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S Wallace

Publications and source records attributed to S Wallace.

At least 55 records · Page 3Linked to original sources
PubMed2000

Assessment of resistance to paclitaxel of murine tumors by (99m)Tc-MIBI/(201)Tl dual-radionuclide imaging.

This study investigated P-glycoprotein (Pgp) expression by murine tumors with and without resistance to paclitaxel and the role of (99m)Tc-2-methoxyisobutylisonitrile (MIBI)/(201)Tl imaging in predicting the effect of paclitaxel. Antitumor effect of paclitaxel and biodistribution of the radiopharmaceuticals were evaluated in mice bearing four tumor types. Pgp expression did not correlate with the antitumor efficacy of paclitaxel. Although the absolute uptake of (99m)Tc-MIBI did not correlate with Pgp expression, (99m)Tc-MIBI could predict paclitaxel sensitivity by its higher uptake.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

Menkes kinky hair disease: an unusual case.

Menkes disease is a rare X-linked recessive disease of copper metabolism. Clinical manifestations begin in the first few months of life or even in the neonatal period. Hypothermia, hypotonia, poor weight gain, seizures and neurodevelopmental delay or regression are seen. Outcome is poor, with death occurring usually by 3 years of age. A characteristic facial appearance with steely hair suggest the diagnosis. Neuroimaging usually shows cortical atrophy, extra-axial fluid collections and progressive and extensive degeneration of grey matter with secondary demyelination. We describe an atypical, but biochemically proven case of Menkes disease with atypical clinical and radiological features. Our patient had a large head, atypical electron microscopy appearances of the hair and predominant diffuse white matter involvement on neuroimaging, but a low serum copper level and a high 64CU uptake in fibroblasts (89.5 ng/mg of protein) confirmed the diagnosis.

Brain↗
PubMed2000

Retinitis and dementia in a pregnant girl: an unusual case.

A 14-year-old pregnant Caucasian girl presented with a 1-week history of dementia. She had presented 1 year prior with acute unilateral visual impairment and was noted to have macular degeneration of presumed infective aetiology. This evolved to a pigmentary macular lesion. During the course of the current presentation she developed myoclonic jerks. An electroencephalogram revealed periodic spike and slow wave complexes at 1-2 second intervals. Blood and cerebrospinal fluid examination showed raised anti-measles IgG antibody titres. Intrathecal synthesis of anti-measles virus antibody was demonstrated unequivocally and a diagnosis of subacute sclerosing panencephalitis was made. A healthy male infant was delivered by elective caesarean section at 33 weeks' gestation. She continued to deteriorate clinically despite treatment with intraventricular alpha-interferon. She had not had primary immunization against measles.

Adolescent↗
PubMed2000

Reproducibility and complications in gene searches: linkage on chromosome 6, heterogeneity, association, and maternal inheritance in juvenile myoclonic epilepsy.

Evidence for genetic influences in epilepsy is strong, but reports identifying specific chromosomal origins of those influences conflict. One early study reported that human leukocyte antigen (HLA) markers were genetically linked to juvenile myoclonic epilepsy (JME); this was confirmed in a later study. Other reports did not find linkage to HLA markers. One found evidence of linkage to markers on chromosome 15, another to markers on chromosome 6, centromeric to HLA. We identified families through a patient with JME and genotyped markers throughout chromosome 6. Linkage analysis assuming equal male-female recombination probabilities showed evidence for linkage (LOD score 2.5), but at a high recombination fraction (theta), suggesting heterogeneity. When linkage analysis was redone to allow independent male-female thetas, the LOD score was significantly higher (4.2) at a male-female theta of.5,.01. Although the overall pattern of LOD scores with respect to male-female theta could not be explained solely by heterogeneity, the presence of heterogeneity and predominantly maternal inheritance of JME might explain it. By analyzing loci between HLA-DP and HLA-DR and stratifying the families on the basis of evidence for or against linkage, we were able to show evidence of heterogeneity within JME and to propose a marker associated with the linked form. These data also suggest that JME may be predominantly maternally inherited and that the HLA-linked form is more likely to occur in families of European origin.

Alleles↗
PubMed2000

Conjugation of camptothecins to poly-(L-glutamic acid).

Conjugation of water-insoluble cancer chemotherapeutic drugs to macromolecular polymers can lead to improved pharmaceutical properties and improved therapeutic ratios due to accumulation of the polymer-drug conjugate in tumor tissue through the enhanced permeability and retention (EPR) to macromolecules associated with tumor vasculature. Pharmaceutical shortcomings of certain active camptothecins including difficulty in formulation and instability of the active lactone form due to interactions with human albumin might be improved by conjugation to polymers. In this report, conjugations of camptothecin (CPT), 10-hydroxy-CPT, and 9-amino-CPT to poly-(L-glutamic acid) (PG) are described; coupling was accomplished either through the 20(S)-hydroxyl or 9 and 10 substituents with and without the use of a glycine linker. Studies using a PG paclitaxel conjugate (PG-TXL), which is currently in Phase I testing, demonstrated that PG enhanced aqueous solubility, prolonged plasma residence time, and greatly increased the distribution of paclitaxel to tumor tissue in a murine model. In this report, we describe the use of similar conjugation technology for CPT derivatives and demonstrate that these difficult to formulate compounds can be rendered water soluble, that their maximum tolerated doses are increased, and that they retain substantial anti-tumor activity in syngeneic and xenogeneic tumor models. Preliminary data suggest that PG with molecular weights between 37 and 50 kDa with CPT loading between 14% and 37% with or without glycine linkers display enhanced efficacy compared with nonconjugated camptothecins administered at their maximum tolerated dose.

Animals↗
PubMed2000

Perceptions of health and use of ambulatory care: differences between Korean and White elderly.

This study identifies whether culturally based differences in perceptions of health resulted in differences in ambulatory care use among the elderly. METHODS. The authors conducted stratified Poisson regressions on data from a 1992 survey of older Koreans and Whites in Los Angeles County. The models included measures of demographics, health, functioning, income, insurance, social support, and culture (perceptions of health or other beliefs). RESULTS. Descriptive findings showed older Koreans had more ambulatory physician visits, poorer functioning, and poorer perceptions of their health than Whites. Multivariate findings showed that positive perceptions of health independently reduced office visits for both Koreans and Whites, but the effect was significantly smaller for Koreans. Other cultural differences also affected use. DISCUSSION. The findings highlight differences between older Koreans and Whites' responses to physical and socioeconomic conditions and the importance of cultural sensitivity in the health care delivery system.

Aged↗
PubMed2000

Helical CT of prostate cancer: early clinical experience.

OBJECTIVE: [corrected] This study was undertaken to determine whether helical CT can reveal carcinoma of the prostate detected at transrectal sonographically guided biopsy. MATERIALS AND METHODS: Helical CT of the prostate was performed in 35 patients: 25 with proven prostate cancer (group I) and 10 without cancer detected at biopsy (group II). All patients in group I had cancer in the peripheral zone, and three of these showed foci of cancer in the transitional zone. All patients of group II had undergone at least two sets of biopsy before CT. In group I, areas of contrast enhancement in the peripheral zone of the prostate were defined as suggestive of cancer and correlated with the histopathologic findings. RESULTS: Helical CT revealed cancer in 22 (88%) of 25 patients with proven prostate cancer. Transrectal sonographically guided biopsy detected 102 cancer sites in the peripheral zone and three in the transitional zone in these 25 patients. Helical CT accurately revealed 59 peripheral zone cancer sites (58%) but did not reveal 43 cancer sites (42%). Abnormal contrast enhancement in the peripheral zone that was not caused by cancer was seen in 10% of suspicious lesions. The three cancer sites in the transitional zone were indistinguishable from benign nodular changes. CONCLUSION: Prostate cancer detected at transrectal sonographically guided biopsy appears on helical CT of the prostate as focal or diffuse areas of contrast enhancement in the peripheral zone. A prospective study has been initiated to determine the accuracy, sensitivity, and specificity.

Aged↗
PubMed2000

Comparison of action of paclitaxel and poly(L-glutamic acid)-paclitaxel conjugate in human breast cancer cells.

The new anticancer agent poly(L-glutamic acid)-paclitaxel (PG-TXL) is a conjugate of paclitaxel and the water-soluble polyglutamate carrier. The observation that PG-TXL appears to possess antitumor activity superior to free paclitaxel in preclinical studies suggests that PG-TXL might possess favorable pharmacokinetic properties and/or have a mechanism of action different from that of paclitaxel. The purpose of this study was to compare the pharmacological action of PG-TXL and free paclitaxel in a panel of breast cancer cell lines with emphasis on their ability to induce apoptosis, their effects on cell cycle progression, and their cellular uptake. Morphological analysis and biochemical characterizations demonstrated that both compounds have similar abilities to induce apoptosis in cells expressing wild-type p53 (MCF-7) or mutant p53 (MDA-MB435 and MDA-MB453). Although MCF-7 cells were less sensitive to each compound than MDA-MB435 and MDA-MB453 cells, transfection experiments demonstrated that p53 did not appear to play a significant role in drug-induced cell death with either agent. Flow cytometry analysis further revealed that both free paclitaxel and PG-TXL induced a characteristic G2/M arrest in the cell cycle, consistent with the disturbance of microtubule polymerization as their mechanism of action. Western blot analysis showed that paclitaxel and PG-TXL downregulated HER2/neu expression in a similar fashion. HPLC analysis revealed that paclitaxel was released from the PG-TXL conjugate in vitro. The released paclitaxel, not the glutamic acid polymer, was subsequently transported into the cells. These results suggest that PG-TXL exerts its anticancer activity by continuous release of free paclitaxel, and that the favorable pharmacokinetics and drug distribution of the PG-TXL conjugate in vivo are likely the main factors contributing to its superior anticancer activity.

Antineoplastic Agents, Phytogenic↗
PubMed2000

Tumor irradiation enhances the tumor-specific distribution of poly(L-glutamic acid)-conjugated paclitaxel and its antitumor efficacy.

The poly(L-glutamic acid)-paclitaxel (PG-TXL) conjugate has been shown to exhibit significantly greater antitumor activity than conventionally formulated paclitaxel (TXL) against solid tumors (Li et al., Cancer Res., 58: 2404-2409, 1998). Here we report that local tumor irradiation enhanced the distribution of PG-TXL given 24 h later to ovarian OCa-1 carcinoma implanted i.m. in C3Hf/Kam mice. Radiation significantly increased tumor uptake of PG-TXL and tumor vascular permeability, caused elevation of the serum concentration of vascular endothelial growth factor, and arrested OCa-1 cells in the G1 phase of cell cycle. The enhancement factors, as measured by incremental tumor growth delay compared with PG-TXL alone, ranged from 1.36-4.44. Complete tumor regression was also observed at a higher radiation dose (>10 Gy) and a higher PG-TXL dose (>80 mg equivalentTXL/kg). Furthermore, combined radiation and PG-TXL produced a significantly greater tumor growth delay than treatment with radiation and TXL when both drugs were given at the same equivalent TXL dose of 60 mg/kg 24 h after tumor irradiation (enhancement factors, 4.44 versus 1.50). These data suggest that conjugation of TXL to poly(L-glutamic acid) is necessary for improved response and that the supra-additive effect of combined radiation and PG-TXL therapy is due in part to modulation of the enhanced permeability and retention effect of macromolecules by radiation. We propose a treatment strategy combining radiation and macromolecular chemotherapy that may have important clinical implications in terms of scheduling and optimization of the therapeutic ratio.

Animals↗
PubMed1999

Serotonin transporter (5-HTT) and gamma-aminobutyric acid receptor subunit beta3 (GABRB3) gene polymorphisms are not associated with autism in the IMGSA families. The International Molecular Genetic Study of Autism Consortium.

Previous studies have suggested that the serotonin transporter (5-HTT) gene and the gamma-aminobutyric acid receptor subunit beta3 (GABRB3) gene, or other genes in the 15q11-q13 region, are possibly involved in susceptibility to autism. To test this hypothesis we performed an association study on the collection of families from the International Molecular Genetic Study of Autism (IMGSA) Consortium, using the transmission disequilibrium test. Two polymorphisms in the 5-HTT gene (a functional insertion-deletion polymorphism in the promoter and a variable number tandem repeat in the second intron) were examined in 90 families comprising 174 affected individuals. Furthermore, seven microsatellite markers spanning the 15q11-q13 region were studied in 94 families with 182 affected individuals. No significant evidence of association or linkage was found at any of the markers tested, indicating that the 5-HTT and the GABRB3 genes are unlikely to play a major role in the aetiology of autism in our family data set.

Autistic Disorder↗
PubMed1999

Evaluation of In-111 DTPA-paclitaxel scintigraphy to predict response on murine tumors to paclitaxel.

UNLABELLED: Our goal was to determine whether scintigraphy with 111In-DTPA-paclitaxel could predict the response to chemotherapy with paclitaxel. METHODS: Ovarian carcinoma (OCA 1), mammary carcinoma (MCA-4), fibrosarcoma (FSA) and squamous cell carcinoma (SCC VII) were inoculated into the thighs of female C3Hf/Kam mice. Mice bearing 8 mm tumors were treated with paclitaxel (40 mg/kg). The growth delay, which was defined as the time in days for tumors in the treated groups to grow from 8 to 12 mm in diameter minus the time in days for tumors in the untreated control group to reach the same size, was measured to determine the effect of paclitaxel on the tumors. Sequential scintigraphy in mice bearing 10 to 14 mm tumors was conducted at 5, 30, 60, 120, 240 min and 24 hrs postinjection of 111In-DTPA-paclitaxel (3.7MBq) or 111In-DTPA as a control tracer. The tumor uptakes (% injection dose/pixel) were determined. RESULTS: The growth delay of OCA 1, MCA-4, FSA and SCC VII tumors was 13.6, 4.0, -0.02 and -0.28 days, respectively. In other words, OCa 1 and MCA-4 were paclitaxel-sensitive tumors, whereas FSA and SCC VII were paclitaxel-resistant tumors. The tumor uptakes at 24 hrs postinjection of In-111 DTPA paclitaxel of OCA 1, MCA-4, FSA and SCC VII were 1.0 x 10(-3), 1.6 x 10(-3), 2.2 x 10(-3) and 9.0 x 10(-3) % injection dose/pixel, respectively. There was no correlation between the response to chemotherapy with paclitaxel and the tumor uptakes of 111In-DTPA-paclitaxel. CONCLUSIONS: Scintigraphy with 111In-DTPA-paclitaxel could not predict the response to paclitaxel chemotherapy. Although there was significant accumulation of the paclitaxel in the tumor cells, additional mechanisms must be operative for the agent to be effective against the neoplasm. 111In-DTPA-paclitaxel activity is apparently different from that of paclitaxel with Cremophor.

Animals↗
PubMed1999

Verification of brachytherapy dosimetry with radiochromic film.

The aim of this work is to empirically validate the optimized dose distribution calculated by the Nucletron Brachytherapy Planning System (v. 13.3) at a distance of 1.0 cm from a stepping source of high-dose-rate-iridium 192 (192Ir). The longitudinal dose distribution at 1.0 cm from a straight pathway of multiple-source positions is measured using radiochromic film and compared with the planning system's calculated results. The optical density of the exposed films was determined with a modified Scanditronix film scanner, and the film was calibrated with 192Ir using manually calculated exposure times. A calibration equation was used to convert scanner output to dose. Our results illustrate the significance of exacting geometry in the experimental setup due to the inverse square law and the small distances involved. The dose distribution calculated by the Nucletron Brachytherapy Planning System (v. 13.3), at a distance of 1.0 cm, is validated to within +/-4% of the measured dose distribution. The advantages and limitations of radiochromic film as a dosimetry tool are also addressed in this work.

Brachytherapy↗
PubMed1999

Evidence for linkage of adolescent-onset idiopathic generalized epilepsies to chromosome 8-and genetic heterogeneity.

Several loci and candidate genes for epilepsies or epileptic syndromes map or have been suggested to map to chromosome 8. We investigated families with adolescent-onset idiopathic generalized epilepsy (IGE), for linkage to markers spanning chromosome 8. The IGEs that we studied included juvenile myoclonic epilepsy (JME), epilepsy with only generalized tonic-clonic seizures occurring either randomly during the day (random grand mal) or on awakening (awakening grand mal), and juvenile absence epilepsy (JAE). We looked for a gene common to all these IGEs, but we also investigated linkage to specific subforms of IGE. We found evidence for linkage to chromosome 8 in adolescent-onset IGE families in which JME was not present. The maximum multipoint LOD score was 3.24 when family members with IGE or generalized spike-and-waves (SW) were considered affected. The LOD score remained very similar (3.18) when clinically normal family members with SW were not considered to be affected. Families with either pure grand mal epilepsy or absence epilepsy contributed equally to the positive LOD score. The area where the LOD score reaches the maximum encompasses the location of the gene for the beta3-subunit of the nicotinic acetylcholine receptor (CHRNB3), thus making this gene a possible candidate for these specific forms of adolescent-onset IGE. The data excluded linkage of JME to this region. These results indicate genetic heterogeneity within IGE and provide no evidence, on chromosome 8, for a gene common to all IGEs.

Adolescent↗
PubMed1999

Dose errors in the near field of an HDR brachytherapy stepping source.

The dose rate at point P at 0.25 cm in water from the transverse bisector of a straight catheter with an active stepping source (Nucletron microSelectron HDR source) with a dwell length of 2 cm was calculated using Monte Carlo code MCNP 4.A. The source step sizes were 1 cm and 0.25 cm. The Monte Carlo (MC) results were used for comparison with the results calculated with the Nucletron brachytherapy planning system (BPS) formalism, first with BPS variants and then with its respective MC calculated radial dose function and anisotropy function. The dose differences at point P calculated using the BPS formalism and variants are +15.4% and +3.1% for the source step size of 1 cm and 0.25 cm respectively. This reduction in dose difference is caused by the increased importance of errors in the anisotropy function with the smaller step size, which counter the errors in the radial dose function. Using the MC calculated radial dose function and anisotropy function with the BPS formalism. 1% dose calculation accuracy can be achieved, even in the near field, with negligible extra demand on computation time.

Algorithms↗
PubMed1999

Hepatic microcirculatory changes induced by hepatic artery embolization in rats: original investigation.

RATIONALE AND OBJECTIVES: To evaluate the effects of hepatic artery embolization (HAE), hepatic microcirculatory changes induced by HAE were assessed quantitatively in rats. METHODS: Using in vivo microscopy, the blood-flow velocity (BFV) through terminal portal venules (TPVs) and terminal hepatic venules (THVs) was measured during HAE with gelatin sponge powder (GSP), iodized oil (Lipiodol, 0.1, 0.2, and 0.4 mL/kg), or 0.1 mL/kg Lipiodol followed by GSP. RESULTS: After HAE with GSP, BFV through TPVs decreased significantly, but BFV through THVs did not decrease. After HAE with Lipiodol (0.2 and 0.4 mL/kg), BFV through TPVs decreased significantly, but BFV through THVs did not. After HAE with Lipiodol followed by GSP, BFV through both TPVs and THVs decreased significantly. CONCLUSIONS: Neither GSP nor Lipiodol adversely affects hepatic microcirculation when administered alone; however, HAE with a combination of Lipiodol and GSP does adversely affect hepatic microcirculation.

Animals↗
PubMed1999

Flow cytometric analysis of microsporidia belonging to the genus Encephalitozoon.

Flow cytometry was used in the identification of human microsporidia belonging to the genus Encephalitozoon. Microsporidian spores of Encephalitozoon hellem, E. cuniculi, and E. intestinalis were propagated in axenic cultures of monkey kidney E6 cells, purified with Percoll, and exposed to homologous and heterologous rabbit antiserum and monoclonal antibody prepared against E. hellem spores. After reaction to goat anti-rabbit immunoglobulin G (IgG) or goat anti-mouse IgG conjugated to fluorescein isothiocyanate, fluorescence histograms from gated data on light-scatter profiles showed that rabbit anti-E. hellem serum was reactive to E. hellem spores but also had cross-reactivity to spores of E. cuniculi and E. intestinalis. On the other hand, fluorescence histograms showed that rabbit anti-E. cuniculi and rabbit anti-E. intestinalis sera were reactive with homologous spores only. Monoclonal antibody prepared against E. hellem reacted only with spores of E. hellem. Neither the polyclonal antibodies nor the monoclonal antibodies reacted with Cryptosporidium parvum oocysts. Fluorescence histograms of spores treated with 10% formalin also showed reactivity, but the number of events in the most intense peaks of fluorescence was fewer (7 to 42%, depending on species) than the number of events in the most intense peaks of fluorescence for nontreated spores. By flow cytometry, formalin-treated and nontreated spores of Encephalitozoon were identified to the species level by using gated data on light-scatter profiles and analyzing the fluorescence histograms from the indirect immunofluorescence of the spores. Once a procedure is established for the isolation of Encephalitozoon spores from clinical specimens, identification of spores by flow cytometry may be useful not only for diagnosis but also for epidemiologic studies.

AIDS-Related Opportunistic Infections↗
PubMed1999

Changes in rat liver microcirculation after experimental hepatic arterial embolization: comparison of different embolic agents.

PURPOSE: To evaluate the effects of hepatic arterial embolization on hepatic microcirculation in the rat liver by using different particulate agents. MATERIALS AND METHODS: Polylactic acid microspheres, polyvinyl alcohol particles, and absorbable gelatin powder were injected into the hepatic artery of 50 rats. Saline was used as the control agent. Flow characteristics of hepatic microcirculation were qualitatively assessed on days 0 and 7 after embolization by using in vivo microscopy. Histologic specimens of the rat liver were analyzed. RESULTS: The polylactic acid (1-5 microns) injected into the hepatic artery was seen circulating through the sinusoids into the central venules. The slowing of flow observed with the injection of larger (50-200-micron) particles reflected the arterial occlusion occurring more proximally. After 7 days, all embolic agents caused vascular occlusion that led to necrosis and fibrosis. Networks of irregular, high-speed vessels that resembled arterioles and bypassed the normal sinusoids were observed. CONCLUSION: The necrotic areas observed after experimental distal occlusion of the hepatic arteries in the rats were bypassed by vessels similar to the capillarized sinusoids observed in the cirrhotic liver in humans. These vessels acted as sinusoidal shunts in the embolized territories.

Animals↗