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Biomedical subjects

A D Johnson

Publications and source records attributed to A D Johnson.

At least 109 records · Page 6Linked to original sources

Nevoid basal cell carcinoma syndrome: bilateral ovarian fibromas in a 3 1/2-year-old girl.

A 3 1/2-year-old black girl with bilateral ovarian fibromas was subsequently diagnosed as having nevoid basal cell carcinoma syndrome at the age of 4 years, when basal cell tumors and pits of the hands and feet were noted on examination. This case is unusual because of the development of bilateral ovarian fibromas at an extremely early age. Prepubertal patients with this ovarian tumor should be thoroughly investigated for the possibility of nevoid basal cell carcinoma syndrome.

Basal Cell Nevus Syndrome↗

Results of treatment of cancer of the cervix in Wellington: 1975-9.

A review was undertaken of all patients treated for invasive carcinoma of the cervix in the Wellington region in the period 1975 to 1979. A total of 84 patients were assessed for the results and complications of treatment. Forty-one were stage I, 18 stage II, 18 stage III, and seven stage IV (FIGO staging). Treatment by different combinations of surgery and radiotherapy for each stage are described. Actuarial survival at five years is 54% for all stages. For stage I it is 86%, stage II 54%, and stage III 44%. There were only seven patients in stage IV. Seven patients (8.3%) suffered major complications, mainly gastrointestinal or genitourinary. Most complications occurred in patients treated with a combination of radical surgery followed by high dose external radiotherapy. This treatment should be reserved for selected patients who can be identified as having a very high risk of recurrence in the pelvis after surgery. Invasive cancer of the cervix is a highly treatable disease, with over half the patients surviving free of disease at five years, but screening programmes for early detection are essential.

Adenocarcinoma↗

Functional and physical characterization of transcription initiation complexes in the bacteriophage lambda OR region.

We have used transcriptional activity assays and DNase I footprinting techniques to examine in vitro the binding of Escherichia coli RNA polymerase and lambda repressor protein to the bacteriophage lambda rightward promoter-operator region. For the lambda PR promoter, the activity and physical binding results determined at several repressor concentrations correlated very well. Good agreement was also found for repression of PRM, which occurred at higher repressor concentrations; however, our results indicate that at low repressor concentrations, RNA polymerase can physically occupy PRM in a transcriptionally inactive form. These inactive complexes formed with a binding constant similar to that previously measured for "closed complexes" at PRM. A kinetic study of PR open complex formation on an OR2-template in the presence of lambda repressor showed that decreased initiation frequency from this promoter was due largely to a decrease in KB. The kinetically determined inhibition constant for repressor (Ki = 4 nM) was similar to the dissociation constant (Kd approximately 2 nM) determined from the footprinting studies.

Bacteriophage lambda↗

A repressor (MAT alpha 2 Product) and its operator control expression of a set of cell type specific genes in yeast.

The product of the yeast MAT alpha 2 gene, alpha 2 protein, negatively regulates expression of a class of yeast cell type specific genes, the a-specific genes. In this paper we show that alpha 2 is a sequence-specific DNA binding protein. It recognizes a 32 base pair DNA sequence (operator) located upstream of an a-specific gene, STE6. A strongly homologous sequence is present upstream of each of the other four known a-specific genes. A synthetic STE6 operator, when placed in a test promoter (CYC1), brings the promoter under negative control by alpha 2 in vivo. This operator brings about repression when it is placed between the CYC1 upstream activation sequence (UAS) and the transcription start and when it is placed upstream of the UAS, outside the promoter. Thus, the operator need not overlap with essential promoter sequences to permit repression by alpha 2.

Base Sequence↗

Growing Xenopus oocytes have spare translational capacity.

Previous studies have shown that exogenous mRNAs injected into full-grown (stage 6) Xenopus oocytes are translated only at the expense of endogenous messages; translational capacity is limited. In this report, we demonstrate that injection of globin mRNA into small, stage 4 oocytes results in an increase in total protein synthesis without a concomitant decrease in the translation of endogenous mRNAs. The absence of competition with endogenous messages in stage 4 oocytes, injected with globin mRNA, compared with stage 6 oocytes, was not due to differential turnover of the injected mRNA. Hybridization of RNA from mRNA-injected oocytes at both stages revealed that similar amounts of globin mRNA were present. These results are interpreted to mean that protein synthesis in growing oocytes is limited by the availability of mRNA and not components of the translational machinery. This conclusion, however, does not apply to all mRNA classes. The capacity of stage 4 oocytes to translate a mRNA (zein) on membrane-bound polysomes is as restricted as reported previously for stage 6 oocytes. This result suggests that putative membrane binding sites or rough endoplasmic reticulum content are limited in oocytes at both stages. The possible role of association of injected mRNA with endogenous proteins that prevent translation is discussed.

Animals↗

Wedge and subselective pulmonary angiography in pulmonary hypertension secondary to venous obstruction.

Pulmonary wedge or subselective angiography provided key diagnostic information in two cases of pulmonary hypertension secondary to pulmonary venous obstruction. Whereas conventional pulmonary angiograms and ventilation-perfusion lung scans were interpreted as showing embolism, plain radiographs demonstrated Kerley B lines, suggesting venous obstruction. Subselective or wedge angiography of nonopacified arteries verified their anatomical patency and also revealed venous stenoses, collaterals, and atrophy indicative of obstruction.

Adult↗

Mitral valve E point-septal separation as an index of left ventricular function with valvular heart disease.

Echocardiographic mitral valve E point-septal separation (EPSS) has been found to be a useful hemodynamic index. Prior studies have shown a high negative correlation between EPSS and left ventricular ejection fraction (EF) in selected patients, but the utility of this index with valvular heart disease has not been examined in detail. Cardiac catheterization and M-mode echocardiographic data were retrospectively analyzed from 30 patients with aortic stenosis, 18 patients with chronic aortic regurgitation, and 25 patients with chronic mitral regurgitation. For aortic stenosis patients (including those with coronary artery disease), an excellent correlation (r = -0.89, p less than 0.001) was observed between EPSS and angiographic EF. More modest correlations were noted for patients with aortic regurgitation (r = -0.58, p less than 0.01) and mitral regurgitation (r = -0.63, p less than 0.001). For patients with aortic regurgitation, correlation improved to r = -0.83 by excluding subjects with marked (greater than 4 mm) fluttering of the anterior mitral valve leaflet. For patients with mitral regurgitation, the EPSS-EF correlation improved to r = -0.72 after excluding patients with atrial fibrillation. Compared with other echocardiographic indices of left ventricular function (percent shortening of the minor diameter or echo-derived EF), the EPSS demonstrated an equivalent or superior correlation with angiographic EF for each valvular lesion studied. We conclude that EPSS is a highly reliable index of left ventricular function with aortic stenosis, but its utility in unselected patients with chronic mitral or aortic regurgitation is limited.

Adult↗

Quantitative model for gene regulation by lambda phage repressor.

A statistical thermodynamic model has been developed to account for the cooperative interactions of the bacteriophage lambda repressor with the lambda right operator. The model incorporates a general theory for quantitatively interpreting cooperative site-specific equilibrium binding data. Values for all interaction parameters of the model have been evaluated at 37 degrees C, 0.2 M KCl, from results of DNase protection experiments in vitro [A. D. Johnson, B. J. Meyer, & M. Ptashne, Proc. Natl. Acad. Sci. USA (1979) 76, 5061-5065]. With these values, the model predicts repression curves at the divergent promoters PR and PRM that control transcription of genes coding for the regulatory proteins cro and repressor, respectively. At physiological repressor concentrations, repression at PR is predicted to be nearly complete whereas PRM is predicted to remain highly active. The results demonstrate the importance of cooperative interactions between repressor dimers bound to the adjacent operator sites OR1 and OR2 in maintaining a stable lysogenic state and in allowing efficient switchover to the lytic state during induction.

Bacteriophage lambda↗

lambda Repressor and cro--components of an efficient molecular switch.

In a lysogen, most genes of phage lambda are repressed; in response to a transient induction signal, they are efficiently switched on. The switch, which consists in part of a tripartite operator to which two regulatory proteins bind, depends not only on DNA--protein interactions, but also on effects transmitted from one DNA-bound protein to another. lambda Exemplifies a strategy that facilitates efficient switching between two physiological states in response to a transient signal.

Animals↗

Coronary artery disease and ventricular function in angina.

Coronary arteriograms and left ventriculograms of 500 patients with coronary artery disease and angina pectoris were correlated with respect to coronary arterial pattern and left ventricular dyssynergy. We found that the severity of left ventricular dyssynergy was not altered by coronary arterial pattern. The concept of dividing the left ventricle into anterior and posterior zones was validated. Patients with anterior dyssynergy alone or combined anterior and posterior dyssynergy had comparably more severe coronary artery disease in the anterior region than did patients with normal left ventriculograms or posterior dyssynergy alone. Patients with posterior dyssynergy alone or combined anterior anterior and posterior dyssynergy had comparably more severe coronary artery disease in the posterior region than did patients with normal left ventriculograms or anterior dyssynergy alone. Lesions of greater than 90% reduction of coronary arterial luminal diameter best correlated with motion abnormalities of the left ventricular wall.

Angina Pectoris↗

Functional studies of rabbit T lymphocytes.

Rabbit spleen and mesenteric lymph node cells were treated with a monoclonal anti-rabbit T-lymphocyte antibody (MAb) and complement and the effect of the treatment on various lymphocyte functions was determined. Lysis of spleen and mesenteric lymph node cells reactive with this MAb, 9AE10, essentially eliminated their proliferative responsiveness to allogeneic lymphocytes in the mixed lymphocyte reaction and to the T-cell mitogens, concanavalin A and phytohaemagglutinin; responsiveness to the B-cell mitogen, anti-immunoglobulin (Ig) was not decreased by lysis of 9AE10+ cells. In addition, the 9AE10+ cells were found to be necessary for the secondary in vitro antibody response to the T-dependent antigen sheep red blood cells (SRBC), as removal of 9AE10+ cells blocked the generation of plaque forming cells (PFC) in culture. The PFC's themselves were not sensitive to lysis by 9AE10 MAb and complement Thus, the 9AE10 MAb appears to recognize cells which have functions characteristic of T lymphocytes and this monoclonal antibody will be useful in further studies of the rabbit cellular immune system.

Animals↗