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Biomedical subjects

L H Robinson

Publications and source records attributed to L H Robinson.

At least 19 recordsLinked to original sources
PubMed2000

HIV type 1 protease cleavage site mutations and viral fitness: implications for drug susceptibility phenotyping assays.

The recombinant virus assay (RVA) is a method for assessing the susceptibility of human immunodeficiency virus type 1 (HIV-1) plasma isolates to antiretroviral drugs. The RVA involves the production of viable virus in vitro by homologous recombination of RT-PCR products from plasma virus with a noninfectious reverse transcriptase (RT) or protease (PR)-deleted cloned HIV-1 provirus. In this study, we have constructed RVA plasmids with contiguous deletions in RT, PR, and the p7/p1 and p1/6 gag protease cleavage sites (CS). The deletions in these plasmids allow generation of recombinant viruses with all loci currently identified as important for resistance to anti-HIV-1 drugs being derived from the clinical isolate, including CS mutations that compensate for the reduced fitness of viruses resistant to protease inhibitors (Doyon et al., J Virol 1996:70:3763-3769). We have also used these new constructs to generate viruses with or without compensatory CS mutations, and examined the effects on fitness. In the case of an indinavir-selected virus, fitness was restored close to that of a wild type virus when a vector deleted in the CS and PR was used. With an amprenavir-selected isolate, virus fitness was incompletely restored by including the CS, and this defect appeared to be partially due to reduced infectivity of the virions. We conclude that the CS mutations were required for optimum detection of resistance in the RVA, but that virus fitness can remain compromised even in the presence of compensatory CS mutations.

Anti-HIV Agents↗
PubMed1995

Small cell osteosarcoma of the soft tissue.

The lesion we described is an osteoid producing mitotically active spindle cell soft tissue neoplasm, which has light and ultrastructural features of an osteosarcoma. By immunohistochemistry it marks with p30/32MIC2-directed antibodies but fails to react with antibodies associated with other soft tissue neoplasms. The precise histogenesis of the lesion is unknown, but failure to elicit a periosteal reaction makes the periosteum less likely to be the primary tissue of origin. The failure to demonstrate any radiologic or histologic evidence of involvement of the underlying bone leaves the soft tissue as the most reasonable site of origin, although the parosteal region cannot be completely excluded.

Adult↗
PubMed1995

Quiescent viral genomes in human fibroblasts after infection with herpes simplex virus type 1 Vmw65 mutants.

The development and utilization of a tissue culture system for the analysis of quiescent, nonreplicating herpes simplex virus type 1 (HSV-1) genomes is described. It was demonstrated previously that the HSV-1 Vmw65 mutant in1814, which is impaired for immediate early (IE) transcription, was retained for many days in human fetal lung (HFL) fibroblasts in a quiescent 'latent' state. Molecular analysis of the viral genome was not possible, however, due to residual expression of IE proteins and consequent cytotoxicity at high m.o.i. In the study reported here, IE transcription was reduced further by pretreatment of cells with interferon-alpha (IFN-alpha) and by the use of mutant in1820, a derivative of in1814 in which the Vmw110 promoter was replaced by the Moloney murine leukaemia virus (Momulv) enhancer. The Momulv enhancer was not expressed under IE conditions; thus in1820 was more impaired for replication than in1814 and behaved as if deficient for both Vmw65 and Vmw110. In cells pretreated with IFN-alpha and subsequently infected with in1820 cytotoxicity was overcome, enabling a tissue culture system to be developed in which all cells stably retained at least one quiescent viral genome. To assist the analysis of gene expression, in1820 was further modified by insertion of the Escherichia coli lacZ gene controlled by the human cytomegalovirus enhancer (mutant in1883) or the HSV-1 immediate early Vmw110 promoter (in1884). Expression of beta-galactosidase was not detected after infection of IFN-alpha-pretreated cells with in1883 or in1884 but could be induced in almost all cells containing a viral genome, by superinfection of cultures. In1820-derived viruses were retained for at least 9 days and were not reactivated by subculture of cells. A regular arrangement of nucleosomes, as found in cellular chromatin, was not detected on the viral genome at the thymidine kinase locus. The non-linear genome was a template for reactivation with no requirement for prior conversion to a linear form. A small number of remaining linear genomes resulted from incomplete uncoating of input virus.

Cell Line↗
PubMed1994

Inefficacy of low-dose continuous oral etoposide in non-small cell lung cancer.

Etoposide is more active in small cell lung cancer when given over 5 days than as a single injection. To examine this concept further, we designed this Phase II study in NSCLC using continuous low-dose oral etoposide. We enrolled 19 patients with measurable disease and the standard eligibility criteria. 16 had no prior chemotherapy. Etoposide was given at a dose of 50 mg by mouth daily. The median duration of therapy was 63 days (14-212 days). Toxicity was mild myelosuppression and GI symptoms. Therapy was discontinued because of progression of disease in 13 patients, toxicity (GI) in 3 patients; intercurrent disease, self-removal, and other reasons in 1 patient each. No complete or partial responses were seen (95% CI: 0-17.6%). The median survival after entry into the trial was 159 days (41-571+ days). We conclude that low-dose continuous oral etoposide is a well-tolerated but ineffective regimen in non-small cell lung cancer.

Administration, Oral↗
PubMed1989

Grandparenting: intergenerational love and hate.

Grandparenthood can have multiple meanings for grandparents just as grandchildhood can have diverse meanings for grandchildren. Ideally the joys of being a grandparent help to compensate for life's sorrows, although premature grandparenthood may be experienced instead as a nuisance or even a burden if grandparents have to assume parental responsibilities. Of course, storybook grandparents including the grandfathers of Heidi, Little Lord Fauntleroy, and the Box Car Children, never seem to resent having to act as surrogate parents. They enjoy it and do a superb job of meeting their grandchildren's needs. The popularity of these stories is probably due to the vicarious pleasure they provide for children who are angry at their parents and fantasizing about more gratifying caretakers--their grandparents. Grandparents who have a good relationship with their adult children and the children's spouses are more likely to develop a gratifying relationship with their grandchildren, though occasionally grandparents and grandchildren unite against the generation in between. Children utilize grandparents as objects for identification, as links to their history and as a source of pleasure and comfort. When idealization is given up in adolescence, the grandparent-grandchild relationship often continues to be mutually accepting and relatively free of conflict. Grandparents are provided a third opportunity to resolve developmental crises as they observe and try to help grandchildren struggling with the same crisis.

Adolescent↗
PubMed1988

Congenital optic atrophy and brachytelephalangy: the Berk-Tabatznik syndrome.

Here we report on a prepubertal boy with the Berk-Tabatznik syndrome. Manifestations included short stature, congenital optic atrophy, and hypoplasia of the cervical vertebral bodies and distal phalanges. Prognosis was adversely affected by visual and auditory difficulties. The cause of this condition remains unknown.

Deafness↗
PubMed1985

Periosteal osteosarcoma.

An analysis of 6 patients with periosteal osteosarcoma treated by the authors along with a review of 55 patients reported in the literature demonstrates that periosteal osteosarcoma is distinctly different from conventional osteosarcoma or periosteal chondrosarcoma. Periosteal osteosarcoma is a less aggressive tumor than conventional osteosarcoma. It is a relatively well-differentiated chondroblastic osteosarcoma occurring on the surface of the long bones of the extremities. Three patients demonstrated frank medullary invasion of tumor, two grossly and one microsurgically. Patients treated with marginal resection had a 70% local recurrence rate. Patients receiving wide resection or primary amputation have survived longer with less recurrence of disease. Overall, 10 of 61 patients are dead with metastatic disease with a mean reported follow-up of 6 years and 7 months. Adjunctive therapy has been of no demonstrable aid in terms of prolonging survival. Medullary extension of this tumor should not be used to exclude this diagnosis. The authors believe that the treatment of choice is wide resection without adjunctive chemotherapy.

Adolescent↗
PubMed1984

Peripheral right upper lobe collapse in the newborn.

Three forms of peripheral right upper lobe collapse are described. One form has a straight or slightly concave medial border that mimicks pleural fluid. A second variety protrudes from the inferior lateral aspects of the atelectatic right upper lobe producing a triangular opacity that tapers inferiorly toward the chest wall. A third variety produces a convex medial interface with the lung that simulates an extrapleural mass or loculated fluid.

Diagnosis, Differential↗
PubMed1984

Dose efficiency of screen-film systems used in pediatric radiography.

Twenty-one screen-film systems were examined using contrast-detail-dose methods in order to determine which were most dose-efficient for use in pediatric radiography. With a given screen, dose efficiency in the noise-limited region (contrast approximately equal to 0.05) was more or less constant (within the range of experimental error) with changes in film speed. When screens with decreased phosphor thickness were used, dose efficiency deteriorated markedly. For a given speed of up to two times Par, rare-earth phosphors offered no advantage over calcium tungstate systems with regard to low-contrast dose efficiency; however, they did increase the speed of the system. Anti-crossover film proved to be an effective means of improving high-contrast detail while maintaining low-contrast dose efficiency.

Calcium Compounds↗
PubMed1984

Outpatient management of the suicidal child.

Susceptible children may become depressed and suicidal in response to stressful social factors including loss or separation from parents, parental abuse, neglect, rejection, pressure, or a chaotic, disorganized family environment. Psychological factors that predispose children to suicidal behavior include inadequate ego-defenses to cope with feelings engendered by the adverse environmental circumstances. Often these children relate poorly to others and are excessively dependent. Outpatient management is possible if the parents are able to be appropriately supportive and protective. Intensive psychotherapy is often necessary to modify a basic depressive outlook on life and to resolve inner conflict about self-worth. The suicidal child must be helped to give up perfectionistic attitudes and to alter aggressive responses to loss and disappointment. Work with parents is important, particularly when the child's suicidal state is reactive to inappropriate parental behavior. Antidepressant drugs may prove to be a useful adjunct.

Child↗
PubMed1984

Localized bowel distension in the newborn: a review of the plain film analysis and differential diagnosis.

Neonatal abdominal plain films were prospectively analyzed over a 41-month period in order to generate a differential diagnosis for focal bowel distension during the first 6 weeks of life. A total of 31 examples of locally distended bowel were collected. The study discredits the concept that asymmetrically distended bowel in the newborn is usually caused by necrotizing enterocolitis (only 9/31 cases) and indicates that distended bowel in the lower abdomen or left upper quadrant is often caused by air trapping in normal but redundant rectosigmoid (11 cases) or in distal transverse colon (three cases). Five other pathologic conditions not normally specified in differential diagnoses of focally distended bowel included inguinal hernia (three cases), small bowel atresia (two cases), midgut volvulus (one case), Hirschsprung's disease (one case), and small left colon (one case). The study emphasizes the value of sequential supine and prone filming for distinguishing normal from pathologic dilated loops of bowel.

Aerophagy↗
PubMed1979

Villous polyps of the urethra: a report of two cases.

Two patients with villous polyps of the prostatic urethra are described. The article supports previous observations that the lesion has the morphologic appearance of prostatic tissue. A review of the literature reveals that this rare lesion appears to be specific for the prostatic urethra and behaves as a benign tumor.

Adult↗
PubMed1977

HindII, HindIII, and HpaI restriction fragment maps of bacteriophage lambda DNA.

The site-specific restriction endonucleases isolated from Hemophilus influenzae strains Rc (HincII) and Rd (HindII + III), and Hemophilus parainfluenzae (HpaI) were used to digest bacteriophage lambda DNA into 34, 40, and 15 specific fragments, respectively. The sites cleaved by each of these enzymes were localized on the lambda physical map and the fragments resulting from these cleavages were electrophoretically identified on gels by (1) analysis of the digestion profiles of deletion and transducing derivatives of lambda; and (2) digesting individual fragments produced by one restriction endonuclease with another restriction endonuclease. This paper presents the HindII, HindIII, and HpaI restriction fragment maps for the entire lambda genome, and the data used to derive these maps for the region of the lambda genome between the attachment site (at 57.3% lambda) and the right vegetative end (100% lambda). The data for mapping the left arm of lambda may be found in the accompanying paper (Robinson and Landy, 1977).

Chromosome Mapping↗