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Biomedical subjects

J Hale

Publications and source records attributed to J Hale.

At least 19 recordsLinked to original sources
PubMed2000

In vivo demonstration that human parathyroid hormone 1-38 inhibits the expression of osteoprotegerin in bone with the kinetics of an immediate early gene.

Osteoprotegerin (OPG) is a potent inhibitor of osteoclast formation and function. To elucidate how OPG is regulated in bone, we examined (1) the expression and localization of OPG protein in bone tissue, (2) the effect of human parathyroid hormone 1-38 (hPTH 1-38) on OPG messenger RNA (mRNA) levels in rat femur metaphyseal and diaphyseal bone, and (3) the effect of hPTH(1-38) on expression of OPG mRNA in cultured osteoblast-like cells derived from the metaphysis and diaphysis, and in ROS 17/2.8 osteosarcoma cells. Because PTH has been shown to stimulate osteoblast activity via the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signal transduction pathway we also investigated whether PTH action on OPG in vivo is dependent on activation of cAMP/PKA pathway. Immunohistochemistry was used to evaluate OPG protein expression and Northern blot hybridization was used to analyze OPG mRNA expression both in vivo and in vitro. Immunohistochemistry of OPG protein expression in the rat distal femur metaphysis revealed that it was localized predominantly in preosteoblasts, osteoblasts, lining cells, and the osteoid layer, with occasional immunoreactivity in osteocytes and cells of the bone marrow. Subcutaneous (sc) administration of a single injection of hPTH(1-38) at 80 microg/kg induced a rapid and transient decrease in OPG mRNA expression in both metaphyseal and diaphyseal bone. The decrease in OPG message was evident by 1 h and mRNA levels returned to baseline after 3 h. PTH analog PTH(1-31), which stimulates intracellular cAMP accumulation, inhibited OPG expression, whereas PTH analogs (3-34 and 7-34) that do not stimulate cAMP production had no effect on expression. In contrast to PTH, prostaglandin E2 (PGE2) had no effect on OPG mRNA expression in vivo in the metaphyseal bone cells, under conditions in which PGE2 does promote expression of the c-fos gene. The in vivo effects of hPTH(1-38) on OPG mRNA were confirmed in isolated primary osteoblast cultures derived from either metaphyseal or diaphyseal bone as well as in ROS 17/2.8 osteosarcoma cells. We propose that the rapid and transient decrease in OPG expression may initiate a cascade of events resulting in the differentiation of osteoclast progenitor. Such a spatially and temporally programmed effect of PTH might contribute to bone turnover.

Animals↗
PubMed1998

Laparoscopic cryoablation of hepatic metastases.

OBJECTIVE: To evaluate the feasibility of laparoscopic cryoablation for the management of hepatic metastases. DESIGN: Retrospective review. SETTING: Tertiary referral center. PATIENTS: Nine patients were evaluated by laparoscopy for planned laparoscopic cryoablation of hepatic metastases at The Cleveland Clinic Foundation, Cleveland, Ohio, from April 1996 to May 1997. RESULTS: Laparoscopic exploration revealed diffuse extrahepatic disease not identified by preoperative studies in 2 patients. The remaining 7 patients underwent 9 cryotherapy sessions. During 4 of the cryotherapy sessions, ultrasonography demonstrated unrecognized additional treatable hepatic lesions. An average of 3 lesions (range, 2-5) were treated. Operative time averaged 3.5 hours with a mean intraoperative blood loss of 235 mL. One patient had significant intraoperative hemorrhage requiring conversion to open hepatic resection for bleeding control. Eight of the 9 patients tolerated normal diets and ambulated independently on the first postoperative day. Following cryotherapy, 4 of the patients developed fever without an infectious source. One patient developed a postoperative bile leak requiring percutaneous biliary stenting. Postoperative hospital stay averaged 4.5 days (median, 4 days; range, 2-14 days). At a mean follow-up of 9 months, 4 of the 7 patients treated are alive without evidence of disease, 2 are alive with disease, and 1 patient with a pancreatic primary tumor has died of disease. CONCLUSIONS: Laparoscopy with laparoscopic ultrasonography is a useful tool in evaluating patients with hepatic metastases. Laparoscopic cryoablation is feasible and may result in lower postoperative morbidity in patients receiving aggressive treatment for inoperable hepatic metastases.

Cryosurgery↗
PubMed1998

Mate choice and mate competition influence male body size in Japanese medaka.

A sexual size dimorphism usually occurs when size-dependent reproductive advantages exist in only one sex. Studies on Japanese medaka, Oryzias latipes, have demonstrated reproductive size advantages in females but not in males, even though males and females are similar in body size. We conducted mate-choice and mate-copying tests in which a female could first associate with, then mate with, either a large (>/=1 sd+X standard length) or a small male (</=1 sd-X standard length). Large males obtained a mating advantage in both tests, and both mate choice and mate competition influenced their mating success. In the majority of trials, females associated with large males. Association preferences of females corresponded to their mating preferences when mate competition between males was weak; however, when mate competition was strong, large males obtained almost every mating regardless of female association preference. Preference for large males may provide females with a reproductive advantage if males mate multiply because small males become sperm-depleted sooner than large males. We found no indication that females copied the mating decisions of other females. Repeatability of female mating preference was low, not because females mated at random with respect to male size, but because most females consistently preferred large males. We also conducted mating tests at four density levels and found that large males maintained their mating advantage relative to small males at all densities. Thus, male and female medaka may be similar in body size because large size provides a fecundity advantage for females, as demonstrated in previous studies, and large size provides a mating advantage for males, as demonstrated in our study. Copyright 1998 The Association for the Study of Animal Behaviour. Copyright 1998 The Association for the Study of Animal Behaviour.

Journal Article↗
PubMed1998

Renal cryosurgery: experimental evaluation of treatment parameters.

OBJECTIVES: Cryosurgery represents a minimally invasive alternative for the management of small or equivocal lesions of the kidney. We evaluated the relationship between ultrasonographic appearance and intrarenal temperatures and the effect of renal artery occlusion on the efficacy of the freezing process in a canine model. METHODS: Ten animals were treated with intraparenchymal cryoablative therapy with (n = 5) or without (n = 5) renal artery occlusion using a rapid freeze technique. Intrarenal temperatures were measured 1.0 cm away from the cryoprobe at various times during the freezing process. The distance from the cryoprobe to the ice ball as monitored by ultrasonography was also determined. The contralateral kidney was removed to facilitate studies of renal function and all animals were killed on day 28 for autopsy and histopathologic examination. RESULTS: A target temperature of less than -20 degrees C was achieved 3.1 mm behind the ice ball in all animals tested. The ice ball stabilized at a radius of 16 mm with prolonged treatment, suggesting that multiple probes will be required to treat renal lesions greater than 2.5 cm in diameter. Renal artery occlusion did not significantly alter the freezing process and provided no practical advantage. Renal function remained stable (final serum creatinine level 1.5 mg/dL or less) in all but 1 animal in which an obstructive stricture of the ureteropelvic junction developed. Effective tissue ablation was confirmed at the treatment site in all instances. CONCLUSIONS: Renal cryoablative therapy is a nephron-sparing modality that can be delivered in a safe, efficacious, and reproducible manner. The treatment parameters defined in this study should allow for intelligent patient selection and rational administration of renal cryotherapy.

Animals↗
PubMed1998

Laparoscopic renal cryoablation: initial clinical series.

OBJECTIVES: To present the technique and short-term results of retroperitoneal laparoscopic renal cryoablation. METHODS: Ten patients underwent laparoscopic renal cryoablation of 11 exophytic renal tumors ranging in size from 1.5 to 3 cm identified on computed tomography. Tumors were located at the upper (3), middle (5), or lower (3) pole of the kidney. Three patients had a solitary kidney. A 3-port retroperitoneal laparoscopic approach was used to create renal cryolesions. Puncture cryoablation was performed with a 4.8-mm cryoprobe. Real-time, endoscopic, steerable, color Doppler ultrasound was used to monitor the evolving cryolesion. All patients have completed a minimum follow-up of 3 months (mean 5.5, range 3 to 9). RESULTS: Cryoablation was technically successful in all 10 patients (11 tumors). Under ultrasound guidance, the ice ball was intentionally created up to 1 cm beyond the tumor edge with the aim of achieving negative margins. Mean surgical time was 2.4 hours, cryoablation (double freeze-thaw) time 12.9 minutes, cryoprobe tip temperature -186 degrees C, and blood loss 75 mL. Systemic temperature remained unaltered. Hospital stay was less than 23 hours in 9 of 10 patients. Follow-up magnetic resonance imaging at 1 day and 1, 2, and 3 months identified the punched-out, nonenhancing, spontaneously resorbing, renal cryolesion. Follow-up biopsies of the cryoablated tumor site were negative for cancer in the 3 patients who have undergone the biopsy. CONCLUSIONS: The initial series of laparoscopic renal cryoablation is presented. The retroperitoneoscopic approach, by avoiding the peritoneal cavity, minimizes the chances of the bowel coming in contact with the evolving cryolesion, and the potential sequelae thereof. Laparoscopic renal cryoablation is currently developmental and long-term data are awaited. Nevertheless, it is potentially an attractive addition to available nephron-sparing surgical techniques.

Aged↗
PubMed1998

An exploration of GPs' use of MRI: a critical incident study.

BACKGROUND: Direct access to Magnetic Resonance Imaging (MRI) is becoming available to GPs in the UK, offering major benefits for the improved diagnosis and management of certain clinical conditions. Variations in usage of this service may be large, and effective locally produced guidelines are not currently available. The Department of General Practice is conducting a research programme to develop and evaluate methods to optimize MRI use by GPs. OBJECTIVES: We aimed to describe the current use of MRI by GPs in South Glamorgan; to summarize their reasons for requesting MRI; and to produce criteria to assess the appropriateness of magnetic resonance (MR) scan requests. METHODS: Using the critical incident technique, 25 GPs were interviewed about recent scans requested for patients with knee and lumbar spine complaints. A local panel of primary and secondary care doctors was convened to develop criteria for assessing MR scan requests. RESULTS: Sixty-two scan requests were discussed. Doctors' reasons for requesting MR scans were identified and classified. Reasons for requests included personal, contextual and biomedical variables. Fifteen patients (24%) were managed in primary care following MRI when otherwise they would have been referred. When referrals were made, GPs felt able to reinforce the request and occasionally to direct the patient somewhere more appropriate. The panel reviewed the interview data to produce objective criteria to assess scan requests. The criteria reflect the relative importance of non-biomedical variables in the decision to request MRI. CONCLUSION: The study identified those reasons which are important to GPs when requesting MR scans and the impact of this new technology upon patient management. Interview data have been used to inform locally developed consensus criteria, which will be made available as practice guidelines as the research programme progresses.

Aged↗
PubMed1997

The role of intraoperative ultrasonography during laparoscopic adrenalectomy.

BACKGROUND: The role of laparoscopic intraoperative ultrasonography (IOUS) in intraoperative decision making has grown rapidly in recent years. The purpose of this study was to evaluate its usefulness during laparoscopic adrenalectomy. METHODS: Since 1995, laparoscopic ultrasonography has been used to evaluate the adrenal gland and surrounding organs in selective laparoscopic adrenalectomies. IOUS was performed in 19 of 114 laparoscopic adrenalectomies. RESULTS: IOUS effected a change in management in 68% of these patients. IOUS displayed the location of the gland after a failed attempt at open resection; the adrenal vein, expediting control in four operations; no extraadrenal involvement by two large lesions (benign); vascular invasion in one tumor (carcinoma), prompting open resection; periadrenal invasion by one metastatic cancer and lymph node involvement in another; a 7 mm hyperaldosteronoma; no adenoma in two cases; bilateral hyperplasia; and a 14 cm cyst originating from the adrenal gland. IOUS facilitated partial adrenalectomy in two patients and revealed centrally located adenomas in two others requiring total adrenalectomy. CONCLUSIONS: Laparoscopic IOUS during adrenal operation is valuable in selected cases. It is helpful to locate the gland and vein, confirm the presence or absence of abnormality, discern the resectability of large masses, and facilitate a partial adrenalectomy when desirable.

Adrenal Glands↗
PubMed1996

Evidence of free and bound leptin in human circulation. Studies in lean and obese subjects and during short-term fasting.

Little is known about leptin's interaction with other circulating proteins which could be important for its biological effects. Sephadex G-100 gel filtration elution profiles of 125I-leptin-serum complex demonstrated 125I-leptin eluting in significant proportion associated with macromolecules. The 125I-leptin binding to circulating macromolecules was specific, reversible, and displaceable with unlabeled leptin (ED50: 0.73 +/- 0.09 nM, mean +/- SEM, n = 3). Several putative leptin binding proteins were detected by leptin-affinity chromatography of which either 80- or 100-kD proteins could be the soluble leptin receptor as approximately 10% of the bound 125I-leptin was immunoprecipitable with leptin receptor antibodies. Significantly higher (P < 0.001) proportions of total leptin circulate in the bound form in lean (46.5 +/- 6.6%) compared with obese (21.4 +/- 3.4%) subjects. In lean subjects with 21% or less body fat, 60-98% of the total leptin was in the bound form. Short-term fasting significantly decreased basal leptin levels in three lean (P < 0.0005) and three obese (P < 0.005) subjects while refeeding restored it to basal levels. The effects of fasting on free leptin levels were more pronounced in lean subjects (basal vs. 24-h fasting: 19.6 +/- 1.9 vs. 1.3 +/- 0.4 ng/ml) compared with those in obese subjects (28.3 +/- 9.8 vs. 14.7 +/- 5.3). No significant (P > 0.05) decrease was observed in bound leptin in either group. These studies suggest that in obese individuals the majority of leptin circulates in free form, presumably bioactive protein, and thus obese subjects are resistant to free leptin. In lean subjects with relatively low adipose tissue, the majority of circulating leptin is in the bound form and thus may not be available to brain receptors for its inhibitory effects on food intake both under normal and food deprivation states.

Carrier Proteins↗
PubMed1996

Astrocytes infected with replication-defective adenovirus containing a secreted form of CNTF or NT3 show enhanced support of neuronal populations in vitro.

Neurotrophic factors have been shown to ameliorate neuronal death in several in vitro and in vivo models of neurodegenerative disease. However, delivery of polypeptide growth factors to compromised neurons in the CNS is problematic as the blood-brain barrier prevents systemic delivery, and chronic in-dwelling cannulae are required for intraparenchymal delivery. To circumvent these problems and specifically target neurotrophic factors to the environment surrounding degenerating neurons in the CNS, we have generated replication-defective adenovirus (Ad) vectors that contain a secretable form of ciliary neurotrophic factor (sCNTF) or neurotrophin-3 (NT-3). In this study, we demonstrate that sCNTF/Ad and NT-3/Ad can efficiently infect primary astrocytes, resulting in gene transcription and the production of functional protein. Using Northern blot analysis, dose-dependent expression of sCNTF or NT-3 mRNA was detected 7 days after infection. The levels of mRNA expressed in transgenic astrocytes was dependent on virus titer and increased with increasing virus concentration. sCNTF or NT-3 protein was also detected in astrocyte supernatants by immunoblot analysis and 2-site ELISA. ELISA indicated that astrocytes infected with sCNTF/Ad or NT-3/Ad secreted neurotrophic factors at a rate of approximately 120 pg/10(6) cells/h and 350 pg/10(6) cells/h, respectively. To test for secretion of bioactive sCNTF or NT-3 protein, E8 chick ciliary ganglion or nodose ganglion neurons were grown in medium conditioned by control astrocytes or astrocytes treated with sCNTF/Ad or NT-3/Ad, showing a robust and dose-dependent increase in neuronal survival when compared to control supernatant. In addition, motor neurons plated onto astrocyte monolayers pretreated with sCNTF/Ad showed a two- to fourfold increase in ChAT activity when compared to those grown on astrocytes pretreated with Lac-Z/Ad. This study demonstrates that, using replication-defective adenovirus, primary astrocytes can be efficiently engineered to secrete bioactive sCNTF or NT-3, resulting in enhanced survival of responsive peripheral and central neuronal populations.

Adenoviridae↗
PubMed1996

Intraoperative evaluation of renal cell carcinoma: a prospective study of the role of ultrasonography and histopathological frozen sections.

PURPOSE: Nephron sparing surgery is being performed increasingly for treatment of renal cell carcinoma, including in select patients with a normal contralateral kidney. The number of tumors in the involved kidney (single versus multiple) and presence or absence of perinephric fat involvement (pathological stage T1 to 2 versus T3A) are important prognostic factors. In a prospective study we evaluated the accuracy of intraoperative histopathological frozen section analysis of renal capsular biopsies for assessing local tumor stage, and the accuracy of intraoperative ultrasonography for assessing tumor focality. MATERIALS AND METHODS: Intraoperative frozen section biopsies and ultrasonography were compared with information obtained from preoperative computerized tomography (CT), intraoperative inspection of the kidney by the surgeon and permanent histopathological specimens. RESULTS: We evaluated 99 patients (102 kidneys) with localized sold renal masses undergoing either radical nephrectomy (48) or nephron sparing surgery (54). Final pathological analysis revealed 95 renal cell carcinomas (stage T3A in 24), 6 oncocytomas and 1 angiomyolipoma. Multiple tumors were detected in 18 of 102 kidneys overall. Frozen section analysis identified 87% of the stage T3A lesions with no false-positive results, compared to CT, which only identified 67%. Ultrasonography identified 14 of 18 multifocal tumors (78%) and was not more accurate than the combination of CT and intraoperative inspection. However, during nephron sparing surgery ultrasonography was useful to localize the intrarenal extent of tumors (17 cases). CONCLUSIONS: Our results clarify the role of intraoperative ultrasonography and frozen section analysis in patients undergoing nephron sparing surgery for renal cell carcinoma. Frozen section analysis may be useful in select patients with small peripheral tumors who are under consideration for elective nephron sparing surgery.

Carcinoma, Renal Cell↗
PubMed1996

Causes of owl mortality in Hawaii, 1992 to 1994.

Eighty-one barn owls (Tyto alba) and five Hawaiian owls or pueo (Asio flammeus sandwichensis) from Kauai, Oahu, Lanai, Molokai, Maui and Hawaii (USA) were evaluated for cause of death, November 1992 through August 1994. The most common cause of death in barn owls was trauma (50%) followed by infectious disease (28%) and emaciation (22%). Most traumas apparently resulted from vehicular collisions. Trichomoniasis was the predominant infectious disease and appeared to be a significant cause of death in barn owls in Hawaii. Pasteurellosis and aspergillosis were encountered less commonly. No predisposing cause of emaciation was detected. Stomach contents from 28 barn owls contained mainly insects (64%) of the family Tetigoniidae and Gryllidae, and rodents (18%); the remainder had mixtures of rodents and insects or grass. Three pueo died from trauma and one each died from emaciation and pasteurellosis. We found no evidence of organochlorine, organophosphorus, or carbamate pesticides as causes of death in pueo or barn owls.

Animals↗
PubMed1995

The role of neuropeptide Y in the antiobesity action of the obese gene product.

Recently Zhang et al. cloned a gene that is expressed only in adipose tissue of the mouse. The obese phenotype of the ob/ob mouse is linked to a mutation in the obese gene that results in expression of a truncated inactive protein. Human and rat homologues for this gene are known. Previous experiments predict such a hormone to have a hypothalamic target. Hypothalamic neuropeptide Y stimulates food intake, decreases thermogenesis, and increases plasma insulin and corticosterone levels making it a potential target. Here we express the obese protein in Escherichia coli and find that it suppresses food intake and decreases body weight dramatically when administered to normal and ob/ob mice but not db/db (diabetic) mice, which are thought to lack the appropriate receptor. High-affinity binding was detected in the rat hypothalamus. One mechanism by which this protein regulated food intake and metabolism was inhibition of neuropeptide-Y synthesis and release.

Animals↗
PubMed1995

An algorithm for MR angiography image enhancement.

This study describes a three-dimensional (3D) filtering algorithm for magnetic resonance angiography (MRA) image enhancement. Based on the properties of 3D MRA data, the algorithm uses the dispersion range of the 13 outputs of a 3D directional low-pass filter bank to identify the vessel structure and control the processing of MRA data. Vascular structures in the data are preserved while the components of static tissues and isolated noise impulses are reduced by the processing. As a result, the small vessels have been enhanced and visibility of vessels in the projected image has been improved.

Algorithms↗
PubMed1995

Trends in susceptibility of Neisseria gonorrhoeae to ceftriaxone from 1985 through 1991.

The antimicrobial susceptibilities of 16,441 gonococcal isolates from Seattle-King County were determined for ceftriaxone, cefoxitin, penicillin G, and tetracycline. From 1985 to 1989, ceftriaxone, in combination with doxycycline, was increasingly used for treatment of gonorrhea, and by 1989, it was used as therapy for > 80% of cases in Seattle-King County. MICs of ceftriaxone correlated significantly (P < 0.001) with those of the other beta-lactam antibodies included in this study. Geometric mean MICs of penicillin G for isolates that did not produce beta-lactamase increased from 1985 to 1991. The geometric mean MICs of cefoxitin, ceftriaxone, and tetracycline began to decline in 1987 but increased in 1990 and 1991. The percentage of strains with decreased susceptibility to ceftriaxone (MIC, 0.06 to 0.25 microgram/ml) rose from 0.3% in 1985 to 5.3% in 1987 but subsequently declined steadily to 2.6% in 1991, despite increased use of ceftriaxone as routine therapy for gonorrhea. Changes in patterns of antimicrobial susceptibility may be related not only to antimicrobial selection pressures but also to less well understood population shifts among Neisseria gonorrhoeae strains within a community.

Ceftriaxone↗