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Biomedical subjects

D E Moore

Publications and source records attributed to D E Moore.

At least 91 records · Page 5Linked to original sources

Reactions of nitroimidazoles with free radicals--enhancement of reaction by u.v. irradiation.

The free-radical reactivity of the nitroimidazole derivatives metronidazole, misonidazole, benznidazole and ornidazole was investigated by observing their effect on the polymerization of acrylamide in aqueous solution. Free-radical polymerization was initiated by the thermal decomposition of potassium peroxydisulphate at 50 degrees C. Measurement of the polymerization rate showed an inhibitory effect of the nitroimidazoles which was greatly enhanced when the system was irradiated with u.v. light near their absorption maximum of 320-325 nm. Analysis of the competitive kinetics of the system enabled calculation of the rate constant for reaction of the ground state and photoexcited nitroimidazole with the polyacrylamide free radicals. No significant difference between the various nitroimidazoles could be found in the dark reaction, but in the u.v.-irradiated system the order of reactivity (misonidazole greater than benznidazole greater than metronidazole approximately equal to ornidazole) was the same as the reported relative mutagenic, cytotoxic and radiosensitizing potency of the compounds. These results imply that the excited states of the nitroimidazoles are important to their activity in radical-radical reactions.

Acrylic Resins↗

A candidate carrier protein for beta-human chorionic gonadotropin: 54,000-molecular-weight fragment of tetanus toxin.

As an alternative to intact tetanus toxoid as a carrier for beta-human chorionic gonadotropin (beta-hCG), a fragment of tetanus toxin was sought that had a relatively low molecular weight, yet was highly immunogenic. Purified culture filtrate tetanus toxin was subjected to limited enzymatic digestion with papain, and the resulting fragments separated by column chromatography on Sephadex G-150. Four fractions were thus identified. Fraction II was found to have a molecular weight of 54,000 by SDS-polyacrylamide gel electrophoresis. This fragment was covalently linked to the beta-subunit of hCG (beta-hCG-TTII) using carbodiimide hydrochloride. The ability of beta-hCG-TTII to stimulate production of anti-hCG sera in rabbits was measured by 125I-hCG radioimmunoassay. At sera dilutions of 1:40,000, an average 125I-hCG binding capacity of 34.7 +/- 5.86% (mean +/- SD) was observed 8 weeks after the final immunization. Tetanus toxin Fragment II has the potential for future application in active immunization studies involving hormone-carrier conjugates.

Animals↗

Sex hormone-binding globulin changes during the menstrual cycle.

Although sex hormone-binding globulin (SHBG) production is stimulated by estrogen, no change in SHBG has been demonstrated during the menstrual cycle. To further study possible cyclic changes in serum SHBG, 12 women with a normal menstrual and fertility history had daily SHBG measurements during a menstrual cycle. SHBG was measured by dextran-coated charcoal saturation analysis and RIA. Serum LH was measured by mouse Leydig cell bioassay and RIA, and FSH, estradiol (E2), and progesterone were determined by RIA. In 10 women, a significant increase in mean SHBG by both methods occurred during the luteal phase of the cycle, immediately after the preovulatory increase in serum E2 (P less than 0.001). Two women had no SHBG increase; although each had a significant rise in serum E2 before the LH surge, luteal phase E2 levels were similar to those in the early follicular phase. In one of these women, a rise in SHBG was demonstrated by RIA. This study demonstrates that SHBG changes during the menstrual cycle in association with E2 changes, and it appears to be a marker for the endogenous estrogen changes that occur in normal ovulating women.

Adult↗

Current trends in antifertility vaccine research.

We review the major advances that have recently occurred in the area of antifertility vaccines by examining the immunogenic potential of gamete, embryonic and placental antigens. In human trials using beta-human chorionic gonadotropin coupled with tetanus toxoid as the immunogen, the major problems with antifertility vaccines relate to specificity and maintaining an adequate antibody titer to disrupt gestation. Possible complications include cross-reaction with other body tissues, immune complex deposition, cytotoxicity, impaired immunologic tumor surveillance and nonreversibility.

Adjuvants, Immunologic↗

Busulfan versus cyclophosphamide treatment in the early and late stages of granulocytic leukemia in guinea pigs.

A transplantable granulocytic leukemia (GL-13-BC) in strain 13 guinea pigs, which has many similarities to human CML, was used to test the antineoplastic effects of two alkylating agents, busulfan and cyclophosphamide, administered in the late and early stages of the disease. Busulfan had a pronounced cytoreductive effect on circulating leukemic cells in the late, pre-blast crisis stage of this disease but all treated animals, succumbed to the leukemia with only a marginal increase in survival time relative to that of untreated controls. In this respect the guinea pig model resembles human CML. Survival time was moderately increased with early busulfan treatment but, as in the late treatment group, all animals succumbed to the leukemia. A pronounced cytoreductive action on leukemic cells was also observed in guinea pigs treated with cyclophosphamide. Late treatment with this drug produced highly variable effects on the survival time of leukemic guinea pigs; of the nine animals treated, no effect was observe in five, three showed a significant increase in survival time and one animal was still in remission without treatment when the experiment was concluded. Early treatment with cyclophosphamide produced the most striking finding of this study. Two treatments with this drug produced a complete remission in all of the treated guinea pigs. This remission lasted without further treatment for the duration of the study (greater than 200 days) while all untreated controls died within 27-37 days after receiving leukemic cell transplants. The relevance of these findings to the treatment of human CML is discussed.

Animals↗

Regional chromosomal localization of N-ras, K-ras-1, K-ras-2 and myb oncogenes in human cells.

The identification of transforming genes in human tumor cells has been made possible by DNA mediated gene transfer techniques. To date, it has been possible to show that most of these transforming genes are activated cellular analogues of the ras oncogene family. To better understand the relationship between these oncogenes and other human genes, we have determined their chromosomal localization by analyzing human rodent somatic cell hybrids with molecularly cloned human proto-oncogene probes. It was possible to assign N-ras to chromosome 1 and regionally localize c-K-ras-1 and c-K-ras-2 to human chromosomes 6pter-q13 and 12q, respectively. These results along with previous studies demonstrate the highly dispersed nature of ras genes in the human genome. Previous reports indicated that the c-myb gene also resides on chromosome 6. It has been possible to sublocalize c-myb to the long arm of chromosome 6 (q15-q21). The non-random aberrations in chromosomes 1, 6 and 12 that occur in certain human tumors suggest possible etiologic involvement of ras and/or myb oncogenes in such tumors.

Animals↗

Photolytic decomposition of hydrochlorothiazide.

Hydrochlorothiazide decomposes upon irradiation with near-UV light (lambda greater than 310 nm) both in methanol and aqueous solutions. In the photolysis the chlorine substituent is removed to be replaced by either--H or--OR from the solvent ROH. Hydrolysis of the thiadiazine ring is superimposed upon the dechlorination. The presence of oxygen inhibits the decomposition. The mechanism of the photolysis is suggested to involve cation radical formation which facilitates the hydrolysis step. 5-Chloro-2,4-disulphonamido-aniline, the normal hydrolysis product from hydrochlorothiazide, is also susceptible to photolytic dechlorination by a similar mechanism.

Chemical Phenomena↗

Photolytic degradation of frusemide.

Irradiation with 365 nm u.v. light of frusemide (4-chloro-N-furfuryl-5-sulphamoyl-anthranilic acid) in methanol results primarily in photoreduction to N-furfuryl-5-sulphamoylanthranilic acid and photohydrolysis to 4-chloro-5-sulphamoylanthranilic acid (saluamine).

Chemical Phenomena↗

Increased frequency of serum antibodies to Chlamydia trachomatis in infertility due to distal tubal disease.

186 infertile women underwent standard infertility investigations (including hysterosalpingography and, in 87 women, laparoscopy) and tests for the presence of antibody to Chlamydia trachomatis. 73% of the women with distal occlusion of the fallopian tubes and 21% with peritubal adhesions alone had antibodies to C. trachomatis, but none of those with normal tubes did (p less than 0.001 and less than 0.005, respectively). No other infertility factors were associated with an increased frequency of antibodies to C. trachomatis. Since the presence or absence of antibodies to C. trachomatis was as discriminatory in the detection of tubal disease in infertile women as was the hysterosalpingogram, the serological test for C. trachomatis should become part of a routine infertility investigation.

Acute Disease↗

The prevention of postoperative pelvic adhesions: an animal study comparing barrier methods with dextran 70.

There are two major approaches to the prophylaxis for adhesions: chemical methods (e.g., dextran) and barrier methods. Theoretically, dextran prevents the formation of adhesions by a surface-coating or hydroflotation effect, whereas the barrier methods either prevent the formation of or mask adhesions by covering and isolating the injured area with an inert substance. This study compared the efficacy of two different concentrations of dextran 70 and various barriers in preventing the formation of adhesions in the female rabbit pelvis. Symmetrical cut and scrape lesions were made on both sides of each rabbit's uterus; for the barrier-treated animals, the lesions on one side were covered with a barrier, and the contralateral side served as a control. The barriers tested were: Gelfilm, Surgicel, Silastic, Gelfoam paste, amnion, peritoneum, and omentum (five rabbits per subgroup). The same cut and scrape lesions were induced in 16 additional rabbits in the chemical group. These rabbits were subsequently treated with 10 ml/kg of intraperitoneal 6% dextran 70 (five rabbits), and 32% dextran 70 (five rabbits), and were compared with six external control rabbits. The severity of the adhesions that formed was graded by a numerical scoring system. The barrier methods tested resulted, generally, in an increased formation of adhesions when a comparison was made with control and with dextran-treated animals. The degree of formation of adhesions in the dextran-treated rabbits did not differ from that in the control animals. The data suggest that the barrier methods actually promote the formation of adhesions whereas the findings with dextran 70 were inconclusive.

Amnion↗

Benefits of the sperm (hamster ova) penetration assay in the evaluation of the infertile couple.

The males of 310 infertile couples and 30 control couples (current pregnancy) were evaluated with the sperm (hamster ova) penetration assay (SPA) and seminal fluid analysis (SFA). The SPA was found to have a sensitivity of 100% and a specificity of 97% compared to 41% and 90%, respectively, for the SFA. The highest degree of concordance of the two tests existed when both tests were abnormal and no female factor was identified. The poorest concordance occurred when the SFA was normal and no female infertility factor was identified. In almost all cases of unexplained infertility where no female infertility factor was present, the problem could be assigned to the man, as evidenced by an abnormal SPA. The SFA seemed to have some predictive value with respect to the outcome following treatment of the man.

Animals↗

The relationship of pyospermia and seminal fluid bacteriology to sperm function as reflected in the sperm penetration assay.

The relationship of the parameters of seminal fluid analysis (SFA) and seminal fluid leukocyte concentration to the in vitro sperm penetration assay (SPA) was studied in 217 men from infertile couples. Significant positive correlations were found between the SPA and sperm count, sperm motility, and morphologically normal sperm. The total number of leukocytes per milliliter, the number of polymorphonuclear leukocytes per milliliter (PMN), and the number of lymphocytes per milliliter were negatively correlated with the results of the SPA. The strongest correlation with an abnormal SPA (less than 11% of eggs penetrated) was the presence of greater than or equal to 1 PMN/100 sperm (8.17 increased relative risk of an abnormal SPA). The most important predictor variables of the percent penetration of the sperm penetration assay were total numbers of leukocytes per milliliter, sperm count, and sperm motility. Microbiologic studies of semen were not correlated with SPA results or number of leukocytes in the semen.

Female↗

A deletion in chromosome 1 in cells of a transplantable granulocytic leukemia (GL-13) in guinea pigs.

Chromosomes were examined in leukocytes from a unique transplantable granulocyte leukemia (GL-13) of strain 13 guinea pigs. The GL-13 leukemia has many similarities to human chronic myelogenous leukemia (CML). It has remained predominantly diploid after 90 transplant generations and is characterized cytogenetically by a terminal deletion of the long arm of one of the #1 pair of chromosomes. No other chromosomal abnormality was observed. These findings lend further support to the conclusion that the GL-13 leukemia may be a useful model for the study of human CML.

Animals↗