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Biomedical subjects

J Farley

Publications and source records attributed to J Farley.

At least 37 records · Page 2Linked to original sources
PubMed1997

Circulating and skeletal insulin-like growth factor-I (IGF-I) concentrations in two inbred strains of mice with different bone mineral densities.

Recent work has demonstrated differences in femoral bone mineral density between two common inbred strains of mice, C3H/HeJ (C3H) and C57BL/6J (B6), across a wide age range. To investigate one possible mechanism that could affect acquisition and maintenance of bone mass in mice, we studied circulatory and skeletal insulin-like growth factor-I (IGF-I) and femoral bone mineral density (F-BMD) by pQCT in C3H and B6 progenitor strains, as well as serum IGF-I obtained from matings between these two strains and mice bred from subsequent F1 intercrosses (F2). Serum IGF-I measured by radioimmunoassay was more than 35% higher in virgin progenitor C3H than virgin B6 at 1, 4, 8, and 10 months of age, and in 8-month-old C3H compared with B6 retired breeders (p < 0.001). In the progenitors, there was also a strong correlation between serum IGF-I and serum alkaline phosphatase (r = 0.51, p = 0.001). In the 4 month F1 females IGF-I levels and F-BMD were intermediate between C3H and B6 progenitors. In contrast, groups of F2 mice with the highest or lowest BMD also had the highest or lowest serum IGF-I (p = 0.0001). IGF-I accounted for > 35% of the variance in F-BMD among the F2 mice. Conditioned media from newborn C3H calvarial cultures had higher concentrations of IGF-I than media from B6 cultures, and cell layer extracts from C3H calvariae exhibited greater alkaline phosphatase activity than cultures from B6 calvarial cells (p < 0.0001). The skeletal content of IGF-I in C3H tibiae, femorae, and calvariae (6-14 weeks of age) was also significantly higher than IGF-I content in the same bones of the B6 mice (p < 0.05). These data suggest that a possible mechanism for the difference in acquisition and maintenance of bone mass between these two inbred strains is related to systemic and skeletal IGF-I synthesis.

Aging↗
PubMed1997

Potentiation of phototactic suppression in Hermissenda by compound conditioning results in potentiated excitability changes in type B and A photoreceptors.

Ocular photoreceptor responses were recorded from Hermissenda exposed to compound conditioning, light conditioning, or one of several control treatments. Type A photoreceptors from light-conditioned animals responded with smaller generator potentials than those from untrained animals; type B photoreceptors from light-conditioned animals responded with greater generator potentials and action potential frequencies than cells from controls. These photoresponse changes were accompanied by increases and decreases in the input resistances of type B and A photoreceptors, respectively. The same photoresponse changes occurred in exaggerated form in cells from compound-conditioned animals, but no additional input resistance changes were observed. The results suggest that potentiation of phototactic suppression by compound conditioning involves a facilitation of the same photoreceptor excitability changes produced by mere pairings of light and rotation.

Animals↗
PubMed1997

Potentiation of phototactic suppression in Hermissenda by a chemosensory stimulus during compound conditioning.

Modifications of Hermissenda's phototactic behavior by compound pairings of light, scallop extract, and rotation were assessed. In general, the scallop extract potentiated phototactic suppression. Potentiation was dependent on (a) conjunctive presentations of scallop and light, (b) number of conditioning trials, and (c) scallop extract concentration. In related experiments, no second-order conditioning or sensory preconditioning of phototactic suppression was observed, indicating that within-compound associations did not contribute appreciably to potentiation. These results represent the first detailed analysis of compound conditioning in a mollusk using discrete presentations of well-characterized conditioned stimuli from distinct sensory modalities.

Animals↗
PubMed1997

Ionic basis of learning-correlated excitability changes in Hermissenda type A photoreceptors.

Repeated pairings of light and rotation (conditioning) result in persistent changes in excitability of Hermissenda type B and A photoreceptors, which are correlated with pairing-specific reductions in phototactic behavior. Although considerable attention has been devoted to characterization of conditioning-produced neurophysiological changes that occur in type B cells, less information is available concerning the changes produced in type A cells. Here we recorded from identified, synaptically isolated lateral and medial type A photoreceptors from conditioned, random-control, or untrained animals on retention days following conditioning. Type A photoreceptors from conditioned animals responded to light with a receptor potential that was significantly smaller than those of random-control or untrained animals, which did not differ. The phototactic suppression and type A cell light response magnitudes were negatively correlated for individual conditioned animals. Animals exhibiting strong phototactic suppression also showed small light responses. Expression of the training-associated light response difference was a calcium-dependent phenomenon: reducing extracellular calcium to < 1 microM enhanced the generator potential of A cells, regardless of conditioning history, and greatly reduced the differences in generator potential amplitude attributable to training. Voltage-clamp studies revealed that conditioning resulted in a two- to threefold increase in the amplitude of a voltage-dependent, sustained outward K+ current (I(Delayed)). I(Delayed) magnitudes were positively correlated with phototactic suppression for individual conditioned animals: type A cells of animals exhibiting strong phototactic suppression expressed large values of I(Delayed). I(Delayed) is a composite current, consisting of at least three separable components: 1) residual A current (I(A)); 2) slow, tetraethylammonium-sensitive calcium-activated K+ current (I(K-Ca)); and 3) a delayed-rectifier-type, voltage-dependent K+ current (I(K,v)). Analysis of these currents failed to reveal significant training-associated changes in I(A) or I(K-Ca). But I(K,v) was enhanced by approximately 60-150% in both lateral and medial cells and thus contributes to the conditioning-associated increase in I(Delayed).

Analysis of Variance↗
PubMed1996

The increase in spinal bone density that occurs in response to fluoride therapy for osteoporosis is not maintained after the therapy is discontinued.

In 44 osteoporotic subjects who had been treated with fluoride for 37 +/- 16 months, the fluoride was discontinued because they had shown fluoride-dependent increases in trabecular spinal bone densities from low initial levels (below the fracture threshold) to values that were equivalent to normal peak bone densities in the spines of young adults. During the subsequent period, after discontinuation of the fluoride therapy (i.e. 19 +/- 9 months), spinal bone density decreased in 73% of the subjects (i.e. 32 of 44, p < 0.03), at a rate that was comparable to the rate of the previous gain that had occurred during the treatment with fluoride (i.e. -3.23 +/- 2.39 mg/cm3 per month, compared with + 3.91 +/- 1.96 mg/cm3 per month in this, subgroup of patients, p < 0.001). Although 9 of the 44 subjects showed continuing increases in spinal bone density after discontinuation of the fluoride therapy, spinal bone density decreased in the entire group of 44 at an average rate of -1.02 +/- 4.72 mg/cm3 per month (p < 0.001, compared with the rate of the previous gain during the treatment with fluoride; i.e. +3.83 +/- 1.82 mg/cm3 per month). Surprisingly, our data showed that the rate of decrease in spinal bone density during the post-fluoride period was not affected by concurrent (undesigned) treatment with calcium, calcium plus estrogen, or calcium plus calcitriol. The cessation of fluoride therapy was also associated with a decrease in serum alkaline phosphatase activity (i.e. a decrease from the elevated levels that were observed during the period of fluoride therapy, back to the original, pre-treatment levels; p < 0.001), and that the rate of spinal bone loss after cessation of fluoride could be correlated with the prior rate of increase in serum alkaline phosphatase activity that had occurred during the treatment with fluoride (n = 44, r = 0.312, p = 0.039). Together, the observations from this retrospective analysis of data obtained from our clinical subjects suggest that fluoride-treated osteoporotic subjects who have exhibited increases in trabecular spinal bone density are at risk for bone loss after discontinuation of the fluoride therapy.

Adult↗
PubMed1995

Paradoxical effects of phosphate to directly regulate the level of skeletal alkaline phosphatase activity in human osteosarcoma (SaOS-2) cells and inversely regulate the level of skeletal alkaline phosphatase mRNA.

Recent studies indicate that the amount of alkaline phosphatase (ALP) activity in human osteoblast-line cells is proportional to the concentration of phosphate in the culture medium. The current studies were intended to extend those observations and to determine whether the effects of phosphate (and phosphate esters and analogs) to alter the cellular level of ALP activity, in human osteosarcoma SaOS-2 cells, reflected regulation at the level of transcription. Consistent with previous findings, we found direct, time- and dose-dependent correlations between the concentration of phosphate and the amount of ALP activity/mg cell protein (P < 0.05). Surprisingly, we also found a negative correlation between the phosphate concentration in the medium and the level of skeletal ALP mRNA (e.g., r = -0.98, P < 0.01 at 24 hours). As the highest cellular levels of skeletal ALP activity were associated with the lowest levels of ALP mRNA, these data indicated that the phosphate-dependent increase in ALP activity was not mediated by an increase in transcription and, conversely, that the effect of phosphate withdrawal to decrease ALP activity was not mediated by a decrease in transcription.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗
PubMed1995

Temporal location of unsignaled food deliveries: effects on conditioned withdrawal (inhibition) in pigeon signtracking.

Standard models of Pavlovian conditioning neglect local effects of unsignaled unconditioned stimuli (USs) on learning and performance. Using the approach-withdrawal behavior of pigeons toward keylights as conditioned stimuli (CSs), the authors varied the specific times (5-110 s) that USs occurred before or after a CS. Withdrawal from a CS generally increased as the time between a US before and/or after the CS was lengthened. Combinations of 2 distant USs produced more withdrawal from the CS than either US alone, whereas combinations of a distant and a nearby US yielded behavior intermediate between that for either US alone. Postacquisition retardation tests supported similar conclusions. Based on the temporal isolation of CSs and USs, a tentative model was offered to summarize these data. The results and the model suggest that a more molecular, possibly perceptual approach to Pavlovian excitation and inhibition is needed.

Animals↗
PubMed1995

Human bone cell phenotypes differ depending on their skeletal site of origin.

This report describes skeletal site-related differences in human osteoblastic cell metabolism in studies of four patients. Northern analyses of the constitutive growth factor messenger ribonucleic acid (mRNA) expression pattern in mandibular and iliac crest-derived human osteoblastic cells (based on within-patient comparisons) revealed higher mRNA levels for strong mitogenic growth factors such as basic fibroblast growth factor (bFGF) and insulin-like growth factor II (IGF-II) in the rapidly proliferating and less alkaline phosphatase (ALP)-expressing mandibular osteoblastic cells compared to those in the lower bFGF and IGF-II mRNA levels in slowly proliferating iliac human osteoblastic cells exhibiting a higher ALP expression level. In contrast, transforming growth factor-beta (TGF beta) mRNA was more abundant in iliac human osteoblastic cells than in mandibular osteoblastic cells. Furthermore, we found that there was a proportionality, based on data from both sites, between the level of constitutive TGF beta mRNA and the response to exogenously administered bFGF or IGF-II. A comparable pattern of growth characteristics and mRNA expression was also observed in transformed human osteoblastic cells that had been subcloned in sublines expressing high and low levels of the human osteoblastic differentiation marker ALP. These findings are consistent with 1) skeletal site-related differences in human bone cell phenotypes, and 2) decreased IGF-II and bFGF expression and increased TGF beta expression and responsiveness to bFGF and IGF-II in human bone cells exhibiting a high ALP expression.

Alkaline Phosphatase↗
PubMed1994

Mosquitoes or malaria? Rockefeller campaigns in the American South and Sardinia.

Most members of the International Health Division of the Rockefeller Foundation remained convinced that diseases were the fundamental cause of human poverty and underdevelopment and that destruction of the larval stages of vector mosquitoes was the cheapest and most effective way to eliminate one of the most important of such diseases, malaria. But the validity of both their assumptions remains in question despite campaigns in the American South and elsewhere during the 1920s and 1930s and an unsuccessful attempt at "species eradication" in Sardinia immediately after World War II.

Alabama↗
PubMed1993

Dibutyryl cyclic adenosine monophosphate differentially regulates cell proliferation in low and high alkaline phosphatase SaOS-2 human osteosarcoma cells: evidence for mediation by the insulin-like growth factor-II system.

In the present study, we have sought to determine whether a given signal transduction pathway can have diverse effects on subpopulations of cells of a lineage depending upon the stage of differentiation. To test this hypothesis, we selected the cyclic adenosine monophosphate (cAMP) signal transduction pathway because of its recognized importance in mediating the actions of many hormones, e.g., parathyroid hormone which acts on the bone-forming cells, the osteoblasts. Subpopulations of human osteosarcoma SaOS-2 cells with low (LSaOS) and high (HSaOS) alkaline phosphatase (ALP) content were chosen as model systems for preosteoblasts (pre-OB) and osteoblasts (OB), respectively. Dibutyryl cyclic AMP (DBcAMP) treatment of serum free cultures produced a differential effect on the proliferation of LSaOS cells (40 +/- 5% of control at 1 mM DBcAMP, P < 0.001) compared with HSaOS cells (no statistically significant effect). The finding supports the hypothesis. Next, we sought evidence for mediation, at least in part, by the insulin-like growth factor (IGF)-II regulatory system. We report that the basal expression of IGF-II, IGF binding protein (IGFBP)-3, and IGFBP-4 was higher in LSaOS cells than in HSaOS cells with the opposite true for type I IGF receptor. DBcAMP treatment of LSaOS cells decreased IGF-II and IGFBP-3 but increased IGFBP-4 and type I IGF receptor; no effect was observed for the type II IGF receptors. DBcAMP treatment of HSaOS cells had no detectable effect on IGF-II; IGFBP-3, or type I and type II IGF receptor expression; only IGFBP-4 expression increased with DBcAMP. These observations suggest that the differential regulation of cell proliferation by the cAMP signal transduction pathway may be mediated, at least in part, by the IGF-II regulatory system.

Alkaline Phosphatase↗
PubMed1993

Management of advanced ovarian epithelial cancer in the renal transplant patient.

Stage IIIC, grade 1 papillary serous adenocarcinoma of the ovary was diagnosed in a 28-year-old renal transplant recipient. She had been treated with the immunosuppressive agents azathioprine and methylprednisolone for 7 years prior to the discovery of the ovarian cancer. Surgical excision of the tumor was suboptimal due to involvement of the allograft; however, the patient achieved a complete clinical response after eight courses of cisplatin and cyclophosphamide. Since multiagent immunosuppressant therapy may have contributed to the development of the ovarian carcinoma, the intensity of immunosuppression was decreased by discontinuing the azathioprine as soon as the diagnosis of ovarian cancer was made. The methylprednisolone, however, was continued to decrease the possibility of organ rejection. After completion of chemotherapy, the patient was started on a daily regimen of low-dose oral cyclophosphamide as an immunosuppressant. Four months following the completion of cytotoxic therapy, she developed clinically evident disease in the pelvis. Subsequent salvage therapy with carboplatin failed. The patient died from progressive disease 26 months after initial diagnosis. She never developed evidence of renal rejection. Combined modality cancer therapy, preservation of allograft function, and modification of immunosuppressant therapy are important goals in the renal transplant patient with advanced ovarian carcinoma.

Adult↗
PubMed1992

Clinical surveillance of gynecologic cancer patients.

A survey of gynecologic oncologists was used to determine the optimum follow-up plan for asymptomatic, disease-free patients previously treated for a gynecologic malignancy. Ninety-four (91%) of 103 questionnaires were completed and returned. The majority of respondents recommended a clinic visit for these patients every 3 months for the first year after the completion of therapy, every 3 or 4 months for the second year, every 6 months for the following 3 years, and then annually after this initial 5-year period. Breast, abdominal, lymph node, and pelvic examinations, as well as a pap smear and stool guaiac, were done at each of these clinic visits. A yearly chest X ray was performed by the majority of the survey respondents for the first 3 years following initial treatment. Determinations of serum CA-125 and ovarian germ cell tumor markers were done at each follow-up appointment during the first 5 years after therapy if they were previously elevated. The patients' smoking habits were discussed with them by the majority of respondents. Mammograms were performed periodically before age 50 and then yearly after age 50 by most respondents. Serum cholesterol determinations were accomplished every 5 years or more frequently if indicated. Calcium supplementation was recommended for postmenopausal patients. The majority of respondents did not recommend routine vitamin supplementation or surveillance sigmoidoscopy.

Ambulatory Care↗
PubMed1991

Adverse reactions to the preschool (fifth) dose of adsorbed diphtheria-pertussis-tetanus vaccine in Canadian children.

OBJECTIVE: To quantify accurately the rate of adverse reactions after the preschool (fifth) dose of adsorbed diphtheria toxoid-pertussis vaccine-tetanus toxoid (DPT) vaccine and to test the hypothesis that large local reactions are attributable to the diphtheria toxoid. DESIGN: Double-blind randomized controlled trial. SETTING: Suburban community public health unit. PARTICIPANTS: Healthy children 4 to 5 years of age with a history of having received four doses of adsorbed DPT vaccine. INTERVENTIONS: Subjects were given either the standard DPT vaccine (with 25 Lf units of diphtheria toxoid) or a modified DPT vaccine (with 10 Lf units of diphtheria toxoid). They were assessed 24 hours later by a nurse. Serum samples obtained before vaccination were tested for diphtheria and tetanus antitoxin levels by means of neutralization assay and enzyme-linked immunosorbent assay. MAIN OUTCOME MEASURES: Rates of large local reactions (an area of redness or swelling or both of 5 cm or greater) 24 hours after vaccination in the two groups. Relation between serum antitoxin levels before vaccination and the rate of large local reactions in each group. RESULTS: Of the 250 subjects enrolled 124 received the standard vaccine and 126 the modified one. Large local reactions occurred in 71% of the subjects receiving the standard vaccine and 52% of those receiving the modified one (p less than 0.01). In the former group large erythematous reactions occurred significantly more often in those with an elevated prevaccination diphtheria antitoxin level than in those without an elevated level; no relation was found between such reactions and the prevaccination tetanus antitoxin level. Reduced arm movement was evident in 45% of the children in the two groups. Few had systemic adverse reactions. CONCLUSIONS: Large local reactions occur frequently after the preschool administration of the DPT vaccine. These reactions are uncomfortable but not serious. They result in part from the large amount of diphtheria toxoid in the standard DPT vaccine.

Child, Preschool↗