bluuebunny/crossref_metadata_2025_split huggingface dataset:
Founder Effect in Patients with Unverricht‐Lundborg Disease on Reunion Island
Authors: Moulard Bruno , Darcel Françoise , Mignard Didier , Jeanpierre Marc , Genton Pierre , Cartault François , Yaouanq Jacqueline , Roubertie Agathe , Biraben Arnaud , Buresi Catherine , Malafosse Alain 
Published: September 2003

Summary:  Purpose: Unverricht‐Lundborg disease (ULD) is the most frequent form of progressive myoclonus epilepsy. ULD is caused mostly by a homozygous expansion of a dodecamer repeat in the cystatin B gene (CSTB) promoter. We present here a clinical and molecular study of 14 ULD patients originating from Reunion Island, a French island in the Indian Ocean. Methods: These ULD patients were clinically evaluated, and the diagnosis of ULD was confirmed molecularly. We analyzed 12 microsatellites flanking CSTB and estimated the date of introduction of the ULD mutation on Reunion Island. Results: These cases were clinically very similar, with the typical myoclonus syndrome associated with generalized tonic–clonic seizures, cerebellar involvement and, in some cases, mild mental deterioration. The mean age at onset was 9.6 years (range, 5–14 years), and the mean disease duration was 27 years (range, 5–47 years). The 14 patients harbored the typical ULD mutation, with variable degrees of expansion (mean of 56.3 repeats; range, 49–63). A founder effect was detected, with all but one of the Reunion ULD chromosomes displaying expansions belonging to the same haplotype, 1‐1‐1‐2‐6‐4‐3. We estimated the date of arrival of the most recent common ancestor (MRCA) of these patients on Reunion Island to the middle of the eighteenth century. Conclusions: These Reunion ULD patients displayed a homogeneous phenotype. Our molecular results are compatible with the instability of the repeat expansion and revealed a founder effect in Reunion ULD patients and the existence of a MRCA about 12 generations ago.
Voltage‐Dependent Block of N‐Methyl‐d‐Aspartate Receptors by the Novel Anticonvulsant Dibenzylamine, a Bioactive Constituent of l‐(+)‐β‐Hydroxybutyrate
Authors: Donevan Sean D. , White H. Steve , Anderson Gail D. , Rho Jong M. 
Published: September 2003

Summary:  Purpose: Previously we demonstrated that l‐(+)‐β‐hydroxybutyrate (L‐BHB), acetoacetate (ACA), acetone, and dibenzylamine (DBA) were anticonvulsant in an audiogenic seizure–susceptible model, and that DBA was a bioactive contaminant identified in commercial lots of L‐BHB. In the present study, we asked whether these effects could be mediated by ionotropic glutamate or γ‐aminobutyric acidA (GABAA) receptors. Methods: We studied the effects of both stereoisomers of BHB (as well as the racemate), ACA, and DBA on N‐methyl‐d‐aspartate (NMDA), α‐amino‐3‐hydroxy‐5methyl‐4‐isoxazole‐proprionic acid (AMPA), and GABAA receptors in cultured rodent neocortical neurons by using whole‐cell voltage‐clamp recording techniques. Results: Only L‐BHB and DBA exerted a concentration‐ and voltage‐dependent block of NMDA‐evoked currents, whereas none of the tested substrates affected AMPA‐ or GABA‐activated currents. The kinetics of whole‐cell block by L‐BHB and DBA were similar, providing additional evidence that DBA is responsible for the anticonvulsant activity of L‐BHB. Conclusions: BHB and ACA do not exert direct actions on GABAA or ionotropic glutamate receptors in cultured neocortical neurons. In addition, we provide additional evidence that DBA is responsible for the anticonvulsant activity of L‐BHB, and that this action may be mediated in part by voltage‐dependent blockade of NMDA receptors.
Association Analysis of a Polymorphism of Interleukin 1β (IL‐1β) Gene with Temporal Lobe Epilepsy in a Chinese Population
Authors: Jin Liri , Jia Yanbin , Zhang Boyu , Xu Qi , Fan Yu , Wu Liwen , Shen Yan 
Published: September 2003

Summary:  Purpose: Temporal lobe epilepsy with hippocampal sclerosis (TLE‐HS+) is one of the most common medically intractable epilepsies. Although the pathogenesis of HS+ still remains highly controversial, genetics may play a role as a predisposing factor. Previous evidence in a Japanese population shows that the homozygotes for allele 2 at position –511 of the interleukin (IL)‐1β gene promoter region (IL‐1β‐511*2/2) confers susceptibility to the development of HS. However, this result has not been confirmed in populations of European ancestry. Given that the discrepancy may be attributed to ethnic differences, our aim in this study was to test the validity of a previous report in another Asian population. Methods: This study consisted of total 112 nonlesional TLE patients of Chinese ancestry, and 115 ethnically matched control subjects. A 304‐base pair fragment in position of IL‐1β‐511 was amplified by polymerase chain reaction (PCR). The PCR products were digested with restriction enzyme AvaI, and run on a 12% polyacrylamide gel. We compared the frequency of this gene variation among 67 refractory TLE‐HS+ patients, 45 patients without HS (TLE‐HS−), and normal control subjects. Results: The heterozygous type (−511*1/2) is the most common genotype in our patient groups and controls. Allele 1 (−511C) and allele 2 (−511T) showed equal frequency (∼50%), which is similar to that (46%) in Japanese. Analysis of genotype and allele distribution showed no significant difference among the three groups (p > 0.05). Conclusions: In contrast with the lower frequency in the white population (35 and 34%) and higher rate in the population of African ancestry (60%), the allele –511T frequency in our present study is ∼50%, indicating differences in the distribution of allele frequencies in IL‐1β‐511 among different ethnic groups. In this Chinese population, however, we still did not find a strong association between IL‐1β‐511 polymorphism and the development of HS.
Efficacy of Topiramate in Children with Refractory Status Epilepticus
Authors: Kahriman Mustafa , Minecan Daniela , Kutluay Ekrem , Selwa Linda , Beydoun Ahmad 
Published: September 2003

Summary:  Purpose: Status epilepticus (SE) is a life‐threatening medical condition associated with significant morbidity and mortality that requires urgent medical intervention. Although several agents are available to treat SE, they occasionally fail to abort seizure activity. Topiramate (TPM) was anecdotally reported to be effective in adult patients with refractory SE. In this study, we evaluated the efficacy of TPM administered to children with this condition. Methods: We retrospectively reviewed the pediatric SE database at the University of Michigan Medical Center and identified three children with refractory SE who were treated with TPM. Those children failed to respond to treatment with benzodiazepines, phenytoin, phenobarbital, midazolam, or pentobarbital. Additional treatment with TPM was administered by nasogastric tube. All patients were continuously monitored by 21‐channel digital EEG machines, and the diagnosis of SE was made by a board‐certified neurophysiologist. Results: The ages of the three children were 4.5 months, 34 months, and 11 years. TPM was initiated at 2 mg/kg/day in two children and at 3 mg/kg/day in the third. The status was terminated in all three children within 24 h of maintenance therapy with TPM at 5–6 mg/kg/day. Conclusions: These results support the potential efficacy of TPM for children with refractory SE. Larger prospective series are needed to confirm those results.
Gene expression profiling in CD34 cells to identify differences between aplastic anemia patients and healthy volunteers
Authors: Zeng Weihua , Chen Guibin , Kajigaya Sachiko , Nunez Olga , Charrow Alexandra , Billings Eric M. , Young Neal S. 
Published: September 2003

Abstract
An immune pathophysiology for acquired aplastic anemia (AA) has been inferred from the responsiveness of the patients to immunosuppressive therapies and experimental laboratory data. To address the transcriptome of hematopoietic cells in AA, we undertook GeneChip analysis of the extremely limited numbers of progenitor and stem cells in the marrow of patients with this disease. We pooled total RNA from highly enriched bone marrow CD34 cells of 36 patients with newly diagnosed AA and 12 healthy volunteers for analysis on oligonucleotide chips. A large number of genes implicated in apoptosis and cell death showed markedly increased expression in AA CD34 cells, and negative proliferation control genes also had increased activity. Conversely, cell cycle progress–enhancing genes showed low expression in AA. Cytokine/chemokine signal transducer genes, stress response genes, and defense/immune response genes were up-regulated, as anticipated from other evidence of the heightened immune activity in AA patients' marrow. In summary, detailed genetic analysis of small numbers of hematopoietic progenitor cells is feasible even in marrow failure states where such cells are present in very small numbers. The gene expression profile of primary human CD34 hematopoietic stem cells from AA was consistent with a stressed, dying, and immunologically activated target cell population. Many of the genes showing differential expression in AA deserve further detailed analysis, including comparison with other marrow failure states and autoimmune disease.
Efficient and Clean Aldol Condensation Catalyzed by Sodium Carbonate in Water
Authors: Zhang Ze , Dong Ya-Wei , Wang Guan-Wu 
Published: September 2003

Abstract
Efficient and environmentally friendly synthesis of chalcone and azachalcone was performed by aldol condensation of aldehydes with ketones in pure water catalyzed by sodium carbonate. In this convenient methodology, side reactions were avoided and thus high yields were achieved.
Spontaneous rupture of the spleen in AL amyloidosis
Authors: Oran B. , Wright D.G. , Seldin D.C. , McAneny D. , Skinner M. , Sanchorawala V. 
Published: September 2003

AbstractThe frequency of splenic involvement in AL amyloidosis is not precisely known. However, splenomegaly has been reported in 4–13% of patients. We report four cases of spontaneous splenic rupture in patients with AL amyloidosis. Splenic rupture was the initial manifestation of the disease in one of these patients. The other three experienced splenic rupture during or after high‐dose intravenous melphalan with autologous peripheral blood stem cell transplantation (HDM/SCT): one during stem cell mobilization with G‐CSF prior to HDM/SCT and two after hematopoietic recovery following treatment. Two of the four patients had Factor X deficiency, the most common coagulation abnormality associated with AL amyloidosis. All four patients underwent splenectomy without significant postoperative complications. Splenic rupture in AL amyloidosis as a complication of aggressive treatment with HDM/SCT has not been reported previously. Am. J. Hematol. 74:131–135, 2003. © 2003 Wiley‐Liss Inc.
Type I Glanzmann thrombasthenia: Most common subtypes in North Indians
Authors: Kannan M. , Ahmed Rafeeq P.H. , Jain Paresh , Kumar Rajive , Choudhry V.P. , Saxena Renu 
Published: September 2003

AbstractThe expression of GPIIb/IIIa on the platelet surface was assessed in 10 patients with Glanzmann thrombasthenia and their families by flow cytometry to determine the common subtype in North Indians. Glanzmann thrombasthenia was diagnosed in patients with bleeding manifestations accompanied by absent/reduced platelet aggregation, secondary to ADP, ADR, arachidonic acid, and collagen. Flow cytometry revealed variable GPIIb/IIIa expression by CD61 and CD41 in patients with Glanzmann thrombasthenia on the basis of CD61 levels, six patients were subtyped as type I because they had absent GPIIb/IIIa, three patients were subtyped as type II because their GPIIb/IIIa levels varied from 7.72% to 20.40%, and one patient was diagnosed as type III, because his clot retraction was 60% and GPIIb/IIIa was 46.0% of normal. Four fathers, three mothers, and five siblings were found to have GPIIb/IIIa levels less than 35% of normal. It is possible that low GPIIb/IIIa levels in family members may reflect their carrier status. It is postulated that flow cytometric estimation of GPIIb/IIIa in parents/siblings may detect carrier status in Glanzmann thrombasthenia. Am. J. Hematol. 74:139–141, 2003. © 2003 Wiley‐Liss Inc.
c‐Met expression in tall cell variant papillary carcinoma of the thyroid
Authors: Nardone Heather C. , Ziober Amy F. , LiVolsi Virginia A. , Mandel Susan J. , Baloch Zubair W. , Weber Randal S. , Mick Rosemarie , Ziober Barry L. 
Published: September 2003

AbstractBACKGROUNDTall cell variant papillary carcinoma of the thyroid demonstrates unusually aggressive clinical behavior compared with the usual form of papillary thyroid carcinoma. The proto‐oncogene c‐met encodes a tyrosine kinase receptor known to influence cell invasion. This current study examined c‐Met expression in tall cell variant tumors compared with other types of papillary thyroid carcinoma and benign thyroid disease.METHODSc‐Met expression in 60 archived thyroid specimens was evaluated by immunohistochemical staining.RESULTSTall cell variant specimens expressed significantly greater levels of c‐Met than other forms of papillary thyroid carcinoma and benign thyroid disease (P < 0.0001). c‐Met expression was significantly different for the following pairs of histologies: tall cell variant versus usual papillary carcinoma of the thyroid (P < 0.0001), tall cell variant versus follicular variant papillary thyroid carcinoma (P < 0.0001), tall cell variant versus benign thyroid (P < 0.0001), and usual papillary carcinoma of the thyroid versus benign thyroid (P = 0.005). In addition, for all types of papillary carcinomas evaluated, c‐Met expression was significantly higher in specimens with extracapsular spread (P = 0.01) and skeletal muscle invasion (P = 0.02), and approached significance for specimens with lymphatic invasion (P = 0.06). After adjusting for extracapsular spread, c‐Met expression was still found to be associated significantly with tall cell histology (P < 0.0001).CONCLUSIONSc‐Met expression is a significant marker for tall cell variant papillary carcinoma of the thyroid and its invasive behavior. This finding may explain the unusually aggressive behavior of this tumor and suggests a role for c‐Met in the early identification of patients with tall cell variant thyroid disease. Cancer 2003;98:1386–93. © 2003 American Cancer Society.DOI 10.1002/cncr.11638
Genetic polymorphisms of estrogen receptor alpha, CYP19, catechol‐O‐methyltransferase are associated with familial prostate carcinoma risk in a Japanese population
Authors: Suzuki Kazuhiro , Nakazato Haruki , Matsui Hiroshi , Koike Hidekazu , Okugi Hironobu , Kashiwagi Bunzo , Nishii Masahiro , Ohtake Nobuaki , Nakata Seiji , Ito Kazuto , Yamanaka Hidetoshi 
Published: September 2003

AbstractBACKGROUNDEstrogen is one of the crucial hormones participating in the proliferation and carcinogenesis of the prostate glands. Genetic polymorphisms in the estrogen metabolism pathway might be involved in the risk of prostate carcinoma development. The authors evaluated the association between genetic polymorphisms in estrogen‐related enzymes and receptors and the risk of developing familial prostate carcinoma.METHODSIn the current study, 101 cases with prostate carcinoma whose first‐degree relatives had prostate carcinoma and 114 healthy age and residence‐matched male controls were enrolled. The genotypes of estrogen receptor (ER) alpha, aromatase (CYP19), and catechol‐O‐methyltransferase (COMT) genes were analyzed.RESULTSFor single polymorphisms, a significant association of the T/T genotype of the PvuII site in the ER alpha gene (odds ratio [OR], 3.44; 95% confidence interval [CI], 1.97–5.99; P = 0.0028), and the C/T and T/T genotypes of the CYP19 gene (OR, 1.77; 95% CI, 1.02–3.09; P = 0.037) with prostate carcinoma risk, was observed. The G/A genotype of the COMT gene showed a weak tendency toward increased risk (OR, 1.48; 95% CI, 0.85–2.57; P = 0.18). Stratification of cases according to clinical stage and pathologic grade showed that the C/T and T/T genotypes of the CYP19 gene were associated significantly with high‐grade carcinoma (OR, 2.59; 95% CI, 1.47–4.46; P = 0.048). The number of high‐risk genotypes (the T/T in ER alpha, the C/T and T/T in CYP19, and the G/A in COMT) significantly increased the risk of developing prostate carcinoma (2 genotypes: OR, 3.00; 95% CI, 1.72–5.23; P = 0.008; 3 genotypes: OR, 6.30; 95% CI, 3.61–10.99; P = 0.002).CONCLUSIONSGenetic polymorphisms of genes in the estrogen metabolism pathway were associated significantly with familial prostate carcinoma risk. Single nucleotide polymorphisms of low‐penetrance genes are targets for understanding the genetic susceptibility of familial prostate carcinoma. Cancer 2003;98:1411–6. © 2003 American Cancer Society.DOI 10.1002/cncr.11639
Use of tamoxifen in the treatment of malignant melanoma
Authors: Lens Marko B. , Reiman Tony , Husain Amna F. 
Published: September 2003

AbstractBACKGROUNDTamoxifen has been used in the treatment of patients with metastatic malignant melanoma either as a single agent or, more commonly, in combination with other chemotherapeutic agents. The aim of the current study was to summarize the available clinical evidence on the role of the tamoxifen in different combination chemotherapy regimens because clinical studies including tamoxifen have produced inconclusive results.METHODSThe authors designed a systematic review and metaanalysis of published randomized controlled trials to assess the benefit of tamoxifen added to various single‐agent or multiagent chemotherapy or biochemotherapy regimens.RESULTSSix randomized trials met the inclusion criteria and were analyzed. These 6 trials involved a combined total of 912 patients. Of this number, 455 patients were randomized to receive tamoxifen added to chemotherapy or biochemotherapy regimens and 457 were randomized to receive chemotherapy or biochemotherapy without tamoxifen. The overall response rate was not improved significantly by the addition of tamoxifen to the chemotherapy regimen (odds ratio [OR], 1.16; 95% confidence interval [CI], 0.75–1.82; test for overall effect: P = 0.14). The results were not statistically significant for complete response (OR, 0.64; 95% CI, 0.33–1.25; test for overall effect: P = 0.19).CONCLUSIONSThe current metaanalysis demonstrated that tamoxifen does not improve the overall response rate, complete response rate, or survival rate when administered along with combined chemotherapy regimens. Currently, the strength of evidence does not support the use of tamoxifen in combination with other systemic chemotherapy for the treatment of metastatic melanoma. Cancer 2003;98:1355–61. © 2003 American Cancer Society.DOI 10.1002/cncr.11644
Isolated limb perfusion with tumor necrosis factor‐α and melphalan for patients with unresectable soft tissue sarcoma of the extremities
Authors: Noorda Eva M. , Vrouenraets Bart C. , Nieweg Omgo E. , van Coevorden Frits , van Slooten Gooike W. , Kroon Bin B. R. 
Published: September 2003

AbstractBACKGROUNDSince 1992, isolated limb perfusion (ILP) with tumor necrosis factor‐α (TNFα) and melphalan has been used for the treatment of patients with unresectable soft tissue sarcomas of the extremities. The authors retrospectively studied the results of limb salvage surgery using TNFα‐ILP at their institution.METHODSFrom 1992 to 2001, 49 patients (mean age, 51 years; range, 14–85 years) underwent ILP for unresectable soft tissue sarcomas of the extremities. All patients received melphalan and TNFα (four patients also received interferon‐γ). The median follow‐up was 26 months (range, from 2 days to 103 months).RESULTSIn 1 patient (2%) who died 2 days after undergoing ILP, response and acute limb toxicity could not be assessed. One patient (2%) attained a clinical complete response (2%), 23 patients (47%) attained a clinical partial response, 17 patients (35%) demonstrated no change, and 7 patients (14%) had tumor progression. Thirty‐one patients (63%) underwent tumor resection. Histologic material also was available from eight amputations and three punctures/biopsies. Pathologic response was complete in 4 patients (8%), partial in 14 patients (29%), and no change was observed in 24 patients (49%). Final response, based on both clinical and pathologic assessment in which pathology was decisive, was complete in 4 patients (8%) and partial in 27 patients (55%), resulting in a final overall response rate of 63%. Local control with preservation of the limb was attained in 28 patients (57%). Four of 32 patients (13%) who had been rendered tumor free by ILP with or without undergoing resection and radiation therapy, developed a local recurrence. The 5‐year disease specific survival rate was 48% for the 49 patients. Acute limb toxicity after ILP was a mild Grade 1–2 reaction in 35 patients (71%) patients, a Grade 3 reaction in 12 patients (25%), and a Grade 4 reaction in 1 patient (2%). Three major ILP‐related complications were encountered, including arterial thrombosis in two patients and a fulminant Clostridial infection leading to death in one patient. There were no severe cardiovascular reactions after ILP.CONCLUSIONSIn patients with unresectable soft tissue sarcomas of the limbs who underwent ILP with TNFα and melphalan followed by resection of the tumor remnant when possible, a 63% overall tumor response rate and a 57% local control rate with limb preservation was achieved. Cancer 2003;98:1483–90. © 2003 American Cancer Society.DOI 10.1002/cncr.11648
Preclinical evaluation of therapeutic effects of targeted cytotoxic analogs of somatostatin and bombesin on human gastric carcinomas
Authors: Szepeshazi Karoly , Schally Andrew V. , Nagy Attila , Wagner Brady W. , Bajo Ana Maria , Halmos Gabor 
Published: September 2003

AbstractBACKGROUNDNew modalities are necessary for the treatment of patients with unresectable gastric carcinoma. The authors investigated whether receptors for somatostatin and bombesin were present in human gastric carcinoma lines and tested the antitumor effects of cytotoxic somatostatin analog AN‐238 and cytotoxic bombesin conjugate AN‐215.METHODSNude mice bearing AGS, Hs 746T, and NCI‐N87 human gastric carcinomas were treated with AN‐238, AN‐215, or their cytotoxic moiety 2‐pyrrolinodoxorubicin (AN‐201). Tumor growth reduction and tumor doubling times were calculated, and histologic characteristics of cell proliferation and apoptosis were examined. The expression of mRNA for somatostatin and bombesin receptors in tumors was investigated by reverse transcriptase–polymerase chain reaction. Subtypes 2 and 5 of somatostatin receptor proteins (sst2 and sst5, respectively) were analyzed using immunohistochemistry and immunoblotting. Binding assays were performed with radiolabeled somatostatin and bombesin analogs.RESULTSCytotoxic bombesin analog AN‐215 powerfully inhibited the growth of AGS carcinomas that expressed high‐affinity subtype 1 bombesin receptors. All three carcinomas expressed high‐affinity sst2 and sst5 receptors. Cytotoxic somatostatin analog AN‐238 exerted a strong inhibitory effect on NCI‐N87 and Hs 746T carcinomas, which exhibited high concentrations of somatostatin receptors, but had a weaker effect on AGS tumors, which expressed the lowest receptor levels. AN‐201 had only nonsignificant effects.CONCLUSIONSExperimental human gastric carcinomas that expressed high‐affinity subtype 1 bombesin receptors were inhibited by cytotoxic bombesin analog AN‐215, and tumors with high concentrations of sst2 or sst5 somatostatin receptors were suppressed by cytotoxic somatostatin analog AN‐238. These findings suggest that this class of targeted compounds should be considered for the therapy of patients with advanced gastric carcinoma. Cancer 2003;98:1401–10. © 2003 American Cancer Society.DOI 10.1002/cncr.11649