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Biomedical subjects

J H White

Publications and source records attributed to J H White.

At least 19 recordsLinked to original sources

Closed circular DNA as a probe for protein-induced structural changes.

Biological systems are replete with examples of DNA formed into a closed loop structure, either alone or in close association with proteins. Such closed circular DNA molecules are subject to a topological constraint that modifies, often in a major way, the structure and reactivity of the DNA. The topological constraint also permits closed circular DNAs to be used as analytical tools to learn about the structure of DNA-protein complexes.

DNA Probes

DNA polymerase delta: gene sequences from Plasmodium falciparum indicate that this enzyme is more highly conserved than DNA polymerase alpha.

Genes encoding proteins homologous to the catalytic subunits of DNA polymerase alpha and delta have been cloned from the human malaria parasite Plasmodium falciparum. These are among the first cellular replicative DNA polymerase genes to be cloned and their sequences allow us to make new statements about the relative degrees of conservation of these two enzymes. The most important finding was that P. falciparum Pol delta showed considerable homology to the only other Pol delta enzyme for which published sequence is available, that of S. cerevisiae, displaying an overall amino acid identity of 45% and identity over a highly conserved central region of 59%. In contrast, the level of identity shown over the equivalent central region of Pol alpha between the P. falciparum and S. cerevisiae sequences is only 32%. The sequence data also allowed us to examine the degree of conservation in putative exonuclease domains of Pol delta. The Pol delta gene of P. falciparum maps to chromosome 10 and evidence is presented for the presence of different sized Pol delta mRNA's in the asexual and sexual erythrocytic stages of parasite development.

Amino Acid Sequence

A formula for the average number of knot interlinks caused by type 2 topoisomerase action.

During the double-stranded passage that takes place because of the topoisomerase action, a plectonemically interwound DNA often becomes knotted. In this process, a portion of the substrate supercoils are converted into interlinks that contribute to the topology of the knot formed. In this appendix, an approximate formula is derived for the average number of these interlinks in terms of the number of supercoils and branches in the substrate. This will give an indication of the complexity of the average knot obtained. When two regions of DNA come together before passage, the substrate is divided into two domains in essentially the same way as intramolecular recombination divides the substrate into two domains (Boles, T. C., White, J. H., and Cozzarelli, N. R. (1990) J. Mol. Biol. 213, 931-951). Nodes formed between DNA segments from different domains are called interdomainal.

DNA Topoisomerases, Type II

Evidence for a factor required for transcriptional stimulation by the chimeric acidic activator GAL-VP16 in HeLa cell extracts.

We provide biochemical evidence for the existence of a transcriptional intermediary factor (TIF) in HeLa whole-cell extracts (WCE) that is distinct from the basic transcription factors and that is required for transcriptional stimulation by the chimeric acidic activator GAL-VP16. We have fractionated HeLa WCE by heparin-agarose chromatography. Of transcriptionally active fractions eluting in a step between 0.24 and 0.6 M KCl, the initial fractions are refractory to GAL-VP16 stimulation, whereas subsequent fractions are strongly stimulated by the activator. Aliquots of GAL-VP16-responsive fractions efficiently complement refractory fractions for transcriptional stimulation. Aliquots of responsive fractions are also far more efficient than those of refractory fractions in overcoming transcriptional inhibition that is brought about by high concentrations of GAL-VP16. Experiments performed with heat-treated WCE support the idea that HeLa cells contain a TIF that is essential for GAL-VP16 stimulation, but that is not required for basal transcription. Addition of recombinant yeast or human transcription factor TFIID (rTFIIDY and rTFIIDH, respectively) to a WCE heated at 48 degrees C for 15 min restores basal transcription, but in neither case is the reconstituted system activated by GAL-VP16. However, a 45 degrees C heat-treated WCE reconstituted with either rTFIIDH or rTFIIDY is stimulated by GAL-VP16, suggesting that a HeLa TIF can be selectively inactivated by heating at 48 degrees C, but not at 45 degrees C. Interestingly, a TFIID fraction partially purified from HeLa cell extracts, but not rTFIIDH, efficiently relieves transcriptional inhibition by GAL-VP16, suggesting that there may be an association between TIF(s) and TFIID and, moreover, that TIF(s) may be the direct target of the acidic domain of GAL-VP16. In summary, our results support the existence of a TIF that is not essential for basal transcription but that is required to mediate the stimulatory activity of the acidic activator GAL-VP16.

Biological Factors

The yeast DNA ligase gene CDC9 is controlled by six orientation specific upstream activating sequences that respond to cellular proliferation but which alone cannot mediate cell cycle regulation.

By fusing the CDC9 structural gene to the PGK upstream sequences and the CDC9 upstream to lacZ, we showed that the cell cycle expression of CDC9 is largely due to transcriptional regulation. To investigate the role of six ATGATT upstream repeats in CDC9 regulation, synthetic copies of the sequence were attached to a heterologous gene. The repeats stimulated transcription strongly and additively, but, unlike conventional yeast UAS elements, only when present in one orientation. Transcription driven by the repeats declines in cells held at START of the cell cycle or in stationary phase, as occurs with CDC9. However, the repeats by themselves cannot impart cell cycle regulation to a heterologous gene. CDC9 may therefore be controlled by an activating system operating through the repeats that is sensitive to cellular proliferation and a separate mechanism that governs the periodic expression in the cell cycle.

Base Sequence

Feminism, eating, and mental health.

Eating disorders are prevalent health problems for women today. The traditional biomedical or psychiatric approaches offer a narrow perspective of the problem, its courses, and its treatment. Analyzing disordered eating from a feminist perspective, this article discusses cultural, political, and social phenomena that have had a significant impact on the development of these disorders. Parallels of eating disorders and other women's mental illnesses and the medicalization of their symptoms is explored. A "new view" of disordered eating in women is proposed that can be advanced only through feminist research.

Body Image

Davidoff-Dyke-Masson syndrome presenting as childhood schizophrenia.

The problem of differential diagnosis of childhood schizophrenia versus gross brain pathology is a difficult one. The clinical picture, for instance, of dementia infantalis (Heller's Disease) is indistinguishable from that of schizophrenia (Shaw & Lucas, 1970). The same is true of some major metabolic disorders (Bray,1970). Coexisting neurological and EEG findings for seizures are not helpful since these are often seen in schizophrenia (Bender, 1947; Fish, 1977). Mental retardation may coexist with schizophrenia or any of the other disorders. The following is an unusual case illustration of a child presenting symptoms of schizophrenia, seizures, and retardation without neurological abnormalities. Until his gross anatomical brain pathology was found by neurologic evaluation, he was subjected to the inappropriate treatment of psychotherapy.

Atrophy

Pedicle skin flap to prevent corneal perforation.

A pedicle skin flap from the lower eyelid was passed through the lower eyelid into the lower fornix and sutured over the cornea in a 36-year-old man with impending perforation caused by lye burns. Perforation was avoided but occurred in the control eye.

Adult

A maternal death associated with prostaglandin E2.

A maternal death following prostaglandin E2 (PGE2) administration is reported. It is suggested that prostaglandin may not be safer than other methods of uterine evacuation for late abortion and fetal death.

Abortion, Therapeutic

A method to correct the contracted socket.

In four patients, rotation of the inferior tarsus around the tarsal-tendon horizontal axis caused a contracted socket with loss of lower fornix and the inability to retain an artificial eye. Exposure of the lower border of the inferior tarsus through a skin incision, separating the tarsus from the overlying orbicularis oculi muscle, and suturing its lower margin to the skin corrected the abnormality.

Anophthalmos