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V Goldberg

Publications and source records attributed to V Goldberg.

At least 19 recordsLinked to original sources
PubMed2004

Estradiol stimulates vascular endothelial growth factor and interleukin-6 in human lactotroph and lactosomatotroph pituitary adenomas.

Estrogens are considered to be critically involved in lactotroph and lactosomatotroph pituitary tumor development. In addition to direct effects, estradiol-induced tumor formation may involve alterations in growth factor and cytokine production. We have studied whether estradiol stimulates the production of the angiogenic vascular endothelial growth factor and the potential tumor progression factor interleukin-6 in 5 lactotroph (LA) and 5 lactosomatotroph (LSA) human pituitary adenoma cell cultures. All tumors secreted heterogenous basal amounts of VEGF (18.0 +/- 1.4 to 425 +/- 26 pg/ml per 24 h) and IL-6 (18.1 +/- 1.5 to 604 +/- 17 pg/ml per 24 h). Estradiol (100 nM) significantly enhanced VEGF release in all LA and LSA cell cultures (47 to 168 % above basal). IL-6 secretion was stimulated in 3 out of 5 LA and in all LSA cell cultures (31 to 287 % above basal). In cell cultures obtained from tumors from which sufficient cells could be isolated, a dose-dependent effect of estradiol (1 to 100 nM) on VEGF and IL-6 production was observed. Stimulation of IL-6 and/or VEGF secretion by estradiol in the majority of human lactotroph and lactosomatotroph adenoma cell cultures studied, suggests that estrogens may contribute to adenoma expansion through the stimulation of these auto-/paracrine-acting adenoma progression factors.

Adult↗
PubMed2001

Effects of the gp130 cytokines ciliary neurotropic factor (CNTF) and interleukin-11 on pituitary cells: CNTF receptors on human pituitary adenomas and stimulation of prolactin and GH secretion in normal rat anterior pituitary aggregate cultures.

Two of the most potent cytokines regulating anterior pituitary cell function are leukemia inhibitory factor (LIF) and interleukin (IL)-6, which belong to the cytokine family using the common gp130 signal transducer. Recently, the expression and action of two other members of this family, IL-11 and ciliary neurotrophic factor (CNTF), on different cell lines has also been demonstrated. We studied the expression of the specific receptor subunits for CNTF in mammotropic, non-functioning and somatotropic tumors and the action of CNTF and IL-11 in the regulation of hormone secretion in these and normal pituitary cells. The mRNA for the alpha chain specific for the CNTF receptor was detected by Northern blot in tumors secreting prolactin (PRL) and GH and in non-functioning tumors. We found that both IL-11 and CNTF exerted a similar stimulatory effect on GH mRNA expression in somatotropic monolayer cell cultures from acromegalic tumors, but these cytokines had no significant influence on GH secretion. CNTF stimulates prolactin secretion in lactotropic monolayer cell cultures from patients with prolactinoma. In monolayer cell cultures from normal rat anterior pituitary, IL-11 and CNTF had no significant effect on the release of either GH or PRL, or on GH mRNA. However, when the cells were cultured in aggregate cultures, in which the three-dimensional structure of the cells is reconstituted, both cytokines, in doses at which they had no effect on monolayer cultures, significantly stimulated both PRL and GH secretion. These data show that IL-11 and CNTF may act as regulatory factors in anterior pituitary cells, in which the three-dimensional structure of the gland is of critical importance.

Adenoma↗
PubMed2000

Osteoarthritis: new insights. Part 2: treatment approaches.

Osteoarthritis is the most common form of arthritis, affecting millions of people in the United States. It is a complex disease whose etiology bridges biomechanics and biochemistry. Evidence is growing for the role of systemic factors, such as genetics, diet, estrogen use, and bone density, and local biomechanical factors, such as muscle weakness, obesity, and joint laxity. These risk factors are particularly important in the weight-bearing joints, and modifying them may help prevent osteoarthritis-related pain and disability. Major advances in management to reduce pain and disability are yielding a panoply of available treatments ranging from nutriceuticals to chondrocyte transplantation, new oral anti-inflammatory medications, and health education. This article is part 2 of a two-part summary of a National Institutes of Health conference that brought together experts in osteoarthritis from diverse backgrounds and provided a multidisciplinary and comprehensive summary of recent advances in the prevention of osteoarthritis onset, progression, and disability. Part 2 focuses on treatment approaches; evidence for the efficacy of commonly used oral therapies is reviewed and information on alternative therapies, including nutriceuticals and acupuncture, is presented. Biomechanical interventions, such as exercise and bracing, and behavioral interventions directed toward enhancing self-management are reviewed. Current surgical approaches are described and probable future biotechnology-oriented approaches to treatment are suggested.

Acupuncture Therapy↗
PubMed2000

The relationship between the clinical performance and large deformation mechanical behavior of retrieved UHMWPE tibial inserts.

Many aspects of the proposed relationship between material properties and clinical performance of UHMWPE components remain unclear. In this study, we explored the hypothesis that the clinical performance of tibial inserts is directly related to its large-deformation mechanical behavior measured near the articulating surface. Retrieval analysis was performed on three conventional UHMWPE and three Hylamer-M tibial components of the same design and manufacturer. Samples of material were then obtained from the worn regions of each implant and subjected to mechanical characterization using the small punch test. Statistically significant relationships were observed between the metrics of the small punch test and the total damage score and the burnishing damage score of the implants. We also examined the near-surface morphology of the retrievals using transmission electron microscopy. TEM analysis revealed lamellar alignment at and below the wear surfaces of the conventional UHMWPE retrievals up to a maximum depth of approximately 8 microm, consistent with large-deformation crystalline plasticity. The depth of the plasticity-induced damage layer varied not only between the retrievals, but also between the conventional UHMWPE and Hylamer-M components. Thus, the results of this study support the hypothesis that the clinical performance of UHMWPE tibial inserts is related to the large-deformation mechanical behavior measured near the articulating surface.

Biocompatible Materials↗
PubMed2000

Interleukin-6 is inhibited by glucocorticoids and stimulates ACTH secretion and POMC expression in human corticotroph pituitary adenomas.

Interleukins and their receptors are expressed intrinsically in the anterior pituitary and regulate hormone production and cell proliferation. It has previously been shown that interleukin-6 (IL-6) regulates hormone secretion in normal pituitary cells and cell lines. Here we examined the effects of IL-6 on propiomelanocortin (POMC) expression and ACTH production in corticotroph adenoma cells in vitro. We found that IL-6 stimulates both ACTH secretion and POMC gene expression in corticotroph adenoma cell cultures. This first demonstration of the stimulatory action of IL-6 on human corticotroph adenoma cell function provides further evidence for a direct action of IL-6 on corticotroph pituitary cells. We have confirmed previous reports of IL-6 production by corticotroph adenoma cells and in addition, demonstrated for the first time that the synthetic glucocorticoid dexamethasone is a potent suppressor of intratumoral IL-6 production. This intratumoral produced IL-6 may be in part responsible, in an autocrine manner, for the stimulation of ACTH synthesis and secretion. Our results suggest that IL-6 might play a role in the pathogenesis of Cushing's disease. However, elevated glucocorticoid levels in patients with Cushing's disease may prevent excessive action of IL-6 on ACTH production and tumor progression of corticotroph adenomas in vivo.

Adenoma↗
PubMed2000

The gp130 cytokines interleukin-11 and ciliary neurotropic factor regulate through specific receptors the function and growth of lactosomatotropic and folliculostellate pituitary cell lines.

Two of the most potent cytokines regulating anterior pituitary cell function are leukemia inhibitory factor and interleukin-6 (IL-6), which belong to the cytokine receptor family using the common gp130 signal transducer. We studied the actions of two other members of this family, IL-11 and ciliary neurotropic factor (CNTF), on folliculostellate (FS) cells (TtT/GF cell line) and lactosomatotropic cells (GH3 cell line). The messenger RNA (mRNA) for the alpha-chain specific for the IL-11 receptor (1.7 kb) and CNTF receptor (2 kb) are expressed on both cell types. In addition, we detected CNTF receptor mRNA in normal rat anterior pituitary cells. IL-11 (1.25-5 nM) dose dependently stimulated the proliferation of FS cells. CNTF, at doses from 0.4-2 nM, also significantly stimulated the growth of these cells. In addition, both cytokines significantly stimulated proliferation of lactosomatotropic GH3 cells, and CNTF stimulated hormone production (GH and PRL) at 24 h by these cells. At 16-72 h, IL-11 stimulates the secretion of the angiogenic factor vascular endothelial growth factor by FS cells. In addition, both GH3 and FS cells express CNTF mRNA. These data suggest that IL-11 and CNTF may act as growth and regulatory factors in anterior pituitary cells.

Animals↗
PubMed2000

High levels of matrix metalloproteinases regulate proliferation and hormone secretion in pituitary cells.

Beside the digestion of the extracellular matrix during tumor invasion and metastasis, more recently, new functions for matrix metalloproteinases (MMPs) have been proposed. We studied the expression and function of these enzymes in pituitary cells. We observed the activities of MMP-2 and MMP-9 together with expression of membrane-type MMP and tissue inhibitor of metalloproteinase-1 in all types of human pituitary adenomas. We found surprisingly high levels of MMP activity and low levels of tissue inhibitor of metalloproteinases, indicating a high level of extracellular matrix-degrading activity in pituitary adenomas. To examine the function of metalloproteinase activity in pituitary cells we used the synthetic MMP inhibitor batimastat. These studies demonstrate that MMPs secreted by pituitary cells can release growth factors anchored to the extracellular matrix that, in turn, control pituitary cell proliferation and hormone secretion. These results define a new additional mechanism for the control of pituitary hormone secretion and indicate new potential therapeutic targets for pituitary adenomas.

Adenoma↗
PubMed1999

Engineering of osteochondral tissue with bone marrow mesenchymal progenitor cells in a derivatized hyaluronan-gelatin composite sponge.

The aim of this study was to investigate the potential of a composite matrix, containing esterified hyaluronic acid and gelatin, to facilitate the osteochondral differentiation of culture-expanded, bone marrow-derived mesenchymal progenitor cells. The cell loading characteristics and the effects of the matrix on cell differentiation were examined in vitro and in vivo. Empty and cell-loaded composites were cultivated for up to 28 days in a chemically defined medium with or without transforming growth factor-beta1 (TGF-beta1). A type II collagen-rich extracellular matrix was produced by cells loaded in the matrix and cultured in the presence of TGF-beta1. Empty and cell-loaded matrices were also implanted subcutaneously in immunodeficient mice. Three types of implant were used: empty (group I), cell-loaded matrices (Group II), and cell-loaded matrices cultured for 14 days in vitro in defined medium with TGF-beta1 (group III). No osteochondral differentiation was found in implanted empty matrices; however, the matrix supported osteochondrogenic cell differentiation in the cell-loaded implants. Preculture in vitro in a chondrogenic medium increased the percentage of osteochondral tissue found in the constructs after 3 weeks. These results indicate the potential use of this composite matrix for delivery of bone marrow-derived mesenchymal progenitor cells for the repair of chondral and osseous defects. The results also indicate that this composite matrix is useful for in vitro tissue engineering.

Animals↗
PubMed1999

Fixation, polyethylene wear, and pelvic osteolysis in primary total hip replacement.

A multicenter retrospective review was performed analyzing 1081 primary total hip replacements in 944 patients using the Harris Galante-I cementless acetabular component with screw fixation. All patients were followed up for a minimum of 5 years with a mean followup of 81 months. Linear polyethylene wear averaged 0.11 mm/year (range, 0-0.86 mm/year). Pelvic osteolysis was seen in 25 patients (2.3%). Migration of the acetabular component was seen in four hips. A subgroup of patients was reanalyzed at a minimum followup of 10 years. The mean linear polyethylene wear rate remained 0.11 mm/year. In this group, only one socket had migrated. There was an association between wear rate and age. On average, younger patients had higher wear rates. The risk for having pelvic osteolysis develop and the need for revision surgery also was age-related. Twenty-two percent of hip replacements (15 hips) in patients younger than 50 years of age at the time of their index operation had pelvic osteolysis develop. In contrast, for patients older than 50 years of age at the time of surgery only 7.8% (eight hips) had osteolysis of the pelvis develop. For patients older than 70 years of age at the time of primary total hip replacement, none had pelvic osteolysis develop.

Adolescent↗
PubMed1998

Frozen section biopsy assessment for the presence of polymorphonuclear leukocytes in patients undergoing revision of arthroplasties.

Despite progress in techniques, early or late deep infection develops in 1 to 5% of patients with prosthetic joint replacements. We report a retrospective review of 64 original frozen sections (FSs) compared with permanent sections, the preoperative clinical and intraoperative findings, and the subsequent culture results. A histologic section, frozen or permanent, was considered positive for infection if there were more than five polymorphonuclear leukocytes (PMNs) per high power field, excluding surface fibrin and inflammatory exudate, in at least five separate microscopic fields. The sensitivity of an FS as a diagnostic test to detect prosthetic infection when present was 43%. The specificity of an FS to correctly identify the absence of infection was 97%. These data support the conclusion that the FS is reasonably specific but not a sensitive diagnostic modality. If the preoperative evaluation is completely negative and the FS does not reveal PMNs, the reimplantation can be performed with minimal concern regarding the possibility of infection. If the preoperative and intraoperative evaluations are completely negative but PMNs are observed in the FS, then the surgeon should consider proceeding with caution; the decision to proceed with reimplantation might be delayed, depending on the surgeon's clinical assessment.

Arthroplasty, Replacement, Hip↗
PubMed1996

Interleukin-2 (IL-2) and IL-6 regulate c-fos protooncogene expression in human pituitary adenoma explants.

We have previously shown that interleukin-2 (IL-2) and IL-6, which are expressed in the anterior pituitary, affect anterior pituitary cell proliferation in normal rats and cell lines. Here we examined their effects on the c-fos expression by human anterior pituitary adenomas. Adenoma cells in culture do not express c-fos mRNA. In adenoma explants, however, c-fos expression was detected and was regulated by IL-2 or IL-6. In different tumors (ACTH-, PRL-, GH-secreting and non functioning adenomas), these interleukins had inhibitory or stimulatory effects but the kind of response does not seem to be associated to tumor type or size. Using blocking antibodies, we observed that intrinsic IL-2 and IL-6 regulate c-fos expression in the same way. Our data suggest that IL-2 and IL-6 are not only involved in the regulation of pituitary adenoma function but may also, given the role of c-fos in cell proliferation, be implicated in the development of human pituitary adenomas.

Adenoma↗
PubMed1994

The effect of patient size and dose of recombinant human erythropoietin therapy on red blood cell volume expansion in autologous blood donors for elective orthopedic operation.

BACKGROUND: Recombinant human erythropoietin (EPO) therapy has been known to enhance erythropoiesis and facilitate autologous blood donation before elective orthopedic operations. However, the optimal EPO dose in this setting remains undefined. To help determine this, we have examined the effect of patient weight and EPO dose on red blood cell (RBC) volume expansion. STUDY DESIGN: Forty-six nonanemic autologous blood donors enrolled at our institution in two previously reported multicenter clinical trials were analyzed. Patients received either placebo or EPO (150, 300, or 600 units [U] per kg) given intravenously at each of six AB blood type donation visits. RESULTS: Total preoperative RBC volume expansion over a 22 day period was 465 +/- 135 mL (mean +/- SD) in patients receiving a placebo and 588 +/- 201 mL, 735 +/- 144 mL, and 881 +/- 292 mL in patients receiving graded concentrations of EPO. When RBC volume increase was corrected for patient weight and EPO dose, patients receiving placebo or EPO (150, 300, and 600 U per kg) expanded RBC volume by 5.9 mL per kg in patients receiving placebo and 7.9, 9.1, and 10.9 mL per kg in patients receiving EPO, respectively (p < 0.02 for each EPO group compared with placebo group). A direct relationship between EPO dose and RBC volume increase (response) over 22 days was determined by the linear regression equation: RBC volume (mL per kg) = 6.34 + 0.0013X, r = 0.98, where X equals total units EPO administered (per kg body weight). CONCLUSIONS: We conclude that EPO dose can be based on anticipated blood losses and transfusion needs in autologous blood donors before orthopedic operation.

Aged↗
PubMed1992

A semiquantitative scale for histologic grading of articular cartilage repair.

This laboratory has developed a semiquantitative scale for grading the natural healing process of defects drilled into articular cartilage. The scale is composed of four parameters: percent filling of the defect, reconstitution of the osteochondral junction, matrix staining and cell morphology; it has a score range from 0 (best) to 14 (worst). The scale was used to evaluate the healing of defects drilled into rabbit knee articular cartilage at 2, 14, 30, 60 and 120 days after surgery. No statistically significant difference in the graded score was found between the two different defect sizes (2.7 and 1.5 mm). However, the differences in score observed between specimens from different sacrifice times were significant (p less than 0.01). Currently many investigators are manipulating cartilaginous lesions in an attempt to improve healing, and this scale will provide a means for quantitatively comparing results from control and experimental groups.

Animals↗
PubMed1991

Glucocorticoids and adrenal androgens in children with end stage renal disease.

UNLABELLED: We studied the effects of chronic renal failure on the pituitary-cortisol axis and adrenal androgen function in 26 patients (16 male and 10 female), aged 6.5 to 22.5 years (mean 14.5). Ten patients were prepubertal, 8 pubertal, and 8 post-pubertal. All of them were on chronic hemodialysis. Pubic hair development was delayed in 56% of the patients. Serum cortisol was increased in 15 out of the 26 patients. Serum delta 4-androstenedione was high in 11 out of 15 patients in Tanner's stage I or II and in 1 out of 11 patients in Tanner's stage III, IV or V (p less than 0.01). Serum cortisol was elevated in 10 out of 12 patients with high serum delta 4-androstenedione and in only 5 out of 14 with normal delta 4-androstenedione (p less than 0.02). Serum dehydroepiandrosterone sulphate was normal in 22 patients and elevated in 4 males. There was a significant inverse correlation between bone age and serum cortisol (r: -0.59; p less than 0.005) and a significant positive correlation between bone age and serum dehydroepiandrosterone sulphate (r: 0.45 p less than 0.01). Serum ACTH was normal. A reduction by 50% in cortisol and 78% in dehydroepiandrosterone sulphate was found after dexamethasone suppression, but delta 4-androstenedione did not suppress after dexamethasone. After ACTH stimulation test cortisol increased by 50% and delta 4-androstenedione by 80%. CONCLUSIONS: The increased levels of cortisol and delta 4-androstenedione with partial resistance to dexamethasone suggest that these patients have a hypothalamic-pituitary dysfunction similar to that found in Cushing's disease or in chronic stress. The difference in the responses of delta 4-androstenedione and dehydroepiandrosterone sulphate observed is consistent with the existence of different mechanisms of control for these two steroids.

Adolescent↗
PubMed1986

Combined FSH and LH secreting pituitary adenoma in a young fertile woman without primary gonadal failure.

A 28 year old fertile woman presented with a history of amenorrhoea and galactorrhoea, and an enlarged pituitary fossa. Serum FSH and LH were repeatedly elevated both basally (32 and 44 mIU/ml) and after LRH (peak values, 108 and 420 mIU/ml). One mg of oestradiol (E2) benzoate im daily for 5 days failed to lower basal or LRH-stimulated serum gonadotrophins. Serum E2 was 170 pg/ml, basal serum prolactin (Prl) was 30 ng/ml and responded briskly to TRH (peak value 103 ng/ml). An 0.8 X 0.8 cm tumour was selectively excised by transsphenoidal surgery. Menses reappeared soon afterwards accompanied by normalization of serum FSH and LH plus biochemical evidence of ovulation. Specific immunostaining of tumoural cells was achieved with either FSH or LH antiserum, and adequate suppression of staining was obtained after preabsorbing each antiserum with and excess of its respective antigen. Our patient appears to be the first documented female with a combined FSH and LH producing pituitary tumour and no prior evidence of primary gonadal failure.

Adenoma↗