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Biomedical subjects

J M Mathis

Publications and source records attributed to J M Mathis.

At least 55 records · Page 3Linked to original sources
PubMed1995

Adenovirus-based p53 gene therapy in ovarian cancer.

Mutations of the p53 tumor suppressor gene are the most common molecular genetic abnormality to be described in ovarian cancer. To determine the feasibility of mutant p53 as a molecular target for gene therapy in ovarian cancer, we constructed an adenovirus vector containing the wild-type p53 gene. The ability of this adenovirus construct (Ad-CMV-p53) to express p53 protein was examined by Western blot analysis in the H358 lung cancer cell line, which has a homozygous deletion of the p53 gene. The ability of the adenovirus vector system to infect ovarian cancer cells was tested using an adenovirus containing the beta-galactosidase reporter gene under the control of the CMV promoter (Ad-CMV-beta gal). The ovarian cancer cell line 2774, which contains an Arg273His p53 mutation, was infected with Ad-CMV-beta gal, and the infected cells were assayed for beta-galactosidase activity after 24 hr. To test the ability of wild-type p53 to inhibit cell growth, the 2774 cell line was infected with Ad-CMV-p53 or Ad-CMV-beta gal, and the effect of these agents on the growth of 2774 cells was determined using an in vitro growth inhibition assay. Western blot analysis of lysates from H358 cells infected with Ad-CMV-p53 showed expression of wild-type p53 protein. When 2774 cells were infected with Ad-CMV-beta gal at a multiplicity of infection (m.o.i.) of 10 PFU/cell, > 90% of cells showed beta-galactosidase activity, demonstrating that these cells are capable of efficient infection by the adenovirus vector. Growth of 2774 cells infected with Ad-CMV-p53 was inhibited by > 90% compared to noninfected cells. The ability of the adenovirus vector to mediate high-level expression of infected genes and the inhibitory effect of Ad-CMV-p53 on the 2774 cell line suggests that the Ad-CMV-p53 could be further developed into a therapeutic agent for ovarian cancer.

Adenoviridae↗
PubMed1995

Ca(2+)-regulated expression of steroid hydroxylases in H295R human adrenocortical cells.

Although changes in the expression of key steroidogenic enzymes such as cytochrome P450 cholesterol side-chain cleavage, 17 alpha-hydroxylase (P450c17), aldosterone synthase, and 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) in the human adrenal cortex are known to be controlled by factors activating the protein kinase A or protein kinase C signaling pathways, little is known concerning the effects of increased intracellular Ca2+. In this study we describe the effects of K+, an agent known to increase intracellular Ca2+ through the opening of voltage-sensitive Ca2+ channels, on steroidogenesis in H295R human adrenocortical cells and corresponding changes in expression of these vital steroidogenic enzymes. Treatment of cells for 48 h with K+ (14 mM) resulted in an increase in aldosterone (3.5-fold) as well as the 17 alpha-hydroxylated steroids cortisol (2.9-fold) and dehydroepiandrosterone (DHEA; 3.7-fold). This action of K+ was accompanied by a dose-dependent (P < 0.05 at 6 mM K+ or above) and time-dependent (P < 0.05 at 24 h and beyond) increase in expression of P450c17 and, to a lesser extent, cytochrome P450 cholesterol side-chain cleavage messenger RNA (mRNA). Treatment with K+ also caused a time-dependent increase in aldosterone synthase mRNA levels, which were detectable by 12 h. Treatment with K+, however, was without effect on 3 beta HSD expression. These effects contrast with those of (Bu)2cAMP, which stimulated a greater increase in cortisol and DHEA secretion as well as P450c17 expression. The effects of K+ treatment also differ from those of AII, which promoted a greater aldosterone secretory response (5.7-fold), but a lesser effect on DHEA secretion (2.2-fold) and P450c17 expression. Although AII and TPA (known activators of protein kinase C) as well as forskolin and (Bu)2cAMP (known activators of protein kinase A) increased the expression of 3 beta HSD mRNA, K+ treatment was without effect, suggesting that elevation of [Ca2+]i in response to K+ did not activate the protein kinase C or protein kinase A signaling pathways. Furthermore, the effects of K+ on steroid secretion and 17 alpha-hydroxylase activity were reproduced by the voltage-sensitive Ca2+ channel activator BAYK 8644, and increases in P450c17 mRNA in response to K+ were reversed by the Ca2+ channel antagonist, nifedipine. We conclude that K+ can modulate the expression of key steroidogenic enzymes in H295R cells through the Ca2+ signaling pathway without involvement of the protein kinase A or protein kinase C pathways.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxysteroid Dehydrogenases↗
PubMed1995

Intraoperative urokinase infusion for embolic stroke during carotid endarterectomy.

Embolic stroke is an infrequent complication of carotid endarterectomy. Somatosensory evoked potential monitoring detected delayed acute neurological deterioration during endarterectomy performed on a 71-year-old woman. Intraoperative arteriography performed via an indwelling shunt revealed thrombus within the middle cerebral artery and distal branches. A microcatheter was placed into the internal carotid artery via the arteriotomy and advanced into the middle cerebral artery. Urokinase was infused into and around the thrombus until almost complete thrombolysis had been achieved. The patient recovered quickly and was discharged without neurological deficit.

Aged↗
PubMed1995

Temporary balloon test occlusion of the internal carotid artery: experience in 500 cases.

PURPOSE: To describe experience with 500 temporary balloon occlusions of the internal carotid artery, with particular emphasis on the techniques and complications. METHODS: Temporary occlusion of the internal carotid artery was accomplished endovascularly using various balloon-catheter combinations. These temporary balloon occlusions were combined, when possible, with cerebral blood flow analysis with stable xenon-enhanced CT. RESULTS: Complications related to this procedure occurred in 16 (3.2%) patients. Eight (1.6%) patients had asymptomatic complications. There were 8 who experienced neurologic changes. Six (1.2%) of these were transient; two (0.4%) were permanent. There were no deaths. CONCLUSIONS: Temporary balloon occlusion of the internal carotid artery, believed helpful in identifying patients at risk of stroke during abrupt carotid artery sacrifice, can be performed with an acceptably low complication rate.

Aortic Dissection↗
PubMed1994

Genetic instability in human ovarian cancer cell lines.

We have analyzed the stability of microsatellites in cell lines derived from human ovarian cancers and found that 5 out of 10 of the ovarian tumor cell lines are genetically unstable at the majority of the loci analyzed. In clones and subclones derived serially from one of these cell lines (2774; serous cystadenocarcinoma), a very high proportion of microsatellites distributed in many different regions of the genome change their size in a mercurial fashion. We conclude that genomic instability in ovarian tumors is a dynamic and ongoing process whose high frequency may have been previously underestimated by PCR-based allelotyping of bulk tumor tissue. We have identified the source of the genetic instability in one ovarian tumor as a point mutation (R524P) in the human mismatch-repair gene MSH2 (Salmonella MutS homologue), which has recently been shown to be involved in hereditary nonpolyposis colorectal cancer. Patient 2774 was a 38-year-old heterozygote, and her normal tissue carried both mutant and wild-type alleles of the human MSH2 gene. However the wild-type allele was lost at some point early during tumorigenesis so that DNA isolated either from the patient's ovarian tumor or from the 2774 cell line carries only the mutant allele of the human MSH2 gene. The genetic instability observed in the tumor and cell line DNA, together with the germ-line mutation in a mismatch-repair gene, suggest that the MSH2 gene is involved in the onset and/or progression in a subset of ovarian cancer.

Adult↗
PubMed1994

Arteriovenous fistula of the scalp after hair transplantation treated by endovascular embolization.

A 27-year-old patient acquired an arteriovenous fistula after punch graft hair transplantation. This lesion was treated by (percutaneous) puncture and injection of a liquid acrylic (N-butyl-2-cyanoacrylate). The fistula was completely obliterated by the endovascular therapy without the need for additional vascular or cosmetic surgery. Endovascular therapy may be helpful as an adjunctive or primary treatment modality for iatrogenic or post-trauma fistulas.

Adult↗
PubMed1994

Transformation of human granulosa cells with the E6 and E7 regions of human papillomavirus.

Ovarian granulosa cells are the primary site of estrogen and progesterone synthesis and play an essential role in the maturation of the developing ovum. Freshly isolated granulosa cells are often used to study the regulation of steroid and protein biosynthesis, but the small number of cells available for these cultures has proven inadequate for many detailed gene regulatory studies. The goal of this study was to develop human granulosa (HG) cell lines that maintain differentiated function. The E6 and E7 open reading frames of high risk strains of human papillomavirus have been used to produce immortalized cell lines. Primary cultures of human luteinized granulosa cells were infected with defective retroviruses containing the E6 and E7 regions of human papillomavirus 16 and with the neomycin phosphotransferase gene to confer G418 resistance. Three of eight clones that were isolated after selection in medium containing G418 were found to produce progesterone following treatment with forskolin or dibutyryl cAMP for 48 h. Forskolin caused these cells to retract in the characteristic rounding response, as described in primary HG cultures. One clone, HGL5, was used for a detailed characterization of differentiated function. HGL5 cells retained the ability to increase progesterone production and convert exogenously added androstenedione to estradiol in response to agonists of the protein kinase-A pathway (forskolin and dibutyryl cAMP), but were not responsive to FSH or LH treatment. A key enzyme in the production of estradiol, cytochrome P450 aromatase, has proven difficult to maintain in long term cultures of granulosa cells. For that reason, we examined the expression of aromatase in the transformed HGL5 clone by monitoring mRNA levels. Aromatase mRNA increased by 4- to 5-fold after forskolin treatment, as determined by Northern analysis. This human granulosa cell culture line maintains many of the functions of normal cells and should provide an important model to study the molecular events controlling granulosa cell differentiation and function.

Aromatase↗
PubMed1994

In vitro evaluation of papaverine hydrochloride incompatibilities: a simulation of intraarterial infusion for cerebral vasospasm.

PURPOSE: To elucidate, in light of reports of complications associated with intraarterial infusion of papaverine hydrochloride, the known propensity of papaverine hydrochloride to form precipitate in combination with other solutions or pharmaceuticals. METHODS: Initially simulating a situation experienced during an intraarterial papaverine infusion for cerebral vasospasm, we mixed various concentrations of papaverine with serum, nonheparinized and heparinized saline, and nonionic contrast material. RESULTS: Papaverine in concentrations of 0.3% (300 mg/100 mL of normal saline) or greater formed a precipitate when mixed with human serum (blood). The precipitate crystals were 50 to 100 microns in size and could be returned to solution simply by the addition of more serum. CONCLUSION: Crystal emboli are a possible transient cause of complications experienced during treatment of vasospasm with its attendant altered flow dynamics.

Cerebral Angiography↗
PubMed1994

Physical characteristics of balloon catheter systems used in temporary cerebral artery occlusion.

PURPOSE: To compare and contrast the physical characteristics of balloon catheter systems used for temporary cerebrovascular occlusion. METHOD: Commonly used temporary occlusion systems were evaluated to determine: (a) balloon compliance; (b) balloon diameter versus volume; (c) balloon pressure versus volume; (d) simulated vessel wall pressure versus volume; (e) balloon failure volume; and (f) balloon deflation rate. Observations were made concerning construction differences that affect the potential safety of a balloon system or the way it is used. RESULTS: The nondetachable balloon system demonstrating the best compliance characteristics and lowest radial pressure generation was the nondetachable silicone balloon (Interventional Therapeutics Corporation, San Francisco, Calif). Diameter versus volume curves for all systems reveal an initial nonlinear expansion that could contribute to vessel overexpansion during occlusion. CONCLUSION: Balloon systems vary in construction, method of introduction, and compliance. Knowledge of these characteristics, as well as of nonlinear balloon expansion, should aid balloon selection and appropriate use while helping to minimize complications.

Animals↗
PubMed1994

Transient severe brain stem depression during intraarterial papaverine infusion for cerebral vasospasm.

A 63-year-old woman had severe, symptomatic cerebral vasospasm secondary to subarachnoid hemorrhage. We initiated simultaneous infusions of papaverine into her left vertebral and left internal carotid arteries. Twenty-five minutes after the infusions had begun, the patient had a transient reaction of respiratory arrest followed by rapid, progressive loss of brain stem function.

Apnea↗
PubMed1994

Therapeutic occlusion of major vessels, test occlusion and techniques.

Temporary and permanent cerebrovascular occlusion have become well-accepted endovascular tools. Temporary vessel occlusion and cerebral blood flow analysis help to predict the adequacy of cerebral collateral flow prior to vessel sacrifice. Permanent cerebrovascular occlusion remains a useful alternative endovascular tool when complex lesions of the cervical region, skullbase, and brain are not treatable by surgical or intralesional techniques.

Angioplasty, Balloon↗
PubMed1994

Provocative pharmacologic testing during arterial embolization.

Provocative pharmacologic testing reliably predicts the safety of arterial embolization. Arteries with intra-axial destinations are tested with a barbiturates and arteries with extra-axial destinations are tested with lidocaine. Testing is quickly and easily performed, essentially risk-free, and reduces the incidence of complications. Despite extensive knowledge of microvascular anatomy, anatomic variations and branches below the limits of angiographic resolution make provocative pharmacologic testing essential to minimize complications during arterial embolization.

Adolescent↗
PubMed1993

Angiotensin increases aldosterone synthase mRNA levels in human NCI-H295 cells.

Understanding the regulation of aldosterone secretion has been hampered by the lack of a cell culture system that remains chronically responsive to angiotensin stimulation. NCI-H295 cells, cultured from a human adrenocortical tumor, express the three major pathways of adrenal steroidogenesis and produce small amounts of aldosterone during basal culture. We have determined changes in aldosterone production and in aldosterone synthase (AS, P45011B2) mRNA levels in these cells in response to angiotensin II (AII) and forskolin. Culture of NCI-H295 cells with 10(-7) M AII or with 10(-5) M forskolin stimulated aldosterone production and increased AS mRNA levels, though the effect of AII was greater. When cells were cultured with increasing concentrations of AII from 10(-11) through 10(-8) M, a dose-dependent increase in AS mRNA levels paralleled increases in aldosterone production. In view of these findings, these human adrenocortical cells should be useful for exploring mechanisms regulating aldosterone production.

Adrenal Cortex Neoplasms↗
PubMed1993

Human NCI-H295 adrenocortical carcinoma cells: a model for angiotensin-II-responsive aldosterone secretion.

Excessive secretion of aldosterone from the adrenal results in the most common form of endocrine hypertension. An understanding of the regulatory processes involved in aldosterone synthesis and release is needed to define the biomolecular mechanisms controlling excessive production of aldosterone. However, in vitro studies regarding the regulatory mechanisms of human aldosterone production have been limited because of difficulties in obtaining tissue and the subsequent isolation of aldosterone-secreting glomerulosa cells. Herein we describe an adrenocortical carcinoma cell line, NCI-H295, which provides a suitable angiotensin-II (AII)-responsive model system to investigate the acute and chronic regulation of aldosterone synthesis. The cells were characterized with regard to the effects of AII on second messenger systems, aldosterone release, and levels of aldosterone synthase (P450c18) mRNA. In the presence of lithium, AII caused a rapid, but transient, increase in the production of inositol tris- and bisphosphates, whereas a prolonged gradual accumulation of inositol monophosphate occurred. Treatment with AII resulted in a 4.5-fold increase in total inositol phosphates in a concentration-dependent manner and an increase in intracellular cytoplasmic free Ca2+. Significant increases in aldosterone (3.5-fold) were detected within 1 h of AII addition. Aldosterone release occurred in a concentration-and time-dependent manner. The type 1 AII (AT1) receptor was shown to be responsible for activation of phosphoinositidase-C, increased intracellular free Ca2+, and aldosterone production, as determined by use of the AT1 receptor antagonist DuP753. In addition, AII treatment resulted in a time-dependent increase in levels of P450c18 mRNA, as detected by RNAse protection assay. In summary, NCI-H295 cells provide a valuable model system to define mechanisms regulating human aldosterone production.

Adrenal Cortex Neoplasms↗