Integrating clinical work and management in healthcare's future.
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Biomedical subjects
Publications and source records attributed to W Burnett.
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Interphase FISH analysis, utilizing dual color XY probes, was performed on 27 patients following allogeneic sex-mismatched bone marrow transplantation and on 31 controls. Of the 123 167 examined interphase nuclei, 63 318 were from 19 of the 21 patients (54 specimens) who engrafted, 31 827 from five of the six patients (29 specimens) who relapsed (four) or failed to engraft (one) and 24 703 from the 31 control specimens. In patients who engrafted, the mean percentage of host cells was 0.26% between day 29 and 5 years following BMT. Microchimerism of 0.7% or less than 1-5 years following BMT was not predictive of relapse. Interphase FISH analysis predicted relapse or failure of engraftment in five of the six evaluable patients. In three of five patients both conventional cytogenetics and interphase FISH of bone marrow cells provided important information regarding engraftment status and degree of chimerism.
During donor evaluation for allogeneic bone marrow transplantation (BMT) of a 28-month-old child with juvenile chronic myelogeneous leukemia (JCML) with 46,XY,-7,+mar karyotype, the potential donor twin brother was found to be thrombocytopenic. Subsequent genotype analysis determined monozygosity with 98% probability. Bone marrow analysis of the twin brother revealed the same 46,XY,-7,+mar karyotype and a diagnosis of JCML was made. Metaphase FISH studies documented that mar chromosome in both twins contains the pericentromeric region of chromosome 7 and thus both twins had a partial monosomy of chromosome 7. A possible embryonic origin of del(7) is proposed.
Previous studies of the relationship between cancer stage, age, and race have not controlled for social class and health care setting. Logistic regression analyses, using information from the New York State Tumor Registry and area-level social class indicators, demonstrated that, in New York City, older Black, lower class women in public hospitals were 3.75 and 2.54 times more likely to have late stage breast or cervical cancer, respectively, than were younger White, high social class women in non-public hospitals.
In the United States, New York City has had the greatest number of subjects at risk of AIDS for the longest period of time. This population therefore serves as an indicator of changes in cancer risk which may emerge among persons at risk from AIDS. Using a proportional incidence method, we surveyed cancers occurring among single (a surrogate for homosexual) young men and married young men in Manhattan, the rest of New York City, and the remainder of New York State. The baseline period was established earlier to be 1973-76, during which time no cases of Kaposi's sarcoma were observed among single men in Manhattan. By 1985, the frequency of Kaposi's sarcoma in this group was increased 1,850-fold (compared with expected cases derived from other registries). In the same group, the increase of non-Hodgkin's lymphoma was 6.2-fold (p for trend less than 0.0001), with excesses of Burkitt's lymphoma and immunoblastic lymphoma being most noticeable. Diagnoses of Hodgkin's disease increased markedly in 1985 but not earlier. Since this pattern did not follow that of the AIDS epidemic in this area, we suggest that Hodgkin's disease is not an AIDS-associated tumor. Hepatoma was diagnosed more frequently in single young men during the 1980s but similar increases also were observed in married men and thus may be unrelated to AIDS. Thus, only Kaposi's sarcoma and non-Hodgkin's lymphoma appear to be AIDS-associated tumors, at least so far. With better treatment and longer survival, it remains possible that other tumors will emerge as part of the AIDS epidemic.
This case-control study provides individual-based data describing the impact of being a cancer patient on the odds of suicide. 5,009 suicides and 17,064 controls are compared. The data indicate that cancer patients are 50 to 100 percent more likely than nonpatients to commit suicide. This and other studies indicate that health status should be considered in future attempts to relate suicide to social environment.
A segment of chick elastin cDNA cloned in the plasmid pBR322 was sequenced by the method of Maxam and Gilbert ((1977) Proc. Natl. Acad. Sci. U. S. A. 74, 560-564) and the 192-base pair insert was found to be derived from the nontranslated region of the 3' end of the mRNA. The nick-translated cDNA was used to identify and to estimate the relative amounts of elastin mRNA in the developing chick embryo aorta by blot hybridization. A single species of 3.5 kilobases hybridized to the cDNA probe and this species increased greatly between day 7 and day 14 of embryonic development. This increase was paralleled by an increase in translatable aortic elastin mRNA and by the in vivo rate of elastin synthesis, demonstrating that the change in synthesis during development is largely controlled by the elastin mRNA content of the aorta.
mRNA was isolated from the thoracic aortas of 16-day chick embryos and used to synthesize blunt-ended heteroduplex molecules consisting of one strand of mRNA and one of cDNA using AMV reverse transcriptase and S1 nuclease. The duplexes were tailed with dCTP and hybridized to the plasmid pBR322 which had been restricted with Pst I and tailed with dGTP. Recombinant plasmids were used to transform E. coli C600 and colonies containing elastin cDNA were selected by in situ hybridization with 32P labeled elastin mRNA and by hybrid selected translation using the nuclease-treated reticulocyte lysate system. mRNA recovered from hybridization to DNA of one clone, pWB1, markedly stimulated incorporation of [3H]valine into a protein which was immunoprecipitable with elastin-specific antibody and had a molecular weight of 72,000, characteristic of tropoelastin. The 230 bp insert of pWB1 was sequenced by the technique of Maxam and Gilbert and found to be derived from a nontranslated region of the 3' end of the mRNA. Nick-translated pWB1 was used to identify and to estimate the relative amounts of elastin mRNA in the developing chick embryo aorta by blot hybridization. A single mRNA species of 3.5 kb hybridized to the pWB1 probe and this species increased greatly in amount between day 7 and day 14. This increase was paralleled by an increase in translatable elastin mRNA and by the rate of elastin synthesis of aortas from various age embryos incubated in vivo. The injection of 150 microgram of hydrocortisone 21-phosphate into 8-day eggs produced a significant increase in both the relative rate of tropoelastin synthesized by the isolated aortas and the relative amount of elastin mRNA. These results suggest that the observed changes in elastin synthesis during development and after hydrocortisone administration are governed by the elastin mRNA content of the aortas.
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Black pigment, extracted from gallstones from patients, has been characterized as polybilirubinate. A similar material with the same physical properties was synthesized from bilirubin. The properties of black pigment are described. A mechanism for black pigment formation is postulated, and the possible relationship of this pigment to the formation of gallstones is discussed.
An analysis of 37 patients over the age of 65 years who underwent emergency surgery for complications of peptic ulcer is presented. A major predisposing factor to these complications was the use of ulcerogenic drugs that were prescribed for chronic musculo-skeletal ailments. The overall mortality was 23.5%, and was mainly related to pre-existing cardio-pulmonary disease.
Microsomal cholesterol 7 alpha-hydroxylase (EC 1.14.13.7) in rat liver was assayed by a single-isotope-incorporation method, and factors influencing its activity were studied. Crude cytosol contained a non-catalytic activator which was heat-stable and on-dialyzable. This activator enhanced cholesterol 7 alpha-hydroxylase catalytic activity. The stimulatory property of this cytosolic activator was not altered by cholestyramine feeding, and was retained after fractionation by ammonium sulfate of saturation up to 65%. 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) stimulated hydroxylase activity at concentrations up to 90 micro M. ATP at concentration greater than 1.2 mM inhibited hydroxylase activity. NaF was stimulatory at concentrations up to 50 mM with a maximum stimulatory effect at 10 mM, and was antagonistic in effect to ATP. HMG-CoA and ATP at the above inhibitory concentrations and higher abolished the activating effect of the cytosolic factor.
Modulation of cholesterol 7 alpha-hydroxylase catalytic activity by adenine nucleotides was studied in rat liver microsomal preparations. Inactivation of cholesterol 7 alpha-hydroxylase showed specific requirements of ATP and ADP. AMP and cyclic AMP were stimulatory and cyclic AMP had no effect in the ATP inactivation. The inactivation reactions by ATP were dependent on Mg2+ ions, a cytosolic factor, and time. Ca2+ ions were less effective whereas Mn2+ ions were highly inhibitory to hydroxylase activity. The inactivation could be reversed in a time-dependent reaction requiring a cytosolic activator that was precipitable by ammonium sulphate of saturation up to 65%. The current data suggest that cholesterol 7 alpha-hydroxylase can exist in two catalytic forms that are reversible.
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On the basis of histological studies, it is proposed that the type of liver-cell death in piecemeal necrosis is apoptosis. The characteristic inconspicuousness of apoptosis explains why the mode of hepatocyte elimination in piecemeal necrosis has hitherto remained obscure. Cell-mediated immune attack induces apoptosis, not classical necrosis, and the occurrence of apoptosis in piecemeal necrosis links the observed morphological changes in chronic active hepatitis with the other evidence for an autoimmune pathogenesis. It is significant that apoptosis does not evoke inflammation or fibroplasia. In attempting to elucidate the cause of the fibrosis that accompanies progression to cirrhosis in chronic hepatitis, it may thus be more relevant to study the effect on fibroblasts of substances liberated during lymphocyte-hepatocyte interactions than the death of the hepatocytes.
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We identified the wives or ex-wives of 227 males of the 256 reported with cancer of the penis to the New York State Cancer Registry from Upstate New York from 1960-64. Utilizing the Registry, death certificates, hospital and physician records, we ascertained those wives who developed cancer at any site from 1951-1975. We generated expected numbers of cases of cancer at each site by applying the age specific incidence rates experienced by women of a specific age in a specific year designated by the age of the wife of the index case in each year, estimating withdrawals from age-specific death rates. Thus, our expected numbers are based on the experience of the women in Upstate New York with traits like those of spouses of the men in the same population with cancer of the penis. We found significantly more cases of cancer of the cervix than expected. This was not true for other sites of cancer.