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Biomedical subjects

L Loeb

Publications and source records attributed to L Loeb.

At least 19 recordsLinked to original sources

Mutagenicity and pausing of HIV reverse transcriptase during HIV plus-strand DNA synthesis.

The unusually high frequency of misincorporation by HIV-1 reverse transcriptase (HIV RT) is likely to be the major factor in the rapid accumulation of viral mutations in AIDS, especially in the env gene. To investigate the ability of HIV RT to copy the env gene, we subcloned an HIV env gene fragment into a single-stranded DNA vector and measured the progression of synthesis by HIV RT. We observed that HIV RT, but not RT from avian myeloblastosis virus, DNA polymerase-alpha or T7 DNA polymerase, pauses specifically at poly-deoxyadenosine stretches within the env gene. The frequency of bypassing the polyadenosine stretches by HIV RT is enhanced by increasing the ratio of enzyme to template. We measured the fidelity of DNA synthesis within a segment of the hypervariable region 1 of the env gene (V-1) containing a poly-deoxyadenosine sequence by repetitively copying the DNA by HIV RT, and then cloning and sequencing the copied fragments. We found that 27% of the errors identified in V-1 sequence were frameshift mutations opposite the poly-adenosine tract, a site where strong pausing was observed. Pausing of HIV RT at the polyadenosine tract could be enhanced by either distamycin A or netropsin, (A-T)-rich minor groove binding peptides. Moreover, netropsin increases the frequency of frameshift mutations in experiments in which HIV RT catalyzes gap filling synthesis within the lacZ gene in double-stranded circular M13mp2 DNA. These combined results suggest that the enhanced mutation frequency may be due to increased pausing at netropsin-modified polyadenosine tracts. Therefore, netropsin and related A-T binding chemicals may selectively enhance frameshift mutagenesis induced by HIV RT and yield predominantly non-viable virus.

Base Composition

Medical futility. Committee on Bioethical Issues of the Medical Society of the State of New York.

The term futile is used in many different ways. It is therefore difficult to decide whether a procedure or treatment such as CPR or hemodialysis or blood transfusion would be futile in a given case. The AMA's guidelines on the appropriate use of DNR orders state that DNR decisions should be made openly. Institutions should have policies and physicians should elicit the patient's preferences about CPR. For physicians, the question is no longer whether we should discuss DNR orders with our patients; instead, the issue is how to do so with compassion and caring. Physicians should share with patients their judgment about what medicine can and cannot do. Then physicians must "make decisions about when to withhold or limit resuscitation openly" in honest and trusting conversation between doctor and patient. Often CPR is an exercise in futility. The medical profession should be vested with the authority to make futility decisions if they are the product of open discussion and shared deliberation between physician and patient, family, or surrogate. Rationing, triage, and medical futility in relation to AIDS patients require careful deliberation and consideration. What was considered medically futile five years ago for an AIDS patient may be appropriate care nowadays. The need for appropriate use or non-use of life-sustaining therapy for the elderly, the terminally ill, patients with AIDS and other incurable illnesses is evident to patients, health care providers, policy makers, and the public. CPR should only be administered if it is expected to confer lasting benefit to the patient. However, if 10% of elderly patients benefit from CPR in the case of out-of-hospital cardiac arrest, how can one consider this procedure futile? Although communication between physician and patient about difficult treatment limitation decisions has markedly improved in recent years, it remains a problem, largely because open dialogue with patients and families about futility is a demanding emotional and intellectual task. The medical profession is charged with setting standards for the proper implementation of judgments regarding futility.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiopulmonary Resuscitation

Spouse abuse.

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Female

Fathers and sons: some effects of prolonged custody litigation.

In all jurisdictions, for a variety of reasons, child custody and visitation issues may be reopened at any time. The children at issue, already likely to have been traumatized by problems in the parental marriage and subsequent separation and divorce, are affected further by still more litigation. The cases of three preadolescent boys who are the subjects of such prolonged litigation are presented. In each, the boys resided with their mothers as the primary custodial parents, the fathers having generally liberal rights of visitation. Regardless of which parent raised further court-related issues after the original agreements, the father-son relationship was most severely affected by continuing legal actions and related parental actions. Each child became increasingly fearful of the next anticipated visit by the father, who was cast into the role of villain by the child. Efforts to improve these damaged relationships through joint parent-child therapeutic attempts were largely of little avail. In spite of what may have been good experience with the person of the judge who dealt with earlier litigation, the children became fearful of what the next might be like or might do, viewing the judge as the person in power to whom parents and attorneys alike deferred. It is suggested that, wherever possible, prolonged litigation be avoided in the best interests of the child and of preserving necessary child-parent relationships.

Child

The resolution of a transsexual wish in a five-year-old boy.

The brief truncated psychoanalytic treatment of a transsexual boy described in this paper demonstrates the development of transference reactions and their subsequent resolution. The analytic situation allowed this young patient to live out again his relationship with his parents in his relationship with the analyst, to recover from wishing to be a member of the female sex, and to work through his conflicted symbiosis with his mother. Carlos became able to individuate and disidentify from her into a separate male child, in order to be able to identify with, and accept, his own biological and psychological maleness. It is to be hoped that our success with this patient will encourage others to treat and study children suffering from gender identity problems via the psychoanalytic approach.

Anxiety, Castration