Biomedical subjects

A Fried

Publications and source records attributed to A Fried.

At least 19 recordsLinked to original sources

PubMed1996

Dexamethasone regulation of marrow stromal-derived osteoblastic cells.

The clonal subtypes of cells in the osteogenic family represented by fibroblastoid MBA-15.33, preosteoblast MBA-15.4, and mature osteoblastic MBA-15.6 cells were used to study the effects of glucocorticoid (dexamethasone). The role of dexamethasone was monitored on cell attachment when plated on various protein substrata (BSA, collagen 1, and Matrigel). A 24 h exposure of the cells to 10(-6) M or 10(-7) M dexamethasone differential affects their attachment preference. MBA-15.33 and MBA-15.4 cells increased their attachment capability on collagen 1, while MBA-15.6 cells' attachment was inhibited. Pretreatment with (10(-6) M) dexamethasone caused an increase in attachment on Matrigel by MBA-15.33 cells and to less extent by MBA-15.4 cells. Additionally, measurements of two enzymatic activities were monitored; one is alkaline phosphatase (ALK-P), and the second is neutral endopeptidase (CD10/NEP). MBA-15.33, MBA-15.4, and MBA-15.6 cells were exposed to dexamethasone or to various growth factors (bone morphogenic protein (BMP-2 and BMP-3), TGF beta, and IGF-1). In some experiments, pretreatment of cells by dexamethasone was followed by exposure to the growth factors. The cells' challenged cellular responses were not uniform and revealed a differential pattern when their ALK-P and CD10/NEP enzymatic activities were measured.

Animals↗

PubMed1996

[Conservative therapy in carpal tunnel syndrome].

A prospective study was designed to determine which patients with carpal tunnel would respond to conservative therapy (splinting and local injection of corticosteroids). The study included 50 hands of 34 patients, aged 25-80 years, with a mean follow-up of 18 months. Conservative therapy was effective in 82% of hands after 8 weeks, but symptoms subsequently recurred, so that by the end of a year only 20% remained asymptomatic. Failure of conservative therapy was predicted by long duration of symptoms, older age, permanent paresthesia, 2-point discrimination threshold above 6 mm, positive Phalen test within 30 seconds, and long motor and sensory distal latency.

Adrenal Cortex Hormones↗

PubMed1996

Intrathecal morphine for analgesia in children undergoing selective dorsal rhizotomy.

Selective dorsal root rhizotomy is performed for relief of spasticity in children with cerebral palsy. Postoperative pain relief can be provided by intrathecal morphine administered at the time of the procedure. We sought to define an optimal dose of intrathecal morphine in children undergoing selective rhizotomy, through a randomized, double-blinded prospective trial. After institutional approval and parental written informed consent, 27 patients, ages 3-10 years, were randomized to receive 10, 20, or 30 micrograms.kg-1 (Groups A, B, and C, respectively) of preservative-free morphine administered intrathecally by the surgeon after dural closure. Postoperatively, vital signs, pulse oximetry, and pain intensity scores were recorded hourly for 24 hr. Supplemental intravenous morphine was administered postoperatively according to a predetermined schedule based on pain scores. There was considerable individual variability in the time to initial morphine dosing and cumulative supplemental morphine dose. Time to first supplemental morphine dose was not different between groups. When compared to Groups A and B, cumulative 6-hr supplemental morphine dose was significantly lower in Group C (38.6 +/- 47 micrograms versus 79.1 +/- 74 and 189.6 +/- 126 for Groups A and B, respectively). By 12 hr, cumulative supplemental morphine dose was similar in Groups A and C. Group B consistently had a higher supplemental dose requirement than Groups A and C at 6, 12, and 18 hr. By 24 hr, there was no difference in cumulative dose among groups. Postoperative pain scores and the incidence of respiratory events, nausea, vomiting and pruritus were comparable among groups. These data suggest that intrathecal morphine at 30 micrograms.kg-1 provides the most intense analgesia at 6 hr following selective dorsal root rhizotomy, but was otherwise comparable to the 10 micrograms.kg-1 dose.

Analgesics, Opioid↗

PubMed1995

PTH and 1,25(OH)2 vitamin D priming to growth factors differentially regulates the osteoblastic markers in MBA-15 clonal subpopulations.

The functional modulation of enzymatic activities of alkaline phosphatase (ALK-P) and neutral endopeptidase (CD10/NEP) in MBA-15.4 and MBA-15.6 marrow stromal osteoblastic cells was studied. The hormonal effects of parathyroid hormone (PTH) and 1,25 (OH)2D3 combined with various growth factors (bone morphogenic protein [BMP-2 and BMP-3], TGF beta and IGF-I) on these cells were monitored. The cell responses of MBA-15.4, a preosteoblastic cell, and MBA-15.6, a more mature osteoblastic cell, to the growth factors and the hormonal challenge were measured by changes of the enzymatic activities (ALK-P and CD10/NEP). The cellular response was not uniform and revealed a differential pattern.

Alkaline Phosphatase↗

PubMed1995

Bone marrow interface: preferential attachment of an osteoblastic marrow stromal cell line.

In this study, we report on the cell adhesion properties of marrow stromal cells to extracellular matrix components such as collagen and noncollagenous proteins. The osteoblastic cells and their non-osteoblastic counter-parts (MBA series) from the marrow stroma differentially recognized a spectrum of extracellular matrix proteins. The osteoblastic cells, MBA-15, preferentially attached to bone matrix proteins, whereas fibroendothelial MBA-2.1 and adipocytic 14F1.1 cells did not. The MBA-15 cells demonstrated a preference in their attachment to fibronectin > mixture of collagens > bone matrix extracts > collagen type I > noncollagenous proteins. Clonal subpopulations derived from the MBA-15 cell line representing various stages along the osteogenic lineage expressed differential attachment preference. MBA-15.4, a less differentiated clonal line, was compared to MBA-15.6, a mature cell line.

Animals↗

PubMed1995

Biliary sludging in critically ill trauma patients.

We used serial weekly ultrasonography to prospectively screen 19 critically ill trauma victims for the development of biliary sludge. Fourteen patients had sludge formation during their hospitalization. Sludge development was positively associated with increased transfusion requirements, but not with any other laboratory or clinical findings, including injury severity scores. The enteral feedings administered to most patients did not prevent sludge formation in the majority of cases; all five patients receiving total parenteral nutrition had sludge. Three patients had complications that could possibly be attributed to the sludge (one case of acalculous cholecystitis and two cases of mild pancreatitis). No such problems occurred in the five patients who did not have sludge. No long-term clinical problems related to sludge have occurred. We conclude that gallbladder sludge frequently develops in critically ill trauma patients and that sludge may be associated with pancreatobiliary complications.

Adolescent↗

PubMed1994

Differential effects of retinoic acid and growth factors on osteoblastic markers and CD10/NEP activity in stromal-derived osteoblasts.

The effects of retinoic acid (RA) on the expression of osteoblastic-related cell markers was examined. A marrow stromal osteogenic cell line, MBA-15, was analyzed by Northern blotting for the expression of bone matrix proteins. These cells constitutively express mRNA encoding for procollagen alpha 2 (I), osteonectin, osteopontin, biglycan, and alkaline phosphatase (ALK-P). Gene expression was unchanged in response to RA triggering for 24 hr. Furthermore, cell growth and enzymatic activities of ALK-P and neutral endopeptidase (CD10/NEP) were studied. These parameters were examined in MBA-15 and clonal populations representing different stages of differentiation. The cell's growth rate was unchanged, while ALK-P activity was greatly increased during the culture period under RA treatment in MBA-15 and in the clonal cell lines examined while CD10/NEP activity displayed a different pattern. MBA-15.4, a preosteoblast cell line, exhibited an inhibition in CD10/NEP activity at the beginning of the culture period, reaching basal level with time. This activity was greatly increased over control level in MBA-15.6, a mature stage of osteoblasts. Furthermore, the response of cell lines to various growth factors was tested subsequent to priming the cultures with RA. A synergistic effect was monitored for ALK-P activity in MBA-15.4 and MBA-15.6 cells under rh-bone morphogenic protein (BMP-2) and purified osteogenin (BMP-3), and an antagonist effect was measured when cells were exposed to transforming growth factor beta (TGF beta). Contrarily, BMP-2 and BMP-3 inhibited the CD10/NEP activity that had remained unchanged following priming of the cell with RA. Insulin-like growth factor I (IGF-I) and basic fibroblast growth factors (bFGF) did not affect either ALK-P nor CD10/NEP activities in both cloned cells. Cellular response to bone-seeking hormone, parathyroid hormone (PTH), and prostaglandin E2 (PGE2) was monitored by activation of intracellular cAMP. Treatment with RA caused a dramatic decrease in MBA-15.6 cell responses to PTH and PGE2, but no significant effects could be observed in other clonal lines.

1-Methyl-3-isobutylxanthine↗

PubMed1994

The efficacy of a sonographic morphology index in identifying ovarian cancer: a multi-institutional investigation.

Transvaginal sonography (TVS) has been shown to be the most effective means to screen for ovarian cancer. TVS is associated with a high sensitivity and specificity. However, the positive predictive value associated with TVS in the diagnosis of malignancy is low. A morphologic scoring index for use with TVS has been used at the University of Kentucky since 1991. The current study was performed to more fully evaluate the efficacy and interobserver variation in ultrasonographic morphology index scores attributed to ovarian tumors. Ultrasound records of 213 patients from five participating centers were reviewed by three independent observers. Morphology index scores were assigned to each tumor in a blinded fashion. The morphology index scores were then compared with the final histopathologic findings. One hundred sixty-nine patients had benign tumors and 44 patients had ovarian malignancies. The mean morphology index scores were significantly higher in malignant ovarian tumors (MI 7.3 +/- 1.9) than in benign ovarian tumors (MI 3.3 +/- 1.8). Statistical evaluation of the morphology index scores revealed a sensitivity of 89% and a positive predictive value of 46%. Interobserver variation was lowest in assessing ovarian volume and higher in the evaluation of wall structure and septal structure. A multilogistic regression model was used to evaluate the predictive power of each component of the morphology index. The use of a morphology index is an effective and cost-efficient method of increasing the positive predictive value of TVS screening for ovarian cancer. Use of this index in large numbers of patients will generate data which should help refine appropriate structural scoring categories and reduce interobserver variation.

Adolescent↗

PubMed1993

Marrow stroma-derived osteogenic clonal cell lines: putative stages in osteoblastic differentiation.

This report documents characterization of five osteogenic cell subpopulations of bone marrow stroma. The clonally derived cell lines were isolated from the parental line MBA-15 known to express osteoblastic-associated features in vitro and to form bone in vivo. The latter, presumably "arrested" at a particular stage along the osteogenic lineage, are useful models to study the processes involved in the differentiation of bone forming cells. The clones differ in their morphology, proliferation rate, quantities and distribution of extracellular matrix proteins, levels of alkaline phosphatase activity and activation of adenylate cyclase by parathyroid hormone and/or prostaglandin E. These properties have been retained during prolonged growth and subculturing through many passages. MBA-15.4 is a presumptive preosteoblast with a fibroblast-like appearance; it proliferates rapidly, synthesizes equal amounts of collagen and noncollagenous proteins, and produces constitutively low levels of alkaline phosphatase. This clone has PGE2-stimulated adenylate cyclase activity and a very low constitutive response to PTH. On the other hand, MBA-15.6 has a large polygonal morphology with limited proliferative potential, synthesizes twice as much noncollagenous proteins as collagen, has high alkaline phosphatase activity, and responds strongly to PTH. The characteristics of the other clones place them between these two categories. The effects of 10(-7) M dexamethasone or 10(-12)-10(-8) M 1,25 dihydroxyvitamin D3 on growth and differentiation further strengthen the variance between these clones. The different in vitro characteristics of the various clones were directly reflected in their bone formation ability in vivo. When transplanted under the renal capsule, MBA-15.33 formed a thick fibrous tissue, MBA-15.4 formed small foci of bone, and MBA-15.6 formed massive woven bone at the same period of time.

Adenylyl Cyclases↗

PubMed1993

A morphology index based on sonographic findings in ovarian cancer.

A morphology index based on morphologic characteristics of ovarian tumors was developed. Specific categories included tumor volume, wall structure, and septal structure. A point scale (0-4) was developed within each category with the total points per evaluation varying from 0-12. Sonograms on 121 patients undergoing exploratory laparotomy for ovarian masses were evaluated using this index. Eighty ovarian tumors had a morphology index score < 5, and all were benign (negative predictive value, 1.000). In postmenopausal patients, a morphology index score > or = 5 had a positive predictive value for malignancy of 0.45. All ovarian malignancies had significant abnormalities in wall structure and all had a total volume in excess of 10 cm3. The findings of the present investigation indicate that the morphology index is a cost effective adjuvant method which significantly increases the specificity and positive predictive value of transvaginal sonography. The routine application of a morphology index to screening sonography should decrease the amount of diagnostic surgery performed in order to detect each case of ovarian cancer.

Adolescent↗

PubMed1993

Diagnosis and treatment of the slit ventricle syndrome.

Slit ventricles are a complication of a functioning shunt. This article examines the diagnosis and treatment of slit ventricles and slit ventricle syndrome, the pathophysiology involved, a rationale for treatment, and the direction of therapy in the near future. The authors conclude that determining which type of SVS is present is the first step in treatment and that the best treatment is a strategy aimed at the specific type of SVS that is responsible for the symptoms.

Brain Diseases↗

PubMed1993

An abnormal gallbladder presenting as a huge, rounded photon-deficient area in radionuclide hepatobiliary imaging.

Tc-99m DISIDA hepatobiliary imaging was used to evaluate a hemophiliac patient presenting with symptoms of acute cholecystitis and gastrointestinal bleeding. There was nonvisualization of this abnormal gallbladder even on 6 1/2-hour delayed DISIDA images. Instead, a huge photon-deficient area was seen in the gallbladder fossa. Ultrasound and computed tomography findings were consistent with an enlarged gallbladder filled with blood.

Adult↗

PubMed1992

Progressive vision loss. A rare manifestation of familial cavernous angiomas.

We studied four generations of a family in which the index case had progressive loss of vision secondary to a cavernous angioma of the optic nerve and chiasm. Magnetic resonance imaging of the brain revealed multiple, asymptomatic intracerebral cavernous angiomas. Brain magnetic resonance imaging scans of the family members revealed multiple cavernous angiomas in the brother and paternal grandfather, but none in the father or his siblings. Autopsy reports of the paternal great grandfather noted multiple cavernous angiomas in the brain and abdominal viscera. We believe our patient to be the sixth reported case in which a cavernous angioma involved the optic chiasm and optic nerve. Magnetic resonance imaging is a sensitive and specific method of detecting cavernous angiomas. Cavernous angiomas have an autosomal dominant pattern of inheritance with variable penetrance. Surgical intervention in patients with symptomatic cavernous angiomas depends on the location and size of the lesion and associated surgical risks.

Adolescent↗

PubMed1991

Subpopulations of marrow stromal cells share a variety of osteoblastic markers.

A series of stromal cell lines derived from mouse bone marrow, representing subpopulations of putative stromal cell types, were examined for the expression of osteoblastic properties. The effects of dexamethasone and specific inhibitors on alkaline phosphatase activity, cAMP response to bone-seeking hormones, and the ability to mineralize extracellular matrix in vitro as well as collagen typing were used as osteoblastic markers. We found that all stromal cell types examined possess some osteoblastic features but differ in the degree of expression. The data provide support to the hypothesis of a common stem cell for marrow stromal cells.

Alkaline Phosphatase↗

PubMed1991

Fusiform dilatations of the carotid artery following radical surgery of childhood craniopharyngiomas.

Between 1982 and 1990, a series of 31 children with craniopharyngiomas underwent initial surgery at the Children's Hospital of Philadelphia with an attempt at total tumor removal. Nine (29%) of them were found to have fusiform dilatation of the supraclinoid carotid artery either at the time of surgery for recurrence (one patient) or on routine surveillance with enhanced computerized tomography 6 to 18 months postoperatively (eight patients). The finding of carotid enlargement was confirmed in seven cases with magnetic resonance angiography and in one case with a formal arteriogram. Eight of the nine patients remain alive at a mean of 3.7 years after diagnosis. None have experienced hemorrhage or other symptoms referrable to fusiform dilatation of the carotid artery, which is believed to result from surgical manipulation of the carotid artery.

Adolescent↗

PubMed1991

Phase I evaluation of coumarin (1,2-benzopyrone) and cimetidine in patients with advanced malignancies.

Fifty-four patients with advanced malignancies were treated on this phase I trial of coumarin and cimetidine. The dose of coumarin was escalated, with three patients treated at each dose level, while the cimetidine dose was held constant at 300 mg four times daily. Patients received coumarin alone as a single daily oral dose for 14 days; on day 15, cimetidine was added and both drugs were continued until progression of disease. This trial was initiated with patients receiving coumarin at 400 mg daily and closed at 7 g daily with four of five patients on this dose experiencing nausea and vomiting. Treatment was generally well tolerated over a wide range of coumarin doses. Symptomatic side effects were few, mild, and usually self limited. Side effects included insomnia, nausea, vomiting, diarrhea, and dizziness. Two patients withdrew from therapy because of daily nausea and vomiting. Typically, nausea, vomiting, and dizziness occurred 2.5-3 hours after a dose of coumarin. In most patients, these side effects abated spontaneously with continuation of therapy. There was no significant hematologic or renal toxicity. Hepatotoxicity occurred in only one patient and was manifested by asymptomatic abnormal elevations of serum hepatic transaminases. This toxicity was reversible upon interruption of therapy. Objective tumor regressions were observed in six patients with renal cell carcinoma. Responses occurred at coumarin doses ranging from 600 mg to 5 g daily. Coumarin is a relatively nontoxic, oral, outpatient therapy that warrants further investigations for the treatment of human malignancies. Because of its low toxicity, there is potential for combining coumarin with chemotherapeutic and/or biological agents in an attempt to improve on efficacy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1990

Neutral endopeptidase (EC 3.4.24.11) is highly expressed on osteoblastic cells and other marrow stromal cell types.

A series of cultured mouse marrow stromal cell lines of different phenotype characteristics were examined for their neutral endopeptidase (NEP) activity using the highly selective chromophoric substrate of enzyme, 3-carboxypropanoyl-alanyl-alanyl-leucine 4-nitroanilide. All the cell lines tested contained appreciable amounts of NEP activity, but the cells expressing an osteoblastic phenotype, MBA-15, showed the high levels. Other non-stromal osteoblastic cell lines, MC-3T3-E1, ROS 17/2.8 cells derived from mouse long bone explants, were also rich in NEP. A four-fold stimulation of NEP activity was observed when certain MBA-15 clones were cultured in the presence of 1 alpha,25-dihydroxyvitamin D3. Since NEP is an effective cell-surface endopeptidase, it may play a role in the dynamics of bone formation, via interaction with biologically active polypeptides.

Amino Acid Sequence↗

PubMed1989

Treatment of renal cell carcinoma with daily low-dose alpha-interferon.

While alpha-interferon has yielded objective tumor regressions in patients with metastatic renal cell carcinoma, such therapy is usually associated with significant toxicity often requiring dose modifications and/or cessation of therapy. In the absence of a clearly defined optimal dose and schedule for alpha-interferon, it appears reasonable to seek a means for improving the therapeutic index for this drug. We report the results of a pilot trial in which patients with renal cell carcinoma were treated with a daily low dose of alpha-interferon. Seventeen patients were treated with alpha-interferon (Roferon-A) at a dose of 1 million U subcutaneously daily. There were no exclusionary criteria for this pilot trial. Sixteen patients were evaluable for response and toxicity. Therapy was well-tolerated with no interruption of therapy for toxicity. No patient experienced the "flu-like" syndrome that is associated with higher doses, and there was no episode of granulocytopenia or thrombocytopenia. Four patients achieved a partial response (PR), with one PR persisting at 20 months. Sites of response included lung (two patients), liver (one patient), and bone (one patient). These results indicate that this regimen is well tolerated and can be expected to render objective responses. Formal Phase II trials are warranted in order to define the response rate for this regimen.

Aged↗