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Biomedical subjects

J Crick

Publications and source records attributed to J Crick.

At least 19 recordsLinked to original sources
PubMed1994

The effects of succimer on the absorption of lead in adults determined by using the stable isotope 204Pb.

The chelating agent succimer (meso-2,3-dimercaptosuccinic acid) is orally effective at inducing a urinary lead diuresis and a decrease in blood lead levels in lead poisoned children and adults. However, there are concerns that succimer may increase the absorption of lead from the gastrointestinal (GI) tract during treatment, particularly in cases of continuing lead exposure, which would compromise its effectiveness in reducing whole body lead stores. This preliminary study investigated the effects of succimer on the absorption of lead in adults using a stable lead isotopic tracer (204Pb). Twelve male subjects were divided into control (no succimer), 10, and 30 mg succimer/kg body wt treatment groups of 4 individuals each. All subjects ingested a single tracer dose (200 micrograms) of 204Pb, followed by a single oral dose of placebo (control) or succimer. Whole blood was collected at intervals of 0, 2, 4, and approximately 26 hr following ingestion of the 204Pb tracer, and composite urine and feces samples were collected over the duration of the study (approximately 26 hr). Mean intestinal excretion of 204Pb was reduced in the succimer-treated groups compared to the control (placebo), whereas urinary diuresis of 204Pb was higher in the succimer groups. The amount of lead 204Pb tracer accounted for at the end of the study was lower in the succimer-treated groups. These results suggest that GI lead absorption was enhanced by succimer and that succimer mediated the redistribution of lead from the circulation to other tissues. However, none of the differences between treatment groups were statistically significant (P < 0.05, t test) because of the relatively large within-group variability. This study demonstrates the utility of microgram doses of a stable lead isotopic tracer to assess the efficacy of clinical chelating agents in humans. Future studies are necessary to further clarify the effects of succimer on the absorption and retention of lead in adults and children. Although, based upon these preliminary data, it appears advisable that patients be maintained in a lead-safe environment while being treated with succimer.

Adult↗
PubMed1991

Hemostatic studies in patients with infective endocarditis: a report on nine consecutive cases with evidence of coagulopathy.

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.

Adult↗
PubMed1987

Genotypic analysis of cutaneous T-cell lymphomas.

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.

Adolescent↗
PubMed1987

Genotypic analysis of large cell lymphomas which express the Ki-1 antigen.

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.

Adolescent↗
PubMed1987

Practical value of genotypic analysis for diagnosing lymphoproliferative disorders.

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.

B-Lymphocytes↗
PubMed1983

Clinical evaluation of a single-pass implantable electrode for all modes of pacing. The "Crown of Thorns" lead.

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.

Adult↗
PubMed1982

Is the acetylcholine receptor a rabies virus receptor?

Rabies virus was found on mouse diaphragms and on cultured chick myotubes in a distribution coinciding with that of the acetylcholine receptor. Treatment of the myotubes with alpha-bungarotoxin and d-tubocurarine before the addition of the virus reduced the number of myotubes that became infected with rabies virus. These findings together suggest that acetylcholine receptors may serve as receptors for rabies virus. The binding of virus to acetylcholine receptors, which are present in high density at the neuromuscular junction, would provide a mechanism whereby the virus could be locally concentrated at sites in proximity to peripheral nerves facilitating subsequent uptake and transfer to the central nervous system.

Acetylcholine↗
PubMed1979

Rhabdoviridae. Report of the Rhabdovirus Study Group, International Committee on Taxonomy of Viruses.

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.

RNA, Viral↗
PubMed1978

Questions concerning the potency of rabies vaccine.

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.

Animals↗
PubMed1977

In vivo interference in vesicular stomatitis virus infection.

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.

Animals↗
PubMed1976

Rabies virus and the problems of rabies vaccination in man.

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.

Antibody Formation↗