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Biomedical subjects

K Davidson

Publications and source records attributed to K Davidson.

At least 109 records · Page 6Linked to original sources
PubMed1983

The relationship between 17 beta-hydroxysteroid dehydrogenase activity and oestrogen concentrations in human breast tumours and in normal breast tissue.

The activity of 17 beta-hydroxysteroid dehydrogenase (17 beta HSD) was measured in human breast tumours and in normal breast tissue from premenopausal, perimenopausal and postmenopausal women. Enzyme activity was higher in tumour tissue than in normal tissue from the same breast and under the conditions of the assay the oxidation of oestradiol was higher than the reduction of oestrone. The physiological status of the women in the study did not relate to the activity of the enzyme in either normal or tumour tissue although fibroadenomas had less activity than adenocarcinomas. In postmenopausal women tumour tissue oestrogens were 2-3 fold higher than in normal tissue from the same breast. Furthermore, tumour tissue concentrations of oestradiol tended to be higher than those of oestrone although in normal tissue the two oestrogens were present in similar concentrations. In plasma from the same women oestrone was the predominant oestrogen. There appears to be no direct relationship between 17 beta HSD activity and oestrogen concentrations but the enzyme may play a part in determining the balance between oestrone and oestradiol according to substrate and cofactor availability.

17-Hydroxysteroid Dehydrogenases↗
PubMed1983

Bronchial carcinoma in von Willebrand's disease. Successful removal after hemostasis with lyophilized cryoprecipitate.

A man with severe von Willebrand's disease who had hemoptysis was followed-up for 2 1/2 years for continued hemoptysis and was discovered to have a bronchial carcinoma. Under close hematological surveillance, an uncomplicated pneumonectomy was performed, using a new factor VIII product--freeze-dried cryoprecipitate. This case illustrates that hemoptysis in von Willebrand's disease cannot always be attributed to the disease itself: that continued hemoptysis requires regular bronchoscopy and that major surgery can be performed in von Willebrand's disease with effective correction of the coagulation defect using freeze-dried cryoprecipitate.

Bronchial Neoplasms↗
PubMed1982

Isolated nephron segments from rabbit models of obstructive nephropathy.

Micropuncture and microcatheterization studies have been used extensively to investigate the pathophysiologic alterations in renal function induced by urinary tract obstruction. The present isolated tubule microperfusion studies were designed to examine the intrinsic alterations in segmental nephron function induced by 24 h of bilateral (BUO) and unilateral (UUO) urinary tract obstruction. Following UUO superficial proximal convoluted tubule reabsorption rate (J(v)) was not different from contralateral control (0.75+/-0.08 vs. 0.73+/-0.11 nl/mm per min, NS). Following UUO J(v) in juxtamedullary proximal convoluted tubules (JMPCT) was reduced 32% (0.69+/-0.06 vs. 0.47+/-0.04 nl/mm per min, P < 0.02). Following UUO J(v) in proximal straight tubules (PST) was reduced 52% (0.25+/-0.02 vs. 0.12+/-0.03, P < 0.01). Thick ascending limb (T-ALH) function was assessed by measurement of ability to lower perfusate chloride ion concentration (DeltaCl). Following UUO DeltaCl was reduced 76% (-39+/-9 vs. -9+/-1 meq/liter, P < 0.001). Cortical collecting tubule (CCT) function was assessed by measurement of antiduiretic hormone (ADH)-dependent osmotic water flow. Following UUO osmotic water flow was reduced 76% (0.90+/-0.08 vs. 0.22+/-0.04 nl/mm per min, P < 0.01) and this ADH resistance could not be overcome by cAMP. Nephron segments were then examined following relief of BUO. There were no differences in intrinsic function following relief of BUO when compared with UUO. We conclude that in UUO and BUO (a) the intrinsic tubular defects are identical, (b) the natriuresis noted is due, in part, to disordered JMPCT, PST, and T-ALH NaCl reabsorption, (c) the impaired concentrating ability is due, in part, to depressed function in T-ALH and ADH resistance of the CCT, and (d) the ADH resistance occurs at a site distal to the intracellular generation of cAMP.

Animals↗
PubMed1982

Influence of photoperiod and temperature on weight gain, food consumption, fat pads and thyroxine in male golden hamsters.

Weight gain in control and pinealectomized male golden hamsters is enhanced by exposure to short photoperiods (LD 8:16). Modest temperature reductions (10 degrees C) enhanced weight gain also, especially in the blinded animals. In the absence of both eyes and the pineal gland, neither temperature nor photoperiod had much or any effect on weight gain. Food consumption on the other hand increased only as a consequence of lowered temperature. Efficiency of food utilization was maximal at higher (22 degrees C) temperature and long photoperiods (LD 16:8). Epididymal fat pads in control animals were consistently increased by short photoperiods in either temperature. They were increased in pinealectomized and decreased in blinded animals as a consequence of lowered temperatures in either photoperiod. Total body weight gain in the several environments was not correlated directly with fat pad weights. Free thyroxine (T4) levels in control animals seemed to be negatively correlated with fat pad weights. Both T4 levels and fat pads were unchanged by temperature or photoperiod in blinded, pinealectomized animals. The data suggest a complex interaction of temperature, light and the pineal gland on body weight, fat deposition and serum T4.

Adipose Tissue↗
PubMed1981

Prior mannitol and furosemide infusion in a model of ischemic acute renal failure.

Tubular transport abnormalities have recently been characterized in a rabbit model of ischemic acute renal failure (ARF). These studies demonstrated severe observable morphologic and functional changes in the proximal nephron together with functional changes in the distal nephron. Tubular debris was often produced by perfusion of proximal nephron segments. In the present study, agents used to prevent ARF were tested in this rabbit model of ARF. Rabbits were infused with either 5% body wt 5% manitol or 20 micrograms . kg-1 . min-1 furosemide in 5% body wt normal saline for the 60 min preceding 60 min of total renal ischemia. Mannitol 1) prevented the development of ARF, 2) maintained fluid reabsorption in the proximal convoluted tubule (PCT) (0.59 +/- 0.03 vs. 0.52 +/- 0.1 nl . mm-1 . min-1) and proximal straight tubule (PST) (0.34 +/- 0.05 vs. 0.39 +/- 0.07 nl . mm-1 . min-1), 3) depressed NaCl reabsorption in the cortical thick ascending limb of Henle's loop (TALH), and 4) did not prevent a decrease in ADH-mediated osmotic water flow in the cortical collecting tubule (CCT). Furosemide 1) partially preserved renal function, 2) partially protected the PCT (0.63 +/- 0.05 vs. 0.38 +/- 0.04 nl . mm-1 . min-1) and PST (0.32 +/- 0.04 vs. 0.22 +/- 0.02 nl . mm-1 . min-1), and 3) did not change the transport capacity of the TALH or the ADH response of the CCT. Preservation of proximal nephron integrity was also reflected by the absence of debris formation. There is a direct relation between an agent's ability to protect the functional integrity of the cells of the proximal nephron and its ability to preserve renal function.

Acute Kidney Injury↗
PubMedDate not supplied

Hostility changes following antidepressant treatment: relationship to stress and negative thinking.

It is unclear whether changes in hostility following treatment are primarily related to improvement in depressive symptoms or are also closely associated with reductions in negative thinking or perceived stress. We evaluated 94 outpatients with major depression before and after eight weeks of fluoxetine treatment by administering the Symptom Questionnaire (SQ) Hostility Scale, the Hamilton Rating Scale for Depression (HAM-D), the Cognitions Questionnaire (CQ) and the Perceived Stress Scale (PSS). We observed significant elevations in scores on these questionnaires in depressed patients as compared to normal controls. Following treatment with fluoxetine, there was a statistically significant reduction in scores on all four questionnaires. We observed that changes in SQ Hostility were significantly positively related to changes in both depression severity and perceived stress, with these relationships remaining significant after adjusting for gender and baseline SQ Hostility. The relationship between SQ Hostility changes and reductions in negative thinking became significant only after adjusting for gender and baseline SQ hostility. Our results suggest that the marked decrease in hostility following antidepressant treatment is related to a reduction in depressive symptoms, stress levels and negative thinking.

Adult↗
PubMedDate not supplied

An historical context for behavioral models of hypertension.

OBJECTIVE: The purpose of this study is provide an historical context for current behavioral models of hypertension. METHODS: A selective sample of the cardiovascular reactivity literature was reviewed, from 1932 to present. RESULTS: In the earliest model, cardiovascular reactivity was regarded as a marker of disease risk; however, in later models, reactivity came to be viewed as a causal influence in the development of hypertension. As the models evolved, the underlying assumptions changed. Thus, the risk marker model assumed that cardiovascular responses to stress were a stable, generalized characteristic of the individual, and therefore the eliciting stimuli were arbitrary. The later models, however, assume that the nature of the eliciting stimulus is a determinant of the cardiovascular response. We describe the increasing complexity of the four models, and contrast their underlying assumptions and the implications of these assumptions. CONCLUSION: We provide an overview of study designs and variables that should be incorporated into studies seeking to understand the ways in which cardiovascular responses to stress may influence the development of hypertension.

Blood Pressure↗
PubMedDate not supplied

Effects of SW 33377, SW 68210 and SW 71425 thioxanthones on in vitro colony formation of freshly explanted human tumor cells.

Thioxanthones are aromatic hydrocarbons with cytotoxic activity against several tumor models. Potential mechanisms of action may include DNA intercalation, inhibition of nucleic acid biosynthesis, and topoisomerase inhibition, as well as formation of intracellular DNA single strand breaks. Such a broad spectrum of expected antitumor activity makes this class of compounds particularly interesting and worth pursuing in clinical studies. SW 33377 (Win 33377, SR 233377) was so promising in vitro that it was taken into Phase I clinical trials for further evaluation. The compound had undesirable cardiac effects, so new analogs were sought that would have similar antitumor effects without the undesirable side effects. In the present study, two new analogs SW 68210 (WIN 68210), and SW 71425 (WIN 71425) are compared to the antiproliferative action of SW 33377 against a variety of freshly explanted human tumor specimens using an in vitro soft agar cloning system. All compounds were more effective with continuous exposure than 1 hour exposure and a concentration-response effect was evident with all compounds. SW 68210 with continuous exposure showed similar activity to SW 33377 at all concentrations. SW 71425 with continuous exposure was less effective at the lower concentrations but was nearly as effective at 10 microg/ml as the other two compounds and was highly effective at 50 microg/ml. At the 10 microg/ml concentration all compounds were similarly effective against breast, colon, non-small cell lung, and ovarian tumors. The two new analogs, SW 68210 and SW 71425 have activity similar to SW 33377 and are both likely candidates for further development.

Antineoplastic Agents↗
PubMedDate not supplied

Following the thread of Ariadne to the health of women.

The health of women has risen to a priority position in medical research. Comparative studies of female morbidity are called for as an intermediary stage for generation of hypotheses and design of deeper studies of determinants, such as social, ecological, and individual factors. In previous studies, we have noted differences in female hospitalization between Heraklion in Greece and Linköping in Sweden. They were related to age and to urban versus rural dwelling, and fit projections for a more archaic and a more technocratic society, respectively. This paper aims at showing how the study of women's health may proceed from relevant hospitalization observations to the next level, of exploring already available indicators of self-perceived health in elderly females.

Age Factors↗
PubMedDate not supplied

Prenatal perineal massage: preventing lacerations during delivery.

OBJECTIVE: To investigate the associations between perineal lacerations and 13 variables associated with the incidence of perineal lacerations. Of particular interest was the variable of prenatal preparation of the perineum. DESIGN: This retrospective descriptive study used a convenience sample of 368 women whose delivery was attended by at least one of two midwives practicing in the Northwest between 1979 and 1995. SETTING AND PARTICIPANTS: All births in the study occurred in a home-based midwifery practice in the Northwest. The sample was primarily white and included 307 multiparous and 61 primiparous women. MAIN OUTCOME MEASURES: The initial chi squares indicated that five of the 13 factors investigated were significantly associated with the degree of laceration: parity, maternal age, maternal position at delivery, length of second stage of labor, and prenatal perineal massage. However, further analyses showed that when parity was controlled, the only factors independently associated with the seriousness of lacerations were parity and prenatal perineal massage. CONCLUSION: This study supports the conclusion that teaching perineal massage to primiparous women and multiparae who had episiotomies with their previous births is a useful intervention. It suggests that further study may help clarify the optimum frequency, timing, and technique of massage.

Adolescent↗
PubMedDate not supplied

5,6 Dihydro-5'-azacytidine (DHAC) restores androgen responsiveness in androgen-insensitive prostate cancer cells.

INTRODUCTION: The androgen resistance of some prostate cancer patients may be due to transcriptional inactivation of the androgen receptor (AR) gene catalyzed by cytosine DNA methyltransferase. MATERIALS AND METHODS: To determine if an inhibitor of cytosine DNA methyltransferase, 5,6-dihydro-5'-azacytidine (DHAC), can restore the androgen sensitivity in androgen-insensitive human prostate carcinoma cell lines in vitro, we cultured androgen-insensitive (PC3, DU-145, and TSUPrl) and androgen-responsive (LNCaP) cells with subcytotoxic concentrations (< or = IC50) of DHAC for 14 days followed by exposure to dihydrotestosterone (DHT) or to hydroxyflutamide for 7 days. RESULTS AND CONCLUSIONS: Only DHAC-treated DU-145 cells showed growth stimulation by 10(-11) to 10(-9) M DHT and a partial inhibition by 10(-5) and 10(-6) M hydroxyflutamide. However, since DU-145 is the only cell line tested that is known to have a hypermethylated AR promoter, the observed effects may be due to a partial demethylation of the AR by DHAC. Our data provide an evidence that cytosine DNA methyltransferase inhibitors can restore androgen responsiveness in androgen-refractory tumor cells, which are then sensitive to growth inhibition by antiandrogens.

Androgens↗
PubMedDate not supplied

Cytotoxic effects of MGI 114 are independent of tumor p53 or p21 expression.

MGI 114, an analog of illudin S, shows potent activity against a broad range of human tumors in vitro and in vivo, including drug resistant tumors. In this study we examined cytotoxicity of MGI 114 against human tumor cell lines (MCF7, MDA.MB.468, EJ1, J82, SCaBER, KG-1, HL60, and IMR-90) with differing expression of p53 and/or p21 (WAF1) tumor suppressor genes. Only MCF7 and IMR-90 express the wild type p53, WAF1 is present in high levels in MCF7 and SCaBER. WAF1 expression can be induced in KG-1, HL60, and IMR-90. The cells were treated with MGI 114 at 0.1, 1.0 and 10 micrograms/ml in 1 h exposure and with 0.01, 0.1 and 1.0 microgram/ml MGI 114 in a continuous exposure. Cell numbers were measured at days 2, 4, and 7. MGI 114 suppressed growth in all cell lines at day 2 after 1 h exposure at the two highest concentrations and at all concentrations in a continuous exposure. Some cells partly recovered from the inhibition by day 4. Expression of WAF1 had no apparent effect on growth suppression by MGI 114, however, cells with inducible WAF1 showed slower recovery from MGI 114 inhibition in comparison with the cells under non-permissive conditions. Overall, MGI 114 effectively inhibited growth of human cancer cells regardless of their p53 and WAF1 status.

Antineoplastic Agents↗
PubMedDate not supplied

Tetracationic porphyrins inhibit angiogenesis induced by human tumor cells in vivo.

BACKGROUND: Cationic porphyrin TMPyP4, but not its isomer TMPyP2, inhibits telomerase in tumor cells in vitro and induces chromosome destabilization in vivo. MATERIALS AND METHODS: To examine the effects of these porphyrins on tumor-induced angiogenesis, 25-200 micrograms TMPyP4 or TMPyP2 were injected daily for 3 days in mice with intradermally implanted primary human tumor cells. Alternatively, tumor cells were exposed for 90 minutes to 2.5-20 microM porphyrins prior to implantation in mice. RESULTS: Either subcutaneous injections (> or = 50 micrograms/mouse) or preincubation with > or = 5 microM porphyrins significantly inhibited angiogenesis. CONCLUSION: Antiangiogenic activity is apparently unrelated to the ability of the porphyrins to inhibit telomerase.

Adenocarcinoma, Clear Cell↗