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Biomedical subjects

J M Mathis

Publications and source records attributed to J M Mathis.

At least 37 records · Page 2Linked to original sources

The effect of monomer-to-powder ratio on the material properties of cranioplastic.

Percutaneous vertebroplasty consists of injecting polymethylmethacrylate cement into the cancellous bone of vertebral bodies for the treatment of various lesions of the spine, including osteoporotic compression fractures. Clinicians practicing vertebroplasty commonly alter the mixture of monomer-to-powder recommended by the manufacturer in an effort to decrease viscosity and increase the working time. The purpose of the current study was to measure the effect that varying the monomer-to-powder ratio has on the compressive material properties of a cement (Cranioplastic) commonly used in vertebroplasty. Cylindrical specimens were prepared varying a monomer-to-polymer ratio of 0.40 to 1.07 ml/g and tested per the American Society for Testing and Materials standard F451. Specimens prepared at 0.53 mL/g, which is near the manufacturer's recommended monomer-to-polymer mixture of 0.57 mL/g, exhibited the greatest mean values for ultimate compressive stress, yield stress, and elastic modulus. Specimens prepared at higher or lower ratios exhibited diminished strength, in some cases by as much as 24%. Although altering the monomer-to-powder ratio affects the cement's material properties, it is as yet unknown if the decrease is clinically significant.

Bone Cements↗

Evidence for ovarian granulosa stem cells: telomerase activity and localization of the telomerase ribonucleic acid component in bovine ovarian follicles.

We have previously postulated that granulosa cells of developing follicles arise from a population of stem cells. Stem cells and cancer cells can divide indefinitely partly because they express telomerase. Telomerase is a ribonucleoprotein enzyme that repairs the ends of telomeres that otherwise shorten progressively upon each successive cell division. In this study we carried out cell cycle analyses and examined telomerase expression to examine our hypothesis. Preantral (60-100 microm) and small (1 mm) follicles, as well as granulosa cells from medium-sized (3 mm) and large (6-8 mm) follicles, were isolated. Cell cycle analyses and expression of Ki-67, a cell cycle-related protein, were undertaken on follicles of each size (n = 3) by flow cytometry; 12% to 16% of granulosa cells in all follicles were in the S phase, and less than 2% were in the G(2)/M phase. Telomerase activity (n = 3) was highest in the small preantral follicles, declining at the 1-mm stage and even further at the 3-mm stage. In situ hybridization histochemistry was carried out on bovine ovaries, and telomerase RNA was detected in the granulosa cells of growing follicles but not primordial follicles. Two major patterns of staining were observed in the membrana granulosa of antral follicles: staining in the middle and antral layers, and staining in the middle and basal layers. No staining was detected in oocytes. Our results strongly support our hypothesis that granulosa cells arise from a population of stem cells.

Animals↗

Surgically confirmed incorporation of a chronically retained neurointerventional microcatheter in the carotid artery.

A woman reported painful thrombosis of the superficial femoral artery 16 months after a transfemoral microcatheter was glued into a cerebral arteriovenous malformation and transected at the groin. When the catheter was removed, a portion was found to be incorporated into the wall of the carotid artery. This case demonstrates that portions of a retained microcatheter may be incorporated into the arterial wall while other portions may remain mobile and cause late peripheral arterial symptoms.

Adult↗

Percutaneous vertebroplasty treatment of steroid-induced osteoporotic compression fractures.

This report describes the case of a woman in whom multiple compression fractures of the lower thoracic and lumbar spine occurred in association with long-term corticosteroid therapy for systemic lupus erythematosus. Pain markedly limited the patient's mobility and daily activities, and conservative therapy with bracing and narcotic analgesics gave little improvement. Affected vertebrae were treated with polymethylmethacrylate, introduced percutaneously under fluoroscopic guidance. The resulting reinforcement of the fractured vertebral bodies eliminated the pain and the need for narcotic analgesics. The utilization of percutaneous verterbroplasty as a therapeutic alternative for the treatment of pain resulting from osteoporotic compression fractures is described.

Adult↗

In vivo studies of adenovirus-based p53 gene therapy for ovarian cancer.

OBJECTIVES: To test the safety, efficacy, and toxicity of gene therapy using wild-type p53-expressing adenovirus (Ad-CMV-p53) in a nude mouse model with intraperitoneal (i.p.) 2774 human ovarian cancer cell line that contains a p53 mutation. STUDY DESIGN: An initial study of adenovirus tolerance was determined in nude mice by a single i.p. injection of increasing doses of Ad-CMV-p53. Nude mice were implanted with an LD100 dose of 1 x 10(7) cells. To study the efficacy and specificity of Ad-CMV-p53 treatment, the mice received treatment with different adenovirus constructs. One group received Ad-CMV-p53 and another group received a control adenovirus construct, Ad-CMV-beta gal. To study the treatment response to Ad-CMV-p53, the mice were divided into groups and received various treatment schedules of 1 x 10(8) pfu of Ad-CMV-p53. RESULTS: The mice tolerated Ad-CMV-p53 without adverse effects at doses of 1 x 10(8) pfu. The response to Ad-CMV-p53 showed significant survival duration in each dose regimen, with a survival time greater than that of untreated animals (P = 0.0173). However, no statistically significant survival advantage was observed between Ad-CMV-p53- and Ad-CMV-beta gal-treated mice. CONCLUSIONS: These studies show that at the adenovirus dose and administration regimen used, there is effective but not specific 2774 tumor growth inhibition in vivo. Efficient introduction of biologically active genes into tumor cells would greatly facilitate cancer therapy. Thus, although promising, these results caution that much effort will be required to realize the potential for clinical application of adenovirus-based ovarian cancer gene therapy.

Adenoviruses, Human↗

Does glutamine supplementation increase radioresistance in squamous cell carcinoma of the cervix?

OBJECTIVE: Glutamine is proposed to protect bowel from radiation. However, glutamine may decrease cancer's radiosensitivity. We evaluate glutamine's effect on the growth rate and radiosensitivity of two cervical carcinoma cell lines in vitro. METHODS: HeLa and CaSki cells were seeded at 3000 cells/well in glutamine-free medium. An increasing amount of glutamine (0.4, 10, and 20 mM) was added to the respective plates, incubated, and irradiated with a single fraction of 0.5, 1, 3, and 6 Gy. Using a growth inhibition assay and photometric analysis, the viable cells were counted on day 8. Cell counts represent a mean +/- standard deviation from six experiments and are expressed in 10(3) cells. Analysis of variance was performed. RESULTS: In nonirradiated HeLa plates, absence of glutamine results in 5.7 +/- 1.2 cells/well. Addition of glutamine at 0.4, 10, and 20 mM to nonirradiated cells significantly (P < 0.0001) increased growth to 79.1 +/- 10.0, 122.5 +/- 9.0, and 114.3 +/- 13.9 cells/well, respectively. In culture plates irradiated with 6 Gy, HeLa cells supplemented with 0.4, 10, and 20 mM of glutamine showed lower cell counts (P < 0.008). A similar significant growth suppression at 6 Gy in comparison to 0.5, 1, and 3 Gy was observed (P < 0.01). CaSki cells showed similar patterns. CONCLUSIONS: Growth of HeLa and CaSki cells in vitro requires a minimum of 0.4 mM of glutamine in the medium. Supraphysiologic glutamine concentration does not increase tumor growth or radioresistance. Glutamine should be evaluated further as a potential bowel radioprotector.

Carcinoma, Squamous Cell↗

Effects of systemic heparinization on the thrombogenicity of hydrophilic and nonhydrophilic catheters in a swine model.

We assessed the effect of systemic heparinization on the in-vivo thrombogenicity of various micro- and guiding catheters in a swine model. Microcatheters were placed through 6-F guiding catheters into the common carotid arteries of swine for 30-min (short-term) and 90-min (medium-term) periods, with and without systemic heparinization. At the end of the placement period the microcatheters were retracted through the guiding catheters and fixed for scanning electron microscopy (SEM). Guiding catheters were harvested after 5 h placement, with and without systemic heparinization, by retraction through 8-F sheaths and fixed for SEM. The surfaces of both hydrophilic and nonhydrophilic microcatheters all demonstrated more accumulation of debris during placement without than with systemic heparinization. The difference was primarily in the amount of fibrillary material on the catheter surface. The guiding catheters also demonstrated increased debris accumulation without systemic heparinization. This suggests that, even when using relatively nonthrombogenic catheters, systemic heparinization is indicated during cerebral angiography.

Animals↗

Mutations in the BRCA1-associated RING domain (BARD1) gene in primary breast, ovarian and uterine cancers.

Germline alterations of BRCA1 result in susceptibility to breast and ovarian cancer. The protein encoded by BRCA1 interacts in vivo with the BRCA1-associated RING domain (BARD1) protein. Accordingly, BARD1 is likely to be a critical factor in BRCA1-mediated tumor suppression and may also serve as a target for tumorigenic lesions in some human cancers. We have now determined the genomic structure of BARD1 and performed a mutational analysis of 58 ovarian tumors, 50 breast tumors and 60 uterine tumors. Seven polymorphisms were detected within the 2.34 kb coding sequence of BARD1 . Somatically acquired missense mutations were observed in one breast carcinoma and one endometrial tumor; in at least one of these cases, tumor formation was accompanied by loss of the wild-type BARD1 allele, following the paradigm for known tumor suppressor genes. In addition, a germline alteration of BARD1 was identified in a clear cell ovarian tumor (Gln564His); again, loss of the wild-type BARD1 allele was observed in the malignant cells of this patient. The Gln564His patient was also diagnosed with two other primary cancers: a synchronous lobular breast carcinoma and a stage IA clear cell endometrioid cancer confined to an endometrial polyp 6 years earlier. These findings suggest an occasional role for BARD1 mutations in the development of sporadic and hereditary tumors.

Adenocarcinoma↗

Systemic sarcoidosis with bilateral orbital involvement: MR findings.

A 43-year-old woman with diplopia had a disconjugate gaze on physical examination. MR images revealed enlarged, abnormally enhancing extraocular muscles and lacrimal glands bilaterally. Biopsy results were consistent with sarcoidosis. Chest radiographs and CT scans were normal. Clinical and MR findings improved after appropriate medical therapy.

Adult↗

Use of a guide catheter as a temporary stent during microcatheter intervention.

Placement of a guiding catheter through a tortuous, narrowed, or intrinsically small vessel may result in severe reduction or occlusion of blood flow. However, nonbraided guiding catheters can be simply modified with a catheter hole punch to create a temporary stent. The stent reestablishes blood flow, which is routed through the distal segment of the guiding catheter while maintaining the guide platform for the introduction of microcatheters and devices necessary to perform intervention.

Blood Vessels↗

Performance characteristics of microcatheter systems in a standardized tortuous pathway.

BACKGROUND AND PURPOSE: Published reports of controlled experiments designed to evaluate the performance of over-the-wire microcatheter systems are rare and have often been based on subjective impressions from small clinical series. This investigation was designed to compare the load forces required to propel state-of-the-art, hydrophilically coated microcatheters from each of four manufacturers through a standardized tortuous pathway constructed of polytetrafluoroethylene tubing. METHODS: Currently available hydrophilically coated microcatheters were provided by four manufacturers. A 20-cm long, three-dimensional pathway simulating the intracranial carotid circulation was constructed of 0.065-in. (inner diameter) polytetrafluoroethylene tubing and immersed in a water bath at 37 degrees C. Testing was performed using an Instron tabletop load frame fitted with a 2-lb load cell. Durability and load force tests were conducted using a 0.014-in. stainless steel noncoated guidewire, with the wire tip protruding 1 cm beyond the catheter tip. At least four samples of microcatheters from each manufacturer were tested. RESULTS: Extensive trackability testing of the guidewire alone established reproducible performance with maximum load forces of less than 8 g. Maximum gram forces for the four reinforced microcatheters were not greatly different, measuring between 9 and 14 g. Excessive buckling of the only nonreinforced catheter was initially overcome early in the pathway in a staccato, stepwise fashion. After reaching a critical load, however, the catheter and guidewire prolapsed. CONCLUSION: All reinforced microcatheters tested established good and reproducible performance in our model. Reinforced microcatheters provided superior trackability over the one nonreinforced device tested.

Angioplasty, Balloon↗

Hemorrhagic complications in embolization of a meningioma: case report and review of the literature.

We report a case of hemorrhage in a parasellar meningioma shortly after embolization of the dural cavernous carotid artery branches supplying the tumor. This represents the first report of hemorrhage within a meningioma resulting from embolization with small (50 to 150-microns) polyvinyl alcohol particles, as well as the first reported case of hemorrhage complicating meningioma embolization from internal rather than external carotid artery branch embolization. We also review previously reported cases of postembolization hemorrhage from meningiomas.

Angiography, Digital Subtraction↗

Endovascular treatment of pulsatile tinnitus caused by dural sinus stenosis.

A patient presenting with progressive pulsatile tinnitus was found to have an ipsilateral dural sinus stenosis. This problem was successfully treated by an endovascular approach with angioplasty and subsequent sinus stenting. The diagnostic evaluation, therapeutic method, and follow-up concerning this problem and its treatment are discussed.

Case Reports↗

Ca(2+)-regulated expression of aldosterone synthase is mediated by calmodulin and calmodulin-dependent protein kinases.

The chronic maintenance of aldosterone production in the adrenal zona glomerulosa is associated with increased expression of aldosterone synthase (P450aldo), the enzyme responsible for the conversion of 11-deoxycorticosterone to aldosterone. The major physiologic regulators of aldosterone production are angiotensin II (ANG II) and (K+) which act in part through increasing intracellular calcium ([Ca2+]i). Recently we demonstrated that increased [Ca2+]i is associated with K+ induction of P450aldo expression. To determine whether Ca2+ regulation of P450aldo is mediated through calmodulin or calmodulin-dependent kinases (CaMK), we investigated the actions of calmidazolium (a calmodulin inhibitor) and KN93 (an inhibitor of CaMK) on expression of P450aldo in human adrenocortical H295R cell line. Treatment with either calmidazolium or KN93 completely inhibited K(+)-stimulated expression of P450aldo mRNA with little effect on ANG II or dibutyryl cyclic AMP-stimulated induction of this transcript. Cellular calcium levels were also increased using the calcium ionophore ionomycin and calcium channel agonist Bay K 8644. These compounds increased P450aldo mRNA and this calcium induction was inhibited by calmidazolium and KN93. These data show that K(+)-stimulated expression of P450aldo mRNA is regulated in a Ca2+ sensitive manner through mechanisms involving calmodulin and CaMK.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Angiotensin II and potassium regulate human CYP11B2 transcription through common cis-elements.

Aldosterone synthase is a mitochondrial enzyme that catalyzes the conversion of 11-deoxycorticosterone to the potent mineralocorticoid aldosterone. The gene encoding aldosterone synthase, CYP11B2, is expressed in the zona glomerulosa of the adrenal cortex. Although the major physiological regulators of aldosterone production are angiotensin II (ANG II) and potassium (K+), the mechanisms by which these compounds regulate CYP11B2 transcription are unknown. Therefore we analyzed the human CYP11B2 5'-flanking region using a transient transfection expression system in the H295R human adrenocortical cell line. ANG II and K+ increased expression of a luciferase reporter construct containing 2015 bp of human CYP11B2 5'-flanking DNA. This response was mimicked by treatment with the calcium channel activator BAYK8644, whereas activation of the protein kinase C pathway with 12-o-tetradecanoylphorbol-13-acetate had no effect. Reporter gene activity was also increased after activation of cAMP-dependent pathways by (Bu)2cAMP. Deletion, mutation, and deoxyribonuclease I footprinting analyses of the CYP11B2 5'-flanking region identified two distinct elements at positions -71/-64 (TGACGTGA) and -129/-114 (CTCCAGCCTTGACCTT) that were both required for full basal reporter gene activity and for maximal induction by either cAMP or calcium-signaling pathways. The -71/-64 element, which resembles a consensus cAMP response element (CRE), bound CRE-binding proteins from H295R cell nuclear extracts as determined by electrophoretic mobility shift analysis. Analysis of the -129/-114 element using electrophoretic mobility shift analysis demonstrated binding of the orphan nuclear receptors steroidogenic factor 1 and chicken ovalbumin upstream promoter transcription factor. These data demonstrate that ANG II, K+, and cAMP-signaling pathways utilize the same SF-1 and CRE-like cis-elements to regulate human CYP11B2 expression.

Adrenal Cortex↗

Thrombogenicity of hydrophilic and nonhydrophilic microcatheters and guiding catheters.

PURPOSE: To assess in a swine model the in vivo thrombogenicity of various microcatheters and guiding catheters as a function of catheter material, catheter coating, and duration of implantation. METHODS: Microcatheters (Tracker 18 and Fastracker 18, Target Therapeutics, Fremont, Calif; Magic 1.8, Balt, Montmorency, France; and Transit, Cordis Endovascular Systems, Miami Lakes, Fla) were placed through 6F guiding catheters (Fasguide, Target Therapeutics, and Envoy, Cordis Endovascular Systems) into the common carotid arteries of swine for 30 minutes (short term), 90 minutes (medium term), and 35 days (long term). Guiding catheters were implanted for 5 hours. At the end of the implantation periods the catheters were retracted and fixed for scanning electron microscopy. RESULTS: The surface of the Fastracker microcatheter was devoid of debris after both short- and medium-term implantation. The Tracker microcatheter had minimal accumulation of cellular elements whereas the Transit microcatheter showed moderate accumulation of nondeformed red blood cells. Neither the Tracker nor the Transit microcatheter showed evidence of increasing debris accumulation after medium-term implantation as compared with short-term implantation. The Magic microcatheter was coated with gross thrombus after both short- and medium-term implantation. The Fasguide guiding catheter was nearly devoid of debris, while the Envoy guiding catheter had moderate thrombus formation. Long-term implantation of the Fastracker microcatheter was well tolerated whereas that of the Transit catheter resulted in vessel occlusion. CONCLUSIONS: Hydrophilic microcatheters and guiding catheters are less thrombogenic than their nonhydrophilic counterparts, but not all hydrophilic coatings are equally hypothrombogenic. Degree of thrombogenicity depends on catheter material rather than surface morphology. Medium-term implantation did not yield increasing thrombus formation relative to short-term implantation.

Animals↗

Differential regulation of 11 beta-hydroxylase and aldosterone synthase in human adrenocortical H295R cells.

In humans the last steps in the synthesis of aldosterone and cortisol rely on the activity of two cytochrome P450 genes termed CYP11B2 (aldosterone synthase; P450aldo) and CYP11B1 (11 beta hydroxylase; P450cl1). The mechanisms which lead to differential expression of these two genes within the adrenal cortex are not well-defined. The human adrenocortical cell line. H295R, was utilized in this study to examine the intracellular second messenger pathways regulating expression of P450aldo and P450c11. using specific ribonuclease protection assays. Treatment of H295R cells with angiotensin II or potassium (K+) caused a time-dependent induction in the level of P450aldo transcripts. While K+ treatment was more specific for the induction of P450aldo mRNA, treatment with angiotensin II increased levels of both P450aldo and P450c11 transcripts. To define the second messenger systems which influence transcript levels for these enzymes, the effects of agonists of the protein kinase A, protein kinase C, and calcium pathways were tested on the expression of P450aldo and P450c11. Activation of the protein kinase A pathway by the agonists, dibutyryl cAMP or forskolin, preferentially increased the P450c11 transcript to a greater degree than P450aldo. Interestingly, activation of the protein kinase C pathway by tetradecanoylphorbol acetate (TPA) did not alter transcripts for either P450aldo or P450c11. The calcium channel agonist BAYK 8644 mimicked the effects of K+ by increasing the transcript for P450aldo. However, the calcium channel blocker nifedipine attenuated the stimulatory effects of angiotensin II and K+ on the levels of P450aldo. However, the calcium channel blocker nifedipine attenuated the stimulatory effects of angiotensin II and K+ on the levels of P450aldo transcripts without affecting the stimulatory effect of dbcAMP. This study demonstrates that the protein kinase A pathway preferentially induces P450c11 mRNA over that of P450aldo. In addition, pharmacologic agents that affect calcium levels provide evidence for an additional regulatory mechanism in modulating the expression of P450aldo. This is of importance since the major physiologic regulators of aldosterone secretion, angiotensin II and K+ are able to increase intracellular calcium but have little effect on intracellular cAMP levels.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗