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Biomedical subjects

S G Carter

Publications and source records attributed to S G Carter.

At least 19 recordsLinked to original sources

Optical measurement and control of spin diffusion in n-doped GaAs quantum wells.

Transient spin gratings are used to study spin diffusion in lightly n-doped GaAs quantum wells at low temperatures. The spin grating is shown to form in the excess electrons from doping, providing spin relaxation and transport properties of the carriers most relevant to spintronic applications. We demonstrate that spin diffusion of the these carriers is accelerated by increasing the density or energy of the optically excited carriers. These results can be used to better understand and even control spin transport in experiments that optically excite spin-polarized carriers.

Journal Article↗

Quantum coherence in an optical modulator.

Semiconductor quantum well electroabsorption modulators are widely used to modulate near-infrared (NIR) radiation at frequencies below 0.1 terahertz (THz). Here, the NIR absorption of undoped quantum wells was modulated by strong electric fields with frequencies between 1.5 and 3.9 THz. The THz field coupled two excited states (excitons) of the quantum wells, as manifested by a new THz frequency- and power-dependent NIR absorption line. Nonperturbative theory and experiment indicate that the THz field generated a coherent quantum superposition of an absorbing and a nonabsorbing exciton. This quantum coherence may yield new applications for quantum well modulators in optical communications.

Journal Article↗

Discomforts of the perimenopause.

The transition to menopause is associated with multiple discomforts that affect the whole physical and psychologic self. The physiology of perimenopausal discomforts, treatment modalities, and self-help measures are described. Nurses can teach women about these multisystem effects and promote comfort and a healthy life-style during this time.

Cardiovascular Diseases↗

Evaluation of synergy between carbovir and 3'-azido-2',3'-deoxythymidine for inhibition of human immunodeficiency virus type 1.

3'-Azido-2',3'-deoxythymidine and carbovir [racemic and (-) enantiomer] were evaluated individually and in combination for antiviral activity against human immunodeficiency virus type 1 replication and cytotoxicity in vitro. The combination of these drugs synergistically inhibited human immunodeficiency virus type 1 replication in C3 and Jurkat cells and in human peripheral blood mononuclear cells, although the same combination also produced synergistic cytotoxicity in human peripheral blood mononuclear cells.

Antiviral Agents↗

Concurrent radiation therapy, 5-fluorouracil, and cisplatin for stage II, III, and IV, node-negative, squamous cell head and neck cancer. Results and surgical implications.

METHODS: Between 1983 and 1989, 42 patients with Stage II, III, and IV, node-negative, squamous cell head and neck cancer were treated with concurrent 5-fluorouracil, cisplatin, and radiation therapy. Two courses of chemotherapy with 30 Gy of concurrent radiation therapy were to be followed in all patients by definitive surgery and then an additional 30 Gy of radiation therapy and one to two courses of chemotherapy. The patients who achieved a complete response to the initial induction treatment, however, did not undergo surgery. RESULTS: After the completion of all therapy, 41 of the 42 patients (98%) were considered disease-free. Only 4 of these 41 had relapses, for a projected Kaplan-Meier disease-free survival rate of 86%. Treatment failure occurred in no patients with Stage II, 1 of 17 patients with Stage III, and 4 of 14 patients with Stage IV disease. Of the 42 patients, 23 (55%) did not require surgery after achieving a complete response to induction therapy, and only 1 of these 23 patients subsequently had a relapse. CONCLUSIONS: Although the value of adding chemotherapy to conventional treatment remains unproven in squamous cell head and neck cancer, this treatment schedule appears promising in node-negative disease. Randomized trials will be necessary, however, to validate the efficacy of this approach and confirm the suggestion by the authors that surgery can be avoided in most patients with N0 disease.

Aged↗

Cooperativity of SV40 T antigen and ras in progressive stages of transformation of human fibroblasts.

Human diploid fibroblasts immortalized by SV40 T antigen provide an experimental system for studying the progression and synergism in transformation by secondary oncogenes. We have utilized the human fibroblast line HAL, which was immortalized with an orgin-defective SV40 genome encoding a temperature-sensitive T antigen, to study the cooperativity between SV40 T antigen and the ras oncogene in the progression of transformation. This study demonstrates that HAL cells possess characteristic growth patterns, requiring 10% serum, are anchorage dependent, and express a temperature-sensitive T antigen. HAL cells rely on the normal functioning of T antigen for continual growth and therefore do not proliferate at 39 degrees C. Three new derivatives of the HAL cell line were generated by microinjection of the ras oncogene. The cell line v-ras-HAL was derived by microinjection of HAL cells with v-Ha-ras DNA. The cell lines c-rasSVneo-HAL and c-rasLTRhygro-HAL were established by microinjection of HAL cells with the plasmids pSV2neoT24 or fpHVT24, respectively, wherein the ras gene is transcriptionally regulated by the cellular promoter and driven by either the SV40 enhancer or an upstream LTR enhancer. The three ras containing cell lines grow in reduced serum concentrations (0 to 5%), are anchorage independent, and express both T antigen and ras p21. The v-ras-HAL and c-rasSVneo-HAL cell lines are still dependent upon the normal functioning of T antigen for continual growth at 39 degrees C, however the c-rasLTRhygro-HAL cell line does proliferate at 39 degrees C in 10% serum-containing medium. Therefore, we propose that neither v-Ha-ras nor c-ras can replace T antigen at 39 degrees C; rather T antigen and ras cooperate in progressive stages of transformation of human fibroblasts.

Antigens, Polyomavirus Transforming↗

Human immunodeficiency virus infection and syncytium formation in HeLa cells expressing glycophospholipid-anchored CD4.

The CD4 molecule, a glycoprotein expressed primarily on the cell surface of specific T lymphocytes, is thought to function in T-cell antigen recognition and activation. In addition, CD4 serves as a receptor for human immunodeficiency virus type 1 (HIV-1) by a direct interaction with the HIV-1 surface glycoprotein (gp120). To further characterize the HIV-1-cell interaction, a HeLa cell line was established that expressed a chimeric molecule of CD4 and decay-accelerating factor (DAF). In the chimeric CD4-DAF molecule the transmembrane and cytoplasmic domains of CD4 were deleted and replaced with the carboxy-terminal 37 amino acids of DAF. This resulted in the anchoring of the extracellular domain of CD4 to the cell membrane via a glycophospholipid linkage. The glycophospholipid-anchored CD4 had a molecular size of approximately 56 to 62 kDa and was released following treatment of the cells with phosphatidylinositol-specific phospholipase C. HeLa cells expressing the CD4-DAF hybrid could be infected with HIV-1, as evidenced by reverse transcriptase activity, p24 core antigen content, and infectious virus production. In addition, transfection of the HeLa CD4-DAF cells with a plasmid that directs the synthesis of HIV-1 envelope glycoproteins or cocultivation with HeLa cells expressing the virus glycoproteins resulted in syncytium formation. These results indicate that the transmembrane and cytoplasmic domains of the CD4 molecule are dispensable for both HIV infection and syncytium formation.

Acquired Immunodeficiency Syndrome↗

Variation of HIV infectibility of macrophages as a function of donor, stage of differentiation, and site of origin.

Heterosexual transmission of HIV-1 is likely to involve transmission of virus present in seminal fluid to inflammatory cells, particularly macrophages, present in the endometrium and peritoneal cavity. We have investigated the susceptibility of peritoneal macrophages and the corresponding autologous blood monocytes from normal women to infection by the BA-L strain of HIV-1. In 10 of 18 examples, peritoneal macrophages showed signs of infection within 4-5 days, which was earlier than the autologous monocytes. In contrast to peritoneal macrophages, lung macrophages from 10 of 11 normal donors failed to show significant reverse transcriptase (RT) values 3 weeks post infection. Monolayer cultures of monocytes cultured for 5 days prior to infection developed RT values similar overall to those of freshly isolated cells although individual donors varied as to which culture condition was optimal. The ease of infection of peritoneal macrophages did not correlate with levels of CD4 antigen or degree of pelvic inflammatory development, nor were macrophages harvested from women early in the menstrual cycle significantly more susceptible to infection than those collected from midcycle on. This unexplained heightened infectibility of peritoneal macrophages in a proportion of normal women suggests that those individuals could be more at risk for heterosexual transmission of HIV-1 infection.

CD4 Antigens↗

Simultaneous versus sequential combined technique therapy for squamous cell head and neck cancer.

Forty-eight patients with locally confined (M0) squamous cell head and neck cancer were prospectively randomized to receive either simultaneous (SIM) or sequential (SEQ) combined technique therapy with a 5-fluorouracil infusion, a cisplatin bolus injection, and radiation therapy. Patients with residual resectable disease underwent surgery after induction therapy, whereas those achieving a complete response to induction did not require surgery. Patients on the two treatment arms were equivalent in all measured variables, including disease extent. Toxicities of the SIM and SEQ arms also were equivalent except for mucositis and the resultant weight loss, which were more severe on the SIM arm (P = 0.002). With a follow-up time ranging from 9 to 41 months, seven of the 24 SIM patients and 14 of the 24 SEQ patients are considered treatment failures. The relapse-free survival is significantly better on the SIM arm (P = 0.03), although an overall survival advantage has not yet been demonstrated (P = 0.13). The achievement of a complete response after induction therapy correlates with both the relapse-free (P = 0.0005) and overall (P = 0.05) survival, and the likelihood of an induction complete response also is significantly better for those treated with the SIM schedule (P = 0.02). Eighteen patients did not require surgery after achieving an induction complete response. Relapse-free survival does not appear to be compromised in this patient subset.

Adult↗

Long-term results after chemoradiotherapy for locally confined squamous-cell head and neck cancer.

The long-term results after simultaneous chemoradiotherapy in 54 patients with previously untreated or minimally treated, locally confined (M0) squamous-cell carcinoma of the head and neck are presented. Multiple concurrent courses of radiation therapy and chemotherapy with cisplatin and a four-day 5-fluorouracil infusion were given. Twenty-eight patients underwent definitive surgery and 26 were treated without surgical resection. Treatment-associated toxicity was significant, including mucositis, myelosuppression, and a mean 12% loss of initial body weight. Of the 54 patients, 51 were ultimately rendered disease free by this combined modality protocol. With a follow-up ranging from 42-68 months, the projected Kaplan-Meier relapse-free survival for the entire patient cohort is 70%, with all relapses occurring within 17 months of patient entry. The projected Kaplan-Meier relapse-free survival for patients with Stage IV disease is 62%. The durability of these remissions suggests that there is a significant likelihood of cure in all patients with locally confined disease, and justifies comparative trials with standard treatment.

Adult↗

Activities of (-)-carbovir and 3'-azido-3'-deoxythymidine against human immunodeficiency virus in vitro.

(-)-Carbovir, the minus optical isomer of carbocyclic-2',3'-didehydro-2',3'-dideoxyguanosine, has been shown to be the biologically active form for the inhibition of human immunodeficiency virus type 1 replication. The concentration of (-)-carbovir required to reduce reverse transcriptase activity by 50% compared with the control was 0.8 microM in H9 cells infected with the HTLV-IIIb strain; the 50% inhibitory concentration for cytotoxicity was greater than 2 mM in these cells. The effect of the timing of drug addition, pre- and postinfection, and the effect of increasing amounts of virus on the antiviral activities of (-)-carbovir and 3'-azido-3'-deoxythymidine were determined.

Antiviral Agents↗

Isolation of recessive (mediator-) revertants from NIH 3T3 cells transformed with a c-H-ras oncogene.

We have generated two serum- and anchorage-dependent revertants from NIH 3T3 cells transformed with multiple copies of the human c-H-ras oncogene. In both revertants, the c-H-ras oncogene was fully expressed. Fusion of either revertant with untransformed cells or of the two revertants with one another resulted in transformed progeny. These results indicated that the two revertants were recessive and in different complementation groups. We believe that in our two revertants some of the genes mediating the transforming activity of the c-H-ras oncogene are defective; we are attempting to identify these mediator genes.

Animals↗

Differential toxicity of carbovir and AZT to human bone marrow hematopoietic progenitor cells in vitro.

We have studied the in vitro effects of carbovir as compared to 3'-azido-3'-deoxythymidine (AZT) on the growth of clonal bone marrow-derived hematopoietic progenitor cells. (-)Carbovir, the enantiomer with anti-human immunodeficiency virus (HIV) activity, exhibited significantly less toxicity to hematopoietic cells than AZT. These in vitro studies suggest that (-)carbovir will exhibit less hematologic toxicity in the therapy of patients infected with HIV either as a single agent or in combination with other agents that inhibit HIV proliferation.

Bone Marrow Cells↗

Efficacy of high-dose oral leucovorin and 5-fluorouracil in advanced colorectal carcinoma. Plasma and tissue pharmacokinetics.

Thirty-one evaluable patients with advanced colorectal cancer were treated with oral leucovorin (LV) 500 mg/m2, administered hourly in four divided doses weekly for 6 weeks. Six patients received intravenous 5-FU at 450 mg/m2 and the remainder at 600 mg/m2 weekly for 6 weeks. This schedule was repeated after a 2-week rest period without medication. None of the patients had received previous chemotherapy. The results of the study showed a overall complete remission (CR) and partial remission (PR) of 45%. All responding patients received the 600-mg/m2 dose of 5-FU. There were five CR and nine PR. An additional seven (23%) patients had stable disease. Two of the seven received the 450-mg/m2 dose of 5-FU and the remainder received 600 mg/m2. The median disease-free interval for CR patients exceeded 25 months, while the interval for PR patients was 11.8 months. The median survival for CR patients was over 26.7 months and 16.5 months for the PR patients. The median survival for stable patients was 9.5 months and 5.5 months for patients with progressive disease. Toxicity included diarrhea in 70% of patients, excess lacrimal secretion in 35%, and nausea and vomiting in 25% There were no treatment-related deaths in this group. The authors conclude from this Phase I study that the optimal 5-FU dose in 600 mg/m2 combined with high-dose oral leucovorin for the treatment of advanced colorectal carcinoma.

Adenocarcinoma↗

Long-term survival after chemoradiotherapy for locally advanced squamous cell carcinoma of the esophagus.

Seven patients with locally far-advanced, inoperable, squamous cell cancer of the esophagus were given two cycles of concurrent radiation and chemotherapy. Each cycle consisted of 5-fluorouracil 1,000 mg/m2/day given as a continuous intravenous infusion over 96 hours, cisplatin 75 mg/m2 given as an intravenous bolus on day 1, and methotrexate 40 mg/m2 given as an intravenous bolus on days 8 and 15. Three thousand rads of radiation were given in 15 fractions between days 1 and 19. Six patients are evaluable for response. Symptomatic relief was obtained by all six and was complete in 4. Five patients achieved a complete response, and two remain alive and disease free. Five of the six evaluable patients survived for at least 12 months. Aggressive chemoradiotherapy may result in significant survival prolongation and symptomatic palliation in this poor-prognosis subset of patients with esophageal cancer.

Adult↗

Thromboembolic events in patients with malignant superior vena cava syndrome and the role of anticoagulation.

In patients with superior vena caval obstruction resulting from malignancy, the importance of vena caval thrombosis and the role of anticoagulation are incompletely understood. The authors discuss this aspect of the management of 25 patients with malignant superior vena cava syndrome. Ten patients were retrospectively reviewed after having been clinically diagnosed without venography, and treated without anticoagulation. Five thromboembolic complications occurred, two of which proved fatal. Fifteen patients were prospectively evaluated by angiography and then treated with anticoagulants. Angiographic evidence of intraluminal subclavian vein or superior vena caval thrombosis was found in five of these patients, and no thromboembolic complications occurred. Of the 20 patients ultimately anticoagulated, two fatal intracranial hemorrhages developed. The authors suggest the need for randomized prospective trials if the role of venography and anticoagulation in this syndrome is to be determined.

Anticoagulants↗

Simultaneous radiotherapy and chemotherapy with 5-fluorouracil and cisplatin for locally confined squamous cell head and neck cancer.

Fifty-four patients with previously untreated or minimally treated locally confined (MO) squamous cell carcinoma of the head and neck were treated with chemoradiotherapy employing multiple courses of simultaneous radiation, cisplatin, and a 4-day 5-fluorouracil infusion. Twenty-eight patients subsequently underwent definitive surgery, and 26 were treated without surgical resection. Of the 54 patients, 51 were ultimately rendered disease free by this combined modality protocol. The projected relapse-free survival rate for the entire cohort is 71%, with a median relapse-free survival time greater than 17 months. Thirteen patients who had tumors that were technically operable did not undergo surgery after achieving a complete response to induction chemoradiotherapy. Only 1 of these patients experienced subsequent local failure. Although the treatment-associated mucositis and local failure. Although the treatment-associated mucositis and myelosuppression were significant, this chemoradiotherapeutic protocol offers a significant chance of relapse-free survival for all patients with locally confined disease and merits comparison with more standard treatment approaches.

Adult↗