Biomedical subjects

S Kim

Publications and source records attributed to S Kim.

At least 55 records · Page 3Linked to original sources

PubMed2005

Difference in root canal length between Asians and Caucasians.

AIM: To investigate whether there is a racial difference in canal length between the Asians and Caucasians. METHODOLOGY: Five hundred and fifteen Asian patients who had received root canal treatment at the Yonsei University Hospital, Korea between 1995 and May 2001 and 324 Caucasoid patients who had received root canal treatment at the Graduate Endodontic Clinic at the University of Pennsylvania, US were selected. The clinical endodontic procedures at both clinics were similar. An electronic apex locator (Root-ZX; J. Morita Co., Kyoto, Japan) was used to measure the initial working lengths and this was verified by conventional radiography. The measurements from both Asian and Caucasian teeth were compared using a Student's t-test and a Mann-Whitney test. RESULTS: The mean difference in canal length of pooled teeth between the Asian and Caucasian teeth was 1.2 mm, with a range from 0 to 2.5 mm. The greatest difference was in the distobuccal canal (2.5 mm) of maxillary first molar teeth followed by the mesiolingual canal (2.3 mm) of mandibular second molar, the buccal canal (2.1 mm) of the maxillary second premolar, the maxillary first molar and the mandibular second molar. CONCLUSION: Tooth lengths in Asians were shorter than Caucasians.

Asian People↗

PubMed2005

Use of Fourier transform infrared spectra of crude bacterial lipopolysaccharides and chemometrics for differentiation of Salmonella enterica serotypes.

AIMS: To evaluate Fourier transform infrared spectroscopy (FTIR) and chemometrics for differentiating intact cells and crude lipopolysaccharide (LPS) extracts from Salmonella serotypes. METHODS AND RESULTS: Intact cells and crude LPS extracts from six different Salmonella enterica serotypes (Typhimurium, Enteritidis, Thomasville, Brandenburg, Hadar and Seftenberg) were used. The crude Salmonella LPS extracts were visualized using deoxycholic acid-polyacrylamide gel electrophoresis (DOC-PAGE) and appeared heterogeneous on the gel with two exceptions: S. Enteritidis and S. Brandenburg, and S. Thomasville and S. Seftenberg. Canonical variate analysis (CVA) of spectra of crude LPS extracts provided 100% correct classification. CVA of spectra of intact cells was not useful for classifying the Salmonella serotypes, having only 47 and 50% correct classifications in the 1200-900 and 4000-700 cm(-1) regions respectively. These data were confirmed by greater Mahalanobis distances between crude LPS spectra than intact cell spectra. CONCLUSIONS: CVA of FTIR spectra of crude LPS extracts from Salmonella serotypes provided a 100% correct serotype classification. SIGNIFICANCE AND IMPACT OF THE STUDY: This study suggests that the FTIR analytical procedure provides chemical detail as well as a better separation of Salmonella serotypes using spectra of crude LPS extracts than analysis using DOC-PAGE.

Deoxycholic Acid↗

PubMed2005

Lipid rafts are required in Galpha(i) signaling downstream of the P2Y12 receptor during ADP-mediated platelet activation.

ADP is important in propagating hemostasis upon its secretion from activated platelets in response to other agonists. Lipid rafts are microdomains within the plasma membrane that are rich in cholesterol and sphingolipids, and have been implicated in the stimulatory mechanisms of platelet agonists. We sought to determine the importance of lipid rafts in ADP-mediated platelet activation via the G protein-coupled P2Y1 and P2Y12 receptors using lipid raft disruption by cholesterol depletion with methyl-beta-cyclodextrin. Stimulation of cholesterol-depleted platelets with ADP resulted in a reduction in the extent of aggregation but no difference in the extent of shape change or intracellular calcium release. Furthermore, repletion of cholesterol to previously depleted membranes restored ADP-mediated platelet aggregation. In addition, P2Y12-mediated inhibition of cAMP formation was significantly decreased upon cholesterol depletion from platelets. Stimulation of cholesterol-depleted platelets with agonists that depend upon Galpha(i) activation for full activation displayed significant loss of aggregation and secretion, but showed restoration when simultaneously stimulated with the Galpha(z)-coupled agonist epinephrine. Finally, Galpha(i) preferentially localizes to lipid rafts as determined by sucrose density centrifugation. We conclude that Galpha(i) signaling downstream of P2Y12 activation, but not Galpha(q) or Galpha(z) signaling downstream of P2Y1 or alpha2A activation, respectively, has a requirement for lipid rafts that is necessary for its function in ADP-mediated platelet activation.

Adenosine Diphosphate↗

PubMed2005

Angiotensin converting enzyme inhibitor prevents left ventricular remodelling after myocardial infarction in angiotensin II type 1 receptor knockout mice.

BACKGROUND: It is well known that angiotensin converting enzyme (ACE) inhibitors and angiotensin II type 1 (AT1) receptor blockers (ARBs) prevent left ventricular (LV) remodelling after myocardial infarction (MI). However, it is still not clear whether inhibition of the AT1 receptor is enough to prevent LV remodelling after MI. OBJECTIVE: To elucidate the effects of ACE inhibitors that are not mediated by the AT1 receptor on LV remodelling, MI was experimentally induced in wild-type (WT-MI) mice and AT1 receptor knockout (KO-MI) mice. METHODS: Mice were divided into six groups: WT-control, KO-control, WT-MI, KO-MI, WT-MI treated with an ACE inhibitor, and KO-MI treated with an ACE inhibitor. Four weeks after MI, cardiac function was assessed by Doppler echocardiography and non-infarcted myocardial mRNA expression by northern blot analysis. RESULTS: Cardiac function decreased significantly in the MI groups compared with the sham operated groups. Additionally, in the MI groups end diastolic dimension, E wave velocity, the ratio of peak velocity of E wave to A wave, deceleration rate of E wave, and mRNA expression of atrial natriuretic peptide, brain natriuretic peptide, and collagens I and III increased significantly compared with the sham groups. LV remodelling after MI was prevented in KO-MI mice compared with WT-MI mice. ACE inhibitor administration significantly attenuated progressive LV remodelling in both WT and KO-MI groups. CONCLUSION: ACE inhibitors can prevent the LV remodelling process that accompanies cardiac dysfunction after MI, even in AT1 KO mice. These findings suggest that ACE inhibitors prevent LV remodelling after MI by mechanisms other than inhibition of angiotensin AT1 receptor mediated effects.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2005

Efficacy of chimeric molecules directed towards multiple somatostatin and dopamine receptors on inhibition of GH and prolactin secretion from GH-secreting pituitary adenomas classified as partially responsive to somatostatin analog therapy.

OBJECTIVE: This study compared the potency of a somatostatin receptor (sstr)2-sstr5 analog, BIM-23244, of an sstr2-dopamine D2 receptor (sstr2-DAD2) molecule, BIM-23A387 and of new somatostatin-dopamine chimeric molecules with differing, enhanced affinities for sstr2, sstr5 and DAD2, BIM-23A758, BIM-23A760 and BIM-23A761, to suppress GH and prolactin (PRL) from 18 human GH adenomas that are partially responsive to octreotide or lanreotide. MATERIALS AND METHODS: The sstr2, sstr5 and DAD2 mRNA levels were determined by RT-PCR. The effect of drugs was tested in cell cultures at various concentrations. RESULTS: In all tumors, the sstr2, sstr5 and DAD2 mRNA levels were coexpressed (mean levels+/-s.e.m. 0.4+/-0.1, 5.3+/-1.9 and 2.0+/-0.4 copy/copy beta-glucuronidase). In 13 tumors, the maximal suppression of GH secretion produced by BIM-23A387 (30+/-3%) and BIM-23244 (28+/-3%) was greater than that produced by octreotide (23+/-3%). In six out of 13 tumors, BIM-23A758, BIM-23A760 and BIM- 23A761 produced greater maximal suppression of GH secretion than octreotide (33+/-5, 38+/-2 and 41+/-2 vs 24+/-2%). Their EC(50) values were 10, 2 and 4 pmol/l. BIM-23A761 was more effective than BIM-23A387 in GH suppression (41+/-2 vs 32+/-4%). The new chimeric molecules produced maximal PRL suppression greater than octreotide (62+/-8 to 74+/-5 vs 46+/-11%). CONCLUSIONS: Novel dopamine-somatostatin chimeric molecules with differing, enhanced activity at sstr2, sstr5 and DAD2, consistently produced significatly greater suppression of GH and PRL than either octreotide or single-receptor-interacting ligands in tumors from patients classified as only partially responsive to octreotide therapy. The higher efficacy of the chimeric compounds was, at least partially, linked to their high affinity for sstr2 (IC50 1-10 pmol/l). The other mechanisms by which such molecules produce an enhanced inhibition of GH remain to be elucidated.

Acromegaly↗

PubMed2005

Association of C-509T and T869C polymorphisms of transforming growth factor-beta1 gene with susceptibility to and progression of IgA nephropathy.

AIMS: Transforming growth factor (TGF)-beta1 is a cytokine with both beneficial anti-inflammatory effects and detrimental profibrotic activity in the pathophysiology and progression of glomerulonephritides. The transcriptional activity of the gene for TGF-beta1 and the plasma levels of TGF-beta1 protein are associated with C-509T polymorphism at the promoter region, and with T869C (Leu 10Pro) polymorphism at codon 10, of the TGF-beta1 gene. METHODS: Using PCR-RFLP and the amplification refractory mutation system PCR, we investigated the C-509T and T869C polymorphisms, respectively, to elucidate whether allele frequency differences exist between IgA nephropathy (IgAN) patients who were followed up for at least 3 years (n = 108) and a normal population (n = 55). We also determined the correlations between the TGF-beta1 polymorphisms and the progression of IgAN. RESULTS: In C-509T polymorphism, there were significant differences in genotype frequency between IgAN patients and normal controls (CC: CT: TT, 20:29:33 vs. 11:31:13, chi2 = 6.299, p = 0.043). In Kaplan-Meier survival analysis, the patients with TT genotype showed a poorer renal survival than those with CC + CT genotypes (p = 0.042). In T869C polymorphism, there were also significant differences in genotype frequency between IgAN patients and normal controls (TT : TC : CC, 4 : 79 : 25 vs. 0 : 52 : 2, chi2 = 12.552, p = 0.002). The initial serum creatinine (Scr) level was higher in the patients with CC genotype than in those with TT + TC genotypes. In Kaplan-Meier survival analysis, the patients with CC genotype showed a poorer renal survival than those with TT + TC genotypes, but not to a statistically significant extent (p = 0.076). In the combined survival analyses, the high TGF-beta1 producer group showed a poor renal survival rate (p = 0.014). CONCLUSION: Compared to normal population, the frequencies of genotypes producing high TGF-beta1 protein were higher in IgAN patients. Moreover, patients with genotypes producing high TGF-beta1 plasma levels showed a poor renal survival rate.

Adult↗

PubMed2005

Integration and application of the Rainfall Runoff Library.

The Rainfall Runoff Library (RRL) provides a convenient platform for implementing environment modelling components such as rainfall runoff models, calibration tools, and objective functions. A rainfall-runoff model widely known and used in South Korea, TANK, is added to the RRL, and used along with the models AWBM and SIMHYD to reproduce the historical time series of daily and monthly runoff at the Soyanggang Dam and Youngcheon Dam catchments located in South Korea. The features of the RRL allow for an easy comparison of different models in a standardised and common framework. Three optimisation methods (Genetic algorithm, Rosenbrock method and Shuffled Complex Evolution algorithm) were applied to calibrate the model parameters using three different objective functions. The applicability of each model to these catchments is discussed based on the resulting statistics.

Algorithms↗

PubMed2005

BIM-23A760, a chimeric molecule directed towards somatostatin and dopamine receptors, vs universal somatostatin receptors ligands in GH-secreting pituitary adenomas partial responders to octreotide.

We report the comparative efficacy of a somatostatin receptor 1 and 5 subtypes (SSTR2 and SSTR5), and dopamine D2 (DAD2) compound, BIM-23A760, in suppressing GH secretion, in cell culture from human GH-secreting tumors, from patients partially responsive to long-term treatments with octreotide or lanreotide. In 18 tumors tested, the SSTR2, SSTR5, and DAD2 mRNAs were coexpressed. The SSTR2-selective analog, BIM-23197, the SSTR5-selective analog, BIM-23268, and the dopamine (DA) analog, BIM-53097, produced a mean maximal suppression of GH secretion (24 +/- 3, 20 +/- 3, and 20 +/- 3%, respectively) that was similar to that obtained with octreotide (23 +/- 3%). Nevertheless, based on individual responses, 60% of the tumors were mostly sensitive to the SSTR2 analog while 19 and 21% of the tumors were mainly responsive to the SSTR5 analog and to the DA analog, respectively. Among a series of new chimeric compounds that bind the SSTR2, SSTR5, and DAD2 receptors with variable affinities, BIM-23A760 produced greater maximal suppression of GH secretion than octreotide (38 +/- 2 vs 24 +/- 2%; p<0.03). The EC50 for BIM-23A760 was 2 pmol/l. In the presence of sulpride, the dose response inhibition of GH secretion by the trihybrid molecule, BIM-23A760, was partially reversed. The trihybrid produced also a maximal suppression of PRL greater than octreotide (74 +/- 5 vs 46 +/- 11%). When SSTRs pan inhibitors such as BIM-23A779 (binding affinity for SSTR1, SSTR2, SSTR3, SSTR5, respectively: 2.5, 0.3, 0.6, 0.6 nmol/l) or SOM230 were tested for their suppressive effects on GH secretion, they were less potent than the previous dopastatin hybrid molecule. After a brief exposure to a SSTR2-selective analog, BIM-23197, or to a DA analog, BIM-53097, the maximal GH suppression was achieved during 12 h. Under exposure to BIM-23A760, in the same conditions, maximal suppression of GH secretion lasted for 24 h. Such a longer biological effect, yet not explained, probably participates in the higher efficacy of BIM-23A760. The higher efficacy of BIM-23A760 is, at least partially, linked to its high affinity for the SSTR2 receptor subtype (IC50: 3 pmol/l). As compared to the dopastatin compound, the lower efficacy of the universal somatostatin ligands in the inhibition of GH secretion of GH-secreting tumors argues for the use of drugs targeted, according to specific receptors expression and functionality which may vary among the various classes of tumors.

Acromegaly↗

PubMed2004

Gold color in onions (Allium cepa): a natural mutation of the chalcone isomerase gene resulting in a premature stop codon.

Unusual gold-colored onions were selected from a F3 family originating from a cross between US-type yellow and Brazilian yellow onions. HPLC analysis showed that the gold onions contained a significantly reduced amount of quercetin, the most abundant flavonoid in onions. This result indicated that an early step in the flavonoid biosynthesis pathway might be abnormal in these onions. The expression of flavonoid synthesis genes isolated from onions was examined in gold onions and compared to that in onions of other colors by RT-PCR. The results showed that all genes were transcribed in gold onions as in red onions. In order to identify any critical mutations in flavonoid synthesis genes encoding enzymes involved in early steps of the pathway, the genomic sequence of chalcone isomerase (CHI) was obtained. A premature stop codon and a subsequent single base-pair addition causing a frameshift were identified in the coding region of the CHI gene in the gold onions. Co-segregation of the mutant allele of the CHI gene and the gold phenotype was investigated in the original F2 segregating population. Genotyping of three color groups (red, yellow and gold) of F2 onions revealed perfect co-segregation of the mutant CHI allele with the gold phenotype. All tested gold F2 onions were homozygous for the mutant CHI allele. This perfect co-segregation implies that the presence of a premature stop codon in the gold CHI gene results in an inactive CHI. Inactivation of CHI results in a block in the flavonoid biosynthesis pathway and the accumulation of chalcone derivatives, including a yellow pigment which might be responsible for the gold color in onions.

Amino Acid Sequence↗

PubMed2004

Pink (P), a new locus responsible for a pink trait in onions (Allium cepa) resulting from natural mutations of anthocyanidin synthase.

A new locus conditioning a pink trait in onions was identified. Unusual pink onions were found in haploid populations induced from an F(1) hybrid between yellow and dark red parents and in F(3) populations originating from the same cross. Segregation ratios of red to pink in F(2), backcross, and F(3) populations indicated that this pink trait is determined by a single recessive locus. RT-PCR was carried out to look for any differential expression of anthocyanin synthesis genes between dark red and pink F(3) lines. The transcript level of anthocyanidin synthase (ANS) was significantly reduced in the pink line. To determine whether this reduced transcription is caused by other regulatory factors or by mutations in the ANS gene itself, ANS gene sequences from both dark red and pink F(3) lines were compared to detect any polymorphisms. Polymorphisms were identified, and subsequently utilized as molecular markers for the selection of ANS alleles. Absolute co-segregation of the pink allele and the ANS allele from the pink line was observed in parents, F(1) and F(3) populations. These results indicate that reduced transcription of the ANS gene caused by mutations in a cis -acting element is likely to result in the pink trait in onions.

Anthocyanins↗

PubMed2004

Patterns of failure in gastric carcinoma after D2 gastrectomy and chemoradiotherapy: a radiation oncologist's view.

The risk of locoregional recurrence in resected gastric adenocarcinoma is high, but the benefit of adjuvant treatment remains controversial. In particular, after extended lymph node dissection, the role of radiotherapy is questionable. Since 1995, we started a clinical protocol of adjuvant chemoradiotherapy after D2 gastrectomy and analysed the patterns of failure for 291 patients. Adjuvant chemotherapy consisted of five cycles of fluorouracil and leucovorin, and concurrent radiotherapy was given with 4500 cGy from the second cycle of chemotherapy. With a median follow-up of 48 months, 114 patients (39%) showed any type of failure, and the local and regional failures were seen in 7% (20 out of 291) and 12% (35 out of 291), respectively. When the recurrent site was analysed with respect to the radiation field, in-field recurrence was 16% and represented 35% of all recurrences. Our results suggest that adjuvant chemoradiotherapy has a potential effect on reducing locoregional recurrence. Moreover, low locoregional recurrence rates could give a clue as to which subset of patients could be helped by radiotherapy after D2 gastrectomy. However, in order to draw a conclusion on the role of adjuvant radiotherapy, a randomised study is needed.

Adenocarcinoma↗

PubMed2004

Ubiquitin-proteasome pathway as a primary defender against TRAIL-mediated cell death.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptotic cell death as well as expression of proinflammatory genes such as CXCL8 in malignant human astrocytoma cells. However, the molecular mechanisms that determine the fate of cells are not yet understood. The ubiquitin (Ub)-proteasome pathway regulates a wide range of cellular functions through degradation of various regulatory proteins; given this, we hypothesized that this pathway may play a central role in TRAIL-mediated signaling. We demonstrate here that inhibition of the Ub-proteasome pathway enhanced TRAIL-mediated cell death of human astrocytoma CRT-MG cells within hours by blocking degradation of active caspase-8 and -3. Proteasome inhibitors suppressed TRAIL-mediated activation of NF-kappaB; however, inhibition of the NF-kappaB pathway alone was not sufficient to enhance TRAIL-mediated cell death. Collectively, these results suggest that the Ub-proteasome pathway may play an important role as an antiapoptotic surveillance system by eliminating activated caspases as well as mediating NF-kappaB-dependent signals.

Apoptosis↗

PubMed2004

Magnifying gastroendoscopy for diagnosis of histologic gastritis in the gastric antrum.

BACKGROUND: We investigated the potential of magnifying endoscopy for diagnosis of histologic gastritis in the gastric antrum. In addition, we investigated whether magnifying endoscopy can be applied for evaluation of Helicobacter pylori eradication therapy. METHODS: We examined 176 Japanese patients including 53 with H. pylori eradication. We evaluated the antrum by magnifying observation and ordinary endoscopic findings, and compared these results. Biopsy specimens were taken from the sites observed. RESULTS: The magnified views were classified into four types. Histology of the biopsy specimens allowed us to match the four magnified views with normal mucosa with fundic glands, normal mucosa with pyloric glands, mucosa with gastritis and intestinal metaplasia/epithelial hyperplasia. The types of magnifying appearances were specific enough for the diagnosis of histologic gastritis (148 out of the 176 (82.4%) cases; sensitivity, 96.3%; specificity, 73.7%). We could accurately diagnose the histologic gastritis by magnifying endoscopy in 49 out of the 53 (92%) cases with H. pylori eradication, while only in 38% by ordinary endoscopy. The accuracy of diagnosis was statistically higher with the use of magnifying endoscopy than with ordinary endoscope (P < 0.001). CONCLUSION: Magnifying gastroendoscopy is useful to judge the histologic gastritis, especially, in cases with H. pylori eradication.

Adult↗

PubMed2004

Incidence and risk factors of renal dysfunction after liver transplantation in Korea.

Renal dysfunction, one of the most common complications after liver transplantation, influences patient outcomes. Little is known, however, about it in Korea. The aims of this study were to determine the incidence and to identify the risk factors for renal dysfunction after liver transplantation. Sixty-two patients who survived over 6 months after transplantation were enrolled. Renal function was classified by creatinine clearance (Ccr, mL/min), which was estimated using the Cockcroft-Gault formula. Twenty-seven patients (44%) showed mild renal dysfunction (60 < or = Ccr < 90), and 27 patients (44%), moderate dysfunction (30 < or = Ccr < 60). The others were found to have normal function (Ccr > or = 90). None displayed severe dysfunction (Ccr < 30). Compared to a control group (Ccr > or = 60), the renal dysfunction group showed lower preoperative Ccr (91 +/- 28.6, 63 +/- 21.9, respectively, P < .01) and lower Ccr at 3 months after transplantation (72 +/- 17.1, 49 +/- 14.6, respectively, P < .05). Age, sex, immunosuppressive drug usage, serum tacrolimus levels, and the frequency of postoperative acute renal failure did not affect the postoperative renal dysfunction. Twenty-six patients received mycophenolate mofetil while reducing the dose of calcineurin inhibitors because of compromised renal function. With mycophenolate mofetil treatment, the renal function seemed to improve, although the difference was not statistically significant (P = .057). These data demonstrate that renal dysfunction is common after liver transplantation and that preoperative renal function is the important factor predicting postoperative renal dysfunction.

Adolescent↗

PubMed2004

Failure of trilineage blood cell reconstitution after initial neutrophil engraftment in patients undergoing allogeneic hematopoietic cell transplantation - frequency and outcomes.

The outcomes of patients who experience the failure to reconstitute a trilineage of blood cells after initial neutrophil engraftment were evaluated in 178 patients with hematologic disorders, who underwent allogeneic HCT. Of 165 qualified patients (five with primary engraftment failure; eight deaths before day 60 of HCT), 43 (26%) satisfied the criteria for the initial (n=22; failure of platelet >20 000/microl or red blood cell transfusion independence/reticulocyte count >/=1.0% by day 60) or subsequent (n=21, ANC <500/microl for >/=3 days, platelet <20 000/microl for >/=7 days, or red blood cells transfusion/reticulocyte <1.0% after initial trilineage reconstitution) failure. GVHD was the most common clinical condition associated with cytopenia (n=24). In all, 20 patients (47%) recovered at least partially with a median of 52 days (range 8-323) later, with 12 of those 20 patients recovering completely. The eventual reconstitution failure rate was 14% (23/163 patients). The number of cell lineages involved in the cytopenia was the only independent variable that predicted partial recovery (1 lineage vs 2-3 lineages with odds ratio of 8.69 (95% CI 1.96-38.60), P=0.004). Five/20 patients with vs 20/23 patients without partial recovery died. Trilineage reconstitution failures after allogeneic HCT need systematic analysis in the future studies.

Adolescent↗

PubMed2004

Lymphocyte recovery as a positive predictor of prolonged survival after autologous peripheral blood stem cell transplantation in T-cell non-Hodgkin's lymphoma.

We performed a retrospective study on recovery and survival of patients with T-cell NHL after autologous peripheral blood stem cell transplantation (APBSCT). Of a total of 39 patients with high-risk T-cell NHL, 33 were analyzed. Six patients who experienced early treatment mortality without full lymphocyte recovery were excluded. We chose absolute lymphocyte count (ALC) recovery as 1000 cells/microl as a cutoff value. ALC recovery day was defined as the first of 3 consecutive days with ALC above 1000 cells/microl. Univariate analysis revealed that age younger than 45 years, good international prognostic index, chemosensitive disease prior to APBSCT, and early ALC recovery (1000 cells/microl within 25 days of APBSCT) were predictors of prolonged survival. Multivariate analyses confirmed that chemosensitive disease prior to APBSCT and early ALC recovery were strongly associated with better overall survival (OS) (P=0.005 and 0.011, respectively) and progression-free survival (PFS) (P<0.001 and P=0.013, respectively). Our finding, that ALC recovery > or =1000 cells/microl is an independent predictor of OS and PFS in T-cell NHL after APBSCT, suggests that earlier immune recovery may contribute to longer survival.

Adolescent↗

PubMed2004

Cyclosporine alone vs cyclosporine plus methotrexate for post-transplant immunosuppression after HLA-identical sibling bone marrow transplantation: a randomized prospective study.

The role of methotrexate (MTX), given with cyclosporine (CS), after HLA-identical sibling bone marrow transplantation needs to be defined. In all, 80 patients with hematologic malignancies were enrolled in a prospective randomized trial. All were given BuCy conditioning. The 40 patients in the CS arm received CS 3 mg/kg/day intravenously, with subsequent oral dosing. Patients in the CS + MTX arm received, in addition to CS, MTX intravenously, 15 mg/m2 on day 1, and 10 mg/m2 on days 3, 6, and 11. Transplantation-related mortality was low in both groups of patients (13 vs 11% for CS vs CS + MTX groups, P = 0.94). The CS group had a significantly higher frequency of chronic graft-versus-host disease (56 vs 32%, P = 0.05). After a median follow-up of 22.1 months (5.1-47.8 months), three of 30 vs 10 of 28 patients with acute leukemia/myelodysplastic syndrome (MDS) in CS group vs CS + MTX group relapsed (P = 0.01) yielding better overall survival for patients with acute leukemia/MDS treated with CS (P = 0.02). After HLA-identical sibling bone marrow transplantation, immunosuppression with CS, with or without MTX, resulted in similarly low transplantation-related mortality. In acute leukemia/MDS, decreased relapse with patient survival prolongation was observed in the CS group.

Acute Disease↗

PubMed2004

Engineering the splice acceptor for improved gene expression and viral titer in an MLV-based retroviral vector.

We have recently developed a retroviral vector that contains a splice acceptor from the human EF1-alpha gene and drives a significantly higher level of gene expression than other well known murine leukemia virus-based vectors. However, one downside of this vector is that viral titer significantly varies depending on the packaging lines used. Results from Northern blot analysis indicated that in certain cell lines the genomic transcript containing the packaging signal sequence was too efficiently spliced to the subgenomic RNA, resulting in low levels of genomic RNA and thus leading to a low viral titer. We tested the possibility of overcoming this problem by introducing mutations around the splice acceptor sequence in such a way that a delicate balance was maintained between the splicing efficiency (which determines the level of gene expression) and the amount of genomic transcript (which influences viral titer). After mutational analysis, one such mutant was found to meet this requirement. The newly constructed vector containing the engineered splice acceptor could indeed drive higher levels of expression in many therapeutic genes than other control vectors, without significantly compromising viral titer.

Base Sequence↗