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Biomedical subjects

J Glass

Publications and source records attributed to J Glass.

At least 55 records · Page 3Linked to original sources
PubMed1996

Therapy of primary CNS lymphoma with methotrexate-based chemotherapy and deferred radiotherapy: preliminary results.

Disease-free survival in primary CNS lymphoma has improved with the advent of methotrexate-based pre-irradiation chemotherapy. Prolonged response durations have been noted in six of eight patients refusing radiation therapy in two of our prior series. We have treated an additional 11 patients with methotrexate-based chemotherapy without subsequent planned irradiation. Some received maintenance chemotherapy. Most have had durable responses with little or no toxicity. Prolonged responses can be maintained without radiation therapy, thus avoiding potential long-term radiation toxicity.

Adult↗
PubMed1996

Neuronal pattern correlates with the severity of human immunodeficiency virus-associated dementia complex. Usefulness of spatial pattern analysis in clinicopathological studies.

The spatial distributional pattern of neurons, in the superior frontal gyrus of 32 subjects who died of acquired immune deficiency syndrome, was examined. The patients were classified as nondemented, mildly demented, and severely demented, and some were treated with the anti-retroviral drug zidovudine. Spatial statistical techniques were employed to investigate the degree of clustering in the individual cases and various groups. We found that the cluster pattern of large and small neurons differed significantly with increasing severity of dementia but was not influenced by the duration of zidovudine treatment. We conclude that this is a sensitive technique for clinicopathological correlations and that the differences may result from loss of specific neuronal populations, which could determine the degree of dementia.

AIDS Dementia Complex↗
PubMed1995

Iron binding, a new function for the reticulocyte endosome H(+)-ATPase.

The significance of the H(+)-ATPase in iron absorption by rabbit reticulocytes is explored using isolated endosomes, effects of inhibitors, and the purified proton pump. We have recently reported H(+)-ATPase-mediated iron transfer across a liposomal membrane (Li et al., 1994). In this report, the effect of H(+)-ATPase inhibitors on iron mobilization is investigated at pH 6.0 in the presence of 15 microM FCCP in order to dissociate 59Fe(III) from transferrin and eliminate the kinetic effects of acidification by the ATPase. Iron transport by isolated endosomes is decreased 50% by the cation pore inhibitor dicyclohexylcarbodiimide (DCCD) for ascorbate-mediated iron mobilization and increased by 40-50% when NADH and ferrocyanide are used as electron donors. In contrast, the ATPase hydrolysis inhibitors N-methylmaleimide (NEM) and 7-chloro-4-nitrobenz-2-oxa-1,3-diazole (NBD) increase iron mobilization when NADH and ferrocyanide are used as reductants but have negligible effects for ascorbate. The differential inhibition or enhancement by DCCD, NEM, and NBD with respect to the reductants used for mobilization indicates that the H(+)-ATPase may be involved in the multiple pathways or iron transport found in isolated rabbit reticulocyte endosomes. Effects of inhibitors of ATP hydrolysis suggest significant structural interactions between the proton pump and sites for iron binding and/or reduction. The isolated H(+)-ATPase binds iron as revealed by using nondenaturing electrophoretic and chromatographic methods. One class of iron binding sites is suggested to be the 17.5 kDa proton pore subunits of the H(+)-ATPase which also covalently react with DCCD.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Chloro-7-nitrobenzofurazan↗
PubMed1995

Preservation of cranial nerve function after treatment of acoustic neurinomas with fractionated stereotactic radiotherapy. Preliminary observations in 26 patients.

Twenty-seven acoustic tumors in 26 patients were treated with multiple fractionated linear-accelerator-based stereotactic radiotherapy (SRT). All patients with intact pretreatment facial nerve function with either small or large tumor volumes have thus far experienced no treatment-related facial neuropathy, including 9 patients with a mean follow-up of 22.4 +/- 1.6 months. The incidence of evaluable trigeminal neuropathy was 13%, and in 5 of 7 patients with serviceable pretreatment hearing, audiometry was unchanged in the immediate posttreatment period. Longer follow-up will be necessary to evaluate hearing preservation after SRT. Tumor response with central necrosis was seen in all assessable patients. SRT can be performed for cerebellopontine angle tumors with accuracy and reproducibility. It achieves a biological response similar to single fraction radiosurgery and may lower the incidence of facial and trigeminal neuropathies.

Adult↗
PubMed1995

Echo-planar MR cerebral blood volume mapping of gliomas. Clinical utility.

Neovascularization is a common phenomenon in gliomas. MR imaging cerebral blood volume (CBV) mapping utilizes ultrasfast echo-planar imaging and simultaneous use of gadolinium-based contrast material. To determine the utility of MR CBV mapping in the clinical evaluation of gliomas, we followed 15 patients with serial studies. This technique provided functional information that was not evident with conventional CT or MR imaging. Low-grade tumors demonstrated homogeneously low CBV, while high-grade tumors often showed areas of both high and low CBV. The maximum tumor CBV/white matter ratio was compared between low- (n = 3) and high-grade gliomas (n = 5) in patients without previous treatment and with histologic verification (n = 8) and was significantly higher in high-grade gliomas (p < 0.01). High CBV foci in nonenhancing tumor areas were present in 2 cases. The distinction between radiation necrosis and active tumor could be made correctly in 3 of 4 cases. The information provided by MR CBV mapping has the potential to be an adjunct in the clinical care of glioma patients.

Adolescent↗
PubMed1994

Regulation of iron uptake and transport by transferrin in Caco-2 cells, an intestinal cell line.

Caco-2 cells grown in bicameral chambers, a model of intestinal epithelial iron transport (Biochim. Biophys. Acta (1991) 1070, 205-208), were used to study the effect of apo-transferrin (apo-Tf) in the basal chamber on 59Fe uptake from the apical surface, intracellular 59Fe distribution, and 59Fe transport into the basal chamber. Caco-2 cells were grown with varying amounts of iron to achieve cells that were either iron-deficient (FeD), or normal iron status (FeN), or iron-loaded (FeH). The effect of apo-Tf was most marked in FeD cells with the transport of 59Fe from 1 microM 59Fe-ascorbate on the apical side to the basal chamber measured as (22.2 +/- 3.0) x 10(4), (8.2 +/- 0.6) x 10(4), and (2.7 +/- 0.4) x 10(4) atoms 59Fe/cell/min in the presence of apo-Tf, BSA, and no added protein, respectively. Unexpectedly in FeD cells total 59Fe uptake (i.e., both 59Fe in the cells and that transported into the basal chamber) was decreased by basolateral apo-Tf with total uptake of (2.6 +/- 0.3) x 10(5), (4.8 +/- 0.6) x 10(5), and (4.8 +/- 0.7) x 10(5) atoms/cell/min with apo-Tf, BSA, and no additions, respectively. Analysis of intracellular 59Fe by isoelectrofocusing in polyacrylamide gels demonstrated 59Fe migrating both with a basic pI and with the pI values of ferritin (Ft) at a ratio of 200:1 (basic pI moiety: ferritin) in FeD cells. The presence of Tf further decreased the small amount of 59Fe in Ft. These studies demonstrate that basolateral Tf affects the apical uptake of 59Fe, the intracellular distribution of 59Fe, and the transport of 59Fe across intestinal epithelium, the latter effect occurring even when cellular content of ferritin is high.

Biological Transport↗
PubMed1994

The H(+)-ATPase from reticulocyte endosomes reconstituted into liposomes acts as an iron transporter.

The H(+)-ATPase from reticulocyte endosomes was purified and reconstituted into liposomes, and protein-dependent iron transport was observed. Reconstitution of the H(+)-ATPase into liposomes was performed by sonicating a lipid mixture, with a composition similar to the reticulocyte plasma membrane, in a buffer containing ferric citrate. The nonencapsulated iron:citrate was removed by gel filtration and the proteoliposomes diluted into 1 mM FerroZine. Upon addition of ascorbate, an initial efflux of 2.9 +/- 0.3 x 10(-2) mumol of iron/mg of ATPase/min and 56 +/-7% of total internal Fe(II) was detected by formation of the Fe(II)-FerroZine complex with an absorbance at 562 nm or radioactivity of 59Fe(II)-FerroZine following separation using gel filtration. Both thiosulfate and ferrocyanide could substitute for ascorbate. Citrate or EGTA could substitute for FerroZine. The initial rate of Fe(II) efflux was decreased by 41 or 17% using 100 microM of the cation channel inhibitor N,N'-dicyclohexylcarbodiimide or 70 microM of the ATP hydrolysis inhibitor N-ethylmaleimide, respectively, but was unaffected by the presence of ATP. The amount of iron transported was decreased 51 or 39% by 100 microM N,N'-dicyclohexylcarbodiimide or 70 microM of the ATPase inhibitor 7-chloro-4-nitrobenz-2-oxa-1,3-diazole. The amount of Fe(III) transport was 80% lower than Fe(II) when reductants were not present internally or externally although the apparent rate constants were identical when ascorbate was externally present. These results suggest that this vacuolar H(+)-ATPase may transport iron.

Animals↗
PubMed1994

Pharmacokinetic properties of nitroxide-labeled albumin in mice.

We have conjugated bovine serum albumin (BSA) with a pyrrolidinyl nitroxide and report on the in vivo pharmacokinetic properties of this conjugate in mice. In vivo EPR measurements of nitroxide were obtained after intravenous injection of 30 mg of labeled BSA by analysis of the nitroxide signal from the tails of mice. Following in vivo nitroxide measurements, the animals were sacrificed by exsanguination and organs were removed for determination of nitroxide levels. The level of nitroxide as determined by in vivo measurements declined exponentially with time and had a half-life (t1/2) of 7 hours. Blood nitroxide levels also declined exponentially with time with an initial t1/2 of 70 minutes and a terminal t1/2 of 10 hours. Nitroxide concentration varied among different organs; no nitroxide was detected within brain whereas lung had high concentrations of nitroxide. Liver and kidney both had relatively low levels of oxidized nitroxide, though total nitroxide (reduced plus oxidized) accumulated in the kidneys with time. Nitroxide-labeled BSA was well tolerated by the mice, is relatively stable, and is mainly confined to the intravascular space. Nitroxide-labeled albumin may be useful as a contrast agent for MRI or EPR imaging.

Animals↗
PubMed1994

Methodological issues in the administration of multiple doses of smoked cocaine-base in humans.

Many methodological issues exist in human laboratory research with smoked cocaine-base that include safety, precision of dose delivery of smoked cocaine, and the lack of an adequate placebo. All of these issues are particularly apparent with studies involving multiple doses of cocaine. Addressing these concerns is important in conducting parametric studies that require examining dose-response effects. The purposes of this study were to determine: 1) the safest interval between doses to deliver smoked cocaine; 2) the accuracy or reproducibility of administering precise and multiple doses of cocaine; 3) the potential for using a control dose of cocaine; and 4) the influence of multiple doses on these parameters. Six black males were given 10 doses of either 5 or 35 mg of cocaine-base at 15-, 30-, and 45-min intervals. The dependent measures included physiological, subjective, and performance responses. These measures were taken prior to dosing and at specific time intervals after each dose of smoked cocaine. The results showed: 1) dosing at 30-min intervals allowed sufficient time for recovery of blood pressure and heart rate to permit up to 10 doses to be safely administered; 2) reproducible blood cocaine levels were obtained with repeated dosing using a heated wire-coil device; 3) significant differences were observed between the 5- and 35-mg dose with 5 mg being a low enough dose to produce minimal effects; 4) acute tolerance was evidenced with multiple doses of cocaine for most of the measures; and 5) considerable between- and within-subject variability was observed in the pattern of responses to cocaine.

Administration, Inhalation↗
PubMed1994

Cytokine dysregulation in HIV-associated neurological disease.

AIDS is associated with three major neurological syndromes: dementia (HIVD), vacuolar myelopathy (VM) and plainful sensory neuropathy (PSN). The pathogenesis of these conditions remains unclear although they all demonstrate a marked increase in macrophage number and activation despite systemic immunosuppression. It was therefore of interest to determine the profile of cytokine and HIV expression in brain, spinal cord and peripheral nerves of AIDS patients with AD, VM and PSN, as compared to AIDS patients without neurological disease and seronegative controls. RNA was extracted from brain, spinal cord and peripheral nerve and RT/PCR for cytokine and HIV mRNA was performed. In situ RT/PCR was performed to determine the number and type of cells expressing cytokine message and this was compared to the number of cells containing HIV DNA detected with in situ PCR. We found a consistent profile of increased TNF alpha and decreased IFN gamma and IL4 in all three syndromes compared to AIDS patients without neurological disease. IL1 did not increase in parallel with TNF alpha IL10 was decreased in the VM tissue. HIV transcripts were increased in the AD brains compared to non-demented controls but were detected only occasionally in spinal cord and not at all in peripheral nerve. Preliminary data from in situ RT/PCR suggests that a large number of cells are expressing. TNF alpha but only a small number are infected with HIV.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS Dementia Complex↗
PubMed1994

Aluminum alters the compartmentalization of iron in Friend erythroleukemia cells.

Aluminum (Al) accumulation in renal failure patients can result in encephalopathy, osteomalacia, and anemia. Since the cellular mechanisms of Al toxicity are not completely understood we used cultured Friend erythroleukemia cells (FEC) as a model system of Al-induced anemia. In this system Al accumulation leads to decreased cell growth and hemoglobin synthesis despite increased iron (Fe) uptake by transferrin (Tf) endocytosis. In FEC we evaluated the effect of Al on the cellular and subcellular accumulation of Fe, ferritin concentration, the uptake of Fe by ferritin, the exit of cellular Fe, and membrane lipid peroxidation. FEC were grown in media with or without the addition of Al-Tf and studies were done at 24, 48, 72, and 96 hours after plating. The highest concentration of intracellular Al was found in mitochondria with lesser amounts in the nucleus, and the least was in cytosol. The rate of Fe uptake was higher in Al-loaded FEC without a proportionally increased rate of exit. This resulted in higher concentrations of Fe in Al-loaded FEC. Subcellular fractionation following the uptake of 59Fe, 125I-Tf in Al-loaded FEC showed increased uptake of 59Fe in the nuclear and mitochondrial compartments with no increase in the cytosol. Al-loaded FEC showed decreased ferritin content and decreased uptake of 59Fe by ferritin. Increased membrane lipid peroxidation occurred in Al-loaded FEC at 96 hours as assessed by cellular malonyldialdehyde accumulation. These results indicate that Al disrupts Fe metabolism in FEC by increasing cellular Fe content with increased compartmentalization of Fe in the mitochondria and nuclei, decreased ferritin content, and decreased uptake of Fe by ferritin.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum↗
PubMed1994

Iron status affects aluminum uptake and transport by Caco-2 cells.

To study the cell biology of aluminum uptake and transport in intestinal epithelia, an in vitro system based on intestine-derived Caco-2 cells grown in bicameral chambers was used. Aluminum was offered on the apical surface of Caco-2 cell monolayers as either aluminum citrate, aluminum lactate or aluminum nitrilotriacetate at 1:2 molar ratios, and the aluminum uptake into the cells and transport into the basal chamber were measured. The kinetics of cellular uptake of aluminum were different for the three chelators, although with all three chelators a final cellular concentration of approximately 50 nmol/mg cell protein was achieved. The total transport of aluminum into the basal chamber was greater for aluminum citrate and aluminum nitrilotriacetate than for aluminum lactate, suggesting that the chelator may direct aluminum into compartments from which aluminum is more easily transported. The iron status of the Caco-2 cells significantly affected both cellular uptake and transport of aluminum. Both iron-depleted and iron-overloaded cells exhibited significantly lower aluminum transport than cells of normal iron status. Aluminum loading of the Caco-2 cells had adverse effects on 59Fe2+ and 59Fe3+ transport compared with that of normal cells. These findings suggest that the Caco-2 cell line grown in bicameral chambers provides a model for studying aluminum transport, that aluminum uptake and transport to the basal chamber were affected by the chelator used, and that aluminum uptake and transport pathways are similar to those of iron.

Aluminum↗
PubMed1994

Role of redox systems on Fe3+ uptake by transformed human intestinal epithelial (Caco-2) cells.

Caco-2 cells were used as a model of human intestinal epithelium to investigate the role of redox systems in transepithelial transport of 59Fe3+. The cells reduced Fe3+ present in the apical medium; the reduction was 50% inhibited by adriamycin and p-chloromercuribenzoate. Addition of [14C]ascorbate to the basolateral medium resulted in accumulation of 14C radioactivity in both cells and apical medium; apical radioactivity increased with time and was probably caused by paracellular flux. The cells provided Fe3+ reduction capacity to the apical incubation medium. Addition of ascorbate to the basolateral medium increased this reduction capacity 2-fold and the cellular uptake of 59Fe3+ 1.8-fold. Adriamycin significantly inhibited both cellular 59Fe uptake and Fe transport into the basolateral side. The results indicate that Caco-2 cells reduce apical Fe3+ by two parallel mechanisms: by a plasma membrane ferrireductase and by the secretion of reductants of either cellular or basolateral origin. The data support a model for Fe3+ intestinal absorption in which cell-mediated Fe3+ reduction occurs before cellular Fe uptake.

Ascorbic Acid↗
PubMed1994

Preirradiation methotrexate chemotherapy of primary central nervous system lymphoma: long-term outcome.

The treatment of primary central nervous system lymphoma with chemotherapy prior to whole-brain radiation therapy (WBRT) has improved outcome considerably in this previously fatal disease. Complete or partial responses to intravenous methotrexate (3.5 gm/sq m with leucovorin rescue every 3 weeks for two to four cycles) were seen in 12 of 13 patients originally treated. A total of 25 patients (including the original 13) have now been treated with one to six cycles of methotrexate every 10 to 21 days prior to WBRT. Twenty-two had partial or complete responses, with a median duration of response of 32 months. Median survival time was 33 months (42.5 months in those responding to therapy). Nine patients are alive and without evidence of disease 9 to 122 months following therapy. Acute and long-term toxicities were minimal. Systemic methotrexate administration prior to WBRT is well tolerated and produces long-term survival.

Adult↗
PubMed1994

Housework, paid work, and depression among husbands and wives.

The National Survey of Households and Families was used to test competing explanations of how the distribution of housework and paid work among couples affects depressive symptomatology. Considerations of equity predict that the fair distribution of labor across spouses will alleviate depression, while role theory predicts that the performance of multiple, engaging roles will inhibit depression, irrespective of equity across spouses. Results confirm that paid employment is associated with reduced depression among both husbands and wives until work hours exceed an upper threshold. However, time spent in housework is universally associated with increased depression, no matter what other role constellations exist. Little evidence supports the notion that equity in the division of labor (either paid or unpaid) inhibits depression, but perceptions of equity are significantly associated with lower levels of depression. In particular, husbands are strongly affected by perceived equity in the performance of paid work, while wives are strongly affected by perceived equity in the performance of housework.

Adult↗
PubMed1993

Intravascular lymphomatosis. A systemic disease with neurologic manifestations.

BACKGROUND: Intravascular lymphomatosis (IL) is a systemic neoplasm that often involves the nervous system, inducing progressive neurologic deficits in the setting of undiagnosed or quiescent extranodal non-Hodgkin lymphoma. METHODS: The clinical and pathologic files of the Massachusetts General Hospital and New York University Medical Center and the English language literature were reviewed to identify all reports of intravascular lymphomatosis (angioendotheliomatosis) or other examples of a diffuse proliferation of neoplastic cells filling capillaries, arterioles, and venules. RESULTS: The authors report seven patients with IL and note 114 patients reported in the literature. Almost two-thirds (63%) of patients had neurologic manifestations, without abnormalities on bone marrow biopsy, chest and abdominal tomographic examinations for adenopathy, and cerebrospinal fluid (CSF) analysis. All patients had one or more of four syndromes, each reflecting a vascular occlusive process: progressive, multifocal cerebrovascular events; paraparesis, pain, and incontinence; a subacute encephalopathy; and peripheral or cranial neuropathies. CONCLUSIONS: The unexplained presence of any one or more of these neurologic syndromes should alert the physician to the possible presence of this disease.

Female↗