Molecular cloning of mouse immunoglobulin heavy chain messenger ribonucleic acids coding for mu, alpha, gamma 1, gamma 2a, and gamma 3 chains.
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Biomedical subjects
Publications and source records attributed to J Jackson.
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Several transition series metals (copper, cadmium, zinc and mercury) and the sulfhydryl reagent, sodium arsenite, enhance the synthesis of specific proteins in chick embryo cells and in human foreskin cells in culture. The proteins are visible 1--3 h after exposure to concentrations ranging from 10 microM to 100 microM depending upon which reagent is used. These proteins comigrate on acrylamide gel electropherograms with the proteins induced by two copper-chelating drugs, kethoxal bis(thiosemicarbazone) and disulfiram, and by heat shock. However, these proteins migrate in a significantly different manner than do the canavanine-enhanced proteins. The four proteins induced in chick embryo cells are distinct from one another as determined by partial proteolytic mapping. Simlarly, the three proteins induced in human cells are distinct. However, the 100-kilodalton and the 70-kilodalton proteins from chick and from human cells appear to be related as judged by this mapping procedure. The 70 kilodalton protein enhanced by kethoxal bis(thiosemicarbazone), disulfiram, arsenite and heat shock have a high degree of similarity according to this technique. The arsenite and canavanine-enhanced 100-kilodalton proteins are related as are the arsenite-enhanced 70-kilodalton and the canavanine-enhanced 75-kilodalton proteins. The canavanine-enhanced 30 kilodalton protein resembles the arsenite-enhanced 25-kilodalton protein rather than the 35-kilodalton species. In view of these findings, it appears that a variety of treatments, namely, chelating drugs, transition series metals, sulfhydryl reagents, heat shock, and amino acid analogous can induced similar, if not identical, proteins in eukaryotic cells.
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A week's census was taken of children attending family doctors or hospital accident and emergency departments in an inner city area of London. Most attendances at general hospitals were for cases of trauma while the children's hospital was used mainly by the very young, coming from a wide catchment area. An over-emphasis on hospital-based primary care would not be appropriate in this area and would run counter to the whole philosophy of British medical practice.
The results of this study demonstrate that skeletal muscle perfusion during bypass requires high flows and mean arterial pressures and that use of vasopressors during bypass impairs skeletal muscle blood flow. Our findings also indicate that skeletal muscle perfusion during bypass decreases metabolic acidosis after operation and prevents decreases in body temperature and poor skeletal muscle blood flow in the post-bypass and early postoperative periods. Our results suggest that perfusing to maintain normal Pmo2 during extracorporeal circulation is superior to more conventional techniques of conducting bypass.
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Familial data on neural tube malformations in Great Britain were submitted to segregation analysis under the mixed model. Maternal and fetal factors cannot be discriminated in the absence of substantial bodies of data on spina bifida survivors who reproduce or on half-sibs. Early abortion studies would allow differential mortality in utero to be taken into account. After fitting the mixed and generalised single locus models, it is concluded that the multifactorial model can provisionally be used for calculation of recurrence risks. Pathogenic hypotheses implicating twinning seem to rest on little evidence.
This paper reports on a study of women in a family practice who have undergone hysterectomy as compared with a group of matched controls. Significant differences were found in the greater number of major surgical procedures (other than hysterectomy) and the reporting of chronic and recurrent symptoms for the study group. Study group women were also found to have a greater number of identified intrapersonal and family problems. There was no significant difference, however, in the number of identified chronic organic problems. Differences which did not reach statistical significance suggest that women in the study group may be more likely to be living without a male partner, to be using long-term medication, and to be smokers. A most important finding was that the group of women who had undergone hysterectomy had also had 2.6 times the number of major surgical operations than the controls, excluding the hysterectomy. There were no differences between the two groups with respect to a number of other factors studied, eg, education, religion, history of psychiatric admission, obesity.
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Antabuse (disulfiram) is widely used in the treatment of chronic alcoholism. We have examined the effect of this drug on malignant transformation by Rous sarcoma virus, on eukaryotic cell synthesis, and on nucleic acid binding. It was found that: (1) Disulfiram inhibits the activity of the RNA dependent DNA polymerase of Rous sarcoma virus and inactivates the ability of the virus to malignantly transform chick embryo cells. The monomer of disulfiram, diethyldithiocarbamate does not affect the virus. (2) Disulfiram induced the synthesis of four proteins in normal chick embryo and human foreskin cells. The monomer diethyldithiocarbamate, induced these proteins also. Cellular DNA synthesis is more sensitive to disulfiram than are RNA and protein synthesis. (3) Disulfiram binds to neither DNA or RNA in the presence or absence of copper. However, diethyldithiocarbamate in the presence of, but not in the absence of, copper binds to HeLa cell DNA and to Rous sarcoma virus 70 S genome RNA. These results indicate that this compound, which causes no symptoms in people who do not consume alcohol, may have significant effects on a cellular level.
Kethoxal bis(thiosemicarbazone) induces the synthesis of four proteins (100 000, 70 000, 35 000 and 25 000 daltons) in normal chick embryo cells. The 70 000 dalton species is produced at the fastest rate 2 hr after exposure to the compound. Pulse-chase experiments revealed neither precursors nor products of these proteins and both actinomycin and cycloheximide inhibited their synthesis. Neither of the two substituents of the inducer, kethoxal or thiosemicarbazide, were active. The four proteins were induced in several other species, but human cells produced only three proteins (100 000, 70 000 and a different 30 000 dalton form).
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Several thiosemicarbazone-metal complexes inhibit the RNA dependent DNA polymerase and the transforming ability of Rous sarcoma virus. Some complexes are equally as active as the free ligand whereas the activity of others is greatly enhanced. The 2-formyl pyridine thiosemicarbazone copper (II) complex is the most potent compound of this class that we tested. Some copper complexes of salicylaldehyde derivatives are very active also, particularly N-n-butyl, N-n-hexyl and N-benzylsalicylaldimine; no nickel complex of any salicylaldehyde compound is active. In addition, other metal ligands, such as dithizone, diacetyl bis (mercaptoethylimine), N-butyl thiocarbamate, 0,0' dimethyl dithiophosphate, potassium dithiooxalate, and cis-PtII(NH3)2Cl2 were tested with varying results.
The copper complex of the antituberculous drug, insonicotinic acid hydrazide (INH), inhibits the RNA-dependent DNA polymerase of Rous sarcoma virus and inactivates its ability to malignantly transform chick embryo cells. The INH-copper complex binds to the 70S genome RNA of Rous sarcoma virus (RSV), which may account for its ability to inhibit the RNA-dependent DNA polymerase. The complex binds RNA more effectively than DNA in contrast to M-IBT-copper complexes, which bind both types of nucleic acids equally. The homopolymers, poly rA and poly rU, are bound by the INH-copper complex to a greater extent than poly rC. Isonicotinic acid hydrazide alone and CuSO4 alone bind neither DNA, RNA, poly (rA), poly (rU), nor poly (rC). However, CuSO4 alone binds poly (rI); INH alone does not. In addition to viral DNA synthesis, chick-embryo cell DNA synthesis is inhibited by the INH-copper complex. The extent of inhibition of cellular DNA synthesis is greater than that of cellular RNA and protein synthesis. No selective inhibition of transformation in cells previously infected with Rous sarcoma virus is observed.
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Prophylactic antibiotics are prescribed frequently for patients requiring permanent transvenous cardiac pacemakers, despite a paucity of data indicating effectiveness. A 10 year retrospective analysis was performed of 298 pacemaker insertion procedures involving 204 patients. On the basis of prestudy criteria relating to timing and dosage of antibiotics, the use of prophylactic antibiotics was judged as adequate or inadequate. There were no postoperative infections in the 108 battery pack replacement procedures despite no or inadequate use of antibiotics in 49 procedures. There were nine infections in the 190 battery pack plus pacing wire procedures for an infection rate of 5 percent. There was no significant difference in infection rate between the group given prophylactic antibiotics and the group given no or inadequate prophylactic antibiotics. Of the 190 battery pack plus pacing wire procedures, no infections occurred in the 50 procedures in which surgical drains were not used (p less than 0.003). In the 140 procedures in which drains were used, there was no correlation between wound infection and absent or inadequate coverage with prophylactic antibiotics. Two severe bacteremic Staphylococcus aureus infections occurred in two patients not given prophylactic antibiotics. The other seven infections were clinically indolent. These results suggest the following: (1) There is no need for prophylactic antibiotics in battery pack replacement procedures; (2) prophylactic antibiotics may decrease the severity of infection in battery pack plus pacing wire procedures; (3) surgical drains should be avoided in battery pack plus pacing wire procedures. A prospective controlled study is necessary to confirm these results.