Biomedical subjects

W Chamberlain

Publications and source records attributed to W Chamberlain.

12 recordsLinked to original sources

PubMed1999

Genetic control of autoimmune myocarditis mediated by myosin-specific antibodies.

Autoimmune disease involves both the development of autoreactivity and the expression of organ damage, and susceptibility is genetically complex. We recently reported that in autoimmune myocarditis susceptibility to antibody-mediated cardiac injury is strain specific. DBA/2 mice develop myocarditis following administration of myosin-specific antibody, while BALB/c mice do not. This susceptibility appears to be controlled by expression of myosin in the myocardial extracellular matrix. CByD2F1 mice are both resistant to induction of myocarditis and do not demonstrate extracellular myosin, indicating a recessive genetic component to these traits. A backcross analysis of susceptibility using DBA/2xCByD2F1 mice revealed a locus on chromosome 12 that is strongly linked with myocarditis. In male mice there was a second region on chromosome 1 that also contributes to disease susceptibility. However, genetic susceptibility in both female and male mice was genetically complex. This study demonstrates that the genetic basis of tissue injury can be analyzed separately from the genetic basis of autoreactivity. Future studies will determine whether the genetic factors identified in this study are also involved in susceptibility to rheumatic fever.

Animals↗

PubMed1997

Nuclear entry, oligomerization, and DNA binding of the Drosophila heat shock transcription factor are regulated by a unique nuclear localization sequence.

In normally growing Drosophila cultured cells the Drosophila heat shock transcription factor (dHSF) is localized in the cytosol and translocates into the nucleus after heat shock. In the cytosol of nonshocked cells, the dHSF is present as a monomer that cannot bind DNA. Upon stress, the dHSF enters the nucleus where it is observed to be a trimer. A novel nuclear localization sequence (NLS) in the dHSF was found to be responsible for stress-dependent nuclear entry. Deletion of the NLS prevents nuclear entry, as expected, yet surprisingly also allows constitutive oligomerization and DNA binding in the cytosol. Further analysis of the NLS by mutagenesis suggests that the two functions of nuclear entry and oligomerization are separable in that distinct residues present in the NLS are responsible for each. Mutations in certain basic residues completely block nuclear entry, as expected for a constitutive NLS. In addition, two residues were found in the NLS that, when altered, allowed constitutive nuclear entry of dHSF independent of stress. These residues may interact with a putative cellular component or possibly other domains of the HSF to prevent nuclear entry in normally growing cells. The NLS can also function autonomously to target a beta-galactosidase fusion protein into the nucleus in a heat shock-dependent fashion.

Amino Acid Sequence↗

PubMed1997

EMS 2000. Expanded scope of practice.

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Cost Allocation↗

PubMed1980

Misdiagnosis of bronchogenic carcinoma: the role of cigarette smoking, surveillance bias, and other factors.

The effects of cigarette smoking and other factors on the accuracy of clinical diagnosis of bronchogenic carcinoma were studied retrospectively in 14,074 autopsies performed over 26 years (1948-1973) at University Hospitals of Cleveland. Within a selected study group of 415 cases diagnosed as bronchogenic carcinoma either clinically, at atuopsy, or both, the disease was diagnosed accurately in 260 cases (63%), overdiagnosed in 38 cases (9%), and underdiagnosed in 117 cases (28%). Misdiagnoses occurred in female patients nearly twice as frequently as in male patients. Elderly men were over- and underdiagnosed more frequently than were young men. An accurate diagnosis of this neoplasm was strongly associated with a histroy of smoking and was also related to the number of hospital admissions, the diagnostic procedures used, and surveillance bias associated with a history of smoking or coughing. In 88% of the misdiagnosed cases, the tumor was either simulated or masked by other diseases. It is estimated from these data that the rate of unavoidable clinical misdiagnosis of the disease is 32% and the true error (overt misjudgment) in clinical diagnosis, 5%. Previous estimates of causal association between smoking and lung cancer would not be affected by the findings of this study.

Adult↗

PubMed1975

A direct vasoconstrictor effect of mannitol on the renal artery.

The direct effect of mannitol on the renal artery was studied using spiral cut strips of canine renal arteries. Spiral strips were equilibrated in Krebs-Henseleit bicarbonate buffer at 37 degrees C. The strips contracted when challenged with increasing doses of mannitol. The force of contraction was directly proportional to the dose of mannitol used. Vasoconstriction is a direct effect of mannitol on the renal artery in the dose range of 10 to 70 milligrams per milliliter. This observation may explain some of the seemingly contradictory data which have accumulated in studies using mannitol.

Animals↗

PubMed1974