Allogeneic hematopoietic cell transplantation for myelodysplastic syndrome: prognostic significance of pre-transplant IPSS score and comorbidity.

We analyzed the clinical significance of pre-transplant International Prognostic Scoring System (IPSS) score and comorbidity in 68 patients who underwent allogeneic hematopoietic cell transplantation (HCT) for myelodysplastic syndrome (MDS) (n=48) or acute myeloid leukemia evolved from MDS (n=20) between December 1995 and January 2008 in a single institute. During a median follow-up period of 41.0 months (range, 3.2-132.0 months), 27 patients died, and 7 relapsed. The 5-year probabilities of overall survival (OS) and event-free survival (EFS) were 60.0 and 57.4%, respectively, and the 5-year cumulative incidences of non-relapse mortality (CINRM) and relapse were 32.7 and 9.9%, respectively. OS, EFS, and CINRM were significantly different according to pre-transplant IPSS score and presence of pre-transplant comorbidity, which were independent risk factors along with Karnofsky performance score in multivariate analyses. In conclusion, pre-transplant IPSS score and comorbidity may stratify the risk of post transplant outcomes in MDS.

Surgical repair of anterior wall vaginal defects.

OBJECTIVE: To compare the clinical efficacy of 3 surgical procedures for central types of anterior vaginal wall defect. METHODS: A total of 138 patients diagnosed with central types of anterior vaginal wall defect who underwent classic transvaginal repair (n=72), transvaginal repair with polypropylene mesh (n=28), and internal repair (n=38) were followed up for at least 1 year. RESULTS: There were no differences in development of fever, vaginal erosion, detrusor overactivity, and voiding difficulty among the 3 groups, but the incidence of postoperative urinary tract infections was significantly higher in the polypropylene mesh repair group. The difference in preoperative and postoperative hemoglobin levels and wound infection incidence were significantly higher in the internal repair group. Moreover, the recurrence rate of the anterior vaginal wall defect was significantly higher at 1 year in the internal repair group. CONCLUSION: Transvaginal surgical repair seems to be more efficacious than internal surgical repair for central types of anterior vaginal wall defects.

Risk factors for pelvic organ prolapse.

OBJECTIVES: To evaluate the risk factors for pelvic organ prolapse (POP) and to determine the relationship between these risk factors and stage or other components of POP. METHODS: 244 patients with primary POP and 314 women without POP were included. Age, parity, smoking, body mass index (BMI), menopause, and hormone replacement therapy (HRT) were investigated. RESULT: Independent risk factors for POP included age over 70, parity higher than 3, and menopause. Age, parity, menopause, and HRT were significantly associated with stage of POP. Genital hiatus (GH) and perineal body (PB) showed a significant positive and negative correlation with age and parity, respectively. Menopause and HRT were also associated with them. CONCLUSION: Age, parity and menopause are possible risk factors of POP and associated with the lengths of GH and PB in POP women. Further, these risk factors and HRT are significantly correlated with the severity of the disease.

Chimerism and mosaicism are important causes of ABO phenotype and genotype discrepancies.

Discrepancies between blood group genotype and RBC phenotype are important to recognize when implementing DNA-based blood grouping techniques. This report describes two such cases involving the ABO blood group in the Korean population. Propositus #1 was a 22-year-old healthy man undergoing pretransfusion testing for minor surgery. Propositus #2 was a 23- year-old male blood donor. RBCs from both propositi were determined to be group AB and demonstrated unusual agglutination patterns on forward typing, which were inconsistent with their ABO genotype determined by allele-specific (AS) PCR. RBCs from propositus #1 demonstrated mixed field agglutination with both anti-A and -B, while RBCs from propositus #2 demonstrated mixed field only with anti-A reagents. Both had B/O genotypes by AS-PCR. Cloning and sequencing of ABO exons 6 and 7 revealed three alleles in both propositi: propositus #1: A102/B101/O04; propositus #2: A102/B101/O01. A panel of nine short-tandem repeat (STR) loci was tested on DNA extracted from blood, buccal mucosal cells, and hair from the propositi and on DNA isolated from their parents' blood. In all tissues tested from propositus #1, three loci demonstrated a double paternal and a single maternal DNA contribution, indicating that he was a chimera or a mosaic; in those from propositus # 2, one STR locus demonstrated a double paternal DNA contribution, indicating that he was a tetragametic chimera. Chimerism and mosaicism are uncommon but important causes of ABO genotype and phenotype discrepancies. The evaluation of patients and donors with unusual or unexpected serology in pretransfusion testing and consensus ABO alleles may include the evaluation of STR loci to detect these phenomena.

The genetic and phenotypic basis of blood group A subtypes in Koreans.

A serological and genetic study of Korean blood donors with phenotypic group A subtypes was performed. There were 176 donors with phenotypic A subtypes identified. Exons 6 and 7 from 57 representative donors were sequenced. The A(var) allele (784 G > A) was cloned and sequenced, and a family study demonstrating its inheritance and unusual serological characteristics was performed. The A102 allele was the most frequently identified allele in phenotypically A2 (58%, 11/19) and A2B (68%, 17/25) donors. Anti-A1 was rarely present amongst A2 and A2B donors. The family study revealed that the A(var) allele was expressed as phenotype A(weak)B in A(var)/B heterozygote members, but as phenotype O in A(var)/O heterozygotes. The most frequent allele in Korean donors with the A2 phenotype differs from its Caucasian counterpart, as does the frequency of anti-A1. The A(var) allele demonstrates allelic enhancement in A(var)/B heterozygotes.

The serological and genetic basis of the cis-AB blood group in Korea.

BACKGROUND AND OBJECTIVES: The cis-AB blood group is rare, although relatively common amongst Koreans. The serological characteristics and genetic basis of Korean cis-AB blood donors were investigated. MATERIALS AND METHODS: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), designed to detect the cis-AB01 allele, was performed on 194 AB samples which demonstrated weak or unusual expression of either or both of the A or B antigens. RESULTS AND CONCLUSIONS: Sixty cis-AB01 donors were identified. cis-AB01/O01 or O02 were the most common genotypes (36/60) detected only in A(2)B(3) donors, and cis-AB01/B101 (nine of 60) was the least common genotype identified only in A(2)B donors. Surprisingly cis-AB01/A102 (15/60) was identified in a variety of phenotypes (A(1)B(3), A(1)B(x) or el, A(int)B(3)).

Relationship between stress urinary incontinence and pelvic organ prolapse.

We investigated the objective coexisting rate of stress urinary incontinence and pelvic organ prolapse, and also compared the treatment outcomes in patients who had both conditions, treated by a corrective operation on the basis of a precise preoperative evaluation. We reviewed 97 cases who underwent urodynamic studies and evaluation of the prolapse according to the Pelvic Organ Prolapse Quantification (POP-Q) system from among patients who were admitted for treatment of either stress urinary incontinence or pelvic organ prolapse. A Burch urethropexy, either alone or with a parvaginal repair, was done to correct the stress urinary incontinence, as well as additional operations to correct prolapse of stage II or more. The patients were evaluated postoperatively for the stress urinary incontinence and the degree of prolapse at every visit. Nineteen of 30 (63.3%) patients who were admitted with stress urinary incontinence had a coexisting pelvic organ prolapse, most often of the anterior wall. In 42 of 67 (62.7%) cases admitted with pelvic organ prolapse there was a coexisting stress urinary incontinence. A total of 61 patients who had both conditions were followed for 12 months postoperatively. The recurrence rate of stress urinary incontinence and prolapse (all of which were stage II) was 3.3% and 18.0%, respectively. It was noted that the greater the preoperative stage, the higher the recurrence rate (stage II 4.35%; stage III 25.0%; stage IV 33.6%). The coexisting rates of pelvic organ prolapse in patients having stress urinary incontinence, and stress urinary incontinence in patients having a pelvic organ prolapse, were both high. Therefore, when a preoperative evaluation that simultaneously considers both conditions and the correcting surgery is based on this evaluation, the recurrence rates of both conditions could be lowered.

Efficient intracellular delivery of an exogenous protein GFP with genetically fused basic oligopeptides.

Several oligopeptides, derived from certain proteins, translocate as a form fused to small molecules or exogenous proteins across the plasma membrane into cells. Some of these oligopeptides, the so-called protein-transduction domains (PTDs), contain a high proportion of basic residues. The translocation of some of these basic PTDs, such as oligoarginines, has been studied as chemically fused forms to other organic compounds. In this study, we also tested to determine whether or not oligoarginines, when fused genetically to an exogenous protein such as GFP, are also able to translocate efficiently across the plasma membrane. The oligoarginine Rn (n = 5,6,7,8,9)-GFP fusion proteins were translocated quite efficiently, and the transduction efficiency increased in proportion to the number of arginine residues. However, the cellular uptake of the oligolysine-GFP fusion proteins was less efficient than that of the corresponding oligoarginine-GFP fusion proteins. When fused to GFP, the translocation efficiency of R5 was similar to that of Tat(49-57)(RKKRRQRRR). This finding suggests that the arginine homo-oligopeptide is more efficient than other PTDs which contain a mixture of basic residues. On the other hand, both the K9- and Tat(49-57)-GFP fusion proteins were transduced with similar efficiencies. It appears that basic oligopeptides may be useful for the efficient translocation of diverse exogenous proteins as genetically fused forms.

Efficient intracellular delivery of GFP by homeodomains of Drosophila Fushi-tarazu and Engrailed proteins.

The 60 amino acid long homeodomain of Antennapedia (Antp), either alone or as a fusion protein with 30-40 amino acid long foreign polypeptides, has been reported to cross biological membranes by an energy- and receptor-protein-independent mechanism. Moreover, the 16 amino acid long third helix of the Antp homeodomain, so-called penetratin, possesses translocation properties when fused to fewer than 100 amino acids as well. These findings led us to study whether such a protein tansduction property is shared by other homeodomains. We report here that homeodomains of two homeoproteins, Fushi-tarazu and Engrailed, are able to transduce a 238 amino acid long green fluorescent protein into cultured cells as efficiently as other well-known protein transduction domains, such as an internal oligopeptide of Tat and penetratin. These findings suggest that such transduction activity of homeodomains might have some physiological roles and that it can be exploited for development of efficient transduction vectors for research use and protein therapy.

An analysis of two tandem promoters of the Drosophila purple gene.

We have analyzed two tandem promoters, separated by only about 400 bp, of the purple (pr) gene of Drosophila melanogaster, by fusing them to the firefly luciferase reporter gene and employing a transient expression assay with Drosophila S2 cells. Both the distal promoter and the proximal promoter were found to function in S2 cells and an about 700 bp long region (-270 to +421), containing both promoters, was sufficient to effect maximal promoter activity. When the two promoters were analyzed separately, the distal promoter was found to be much stronger in its function than the proximal promoter. At least three different kinds of cis elements near the transcription start site appear to play crucial roles in driving constitutive expression from the distal promoter. On the other hand, only a single cis element, which may play a role in tissue-specific expression, appears to be important for the activity of the proximal promoter in S2 cells. We propose that the clustering of important cis elements near the transcription start sites may be responsible for the selective regulation of the two tandem promoters.