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Biomedical subjects

R Parker

Publications and source records attributed to R Parker.

At least 145 records · Page 8Linked to original sources
PubMed1992

Determinants of cisplatin sensitivity in non-malignant non-drug-selected human T cell lines.

We have studied molecular mechanisms of cisplatin sensitivity and resistance in 3 non-malignant, non-drug-selected human T lymphocyte cell lines. HuT 78, H9, and MOLT-4 cells were assessed for sensitivity to cisplatin, DNA damage levels following defined drug exposures, drug accumulation, and DNA repair efficiency as measured by adduct removal from cellular DNA and by host-cell reactivation of cisplatin-modified plasmid DNA. Based on 3-day continuous drug exposures, the IC50 values for the cell lines were: HuT 78, 0.83 microM; H9, 0.45 microM; and MOLT-4, 0.33 microM. These cells retained this order with respect to DNA repair capability, whether measured by platinum-DNA adduct removal from cellular DNA or by host-cell reactivation assays. DNA repair values measured by these two assays were directly related to one another with a linear correlation coefficient of 0.993. At sublethal cisplatin doses the more resistant cells showed the highest levels of drug uptake. When drug uptake levels were 'corrected' for drug-induced cell kill, there were equal levels of DNA repair efficiency for a given level of drug uptake. Absolute levels of cisplatin-DNA adduct repair increased with increasing drug dose. However, at supralethal doses of drug, efficient DNA repair could be overcome in all 3 cell lines with percentage-adduct-removal dropping from a 60-80% range to a less than 30% range. We conclude that in non-malignant non-drug-selected human T cells, DNA repair appears to be the primary determinant of cisplatin sensitivity/resistance and that enhanced DNA repair may be a biologic compensatory mechanism for cells that cannot prevent cellular uptake of DNA-damaging agents.

Cell Line↗
PubMed1992

Clindamycin vaginal cream versus oral metronidazole in the treatment of bacterial vaginosis: a prospective double-blind clinical trial.

Bacterial vaginosis is common among patients seen by gynecologists. Several types of therapy have been proposed. The purpose of this prospective, randomized, double-blind clinical trial was to examine the efficacy of clindamycin vaginal cream for the treatment of bacterial vaginosis. Sixty patients with symptoms of bacterial vaginosis were randomized into the study, and 46 completed the protocol. Twenty-three patients received 2% clindamycin vaginal cream (5 g applied intravaginally at bedtime for 7 days), with placebo oral tablets twice daily for 7 days. The other 23 patients received oral metronidazole tablets (500 mg twice a day for 7 days) and placebo vaginal cream (5 g intravaginally for 7 days). The cure rates for the two regimens were comparable. Twenty-two (97%) of the patients treated with clindamycin vaginal cream had improvement or cure at the first follow-up visit versus 19 (83%) of those taking metronidazole. There was no statistically significant difference between the two results. Side effects for both regimens were comparable. We conclude that 2% clindamycin vaginal cream offers similar efficacy and safety to standard oral metronidazole therapy for bacterial vaginosis.

Administration, Intravaginal↗
PubMed1992

Mutations affecting stability and deadenylation of the yeast MFA2 transcript.

Decay rates of individual mRNAs in the yeast Saccharomyces cerevisiae can vary by 10- to 20-fold. To determine the basis for the rapid degradation of the mRNA encoded by the yeast MFA2 gene we have used a genetic screen to isolate mutations that increase the stability of this transcript. Analysis of point mutations obtained from this screen, and of additional lesions constructed in vitro, indicated that the MFA2 3'-untranslated region (UTR) contains sequences that specify rapid mRNA decay. Moreover, the lesions that affected mRNA decay rate also affected the process of mRNA deadenylation. Mutations in one region of the 3' UTR both decreased the rate of poly(A) shortening and increased the stability of an intermediate form in the decay pathway with an oligo(A) tail (approximately 10 nucleotides). Mutations in a second region primarily increased the stability of the oligo(A) form. These results suggest that the decay of the MFA2 mRNA initiates with the shortening of the poly(A) tail and there are specific sequences within the 3' UTR that stimulate poly(A) tail shortening as well as subsequent steps in the decay pathway. Given the similarity of this decay pathway to that seen for some mammalian mRNAs, these results suggest that mRNA deadenylation may be a common mechanism of mRNA turnover.

Base Sequence↗
PubMed1992

Antimicrobial susceptibilities of a Corynebacterium CDC group I1 strain isolated from a patient with endocarditis.

We encountered a case of native valve endocarditis due to Corynebacterium CDC group I1 which was successfully controlled with antimicrobial agents alone. This organism and three other isolates of this group were susceptible to penicillin, vancomycin, and gentamicin. The combination of penicillin with subinhibitory concentrations of gentamicin resulted in a 1,000-fold decrease in CFU per milliliter at 24 h compared with penicillin alone. Augmentation of killing was noted also with vancomycin plus gentamicin but to a degree that did not meet strict criteria for bactericidal synergism.

Corynebacterium↗
PubMed1992

Increased gene-specific repair of cisplatin interstrand cross-links in cisplatin-resistant human ovarian cancer cell lines.

We have studied several aspects of DNA damage formation and repair in human ovarian cancer cell lines which have become resistant to cisplatin through continued exposure to the anticancer drug. The resistant cell lines A2780/cp70 and 2008/c13*5.25 were compared with their respective parental cell lines, A2780 and 2008. Cells in culture were treated with cisplatin, and the two main DNA lesions formed, intrastrand adducts and interstrand cross-links, were quantitated before and after repair incubation. This quantitation was done for total genomic lesions and at the level of individual genes. In the overall genome, the initial frequency of both cisplatin lesions assayed was higher in the parental than in the derivative resistant cell lines. Nonetheless, the total genomic repair of each of these lesions was not increased in the resistant cells. These differences in initial lesion frequency between parental and resistant cell lines were not observed at the gene level. Resistant and parental cells had similar initial frequencies of intrastrand adducts and interstrand cross-links in the dihydrofolate reductase (DHFR) gene and in several other genes after cisplatin treatment of the cells. There was no increase in the repair efficiency of intrastrand adducts in the DHFR gene in resistant cell lines compared with the parental partners. However, a marked and consistent repair difference between parental and resistant cells was observed for the gene-specific repair of cisplatin interstrand cross-links. DNA interstrand cross-links were removed from three genes, the DHFR, multidrug resistance (MDR1), and delta-globin genes, much more efficiently in the resistant cell lines than in the parental cell lines. Our findings suggest that acquired cellular resistance to cisplatin may be associated with increased gene-specific DNA repair efficiency of a specific lesion, the interstrand cross-link.

Blotting, Southern↗
PubMed1992

Tuberous sclerosis with gingival overgrowth.

A case of tuberous sclerosis with gingival overgrowth is presented. A brief literature review and diagnostic criteria of tuberous sclerosis are discussed. The patient had a full-mouth gingivectomy with frequent post-operative maintenance visits. After 6 months, the overgrowth in conjunction with the tuberous sclerosis returned.

Adult↗
PubMed1992

Single dose oral fluconazole vs intravaginal terconazole in treatment of Candida vaginitis. Comparison and pilot study.

Candida vaginitis develops in approximately one-fourth of women in their childbearing years. Conventional management consists of antifungal creams or tablets/suppositories administered intravaginally. Many patients have stated preferences for oral therapy. A randomized, double-blind placebo trial compared the efficacy of a single oral 200 mg dose of fluconazole with the application of terconazole 80 mg vaginal suppository daily for 3 days. Twenty-two patients (fluconazole = 12, terconazole = 10) were evaluated during a four-month period and favorable clinical responses were observed at both early and late evaluations. Mycologic cure was attained by 75% of the fluconazole group and 50% of the terconazole group at the early evaluation. At the late evaluation, mycologic cure was 75% and 100% respectively. The mean time to onset of symptom relief was 2.4 (1.7) days for the fluconazole group and 1.8 (1.8) days for the terconazole group. The mean time to complete relief of symptoms was 6.08 (2.84) and 6.6 (2.95) days respectively. A statistically significant difference did not exist for any of these measures. Seventy-three percent of the patients preferred oral therapy.

Administration, Intravaginal↗
PubMed1991

Absence of mutagenic effects of continuous and pulsed ultrasound in cultured (AL) human-hamster hybrid cells.

Mutagenic effects of continuous and pulsed ultrasound were looked for using an in vitro assay system, the AL hybrid, that is up to 100 times more sensitive for mutagens such as x-rays and neutrons than the assays used previously to evaluate ultrasound. Cells in suspension in rotated plastic test tubes were insonated with continuous wave ultrasound at 1 MHz, ISPTP = 0.62-40 W/cm2 for 0-40 min. Cells attached in the central region of culture flasks received pulsed exposures at fc = 2.5 MHz, PRF = 1 kHz, 2 and 8 cycles per pulse, with p- = 1.2 MPa (ISPTA = 31-180 mW/cm2) for 0-30 min. Although these exposures were cytotoxic (the plating efficiency was decreased to approximately 65% by the highest doses), induction of mutation, if any occurred, was less than would be expected in this test system from 10-30 cGy of x-ray.

Animals↗
PubMed1991

Ability, achievement, and adjustment in homeless children.

Homeless 3-12-year-old children residing in city shelters were compared with a matched control group of 45 inner city children in terms of cognitive functioning and emotional-behavioral adjustment. School-age children in both groups did not differ significantly on most measures. Preschool homeless children exhibited slower development and more emotional-behavioral problems than did their domiciled peers, and significantly fewer were enrolled in early childhood programs. The feasibility of evaluating this population on standardized instruments is demonstrated, and implications of the study for social policy are discussed.

Achievement↗
PubMed1991

Functional evaluation following microvascular oromandibular reconstruction of the oral cancer patient: a comparative study of reconstructed and nonreconstructed patients.

Over the past decade, the use of free flap transfers in head and neck surgery has led to remarkable advances in the reliability and the ultimate results of oromandibular reconstruction. Stable and retentive dental restorations have been achieved using enosseous implants placed directly into the vascularized bone flaps. However, the functional assessment of patients who underwent primary mandibular reconstruction with these techniques has not been previously reported. A group of 10 reconstructed and 10 nonreconstructed segmental hemimandibulectomy patients were compared using a battery of tests to assess their overall well-being, cosmesis, deglutition, oral competence, speech, length of hospitalization, and dental rehabilitation. In addition, objective measures of the masticatory apparatus (interincisal opening, bite force, chewing performance, and chewing stroke) were used to compare these two groups as well as normal healthy subjects and edentulous patients restored with conventional and implant-borne dentures. The results show a clear advantage for the reconstructed patients in almost all categories. Persistent problems and future directions in oromandibular reconstruction are discussed.

Adult↗
PubMed1991

Immunologic effects of plasmapheresis synchronized with pulse cyclophosphamide in systemic lupus erythematosus.

Extensive immunologic evaluation was made of a patient with severe systemic lupus erythematosus (SLE) undergoing 6 cycles of plasmapheresis combined with pulsed cyclophosphamide therapy. Clinical remission ensued accompanied by normalization of levels of circulating autoantibodies, immune complexes, complement proteins, interleukin 2 (IL-2) and IL-2 receptor. High spontaneous peripheral blood lymphocyte proliferation fluctuated widely with plasmapheresis, but was consistently reduced after cyclophosphamide. Circulating B cells fell by 85% and remained low at one year, despite recovery of the serum IgG level. Circulating T cells declined by 48%, chiefly in the immunologically naive CD4+CD45R+ T cell subset. This was associated with the emergence of a CD8+DR+CDw29+ T cell subset signifying immunologically mature, activated cytotoxic/suppressive T cells, which might have served to control the autoreactive B and T cell populations. Pulsed cyclophosphamide synchronized with plasmapheresis profoundly affected the immune system of our patient. The association of these immunological changes with clinical recovery warrants further investigation of this new therapeutic approach in SLE.

Adult↗
PubMed1990

Lymphokine-activated killer cell cytotoxicity against human colon carcinomas enhanced by monoclonal antibody D612.

The antibody-dependent cellular cytotoxicity (ADCC) properties of a murine monoclonal antibody (MAb), designated D612 (IgG2a), which reacts with human colon carcinomas, was studied using normal human peripheral blood lymphocytes (PBMNC). Although the level of ADCC of PBMNC with D612 varied among different donors, it was 20 to 30 times higher than the lytic activity of control cultures containing isotype-matched control MAb. Incubation of PBMNC with recombinant interleukin-2 (IL-2) resulted in a 2- to 5-fold augmentation in the cytotoxicity of effector cells exposed to MAb. This augmentation was apparent after subtracting nonspecific cellular cytotoxicity from the total cytotoxicity mediated by activated effector cells in the presence of D612. Optimal stimulation of specific ADCC with IL-2 appeared after 24 hr of culture in 500 U/ml of IL-2, resulting in a 3.8 +/- 1.7 fold increase in lytic units. However, stimulation of ADCC was also evident at 10 U/ml of IL-2. Furthermore, antibody dose titrations with untreated and IL-2 activated effectors showed that the threshold dose of MAb needed for efficient ADCC was reduced by 200-fold with IL-2. Depletion of FcR gamma III-positive lymphoid cells markedly reduced D612 ADCC, demonstrating the participation of NK/LAK cells in D612-mediated ADCC. Low levels of ADCC activity were found associated with adherent cells, either untreated or following their activation with gamma-interferon, while D612 was most active with non-adherent effectors. The specificity and ADCC properties of the D612 MAb suggest that it should be considered as a candidate for immunotherapy of colon cancer, particularly when used in combination with IL-2 plus LAK cell treatment.

Antibodies, Monoclonal↗
PubMed1990

Aspects of the glass transition behaviour of mixtures of carbohydrates of low molecular weight.

The glass transition temperature (Tg) values for carbohydrates alone and in binary mixtures have been determined using differential scanning calorimetry. The Tg of the carbohydrate depends strongly on molecular weight and less on structure. The Tg of the binary mixtures was dependent on composition and, in most instances, was linear with respect to mole fraction. The effect of water on depressing the Tg of the carbohydrates and their binary mixtures was also evaluated. The observed behaviour was compared with that predicted from a thermodynamic approach.

Calorimetry, Differential Scanning↗
PubMed1990

Alterations in prealbumin concentration after adrenal autotransplantation for Parkinson's disease.

The cerebrospinal fluid of eight patients with Parkinson's disease who underwent adrenal medullary autotransplantation was analyzed using SDS-polyacrylamide gel electrophoresis. A protein, subsequently identified as prealbumin, was noted to change in concentration over the intraoperative to 18-month postoperative time course. The qualitative changes observed on visual inspection were confirmed and quantified using laser densitometry. The concentration of prealbumin increased by an average of 90% when the intraoperative and 12-month samples were compared. This increase persisted at 18 months. The ratio of prealbumin to albumin also increased from intraoperative to 12 months by an average of 56%. This suggests that the increases in PA are the result of choroid plexus activation rather than a nonspecific breakdown of the blood-brain barrier. Given the association of prealbumin with other nervous system diseases, as well as its known ability to bind multiple substances, these findings may have important implications. Alterations in prealbumin may be responsible for the improvement seen in some patients who receive adrenal medullary autotransplants. Alternatively, prealbumin may be implicated in the pathophysiology of Parkinson's disease.

Adrenal Medulla↗