Contaminant lead in blood-collection tubes for trace-element studies.
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Biomedical subjects
Publications and source records attributed to J Crick.
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Local and generalized changes in coagulation may be important in the genesis of vegetations and embolism in infective endocarditis. To characterize such alterations, serial hematological investigations were performed on nine consecutive patients who satisfied the inclusion criteria. Platelet survival was measured by Indium111 labeling. Acute and convalescent samples were analyzed for fibrinogen, factor VIIIc, antithrombin III (AT III), fibrin/fibrinogen degradation products (FDPs), and platelet aggregation. The results suggest that in the active stage of the disease: (1) hypercoagulability may be caused by a rise in acute phase reactants, (2) an acceleration of coagulation and fibrinolysis may supervene, and (3) in some cases there is a reduction in platelet aggregation, possibly as a result of continued circulation of previously activated "exhausted" platelets.
The gene encoding the beta-chain of the T-cell antigen receptor (TCR) has been analyzed for evidence of rearrangement in skin, blood, and lymph node specimens from 23 cases of known or suspected cutaneous T-cell lymphoma (CTCL). Two cutaneous large cell lymphomas, 4 cases of Sézary syndrome, and 5 cases of advanced (tumor) stages of mycosis fungoides showed clonal rearrangement of the TCR beta-chain gene in all samples, including lymph nodes in which histologic examination revealed only dermatopathic lymphadenitis. These results indicate that DNA analysis provides a valuable means for improving the diagnosis of extracutaneous disease in advanced stages of CTCL. In contrast, the gene was in a germline configuration in all samples from 12 patients with plaque stages of mycosis fungoides or suspected early CTCL, suggesting that in these 2 conditions the T-cell proliferation is either polyclonal or contains very few monoclonal (i.e., neoplastic) cells.
The monoclonal antibody Ki-1 reacts with Reed-Sternberg cells in Hodgkin's disease and with the tumour cells in a minority of large cell non-Hodgkin's lymphomas. This study describes the results of immunophenotypic and DNA analysis in 30 cases of non-Hodgkin's lymphoma, all of which expressed the Ki-1 antigen. The genotypic analysis has been undertaken using both immunoglobulin and T-cell receptor gene probes. Sixteen cases were shown by this method to be of monoclonal T-cell origin, six of B-cell origin, while in eight cases there was no evidence of either T- or B-cell lineage. This confirms previous immunohistological data indicating that non-Hodgkin's lymphomas which express the Ki-1 antigen may be of either T-cell or B-cell origin.
The value of DNA hybridisation (using immunoglobulin and T cell receptor gene probes) was assessed during the diagnosis of problematical lymphoid tissue biopsy specimens. In 14 of 18 specimens (78%), which contained a malignant lymphoproliferation of uncertain aetiology, this technique permitted the demonstration of a monoclonal proliferation of B cells (nine cases) or T cells (five cases). In five further lymph node biopsy specimens, in which the differential diagnosis lay between a reactive or malignant process, a clonal proliferation was shown in three cases. DNA analysis is, therefore, of practical value in resolving many of the diagnostic problems that arise in the assessment of lymphoid tissue biopsy specimens.
Physiological pacing was instituted in 17 patients (11 men and 6 women), mean age 67 years (range 33-77 years), using a variety of multiprogramable generators attached to a permanent single-pass dual chamber electrode. Eleven patients were paced in VAT mode (Cordis 208A or Siemens-Elema 625 generator), two patients in DVI mode (Intermedics Cyberlith IV generator) and four patients in DDD mode (Siemens-Elema 664/P33 or Telectronics Autima unit). Mean intracardiac P wave amplitude was 2.0 mV +/- 0.78/SD, range 0.7-3.6 mV. and mean atrial and ventricular pacing thresholds were 1.0 V and 0.5 V, respectively. Fourteen patients had completely successful A-V pacing during a follow-up period of 4-13 months (mean 7 +/- 2.7 months). Two failures were associated with malposition of the atrial crown and occurred exclusively with the Cordis 208A generator. In both patients generator replacement using a more sensitive unit (Siemens-Elema 625) resulted in successful VAT pacing for most of the time. Complete failure of A-V pacing occurred in only one patient who died from coronary artery disease after four months of follow-up. Thus, all of the remaining 16 patients achieved long-term (6 months) satisfactory physiological pacing using this new lead. We conclude that the "Crown of Thorns" electrode is a successful single-pass unipolar lead and can be used with all types of dual chamber generator for all modes of pacing.
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Defective interfering particles of vesicular stomatitis virus have been named according to their parental derivation and to their genomic length and physical properties. This suggested uniform nomenclature can be adapted for other virus systems.
The family Rhabdoviridae comprises approximately 75 viruses infecting vertebrates, invertebrates and plants. The main characteristics of the member viruses are: (i) the viruses infecting vertebrates and invertebrates are bullet-shaped and the viruses infecting plants are usually bacilliform; (ii) the viruses have particle lengths varying from 130 to 380 nm and widths varying from 60 to 95 nm; (iii) the viruses possess unit-membrane envelopes from which protrude spikes 5 to 10 nm long; (iv) the viruses have precisely coiled helical nuecleocapsids with a diameter of approx. 50 nm; (v) most of the viruses which have been studied contain 5 proteins; the prototype, vesicular stomatitis virus, contains proteins designated L (large), G (glycoprotein), N (nucleoprotein), NS (nonstructural) and M (matrix); N or NS is phosphorylated in most members which have been studied; (vi) the viruses contain single-stranded RNA which is transcribed into several messenger RNA species with sizes corresponding to the structural proteins; (vii) the nucleocapsid contains the RNA-dependent RNA polymerase and is infectious; and (viii) many of the viruses produce morphologically distinct defective-interfering (T) particles.
In pre-exposure immunization the protective effect of rabies vaccines can be correlated with their ability to stimulate the production of neutralizing antibodies and in post-exposure therapy also antibodies would appear to have a major role. Therefore, the potency of the vaccines may conveniently be compared by measuring their antigenicity in animals or by serum blocking tests. Nevertheless, most authorities will license, for human and veterinary use, only those vaccines which reach the required standards in the Habel or NIH tests, both of which depend upon the inoculation of more than 1 dose of vaccine followed by an intracerebral challenge. We have been involved recently in testing batches of vaccine imported into Britain for use in animals and man. Since the U.K. authorities have adopted the NIH test for this purpose we have taken the opportunity to compare some of these vaccines in the NIH test, in a modified NIH test in which the same amount of vaccine was given in a single dose, and in a test in which the production of serum neutralizing antibodies was measured. We have found that one dose of vaccine given on day 0 gave less protection and less neutralizing antibody than the same amount of vaccine given as two separate doses on day 0 and day 7. The greater effect obtained by inoculating the vaccine in two doses could thus be misleading and we suggest the adoption of a test in which a single dose is given.
Inactivated defective interfering and complete particles of vesicular stomatitis virus given intracerebrally to adult mice protect them against challenge with homologous virus whether this is given at the same time or several days later. Two separate protective processes appear to be involved. The first, which comes into operation immediately after inoculation, is also effective against heterologous strains of vesicular stomatitis virus, rabies (another rhabdovirus), and a neurotropic strain of foot-and-mouth disease virus. The second, later effect, which is strain specific, appears to be correlated with the appearance of circulating neutralizing antibody. Our results suggest that the protective effect that Holland and his colleagues described using defective interfering particles of vesicular stomatitis virus may also be accounted for by an immunological mechanism rather than one involving interference.
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The structure of rabies virus and the importance of its glycoprotein in immunization are discussed. The improvement in vaccines for use in man, culminating in the production of the human diploid vaccine is described. Nevertheless problems remain, particularly with regard to post-exposure therapy. Possible disadvantages in the use of subunit vaccines are mentioned and attention is drawn to the discovery of the rabies-related viruses.
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Suspension cultures of BHK-21 cells maintained at 32 to 33 C were infected with the Flury LEP strain of rabies virus. By using a cell concentration of 2.0 x 10(6) to 2.5 x 10(6) cells per ml infected at a multiplicity of 0.05, high titers of extracellular virus were reached in 96 to 120 h, and potent inactivated vaccines were prepared from culture fluids harvested between 96 to 168 h. The addition of 1% bovine serum to the maintenance medium resulted in an increase in virus yields and vaccine potency. Estimation of the number of infected cells by immunofluorescent procedures proved a rapid and reliable guide to the virus content of suspension cultures.