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Biomedical subjects

D Glover

Publications and source records attributed to D Glover.

At least 19 recordsLinked to original sources
PubMed1998

A Drosophila homologue of oxysterol binding protein (OSBP)--implications for the role of OSBP.

The identification of a Drosophila homologue (OSBP-Dm) of mammalian oxysterol binding protein (OSBP) is reported. OSBP-Dm was identified by its ability to overcome the cell cycle arrest induced by over-expression of Wee1p in fission yeast. OSBP-Dm has an overall sequence identity of 52% with mammalian OSBP, and shows a number of highly conserved regions of functional significance. Insects are unable to biosynthesize the steroid core, relying instead on dietary sterols to satisfy their requirements. It is therefore unlikely that OSBP-Dm is involved in feedback inhibition of the mevalonate pathway, as has previously been suggested for its mammalian homologues.

Amino Acid Sequence↗
PubMed1998

Reduction of the Human Placental Vascular Relaxation to Progesterone by Gestational Diabetes

>Background: We have recently described a dose-dependent, endothelium-independent relaxation to progesterone in human placental arteries and veins. This receptor-operated, cAMP-mediated relaxation may be of value in maintaining adequate blood flow in the placental circulation.Objective: To investigate if gestational diabetes alters this relaxation to progesterone.Study design: Isolated human placental vessels from pregnancies complicated by gestational diabetes and well matched controls (uncomplicated term pregnancies), incubated in Krebs-bicarbonate buffer and submaximally precontracted with KCl, were exposed to cumulative doses of progesterone (0.01-30 µmol/liter), nitroglycerin (0.001-1 µmol/liter), arachidonic acid (0.01-10 µmol/liter), forskolin (0.01-10 µmol/liter) and 5-hydroxytryptamine (serotonin, 0.01-10 µmol/liter).Results: The relaxation to progesterone in vessels from patients with gestational diabetes was reduced by 50-100% in both arteries and veins compared with control (for example, relaxation to 10 µmol/liter progesterone was reduced from 52 +/- 7 to 18.8 +/- 5.4% in arteries and from 58 +/- 8 to 19 +/- 5.2% in veins, n = 7-13, P < 0.05), whereas responses to the other vasoactive agents were unchanged.Conclusion: Based on these results, gestational diabetes significantly reduces the relaxation to progesterone in human placental vessels. This alteration of the relaxation to progesterone may lead to an increase in placental vascular resistance and possibly to a reduction of placental blood flow.

Journal Article↗
PubMed1997

GAL4 enhancer traps expressed in the embryo, larval brain, imaginal discs, and ovary of Drosophila.

We have screened a collection of approximately 400 GAL4 enhancer trap lines for useful patterns of expression in the embryo, larval brain, imaginal discs, and ovary using a UAS-lacZ reporter construct. Although similar patterns of expression have previously been reported in the original P[lacZ] enhancer trap screens, these lines are useful for directing ectopic expression of genes in discrete patterns during these stages. In addition, we have identified some unique patterns of expression that have not been previously reported.

Animals↗
PubMed1996

Food preferences among individuals with and without Prader-Willi syndrome.

Eleven individuals with Prader-Willi syndrome and 10 control subjects who had mental retardation due to other causes (with and without overeating histories) participated in two experiments on food preferences. They gave preference rankings for various foods, then chose between a small amount of their most preferred food and an alternative choice of a larger amount of mixed-preference foods (Experiment 1) or an alternative choice of a larger amount of their least preferred food (Experiment 2). Unlike overweight-prone control subjects who selected sweet food over a larger quantity of unpreferred food, subjects with Prader-Willi syndrome selected preferred items only over least-preferred items (Experiment 2) but not over mixed-preference items (Experiment 1). Implications for treatment were discussed.

Feeding Behavior↗
PubMed1995

Treatment of claustrophobias and snake/spider phobias: fear of arousal and fear of context.

Forty-nine individuals with fears of snakes or spiders, and 21 individuals with claustrophobic fear were assigned randomly to two sessions of either in vivo exposure plus relaxation or in vivo exposure plus disconfirmation of misappraisals of bodily sensations. Behavioral, subjective and physiological assessments were conducted pre and post treatment, and 4 weeks later. As hypothesized, disconfirmation of misappraisals of bodily sensations benefited claustrophobic fear reduction, but had little effect on fears of snakes or spiders. However, differential treatment effects failed to generalize to nontargetted phobic situations, or generalize over time. In addition, the two treatments affected basic beliefs about arousal sensations equally.

Adolescent↗
PubMed1995

Predicted versus unpredicted panic attacks: acute versus general distress.

Acute and longer term effects of unpredicted and predicted panic attacks were examined in a sample of patients with panic disorder who self-monitored their panic attacks over a 2-week interval. The study assessed the degree to which experimental observations of the effects of predictability over aversive events are paralleled in the clinical phenomenon of panic. For patients who experienced predicted and unpredicted panics, daily ratings of anxiety and worry about panic increased the day following unpredicted panic attacks and decreased or stabilized the day following predicted panic attacks. These patterns were not replicated in patients who experienced only 1 type of panic; nor were these patterns influenced by the frequency with which panic attacks occurred. Acute distress indexes did not differ during predicted and unpredicted panics, although patients who experienced predicted panic attacks exhibited more pervasive agoraphobic avoidance. The findings are discussed in relation to the safety-signal theory of prediction and alternative conceptualizations.

Acute Disease↗
PubMed1995

Functional conservation of the cell cycle-regulating transcription factor DRTF1/E2F and its pathway of control in Drosophila melanogaster.

The cellular transcription factor DRTF1/E2F is implicated in the control of early cell cycle progression due to its interaction with important regulators of cellular proliferation, such as pocket proteins (for example, the retinoblastoma tumour suppressor gene product), cyclins and cyclin-dependent kinase subunits. In mammalian cells DRTF1/E2F is a heterodimeric DNA binding activity which arises when a DP protein interacts with an E2F protein. Here, we report an analysis of DRTF1/E2F in Drosophila cells, and show that many features of the pathway which regulate its transcriptional activity are conserved in mammalian cells, such as the interaction with pocket proteins, binding to cyclin A and cdk2, and its modulation by viral oncoproteins. We show that a Drosophila DP protein which can interact co-operatively with E2F proteins is a physiological DNA binding component of Drosophila DRTF1/E2F. An analysis of the expression patterns of a Drosophila DP and E2F protein indicated that DmDP is developmentally regulated and in later embryonic stages preferentially expressed in proliferating cells. In contrast, the expression of DmE2F-1 in late stage embryos occurs in a restricted group of neural cells, whereas in early embryos it is widely expressed, but in a segmentally restricted fashion. Some aspects of the mechanisms which integrate early cell cycle progression with the transcription apparatus are thus conserved between Drosophila and mammalian cells. The distinct expression patterns of DmDP and DmE2F-1 suggest that the formation of DP/E2F heterodimers, and hence DRTF1/E2F, is subject to complex regulatory cues.

Amino Acid Sequence↗
PubMed1994

A Drosophila melanogaster homolog of the TIS11 family of immediate early genes that can rescue a cdr1 cdc25 mutant strain of fission yeast.

A Drosophila melanogaster (Dm) embryonic cDNA library was screened for genes capable of inhibiting wee1+/mik1+ protein kinase (Pk) function. We expected to identify homologs of the Schizosaccharomyces pombe gene nim1+. This gene encodes a Pk capable of phosphorylating and so inhibiting the wee1+ Pk that in turn inhibits p34cdc2. Dm cDNAs capable of complementing the temperature-sensitive phenotype of a nim1/cdr1 cdc25 double mutant strain were identified and found to fall into two classes. One class encodes the Dm Cdc2 protein. The second cDNA class encodes a novel protein containing a central motif consisting of two tandem repeats of a putative Zn(2+)-finger motif. This region is highly conserved in the TIS11 family of immediate early genes, which in mammalian cells are rapidly and transiently induced in response to 12-O-tetradecanoyl phorbol-13-acetate (TPA) and to mitogens such as epidermal growth factor and fibroblast growth factor.

Amino Acid Sequence↗
PubMed1994

Intravenous pamidronate disodium treatment of bone metastases in patients with breast cancer. A dose-seeking study.

BACKGROUND: Treatment of the symptoms of bone metastases currently involves the use of narcotic medication, radiation therapy, or hormonal therapy. Pamidronate disodium, a bisphosphonate, may prove helpful in the palliative treatment of bone metastases in patients with breast cancer as demonstrated in this multicenter, dose-ranging trial. METHODS: Ambulatory female patients age 18 years or older with breast cancer metastatic to bone and a life expectancy of at least 3 months were eligible for the study. Bone metastases were confirmed by bone scan or bone survey within 6 months of enrollment. Sixty-one patients were treated as outpatients and were randomized to receive one of four intravenous pamidronate regimens for 12 weeks: 30 mg administered every 2 weeks, 60 mg every 4 weeks, 60 mg every 2 weeks, or 90 mg every 4 weeks. The primary efficacy parameter for this study was pain score. The change from baseline in pain score was determined for each patient at each study visit and at endpoint, defined as the last postbaseline evaluation for each patient before or at week 12. Secondary efficacy variables included narcotic scores, urinary calcium/creatinine and hydroxyproline/creatinine ratios, serum osteocalcin and bone alkaline phosphatase concentrations, and bone lesion (radiologic) response. RESULTS: At 3 months, the regimens of 60 mg every 4 weeks, 60 mg every 2 weeks, and 90 mg every 4 weeks resulted in significant reduction in bone pain beginning by week 6 of treatment. The regimen of 30 mg every 2 weeks was not effective. Narcotic use, as reflected by narcotic scores, did not parallel the pain scores, because there was little evidence of any effect for any of the treatment groups. Reduction in bone pain was accompanied by decreases in urinary calcium/creatinine and hydroxyproline/creatinine ratios, and bone alkaline phosphatase concentrations. Side effects of pamidronate were mild and transient. Radiographic changes consistent with healing of lytic lesions were observed in 15 patients (25%). CONCLUSION: Intravenous pamidronate is a well tolerated treatment that produced significant relief of bone pain in the majority of patients with metastatic breast cancer at the three highest doses tested.

Adolescent↗
PubMed1994

A Drosophila gene encoding a DEAD box RNA helicase can suppress loss of wee1/mik1 function in Schizosaccharomyces pombe.

We describe a screen to isolate cDNAs encoding Drosophila mitosis inhibitors capable of suppressing the mitotic catastrophe phenotype resulting in Schizosaccharomyces pombe from the combination of the wee1-50 mutation with either a deletion allele of mik1, or with overexpression of cdc25+. One plasmid was isolated which could suppress the temperature sensitive lethality of both these strains. The cDNA in this plasmid encodes a protein highly homologous to the DEAD-box family of ATP-dependent RNA helicases, rather than to protein kinases as might be expected. It is possible that the RNA helicase described here may regulate entry into mitosis by down regulating the expression of other genes whose activity may be rate-limiting for entry into mitosis.

Amino Acid Sequence↗
PubMed1994

Pamidronate in the treatment of bone metastases: results of 2 dose-ranging trials in patients with breast or prostate cancer.

Four intravenous regimens of pamidronate (Aredia) were evaluated for palliative treatment of bone metastases in 2 randomized open-label trials in patients with breast cancer (n = 61) or prostate cancer (n = 58). In breast cancer patients, administration of pamidronate 60 mg every 4 weeks, 60 mg every 2 weeks, or 90 mg every 4 weeks for 3 months resulted in statistically and clinically significant reductions in bone pain, with accompanying decreases in biochemical markers of bone turnover; a regimen of 30 mg every 2 weeks was not effective. Healing of bone lesions was observed in 25% of breast cancer patients. In prostate cancer patients, the same regimens of pamidronate produced reductions in bone pain, but no dose-response relationship was apparent. Moreover, there were no consistent changes in biochemical indices in these patients, and no healing of bone lesions occurred. The different response to pamidronate in those 2 patient populations may reflect the different severity of metastatic disease at baseline. Side effects of pamidronate were mild and transient in both studies.

Adult↗
PubMed1994

A cognitive-behavioral approach to temporomandibular dysfunction treatment failures: a controlled comparison.

The effects of cognitive-behavioral treatment for patients with temporomandibular disorders were studied by comparing active treatment to a wait-list control condition. Patients were predominantly women and had been referred to the study after having poor response to dental/physical medicine care. Patients' conditions were evaluated pretreatment and posttreatment based on self-report measures of pain, distress, and jaw function problems. They were examined by a dentist who assessed pain-free opening, muscle palpation pain, and tenderness of the temporomandibular joints. The 5-week cognitive-behavioral treatment included relaxation training, self-monitoring of stressors, and cognitive coping strategies. Treatment had its greatest impact on improving mood, especially anxiety; however, there were some effects on the patients' experiences of pain.

Adult↗
PubMed1993

Cooperation within--the patient care team advantage.

As the demand for post-hospital health care increases, one home care agency has developed a referral process that makes the transition from hospital to home as smooth as possible for both patients and health care professionals.

Aftercare↗
PubMed1991

Chronic fatigue in adolescents.

Nine female and 6 male adolescents (mean age 14.5 +/- 1.7 [SD] years) were evaluated for chronic fatigue associated with at least three additional symptoms present for 18.4 +/- 8.4 months. Eleven subjects experienced the onset of symptoms with an acute illness (seven Monospot-positive). Medical history, physical examination, and laboratory testing yielded little helpful information. Serologic testing for Coxsackie B viruses 1 through 6, cytomegalovirus, Epstein-Barr virus, human herpesvirus 6, and Toxoplasma gondii in subjects and healthy controls provided little evidence for an infectious cause of persistent fatigue. Children's Depression Inventory scores and psychiatric interviews with the Schedule for Affective Disorders and Schizophrenia-Children's Version (K-SADS) identified five subjects with major depression. On the K-SADS, the 10 fatigued subjects without major depression endorsed many secondary symptoms of depression but were less likely than depressed psychiatric clinic patients to endorse primary symptoms such as depressed mood, guilt, and suicidality. At telephone follow-up 13 to 32 months after intake, 4 subjects were completely well, 4 markedly improved, and 7 unimproved or worse. Further research is necessary to determine whether chronic fatigue in adolescents is prodromal depression, a discrete psychosomatic condition, or an infectious or immunologic disorder that mimics depression.

Adolescent↗
PubMed1989

Clinical trials of WR-2721 and cis-platinum.

WR-2721 is an aminothiol compound; in the animal model it protects against the nephrotoxicity, neurotoxicity, and hematologic toxicity of cis-platinum. We initiated Phase I trials of WR-2721 and cis-platinum to determine toxicity when WR-2721 was given prior to escalating doses of cis-platinum. With mannitol diuresis and WR-2721, transient nephrotoxicity occurred in 9 of 30 (27%) patients treated with cis-platinum 150 mg/m2 and 7% of patients given with cis-platinum 120 mg/m2. Bone marrow suppression was mild and infrequent. Mild to moderate peripheral neuropathies occurred in 26% of patients courses following a mean cumulative cis-platinum dose of 725 mg/m2. Objective partial responses were observed in 53 of 118 (45%) patients with measurable disease. Antitumor responses were observed in 25 of 53 patients with metastatic melanoma, 12 of 22 patients with locally recurrent or metastatic head and neck cancer, and 7 of 13 patients with metastatic breast cancer refractory to conventional chemotherapy. Controlled studies of WR-2721 and cis-platinum will be performed in the Eastern Cooperative Oncology Group in these disease sites to better define the activity of this regimen and its toxicity.

Adult↗