Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nitro-compounds containing an acetylated acetohydroxamic acid side chain in the N-1 position of a 5-membered ring nitrogen heterocycle have been synthesized. These compounds, which can generate isocyanates via a Lossen rearrangement, were evaluated in order to test the hypothesis that they may be effective radiation and chemosensitizing agents by nature of their isocyanate-associated carbamoylating potential. Evaluation of one such compound, DJW-77 (1(O-Acetyl-Acetohydroxamic acid)-3-nitropyrazole) as a radiation sensitizer, chemosensitizer and hypoxic cell toxin is reported. In vitro DJW-77 demonstrates a potent selective cytotoxicity toward hypoxic EMT-6 tumor cells, is an effective potentiator of CCNU toxicity and is comparable to MISO with respect to its radiation-sensitizing potential. The activity of the drug is eliminated under aerobic conditions. To test the hypothesis that the activity of DJW-77 is related to isocyanate generation, the non-acetylated analog of DJW-77 (which does not directly undergo the Lossen rearrangement) and the parent 3-nitropyrazole ring structure were evaluated. Neither compound enhanced CCNU toxicity, and on an equimolar basis were inferior to DJW-77 as radiation sensitizers. While the non-acetylated analog was cytotoxic to hypoxic cells, relative to DJW-77 this activity was substantially reduced. These studies indicate that the addition of a side chain capable of generating an isocyanate can enhance the cytotoxicity and sensitizing activity of nitroheterocycles.
Int J Radiat Oncol Biol Phys 1984 Sep
PMID:Preliminary evaluation of isocyanate-generating nitroheterocycles as chemosensitizers, radiosensitizers and hypoxic cell cytotoxic agents. 654 10

Seventy-one patients with symptoms of colorectal disease were evaluated with the rigid 25-cm sigmoidoscope and an inexpensive 35-cm flexible proctosigmoidoscope (American Optical FPS-2) to determine if the latter is a diagnostically reliable alternative for routine sigmoidoscopy. Examination time was comparable, 3.6 min for the rigid and 4.2 min for the flexible sigmoidoscope. Average insertion length was 21 cm for the rigid and 29.5 cm for the flexible instrument. Forty-two patients had more discomfort during the rigid versus nine during the flexible examination. Significant lesions were documented in eight patients with the rigid and 13 with the flexible sigmoidoscope. One rectal carcinoma and seven polyps were detected with both instruments, while an additional nine polyps were documented only with the flexible instrument. The 35-cm flexible proctosigmoidoscope may be a feasible alternative for routine sigmoidoscopy.
Am J Gastroenterol 1983 Sep
PMID:Flexible versus rigid sigmoidoscopy: a comparison using an inexpensive 35-cm flexible proctosigmoidoscope. 661 70

The relationship between circumcision and sexually transmissible disease was studied in 1350 men who attended the Public Health Department Special Treatment Clinic in Perth, Western Australia. Evidence of circumcision was obtained by examination. More than 98% of the men studied gave a verbal report of their circumcision status which was consistent with the examination findings. Eight hundred and forty-eight men had STD; 471 men, who presented to the clinic for diagnosis and treatment but who were found not to have STD, constituted the control group. The results of the study show significant associations between the state of being uncircumcised and four major sexually transmissible diseases--herpes genitalis, candidiasis, gonorrhoea and syphilis. Estimates of the relative risk suggest that uncircumcised men are twice as likely as circumcised men to develop herpes genitalis or gonorrhoea, and five times as likely to develop candidiasis or syphilis. However, the data for syphilis should be interpreted with caution because of the small number of cases. No significant increase in risk was found for any of the other sexually transmissible diseases diagnosed at the clinic.
Med J Aust 1983 Sep 17
PMID:Circumcision and sexually transmissible disease. 668 50

The influence of blood-heparin-mixing proportion on the acid-base- and blood-gas parameters was measured by means of the blood-gas- automation ABL 1 with the help of 15 test persons. More than 0.15 ml heparin per ml blood, i.e. more than 750 I.U. heparin per ml blood falsify the measuring data and may lead to wrong diagnostic and therapeutic measures. In clinical practice for one 2-ml-blood test only the dead space of the plastic of various producers are characterized by acid-base- and gas values considerable differing from each other. However, they do not influence the blood parameters. By heparin-Weddel (Wales), heparin-Spofa (CSSR), heparin-Richer (Hungary) and heparin-Polfa (Poland) the same acid-base- and blood gas values will be obtained.
Z Gesamte Inn Med 1981 Sep 15
PMID:[Effect of heparin on acid-base and blood gas parameters]. 679 37

Enhancement of various antitumor drugs effects by inhibitors of radiation-induced potentially lethal damage (PLD) repair was studied in three murine tumors (EMT-6, RIF-1 and SQ-1). In EMT-6 tumors, PLD repair inhibitors, 3'-deoxyguanosine (3'-dG) and 7904 (a derivative of 3'-deoxyadenosine) showed a marked enhancement of tumor growth inhibition by anticancerous drugs (FT-207 (a derivative of 5-FU), bleomycin, Ara-C, ACNU). However, the effects of mitomycin-C and vincristine were not potentiated by the inhibitors. In SQ-1 carcinomas, another repair inhibitor, ara-A (1-beta-D-arabinofuranosyladenine) (32 mg/kg) potentiated the effect of ACNU. In RIF-1 sarcomas, in which a low PLD repair function has been reported after ionizing radiation exposure, the potentiation was not so marked as in EMT-6 or SQ-1 tumors. Thus, as a possibility, the potentiation by inhibitors of radiation-induced PLD repair might be a result of the inhibition of chemical-induced PLD repair. The study of this field may contribute to the improvement of cancer treatment not only by radiotherapy but also by chemotherapy.
Int J Radiat Oncol Biol Phys 1982 Sep
PMID:Effects of inhibitors of radiation-induced potentially lethal damage repair on chemotherapy in murine tumors. 698 87

An epithelial cell line established from a Chinese hamster kidney, CHK-ACE, was separated into two sublines, CHK-ACE-100 and CHK-ACE-400, by 18 successive passages in medium containing 100 and 400 mg/dl glucose, respectively. Binding of CHK-ACE-100 and CHK-ACE-400 cell to 125I-labeled insulin showed similar pH and time dependency; 125I-labeled insulin, concentration differed in the two sublines, however. Degradation of 125I-labeled insulin, as determined by its ability to bind insulin antibody and cells, was more extensive when preincubated with CHK-ACE-400 cell than with CHK-ACE-100 cells. When CHK-ACE-100 cells were grown in 400 mg/dl glucose for six passages, these cells showed more insulin binding sites than cells grown parallel in 100 mg/dl glucose; whereas CHK-ACE-400 cells grown in 100 mg/dl glucose for six passages showed fewer insulin binding sites than those grown parallel in 400 mg/dl glucose. A slight increase in Kf/Ke ratio was observed in both sublines when grown in 400 mg/dl glucose as compared to 100 mg/dl glucose, indicating attenuated negative cooperativity of the binding sites in cells grown in 400 mg/dl glucose. Tunicamycin, at concentrations from 0.016 to 0.125 micrograms/ml, showed no direct effect on the assay of 125I-labeled insulin binding to CHK-ACE-100 cells; exposure of CHK-ACE-100 cells to tunicamycin, at concentrations from 0.01 to 0.2 micrograms/ml, for 24 h caused a dose-dependent decrease in insulin binding capacity and an increase in Kf/Ke ratio. These data indicate that the number of insulin binding sites in the cultured Chinese hamster kidney epithelial cells increased with high glucose concentrations in the culture medium, whereas tunicamycin, an inhibitor of protein glycosylation, lowered the number of insulin binding sites.
Biochim Biophys Acta 1981 Sep 18
PMID:Insulin binding in cultured Chinese hamster kidney epithelial cells. The effects of glucose concentration in the medium and tunicamycin. 702 31

The purpose of the study was to design an EMT-A course for freshman medical students that maximized practical work and minimized lecture hours. A 48-hour required course was given up to 101 members of the first-year class at The Medical College of Pennsylvania. Ten hours of lecture-demonstration time were included. Test scores were comparable to scores of regular EMT-A candidates and medical students who had a full lecture series included in their course. Means of further decreasing the number of hours of the course are discussed. By decreasing the number of curricular hours, it is hoped that medical schools not having EMT-A certification programs in their preclinical years will be encouraged to do so.
Ann Emerg Med 1982 Sep
PMID:A time efficient EMT-A course for first year medical students. 711 94

Triglycerides, cholesterol and phospholipids in serum and high density lipoproteins (HDL) were assessed in 11 women with previous gestational diabetes before and repeatedly during 6 months of low dose progestogen (lynoestrenol = LYN) contraceptive administration. Eight of these women also were followed in an identical manner during non-hormonal contraception (IUD) and 6 of them during combined oral contraceptive administration (EE + LYN). During the use of IUD or LYN administration neither serum nor HDL lipids changed. The combined OC, EE + LYN, increased serum triglycerides progressively: 73% (P less than 0.01) after 6 months concomitant with a 100%-increment of HDL triglycerides (P less than 0.01) HDL-cholesterol and -phospholipids were not consistently changed. The EE + LYN induced alterations differed from the effects of LYN alone (P less than 0.01). During the use of IUD or LYN administration neither serum nor HDL lipids changed. The combined OC, EE + LYN, increased serum triglycerides progressively: 73% (P less than 0.01) after 6 months concomitant with a 100%-increment of HDL triglycerides (P less than 0.01). HDL-cholesterol and -phospholipids were not consistently changed. The EE + LYN induced alterations differed from the effects of LYN alone (P less than 0.01). These results suggest that low dose progestogens, such as LYN, could be considered as contraceptive alternatives in women with gestational diabetes. However, combined OC should be avoided in these patients. The present findings differ from those obtained in insulin-dependent diabetics and suggest that a diabetic prediposition enhances the effects of synthetic oestrogens and/or diminishes some of the effects of progestogens on lipid metabolism.
Acta Endocrinol (Copenh) 1982 Sep
PMID:Metabolic studies in women with previous gestational diabetes during contraceptive treatment: effects on serum lipids and high density lipoproteins. 712 87

Ten postmenopausal and ten younger women rested for 2 h in a 40 degrees C, 22.2-Torr vapor pressure environment. Sweating response was monitored by resistance hygrometry for onset, a platform balance for whole-body sweat rate, and five individual capsules for regional sweat rate. Other variables measured included forearm blood flow, heart rate (HR), mean skin (Tsk) and rectal (Tre) temperatures, sweat electrolytes (Na+ and K+), oxygen uptake, and plasma volume changes. Preliminary tests included maximal aerobic power (VO2max) and percent body fat. Heat stress did not elicit any significant differences in sweating response between age groups. Indices of heat strain, Tre and HR, were also similar for both groups. The only significant difference between younger and older women was a higher Na+ concentration in the forearm sweat of postmenopausal women. No thermoregulatory responses were related to age, but both sweat rate (r = 0.48) and peak Tsk (r = -0.43) were related to VO2max. For healthy, active, older women aging did not diminish the functional capacity of the sweating mechanism to cope with heat stress while resting in this specific thermal environment.
J Appl Physiol Respir Environ Exerc Physiol 1982 Sep
PMID:Sweating sensitivity and capacity of women in relation to age. 712 89

To explore further the competition between vasoconstrictor and vasodilator reflexes in the regulation of skin blood flow, responses in forearm blood flow (FBF) to the initiation of supine leg exercise were measured by plethysmography against a background of rising internal temperature. In 17 studies involving six men, skin temperature (Tsk) was controlled with water-perfused suits first at normothermic levels, followed by a 40- to 50-min period during which Tsk was held at 38-38.5 degrees C. Supine leg exercise at a moderate intensity (100-150 W) was performed for 5-6 min of each 15 min throughout, yielding one period of exercise performed during normothermic conditions and three periods of exercise performed during the period of elevated Tsk. On the average, FBF fell significantly with the beginning of each period of exercise (P less than 0.05). Furthermore, the amount by which FBF fell tended to increase with increasing levels of preexercise FBF. Thus the average fall in FBF associated with the onset of the last period of exercise, 2.45 ml X 100 ml-1 X min-1, significantly exceeded the 1.12 ml X 100 ml-1 X min-1 fall in FBF seen with onset of work in normothermic conditions. These responses were not due to changes in internal temperature as reflected by esophageal temperatures. However, individual studies occasionally revealed a reduction or abolition of the vasoconstrictor response with the last period of exercise. These findings are in agreement with earlier studies showing a cutaneous participation in the vasoconstrictor responses to exercise but also indicate that sufficient hyperthermia can attenuate or even abolish this response.
J Appl Physiol Respir Environ Exerc Physiol 1982 Sep
PMID:Effect of heat stress on cutaneous vascular responses to the initiation of exercise. 712 99


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