancy risk. Presumably, identifiable co-factors will emerge to explain the trigger for malignant transformation. However, the restricted pattern of tumor phenotype suggest that this process is tightly linked to cells for which HTLV-I has a particularly strong infectious trophism. Interdisciplinary studies are currently under way in a number of laboratories to elucidate the molecular interactions in the HTLV-I associated malignant transformation process in order to correlate these with the epidemiologic data. Thus, lessons are likely to be learned from these molecular and epidemiologic studies which may provide new and important etiologic insights applicable to the prevention and therapy of cancer. Furthermore, with the recent discovery of HTLV-III, a cytopathic form of this class of human retrovirus, the likely cause of acquired immunodeficiency syndrome (AIDS) has been discovered. This has enormous public health implications for the detection, treatment, and prevention of this major medical epidemic. Epidemiologic studies are currently under way to identify what factors associated with virus exposure result in the full-blown AIDS syndrome. In addition, the malignancy potential of this new type of retrovirus is currently the subject of intensive investigation.
[Parametric images in triggered internal cardiac scintigraphy].
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Isolation of human T-cell leukemia virus in acquired immune deficiency syndrome (AIDS).
Several isolates of a human type-C retrovirus belonging to one group, known as human T-cell leukemia virus (HTLV), have previously been obtained from patients with adult T-cell leukemia or lymphoma. The T-cell tropism of HTLV and its prevalence in the Caribbean basin prompted a search for it in patients with the epidemic T-cell immune deficiency disorder known as AIDS. Peripheral blood lymphocytes from one patient in the United States and two in France were cultured with T-cell growth factor (TCGF) an shown to express HTLV antigens. Virus from the U.S. patient was isolated and characterized and shown to be related to HTLV subgroup I. The virus was also transmitted into normal human T cells from umbilical cord blood of a newborn. Whether or not HTLV-I or other retroviruses of this family with T-cell tropism cause AIDS, it is possible that patients from whom the virus can be isolated can also transmit it to others. If the target cell of AIDS is the mature T cell as suspected, the methods used in these studies may prove useful for the long-term growth of these cells and for the identification of antigens specific for the etiological agent of AIDS.
Isolation and transmission of human retrovirus (human t-cell leukemia virus).
Nine new isolates of human T-cell leukemia-lymphoma virus (HTLV) were obtained from cells of seven patients with malignancies of mature T cells and from two clinically normal relatives of a T-cell leukemia patient. These people were from the United States, Israel, the West Indies, and Japan. The virus was detected in the fresh T cells and was isolated from the established T-cell lines. Each isolate is closely related to the first HTLV isolate, and all the new HTLV isolates were transmitted into normal human T cells obtained from the umbilical cord blood of newborns.
Presence of HTLV in a subset of T cells from an infected patient: some immunochemical properties of the infected cells.
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Structural alterations in fibronectin correlated with morphological changes in smooth muscle cells.
Nontransformed cultures of vascular smooth muscle cells proliferate until they form a confluent sheet of cells. Subsequently, the cells become reorganized to form multicellular nodules that are loosely attached to the substrate. The formation of nodules is facilitated by the addition of medium conditioned by nodular cultures. Nodulation is inhibited by the addition of fibronectin. Fibronectins derived from monolayer culture conditioned medium or from plasma are maximally effective while fibronectin isolated from nodular cell conditioned medium is inactive. Analysis by NaDodSO4-polyacrylamide gel electrophoresis reveals that the nodular cell fibronectin has a molecular weight that is about 20-30 kd less than that of monolayer cell fibronectin. Further, nodular cell conditioned medium contains an activity that can convert both plasma fibronectin and monolayer cell fibronectin to the lower molecular weight correlated with the loss of biological activity.
Evaluation of antiarrhythmic activity of prostaglandin F2 alpha in man.
Since prostaglandin (PG) F2 alpha had been shown to act anti-arrhythmically in various animal models and also in preliminary investigations in man, further evaluation of this effect was made in 30 patients with cardiac extrasystoles and in 2 patients with tachycardias. PGF2 alpha was infused intravenously at individually adapted consecutive rates from 5 to 100 micrograms/min each for at least 5 min. In the incidence of extrasystoles a mean maximum decrease of 41% (P less than 0.001) was obtained. One patient showed repeated short interruptions of a ventricular tachycardia. A dose-dependent significant rise in blood pressure and no significant influences on heart rate, PQ interval and QRS interval of the ECG were found. It is concluded that PGF2 alpha has probably no practical importance for the therapy of cardiac arrhythmias.