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Biomedical subjects

J Cornish

Publications and source records attributed to J Cornish.

At least 73 records · Page 4Linked to original sources
PubMed1995

Sources of interracial variation in bone mineral density.

Many studies have demonstrated significant differences in bone mineral density between various racial groups. Although it has been suggested that differences in body weight contribute to such interracial variation, the artifactual effect of the skeletal size inherent in projectional absorptiometry methods has been largely ignored. We have measured bone mineral density by dual-energy X-ray absorptiometry in the lumbar spine and at three femoral sites in 200 premenopausal women of Chinese, Indian, European, or Polynesian origin (50 of similar mean age in each group). In the Chinese and Indian women the measured bone mineral density measurements (g/cm2) were similar, but significantly less, at all sites, than those of European women (p < or = 0.005). The European women were, however, significantly taller than both the Chinese and Indian women (p < 0.0001), and when the scale artifact of absorptiometry was removed by dividing the measured bone mineral density either by the height of the subject, or by the square root of the area over which the X-ray beam was projected, then the differences in mean bone mineral density between the Chinese, Indian, and European women were almost completely eliminated. The Polynesian women were significantly more obese (as judged from mean body mass index) than all the other groups (p < 0.0001) and had significantly greater bone mineral density at all sites than all the other groups both before (p < 0.0001) and after (p < 0.0001) correcting for the scale artifact.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMed1995

A multicenter trial of bupropion for cocaine dependence in methadone-maintained patients.

We conducted a multi-site, placebo-controlled, randomized double-blind clinical trial comparing bupropion HCL (300 mg/day) to placebo for the treatment of cocaine dependence in methadone-maintained subjects. A total of 149 subjects at three sites participated in a 12-week study. Outcome measures included cocaine use, level of depression, and psychosocial functioning. Results showed no significant differences between placebo and bupropion. Exploratory analyses suggested a medication effect for the subset of subjects depressed at study entry. The need to target subgroups of cocaine abusers in future pharmacotherapy trials and the possible role of treatment readiness are discussed.

Adult↗
PubMed1995

An in vivo model for the rapid assessment of the local effects of parathyroid hormone on bone histomorphometry.

The process of bone remodelling is likely to be controlled to a large extent by factors acting locally in a paracrine or autocrine manner, along with some systemic control. In our laboratory we routinely use an in vivo model in which the local effects of factors on bone histomorphometry can be determined. The factor under investigation is injected just above the periosteum of the right hemicalvaria in the adult male mouse. These subcutaneous injections are given daily over a 1-week period and the animals sacrificed at intervals after the last injection. With appropriate staining techniques it is possible to determine the effects of a particular agent on osteoblast and osteoclast numbers; the area of total bone, mineralized bone, osteoid and periosteum; osteoblast, osteoclast and eroded surfaces, and thus to infer the rate of bone formation and bone resorption in the right hemicalvaria compared to the uninjected left hemicalvaria and to vehicle-injected control animals. All these parameters are measured using a bone-dedicated image analyzer. Utilizing this in vivo model, we and others have studied a number of bone-active factors. We report the effects of parathyroid hormone, as well as reviewing results of our studies of leukemia inhibitory factor, amylin, calcitonin and calcitonin gene-related peptide in the model. The results obtained are similar to those found in most other animal models and in man. In conclusion, we describe an in vivo model whereby bone-active factors, injected locally, can be rapidly assessed.

Animals↗
PubMed1994

Ultrastructural study of an antibody-stabilized bladder surface: a new perspective on the elusive glycosaminoglycan layer.

The thin mucus or glycosaminoglycan layer of the bladder may be implicated in the pathogenesis of many bladder disease states. We have developed a specific antimucus, antisera stabilization technique to study the ultrastructural morphological appearance of the layer in both normal and abnormal bladders that should provide a new perspective on this elusive layer.

Cystitis↗
PubMed1994

Continuous therapy with pamidronate, a potent bisphosphonate, in postmenopausal osteoporosis.

There is a need for effective and acceptable therapies for postmenopausal osteoporosis. The bisphosphonates show promise in this role, but the effects of the potent bisphosphonates in established osteoporosis have not yet been reported. We performed a 2-yr, randomized, double blind, placebo-controlled trial of pamidronate (150 mg/day) in 48 postmenopausal osteoporotic women. Bone mineral density of the total body, lumbar spine, and proximal femur was measured every 6 months by dual energy x-ray absorptiometry. Bone mineral density increased progressively in the total body (1.9 +/- 0.7%; P < 0.01), lumbar spine (7.0 +/- 1.0%; P < 0.0001), and femoral trochanter (5.4 +/- 1.3%; P < 0.001) in subjects receiving pamidronate, but did not change significantly in those receiving placebo. There were significant decreases in bone density at both the femoral neck (P < 0.02) and Ward's triangle (P < 0.01) in subjects taking placebo, which did not occur in the pamidronate group. The differences between the treatment groups were significant at all sites (0.0001 < P < 0.05) except Ward's triangle. Vertebral fracture rates were 13/100 patient yr in the pamidronate group and 24/100 patient yr in those receiving placebo (P = 0.07), and there was a nonsignificant trend toward height loss being less in those receiving pamidronate (P = 0.16). It is concluded that pamidronate is an effective therapy in postmenopausal osteoporosis.

Aged↗
PubMed1994

A constituent of human small intestinal mucus that copurifies with mucin and can interfere with raising antibodies to the mucin.

The accuracy of an immunoassay for mucin depends on the antibodies' specificity. During human small intestinal mucin purification on a CsCl gradient, a very antigenic non-mucin contaminant was found at 1.48 g.ml-1 density. This was separated from the mucin (1.42 g.ml-1 density) by dividing the gradient into 26 fractions, but not by dividing it into 8 fractions. Polyclonal antibodies raised against mucin obtained using 8 fractions reacted with mucin and contaminant, but antibodies raised against mucin obtained using 26 fractions reacted only with mucin. The identity of the contaminant is unknown. However, it contained nearly equal amounts of galactose, N-acetylglucosamine and glucose, but did not react strongly with periodate-Schiff reagent. Immunofluorescence microscopy showed it was located in the small intestinal goblet cells and mucus layer. Unless the contaminant is removed before raising polyclonal antibodies to mucin, immunoassays will give inaccurate results.

Animals↗
PubMed1993

The bladder mucus (glycosaminoglycan) layer in interstitial cystitis.

The thin mucus or glycosaminoglycan layer of the bladder may be implicated in the pathogenesis of interstitial cystitis. We developed a specific anti-mucus, antisera stabilization technique to study the ultrastructural morphological appearance of the layer, and have used this technique to compare the surface morphology of 10 control and 10 interstitial cystitis patients. The electron micrographs demonstrate the ultrastructural characteristics of the pathological changes seen in interstitial cystitis but they did not show any significant difference in the morphological appearance of the mucus or glycosaminoglycan layer between the 2 groups.

Adult↗
PubMed1993

The effect of leukemia inhibitory factor on bone in vivo.

The local effects of leukemia inhibitory factor (LIF) on bone turnover in vivo have been examined. Recombinant murine LIF (0.2 micrograms) or vehicle was injected daily for 5 days over the right hemicalvaria, and the mice were killed on day 6 or 13. Effects on calvarial bone morphology were assessed using quantitative histomorphometry of nondecalcified bone tissue. Increased bone resorption was present in LIF-treated hemicalvaria compared with that in the noninjected hemicalvaria or calvaria from mice injected with vehicle alone at both 6 and 13 days. Significant increases in LIF-treated animals were as follows. Eroded surface increased 10-fold (P = 0.022), osteoclast surface increased 5-fold (P = 0.003), osteoclast numbers increased 3-fold (P = 0.002), and the number of osteoclast nuclei increased 3-fold (P = 0.009). Fibrotic tissue was laid down in the resorption defects, and there was an accompanying thickening of the periosteum (3 times greater in LIF-injected animals; P = 0.003), causing the overall thickness of the treated bones to be almost doubled (P = 0.045). Indices of bone formation were increased in animals treated with LIF. Osteoblast numbers, osteoblast surface, and osteoid area were doubled (P = 0.012, 0.016, and 0.058, respectively). Similar effects of LIF were seen in indomethacin-treated animals. Small but statistically significant morphological changes were also seen in the left noninjected hemicalvariae when LIF-treated animals were compared to controls. LIF increased periosteal area (P = 0.01) and total mineralized bone area (P = 0.002). In conclusion, LIF accelerated bone turnover locally in a prostaglandin-independent manner in normal mice, demonstrating its potential to modify in vivo bone cell function dramatically.

Animals↗
PubMed1992

A pilot trial of gepirone vs. placebo in the treatment of cocaine dependency.

An interim analysis of 41 evaluable patients compared gepirone to placebo treatment in a randomized, double-blind, 12-week study of cocaine dependence without opiate abuse. The response to gepirone at a mean dose of 16.25 mg/day did not differ from placebo by measures of time in study, positive urine cocaine screens (greater than 6 weeks), Clinical Global Impressions (CGI) Global Improvements Scale, Cocaine Craving Scale (CCS), Quantitative Cocaine Inventory (QCI), Addiction Severity Index (ASI), Global Assessment Scale (GAS), Hamilton Rating Scale for Depression (HAM-D), and Hamilton Anxiety Scale (HAM-A). Both treatment groups showed similar modest, average improvements during the study in all treatment measures. Adverse events were not treatment limiting. The following demographic and study measures suggested favorable trends for study outcomes: older age, divorced status, higher pre-treatment cocaine use, lower CCS scores, and lower self-reports of cocaine use according to QCI.

Adult↗
PubMed1991

Regulation of osteoblast proliferation by leukemia inhibitory factor.

We recently showed that leukemia inhibitory factor (LIF) stimulates 45Ca release from neonatal mouse calvariae in vitro and that it increases DNA and protein synthesis in this model. To elucidate further the actions of LIF on bone we now report the effects of this cytokine on DNA synthesis and cell proliferation in isolated fetal rat osteoblasts and in the osteogenic sarcoma cell line, UMR-106. In both actively growing and growth-arrested rat osteoblasts, LIF stimulated [3H]thymidine incorporation in a dose-dependent manner. The increase in DNA synthesis was time dependent, was associated with an increase in the number of osteoblasts, and was not blocked by indomethacin. LIF-treated cells showed reduced [3H]thymidine incorporation in comparison with control, as they approached confluence, possibly because of the increased cell density in the LIF-treated cultures. In UMR-106 cells, treatment with LIF inhibited [3H]thymidine incorporation in both actively growing and growth-arrested cultures. The effect was dose dependent and sustained with time. There was a corresponding decrease in cell numbers. It is concluded that although LIF causes an early stimulation of proliferation in isolated osteoblasts, it has opposing effects on UMR-106 cells. It is not possible to determine which of these effects is more relevant to the actions of LIF in vivo. The demonstration of a LIF effect on both these cell types, however, provides further evidence that this cytokine acts directly on osteoblasts.

Animals↗
PubMed1991

Effects of leukemia inhibitory factor on bone resorption and DNA synthesis in neonatal mouse calvaria.

Leukemia inhibitory factor (LIF) is a recently characterized cytokine which has been shown to regulate cell growth and differentiation in a variety of tissues. We have shown that LIF stimulates bone resorption and DNA synthesis in bone organ culture and, in vivo, LIF has been shown to have marked effects on bone remodeling. The present study examines further the dose-response, time course and mechanisms of action of LIF in neonatal mouse calvaria. 45Ca release was significantly increased by LIF at concentrations of 10-5,000 U/ml, and its stimulation of bone resorption increased with time from 24 to 96 hours. These concentrations of LIF also increased DNA synthesis at 24 hours. At 72 hours, low concentrations of LIF produced less marked stimulation of [3H]-thymidine incorporation, and 5,000 u/ml actually inhibited DNA synthesis at both this time point and at 96 hours. The effect of LIF on 45Ca release was partially inhibited when DNA synthesis was blocked by hydroxyurea (50 microM). The resorptive effect of supramaximal concentrations of LIF was not additive to that of parathyroid hormone, 1,25-dihydroxyvitamin D3, prostaglandin E2, or transforming growth factor-beta. Although LIF-stimulated resorption is at least partially dependent on DNA synthesis, these results suggest that there are different mechanisms involved in mediating LIF's effects on bone resorption and DNA synthesis. The demonstration of effects of LIF at low concentrations indicates that this cytokine may be involved in the physiological regulation of bone metabolism in vivo.

Animals↗
PubMed1991

Effective emetic control during conditioning of children for bone marrow transplantation using ondansetron, a 5-HT3 antagonist.

Preparation for bone marrow transplantation (BMT) uses the extremely emetogenic combination of chemotherapy and total body irradiation (TBI). Ondansetron is a selective 5-HT3 antagonist and has clear anti-emetic capabilities. The efficacy of the drug was assessed in 15 children (aged 2-17 years) who received high dose cyclophosphamide (on days -6 and -5) and TBI (days -3 to 0 inclusive). During days -6 to -4 when the emetic effect of cyclophosphamide would be most pronounced, 12 of the 15 patients (80%) had fewer than five emetic episodes during their worst 24-h period, 11 (73%) had fewer than three vomits whilst nine (60%) experienced no vomiting or retching. Eleven patients progressed to TBI and 10 (91%) had fewer than five emetic events in the worst 24-h period (days -3 to +2), six (55%) had no vomiting at all. Of 100 evaluable 'patient-days' 83 (83%) were without any vomiting or retching and a further 10 'patient-days' had only one or two emetic episodes. There were no significant side-effects noted and in particular no extrapyramidal reactions. Headaches and constipation, which have been seen in adult studies, were not reported by patient or parent on any of the study days and transient elevation of liver enzymes were noted in only two patients. Ondansetron has a major role in preparing patients for BMT.

Adolescent↗
PubMed1990

Ultrastructural visualization of human bladder mucous.

Mucous within the urinary bladder appears to play a protective role in shielding the uroepithelium against pathogens. This present study employs specific anti-mucous, antisera stabilization techniques to visualize a thin, continuous layer of mucous closely adherent to the human bladder uroepithelium, in both scanning and transmission electron microscopic analyses.

Adult↗
PubMed1990

Adenylate cyclase blockers dissociate PTH-stimulated bone resorption from cAMP production.

It is uncertain whether adenosine 3',5'-cyclic monophosphate (cAMP) or the inositol-calcium pathway mediates the stimulation of bone resorption by parathyroid hormone (PTH). Incubation of bone organ cultures with cAMP analogues and forskolin has not resolved this question because of the cellular inhomogeneity of bone and the consequent presence of adenylate cyclase-linked receptors for both PTH and calcitonin, hormones with opposite effects on bone resorption. We have used two new inhibitors of adenylate cyclase, 9-(tetrahydro-2-furyl)adenine (SQ 22536) and 2',5'-dideoxyadenosine (DDA), to directly reassess the role of cAMP in PTH-stimulated osteolysis. SQ 22536 (0.01-1.0 mM) and DDA (0.01-1.0 mM) completely blocked PTH stimulation of cAMP production measured in the absence of a phosphodiesterase blocker. In the presence of 1 mM 3-isobutyl-1-methylxanthine, half-maximal inhibition of PTH-induced cAMP production occurred with 0.2 mM SQ and 0.1 mM DDA, respectively. These concentrations of SQ and DDA had no effect on PTH-stimulated 45Ca release from calvaria, although both agents inhibited bone resorption when present at concentrations of 1-2 mM. At these levels, SQ and DDA caused equivalent inhibition of 45Ca release stimulated by 1,25-dihydroxyvitamin D3 but did not affect basal 45Ca release or [3H]-phenylalanine incorporation. It is concluded that substantial blockade of PTH-induced cAMP production does not affect this hormone's stimulation of bone resorption, which is therefore likely to be mediated by another intracellular messenger system, possibly calcium. In millimolar concentrations, SQ and DDA appear to be nonspecific blockers of osteoclastic bone resorption.

1-Methyl-3-isobutylxanthine↗
PubMed1990

Leukemia inhibitory factor: a novel bone-active cytokine.

A number of cytokines have been found to be potent regulators of bone resorption and to share the properties originally attributed to osteoclast-activating factor. One such activity, differentiation-inducing factor (DIF, D-factor) from mouse spleen cells, shares a number of biological and biochemical properties with the recently characterized and cloned leukemia inhibitory factor (LIF). We have assessed the effects of recombinant LIF on bone resorption and other parameters in neonatal mouse calvaria. Both recombinant murine and human (h) LIFs stimulated 45Ca release from prelabeled calvaria in a dose-dependent manner. The increase in bone resorption was associated with an increase in the number of osteoclasts per mm2 bone. The osteolytic effect of hLIF were blocked by 10(-7) M indomethacin. hLIF also stimulated incorporation of [3H] thymidine into calvaria, but the dose-response relationship was distinct from that for bone resorption, and this effect was not blocked by indomethacin. Similarly, hLIF increased [3H]phenylalanine incorporation into calvaria, and this was also not inhibited by indomethacin. It is concluded that LIF stimulates bone resorption by a mechanism involving prostaglandin production, but that a distinct mechanism is responsible for its stimulation of DNA and protein synthesis. The primary structure of LIF differs from that of other fully characterized, bone-active cytokines, and it, thus, represents a novel factor which may be involved in the normal regulation of bone cell function.

Animals↗
PubMed1989

Immunoregulation in Heymann nephritis. I. Cell marker studies.

Immunoregulation was examined in rats with Heymann nephritis (HN), an established model of membranous glomerulonephropathy (MGN). There is little known of the cellular immune events for the induction and maintenance of the autoimmune response in HN. The cell marker studies utilized fluorescein (FITC)-labelled monoclonal antibodies directed to B cells (Mark-I), and T cell subsets: pan T (ER-I), helper/inducer T (ER-2) and suppressor/cytotoxic T (ER-3). Lymphoid subsets were compared in spleen, lymph nodes, peripheral blood and bone marrow, of normal and diseased rats. Animals were investigated during the induction and chronic phases of disease. The induction of HN was associated with an early, significant, but transient increase of the non-specific myeloid component of the defence system. Subsequently, a significant increase was seen in the number of cells of the B lymphocyte lineage in HN animals, which coincided well with the overall increased humoral immune responsiveness. No alterations in the T lymphocyte subsets were noted during the development of this experimental autoimmune disease.

Animals↗