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Biomedical subjects

J M Davis

Publications and source records attributed to J M Davis.

At least 55 records · Page 3Linked to original sources
PubMed2001

Role of the Raf signal transduction cascade in the in vitro resistance to the anticancer drug doxorubicin.

The precise molecular events involved in the development of drug resistance (DR) remain largely unknown. Raf is an intermediate in the signal transduction cascades initiated by growth factors. The hypothesis behind the following studies is that deregulated Raf-1 expression plays a role in the development of drug resistance. A positive correlation was observed between increased Raf-1 activity and increased values for IC50 for doxorubicin in established cell lines. The National Cancer Institute/Adriamycin Resistant (NCI/ADR-RES) cell line exhibited both the highest Raf-1 activity and the highest IC50 values for doxorubicin (Adriamycin). In contrast, the MCF-7 cell line exhibited both lower Raf activity and lower IC50 values for doxorubicin. While MCF-7 cells transfected with either constitutively active DeltaRaf-1 or conditionally active DeltaRaf-1:AR demonstrated increased IC50 values for doxorubicin and a reduced capacity to undergo apoptosis after doxorubicin treatment as compared with parental cell lines. Moreover, growth curves performed show that both the constitutively and conditionally active forms of Raf-1 do not increase growth as compared with the parental MCF-7 cell line. This is important because it implies that higher cell counts between Raf transfectants and the parental MCF-7 cell line are attributable to differences in DR, not growth rates. These observations suggest a role for the Raf-1 protooncogene in the regulation of DR.

Annexin A5↗
PubMed2000

Justification of statistical overlap theory in programmed temperature gas chromatography: thermodynamic origin of random distribution of retention times.

A specific distribution of compounds' standard-state changes of enthalpy and entropy between mobile and stationary phases in programmed temperature gas chromatography (PTGC) is shown to produce the Poisson distribution of retention times often postulated in statistical-overlap theory (SOT). A three-part model is proposed, in which the enthalpy change is Poisson distributed, the average entropy change depends on the enthalpy change, and the actual entropy change varies in a uniformly random manner about the average entropy change. To test the model, the entropy and enthalpy changes of 350 aliphatic and aromatic hydrocarbons in petroleum were calculated with commercial GC software. These changes are shown to follow the three-part model. The model then was used with Monte Carlo methods to mimic the enthalpy and entropy changes. The substitution of the mimicked enthalpy and entropy changes into an equation for the retention temperature in PTGC is shown to produce a Poisson distribution of retention times that is statistically significant. This finding establishes a scientific link between the thermodynamics governing retention in PTGC and the superficially ad hoc assumption of the Poisson retention time distribution in SOT. Similar thermodynamic distributions are found for flavors and fragrances and for tetrachlorodibenzo-p-dioxins and furans, which follow SOT based on the Poisson distribution, but not for polychloronaphthalenes, which do not follow that SOT.

Journal Article↗
PubMed2000

Decrease in reelin and glutamic acid decarboxylase67 (GAD67) expression in schizophrenia and bipolar disorder: a postmortem brain study.

BACKGROUND: Reelin (RELN) is a glycoprotein secreted preferentially by cortical gamma-aminobutyric acid-ergic (GABAergic) interneurons (layers I and II) that binds to integrin receptors located on dendritic spines of pyramidal neurons or on GABAergic interneurons of layers III through V expressing the disabled-1 gene product (DAB1), a cytosolic adaptor protein that mediates RELN action. To replicate earlier findings that RELN and glutamic acid decarboxylase (GAD)(67), but not DAB1 expression, are down-regulated in schizophrenic brains, and to verify whether other psychiatric disorders express similar deficits, we analyzed, blind, an entirely new cohort of 60 postmortem brains, including equal numbers of patients matched for schizophrenia, unipolar depression, and bipolar disorder with nonpsychiatric subjects. METHODS: Reelin, GAD(65), GAD(67), DAB1, and neuron-specific-enolase messenger RNAs (mRNAs) and respective proteins were measured with quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) or Western blot analyses. Reelin-positive neurons were identified by immunohistochemistry using a monoclonal antibody. RESULTS: Prefrontal cortex and cerebellar expression of RELN mRNA, GAD(67) protein and mRNA, and prefrontal cortex RELN-positive cells was significantly decreased by 30% to 50% in patients with schizophrenia or bipolar disorder with psychosis, but not in those with unipolar depression without psychosis when compared with nonpsychiatric subjects. Group differences were absent for DAB1,GAD(65) and neuron-specific-enolase expression implying that RELN and GAD(67) down-regulations were unrelated to neuronal damage. Reelin and GAD(67) were also unrelated to postmortem intervals, dose, duration, or presence of antipsychotic medication. CONCLUSIONS: The selective down-regulation of RELN and GAD(67) in prefrontal cortex of patients with schizophrenia and bipolar disorder who have psychosis is consistent with the hypothesis that these parameters are vulnerability factors in psychosis; this plus the loss of the correlation between these 2 parameters that exists in nonpsychotic subjects support the hypothesis that these changes may be liability factors underlying psychosis.

Activating Transcription Factor 1↗
PubMed2000

Stage III colon cancers: why adjuvant chemotherapy is not offered to elderly patients.

HYPOTHESIS: Adjuvant chemotherapy is not offered to elderly patients with stage III colon cancer. DESIGN: A retrospective review of hospital and office records. SETTING: A suburban community hospital. PATIENTS: The medical records of 69 patients with stage III colon cancer were reviewed. All identified from the Tumor Registry at Jersey Shore Medical Center, Neptune, NJ, were included in this study. RESULTS: Thirty-five patients (51%) did not receive adjuvant chemotherapy. After adjusting for age, women were 5.8 times less likely to receive chemotherapy (P = .002). Patients not receiving chemotherapy were significantly older (78.7 vs 70.4 years; P = .003) than those who received adjuvant chemotherapy. There was no relation found between the year of diagnosis and the administration of chemotherapy. There were 4 major reasons for not receiving chemotherapy: (1) not offered (n = 12, 34%), (2) refused (n = 11, 31%), (3) too old (n = 7, 20%), and (4) significant concomitant disease (n = 5, 14%). CONCLUSIONS: A large group of elderly patients who had been surgically treated for colon cancer and who were eligible for adjuvant chemotherapy either were not referred for treatment or refused treatment. This suggests a bias on the part of surgeons, primary care physicians, and patients against the use of chemotherapy in elderly patients.

Age Distribution↗
PubMed2000

Saliva immunoglobulins in elite women rowers.

Saliva immunoglobulins (sIgA, sIgG, and sIgM) and upper respiratory tract infection (URTI) rates were evaluated in 20 elite female rowers and 19 nonathletes. Also, the influence of carbohydrate versus placebo beverage consumption on saliva immunoglobulin responses to rowing training sessions was measured in 15 rowers and in 5 non-exercising rowers. Saliva samples were collected 1 day before, and 5-10 min and 1.5 h after rowing or rest. Pre-exercise sIgA (but not sIgG or sIgM) concentration was 77% higher in the rowers compared to nonathletes (P < 0.001). Health records kept over 2 months revealed mean 5.2 (SEM 1.2) and 3.3 (SEM 1.1) days with URTI symptoms for the rowers and controls, respectively. For all 39 subjects, and for the 20 rowers separately, no significant correlation was found between URTI symptoms or insulin, cortisol, and growth hormone concentrations and pre-exercise or exercise-related changes in saliva immunoglobulin concentrations or secretion rates. The patterns of change in saliva immunoglobulin concentration and secretion rate did not differ between the carbohydrate and placebo rowing trials, or between exercised and rested athletes. These data indicated an increased sIgA concentration in the female elite rowers compared to the nonathletes, no association between saliva immunoglobulins and URTI, and no effect of a normal 2-hour training session or carbohydrate ingestion on saliva immunoglobulin concentrations or secretion rates.

Adolescent↗
PubMed2000

Transepithelial chloride conductance in amphibian skin: regulatory mechanisms and localization.

The transepithelial transport of Na+ by amphibian skin must be accompanied by the corresponding anion, Cl-, and much effort has been devoted to the characterization of Cl- transport. The transepithelial Cl- conductance, G(Cl), is activated by voltage and adenosine 3',5'-cyclic monophosphate (cAMP), shows rectification, requires the presence of Cl- in the pathway and is influenced by factors modifying intracellular signalling cascades and by metabolic poisons such as cyanide (CN-). Until recently, these findings were interpreted as strong evidence for a transcellular path, for which, given the impermeability of the principal cells for Cl-, the mitochondria-rich cells (MRC) are the only candidate. This was supported by the apparent parallelism between G(Cl) and the density of MRC (D(mrc)). Data accumulated in recent years, however, raise serious doubts as to the validity of this concept. The single-channel conductance derived from various techniques is too small by an order of magnitude to account for the observed G(Cl), the very slow time course of conductance activation is not reconcilable with any known membrane channel gating processes, a more thorough examination of the relationship between G(Cl) and D(mrc) fails to show any consistent pattern and analysis of current density immediately above the transporting epithelium using the vibrating voltage probe shows current peaks associated with only a small fraction of MRC, and even so, these current peaks account for about 20% of the transepithelial current. The remaining 80% of the current cannot be localized to specific structures. Given the increasing evidence for close cellular control of tight-junction function, the foregoing findings are equally consistent with an additional, major, paracellular pathway for Cl-. A comprehensive description of Cl- transport must await the final resolution of the transport pathway(s).

Amphibians↗
PubMed2000

Long-term follow-up of premature infants treated with prophylactic, intratracheal recombinant human CuZn superoxide dismutase.

OBJECTIVE: To examine the long-term effects of treatment with recombinant human CuZn superoxide dismutase (rhSOD) in infants enrolled previously in two placebo-controlled trials. STUDY DESIGN: Records for 46 (88%) infants were examined, with 19 infants having received either single or multiple intratracheal (i.t.) doses of placebo, 12 having received a single i.t. dose of rhSOD, and 15 having received multiple i.t. doses of rhSOD. Mean age at follow-up was 28 months corrected age. Records were examined for neurologic dysfunction, developmental delay, and any significant medical disorders. RESULTS: Four placebo infants (21%) had evidence of neurodevelopmental abnormalities and four infants developed asthma. Four single-dose rhSOD infants (33%) had neurodevelopmental abnormalities and two infants developed asthma. One multiple-dose rhSOD infant had evidence of neurodevelopmental abnormalities and one developed asthma. No other differences were found between the placebo and rhSOD groups. CONCLUSION: Preliminary data suggest that rhSOD is safe and not associated with any long-term adverse effects. Further results will depend on the results of multicenter trials of rhSOD in preterm infants.

Administration, Inhalation↗
PubMed2000

Autologous graft-versus-host disease induction in advanced breast cancer: role of peripheral blood progenitor cells.

The purpose of the present study was to investigate the impact of the use of peripheral blood progenitor cells (PBPCs) on the induction of autologous graft-versus-host disease (GVHD) in patients with advanced breast cancer. 14 women with stage IIIB and 36 women with stage IV breast cancer received cyclosporine (CsA) 2.5 mg kg-1 i.v. daily, d 0-28, and interferon-gamma (IFNg) 0.025 mg/m2 s.c. qod, d7-28, following PBPC-T +/- bone marrow transplantation (BMT). Preceding high-dose chemotherapy consisted of cyclophosphamide 6 g/m2 and thiotepa 800 mg/m2. Histologically proven > or = grade II cutaneous GVHD was induced in18/50 (36%) of patients and was independent of the source of haematopoietic support. In vitro studies showed that post-transplant, 76% of patients had developed auto-cytotoxicity against their own pre-transplant PHA-lymphoblasts. A significant correlation between the occurrence of GVHD > or = grade II and cytolysis was observed in the NK cell-line K562 and the T47D breast cancer cell-line. With a median follow-up of 2(1/2) years, the overall survival (OS) is 58%, the disease-free survival (DFS) 26%, both independent of the development of GVHD and similar to what has been observed in other studies on high-dose chemotherapy in advanced breast cancer. It therefore remains unclear whether the induction of autologous GVHD with the occurrence of auto-cytotoxic lymphocytes can result in an anti-tumour effect in this group of patients.

Adult↗
PubMed2000

Pathogenicity of a special-purpose glass microfiber (E glass) relative to another glass microfiber and amosite asbestos.

This article describes the activity of an E-glass microfiber (104E) during chronic inhalation and intraperitoneal injection studies in rats. Results are compared with another microfiber of similar dissolution rate (k(dis)), code 100/475, and the more durable amosite asbestos, both of which we had previously used in similar experiments (Davis et al., 1996). Rats were exposed to aerosol concentrations of 1000 fibers (longer than 5 microm)/ml, as measured by optical microscopy, for 7 h/day, 5 days/wk. Subgroups of rats were followed for mean lung burden, early and late signs of fibrosis, and tumor incidence. At the end of 12 mo of exposure, the mean number of 104E fibers of all lengths in the lungs was approximately double that for amosite but two-thirds of that for 100/475. For fibers longer than 15 microm, the mean 104E burden was similar to that for the amosite and more than twice that of the 100/475. After a 12-mo recovery period, the retained lung burdens (of fibers of all lengths) were approximately 30% of those at 12 mo for both microfibers, and somewhat higher (approximately 44%) for amosite. Amosite and 100/475 fibers longer than 15 microm were more persistent in the lungs than 104E fibers. The chemical composition of 104E fibers did not appear to have been significantly altered by up to 24 mo of residence in lung tissue, whereas the composition of 100/475 was substantially altered over the same time period. From the inhalation study, out of the pathology subgroup of 43 animals exposed to 104E microfibers, 10 had lung tumors (7 carcinoma, 3 adenoma) and 2 had mesotheliomas, whereas in 42 rats exposed to amosite asbestos, there were 16 lung tumors (7 carcinoma, 9 adenoma) and 2 mesotheliomas. The 104E- and amosite-treated animals had similar levels of fibrosis. In contrast, 38 animals treated with 100/475 had little fibrosis, 4 lung tumors (adenomas), and no mesotheliomas. The greater pathogenicity of the 104E fibers, compared to 100/475 fibers, might be partly explained by the greater numbers of long fibers retained in the lung after 12 mo of inhalation. However, we speculate that modification of surface properties by extensive selective leaching of some glass components reduces the toxic potential of 100/475. In a parallel intraperitoneal injection study, 104E caused considerably more mesotheliomas (21 rats out of 24) than 100/475 (8 rats out of 24). In addition, 104E appeared to be more active than amosite asbestos, since mesotheliomas appeared much more quickly in the 104E-treated animals. In conclusion, we have shown that two microfiber types, 100/475 and 104E, of similar dissolution rates, had markedly different pathogenicity in rats. We believe that this contrast is only partly due to differences in numbers of long fibers and that differences in surface properties of the fibers, possibly due to proportionately greater leaching of 100/475 fibers, play an important role.

Administration, Inhalation↗
PubMed2000

Inhalation of poorly soluble particles. I. Differences in inflammatory response and clearance during exposure.

Results from animal studies have indicated some uncertainties over the validity of a single general occupational control limit for all types of "particulates (insoluble) not otherwise classified" (PNOC) (ACGIH, 2000). Therefore, to examine the extent to which a given control limit may be valid for nontoxic dusts with different physical characteristics, this study compared the pulmonary effects in rats of inhalation exposure to two poorly soluble dusts of similar density and with relatively low toxicity: titanium dioxide and barium sulfate. The objectives were to compare the dusts in (a) their buildup and clearance in the lungs during inhalation; (b) their transfer to lymph nodes; (c) the changes, with time, in the lavageable cell population; and (d) the pathological change from histology. The exposure aerosol concentrations were selected to achieve similar mass and volume lung burdens for both dusts and to attain "overload" over the common exposure periods of about 4 mo and 7 mo. Despite obtaining similar lung burdens for both dusts, there was significantly more translocation of TiO(2) to the hilar lymph nodes than with BaSO(4). It was also found that clearance of TiO(2) was retarded whereas clearance of BaSO(4) was not. Trends in these data were clarified by the use of a simple model of particle clearance. Retardation of particle clearance and translocation to the lymph nodes are markers of the condition known as "overload" in which the alveolar macrophage-based clearance of particles from the deep lung is impaired. In addition, bronchoalveolar lavage showed that TiO(2) caused significantly more recruitment of inflammatory neutrophils to lungs than BaSO(4). These differences between the dusts were not due to differences in toxicity, solubility, or lung deposition. The explanation that the different responses are due to the different particle size distributions of the two dust types is examined in a companion paper (Tran et al., this issue).

Administration, Inhalation↗
PubMed2000

Serotonin and central nervous system fatigue: nutritional considerations.

Fatigue from voluntary muscular effort is a complex phenomenon involving the central nervous system (CNS) and muscle. An understanding of the mechanisms within muscle that cause fatigue has led to the development of nutritional strategies to enhance performance. Until recently, little was known about CNS mechanisms of fatigue, even though the inability or unwillingness to generate and maintain central activation of muscle is the most likely explanation of fatigue for most people during normal daily activities. A possible role of nutrition in central fatigue is receiving more attention with the development of theories that provide a clue to its biological mechanisms. The focus is on the neurotransmitter serotonin [5-hydroxytryptamine (5-HT)] because of its role in depression, sensory perception, sleepiness, and mood. Nutritional strategies have been designed to alter the metabolism of brain 5-HT by affecting the availability of its amino acid precursor. Increases in brain 5-HT concentration and overall activity have been associated with increased physical and perhaps mental fatigue during endurance exercise. Carbohydrate (CHO) or branched-chain amino acid (BCAA) feedings may attenuate increases in 5-HT and improve performance. However, it is difficult to distinguish between the effects of CHO on the brain and those on the muscles themselves, and most studies involving BCAA show no performance benefits. It appears that important relations exist between brain 5-HT and central fatigue. Good theoretical rationale and data exist to support a beneficial role of CHO and BCAA on brain 5-HT and central fatigue, but the strength of evidence is presently weak.

Amino Acids, Branched-Chain↗
PubMed2000

Influence of carbohydrate on cytokine and phagocytic responses to 2 h of rowing.

PURPOSE: This study examined the influence of carbohydrate (C) versus placebo (P) beverage ingestion on the phagocytic and cytokine responses to normal rowing training by 15 elite female rowers. METHODS: Athletes received C or P before, during and after, two, 2-h bouts of rowing performed on consecutive days. Blood was collected before and 5-10 min and 1.5 h after rowing. Metabolic measures indicated that training was performed at moderate intensities, with some high-intensity intervals interspersed throughout the sessions. RESULTS: Concentrations of blood neutrophils and monocytes, phagocytic activity, and plasma IL-1ra were significantly lower postexercise after C versus P ingestion. No differences were observed for oxidative burst activity, IL-6, IL-8, or TNFalpha. Glucose was significantly higher after 2 h of rowing with C ingestion; however, cortisol, growth hormone, epinephrine, norepinephrine, and CRP were not affected by carbohydrate. CONCLUSIONS: These data indicate that carbohydrate compared with placebo ingestion attenuated the moderate rise in blood neutrophils, monocytes, phagocytosis, and plasma IL-1ra concentrations that followed 2-h bouts of training in elite female rowers. No changes in blood hormone concentrations were found.

Adult↗
PubMed2000

Exercise and tumor development in a mouse predisposed to multiple intestinal adenomas.

UNLABELLED: Epidemiological evidence suggests that physical activity may be protective against the development of colon cancer. Potential mechanisms remain largely unexplored due to the paucity of appropriate experimental models. PURPOSE: The purpose of this study was to examine the effect of exercise training on polyp development in an induced mutant mouse strain predisposed to multiple intestinal neoplasia (Min mouse). METHODS: Three-week-old male and female heterozygotes were randomly assigned to control (CON; 10 males, 6 females) or exercise (EX; 11 males, 11 females) groups. In the first week, EX mice were acclimated to treadmill running at 10-18 m x min(-1) for 15-60 min x d(-1). From 4-10 wk of age, mice ran at 18-21 m x min(-1) for 60 min. CON mice sat in Plexiglas lanes suspended above the treadmill for the same time periods. At 10 wk of age, the mice were sacrificed and the intestines removed, opened, and counted for polyps. RESULTS: Skeletal muscle oxidative capacity increased with training as shown by a 64% increase in citrate synthase activity in the gastrocnemius/soleus muscle of EX compared with CON (P = 0.009). There were no significant effects of exercise in the males and females combined on small intestine, colon, or total intestinal polyps (P > 0.05). When analyzed separately, however, there were fewer colon and total polyps in the EX than in the CON males, although the difference was not statistically significant (P = 0.06). CONCLUSIONS: These results suggest that seven weeks of exercise training do not affect the development of intestinal polyps in the Min mouse. Further studies are required to determine if a true sex difference exists or if variations on the current training protocol may affect tumor outcomes.

Adenoma↗
PubMed2000

Effects of carbohydrate and chromium ingestion during intermittent high-intensity exercise to fatigue.

PURPOSE: This study was designed to test the hypothesis that addition of chromium (Cr) to a carbohydrate-electrolyte drink would enhance the reported benefits of carbohydrate on exercise capacity during intermittent high-intensity shuttle running. METHODS: Eight physically active men performed 3 exercise trials while ingesting 6% carbohydrate-electrolyte (CHO), CHO plus chromium picolinate (400 mg) (CHO + Cr+3), or placebo (P) using a double-blind, counterbalanced design. Each trial consisted of 5 3 15 min bouts of shuttle running (walk, sprint, and run at 95 and 55% of estimated VáO2max, separated by 3-min rest). This was followed by a fatigue test (running alternating 20-m lengths at 55 and 95% of estimated VáO2 until fatigue). RESULTS: During the standardized shuttle running, blood glucose was higher with both CHO and CHO + Cr+3 than P. Plasma free fatty acid was higher in P than both CHO and CHO + Cr+3 at 75 min of exercise and at fatigue. In the fatigue test, subjects ran longer with both CHO and CHO + Cr+3 than P. CONCLUSIONS: The data confirm an ergogenic benefit of ingesting CHO during exercise designed to imitate sports like basketball, soccer, and hockey, but do not support the hypothesis that the addition of Cr would enhance this effect.

Adult↗
PubMed2000

Blood pressure and indices of glomerular filtration area in hypertensive and normotensive Prague rats.

The involvement of the kidney in the pathogenesis of hypertension has long been recognised, although the specific renal mechanisms underlying this phenomenon are still unknown. A current hypothesis attributes hypertension to a reduction in glomerular filtration area by glomerular loss. The present study analyses the relationship between glomerular number and volume and conscious systolic blood pressure (SBP) in 4- to 53-week-old hypertensive (PHR) and normotensive (PNR) rats of the Prague strain. Adult PHRs had higher SBP, were larger and had larger kidneys than PNRs, but 20% fewer glomeruli. A significant negative correlation between SBP and glomerular number was found in PHR males, but not in PHR females or PNRs. There was no correlation at all between glomerular volume and SBP and, in young animals, both SBP and glomerular number were higher in PHRs than in PNRs. In addition, in adult PHRs, glomerular volume and SBP were higher in males than in females. In summary, a generally valid, causal relationship linking raised blood pressure to decreased glomerular number or volume could not be demonstrated in the Prague rat model of genetically determined hypertension. The nature of the renal mechanism(s) determining the hypertension in this model remains unknown.

Aging↗
PubMed2000

Validity of clinical trials of antidepressants.

OBJECTIVE: Recent reports have criticized the design of antidepressant studies and have questioned their validity. These critics have concluded that antidepressants are no better than placebo treatment and that their illusory superiority depends on methodologically flawed studies and biased clinical evaluations. It has been suggested that the blind in randomized trials is penetrable-since clinician's guesses exceed chance-and that only active placebo can appropriately camouflage the difference between drug and placebo response. Furthermore, evidence has been cited to suggest that psychotherapy is as effective as antidepressants in both the acute and maintenance treatment of depression. These positions are often accepted as valid and have been broadly discussed in both the lay press and scientific literature. The purpose of this review is to reassess the cited data that support these assertions. METHOD: The authors examined the specific studies that were cited in these reports, evaluated their methodology, and conducted aggregate analyses. RESULTS: Analyses of the original sources failed to substantiate 1) that standard antidepressants are no more effective than placebo, 2) that active placebo offers an advantage over inactive placebo, or 3) that substantial evidence of a medication bias is suggested by raters' treatment guesses exceeding chance. The authors also note that some researchers have suggested that the interpretation of psychotherapy trials can be complicated by "allegiance effects." CONCLUSIONS: The issue of bias or allegiance effects for both antidepressant and psychotherapy research is real. Investigators of all orientations must guard against potential bias. However, studies cited as supporting the questionable validity of antidepressant trials fail upon closer examination to support assertions that these trials are invalid.

Antidepressive Agents↗