Alternative splicing of exon 14 determines nuclear or cytoplasmic localisation of fmr1 protein isoforms

Impaired expression of the FMR1 gene is responsible for the fragile X mental retardation syndrome. The FMR1 gene encodes a cytoplasmic protein with RNA-binding properties. Its complex alternative splicing leads to several isoforms, whose abundance and specific functions in the cell are not known. We have cloned in expression vectors, cDNAs corresponding to several isoforms. Western blot comparison of the pattern of endogenous FMR1 proteins with these transfected isoforms allowed the tentative identification of the major endogenous isoform as ISO 7 and of a minor band as an isoform lacking exon 14 sequences (ISO 6 or ISO 12), while some other isoforms (ISO 4, ISO 5) were not expressed at detectable levels. Surprisingly, in immunofluorescence studies, the transfected splice variants that exclude exon 14 sequences (and have alternate C-terminal regions) were shown to be nuclear. Such differential localisation was however not seen in subcellular fractionation studies. Analysis of various deletion mutants suggests the presence of a cytoplasmic retention domain encoded in exon 14 and of a nuclear association domain encoded within the first eight exons that appear however to lack a typical nuclear localisation signal.      

A complex translocation in a 5-year-old boy with acute myeloblastic leukemia

A complex translocation [t(2;10;11)(q34;q11;q13)], an extra chromosome #8, and a duplication of 17q were the major findings in blast cells found in the bone marrow of a 5-yr-old boy with AML-M2 both before treatment and during relapse. The child died 8.5 mo after diagnosis, despite intensive combination chemotherapy.     

Diagnostic efficiency of carcinoembryonic antigen and CA125 in the cytological evaluation of effusions.

In our previous study, the combination of the concentrations of carcinoembryonic antigen (CEA) and CA125 and the findings from cytological examination in 189 benign and malignant pleural and peritoneal effusions was useful in the diagnosis/classification of malignant effusions. Sensitivity of CEA (level, greater than 5 ng/mL) was 68%; specificity was 99% for the diagnosis of malignant effusions secondary to carcinoma of the lung, breast, gastrointestinal tract, and mucinous carcinoma of the ovary. Sensitivity of CA125 (level, greater than 5000 U/mL) was 85%; specificity was 96% for the diagnosis of malignant effusions in carcinoma of the ovary, fallopian tube, and endometrium. We now expanded the study to include 840 pleural and peritoneal effusions (benign, n = 520; malignant, n = 320) and analyzed the data by the statistical method of Rudolph and colleagues. Based on new cutoff values, ie, CEA level at 6.3 ng/mL and CA125 level at 3652 U/mL, the sensitivities for detection of malignant effusions secondary to carcinomas of the lung, breast, and gastrointestinal tract and mucinous carcinoma of the ovary varied between 75% and 100%; specificity was 98%. Sensitivity of CA125 for detection of malignant effusions from müllerian epithelial carcinoma was 71%; specificity was 99%. The elevated CEA fluid level alone helped to diagnose malignant effusions of the gastrointestinal tract in 54%, breast in 19%, and lung in 16%. The high CA125 fluid level was predictive of müllerian epithelial carcinoma. Adjunctive use of CEA and CA125 levels in fluid enhances the sensitivity of cytological diagnosis and may be predictive of the primary site in patients who present with carcinoma of an unknown primary source.     

Dehydrochlorination of poly(sulfonyl-co-2-chloroethylene)

Poly(sulfonyl-co-2-chloroethylene)s were shown to have an enhanced tendency to undergo dehydrochlorination compared with poly(vinyl chloride). Dehydrochlorination was observed under the following conditions: (a) during preparation of the copolymers by γ-radiation initiated copolymerization of vinyl chloride and sulfur dioxide, (b) by γ-irradiation of the polymer, (c) during ageing, (d) on heating and (e) in solution in basic solvents, such as DMSO. The dehydrochlorination was studied by microanalysis, by IR and UV spectroscopy and by ¹H and ¹³C NMR. Hydrogen chloride was eliminated preferentially from chloroethylene units occurring between two sulfonyl units. The proportion chloroethylene units: sulfonyl units in poly(sulfonyl-2-chloroethylene) decreased from ≈ 2:1 at a copolymerization temperature of 0°C to ≈ 1:1 at a temperature of ?78°C. The results show, that dehydrochlorination of copolymers prepared at low temperatures is a serious problem, especially with initiation by γ-irradiation.     

Wide spread scars, hypertrophic scars, and keloids

Patients with a wide scar may complain of having a "keloid," yet have a hypertrophic or a wide spread scar. The plastic surgeon should make the appropriate clinical diagnosis, because therapy varies depending on the condition present. A wide spread scar is best treated with excision and closure. A buried dermal flap may help to prevent recurrence, which is nevertheless likely to some degree. A hypertrophic scar can be distinguished from a keloid on clinical grounds. Although both may be red, nodular, and itchy, the keloid overgrows the original wound boundary and is much more likely to recur after surgical excision. Nonsurgical treatment of hypertrophic scars and keloids is similar, using repeated intralesional injections of Kenalog 40 mg per cc and sustained pressure on the lesion when possible. Surgical treatment differs for hypertrophic scars or keloids. Scar excision and closure, and selective Z-plasty, may be used in hypertrophic scars. In keloids, aggressive surgery is usually avoided, unless the lesion has a narrow pedicle. Surgery of keloids should be accompanied by intra- and postoperative Kenalog-40 injections, and on occasion by sustained pressure. Very large keloids may be resistant to medical management, and too aggressive for surgery owing to a high likelihood of recurrence. These difficult lesions serve as the impetus for continued biochemical and tissue culture research, seeking a biochemical means of control keloids.     

Improved biological properties of synthetic distearoyl phosphatidyl choline-based liposome in the conscious rat

We have previously produced and tested a liposome preparation based on hydrogenated soy lecithin (HSL-L) for the purpose of designing blood replacement in the form of liposome encapsulated hemoglobin (LEH). While these liposomes had acceptable physicochemical properties which addressed many of the desirable characteristics of "artificial blood," they produced hypotension, hemoconcentration, and thrombocytopenia when administered to rats. The following studies present improved synthetic distearoyl phosphatidylcholine-based liposomes (sDSPC-L) which were compared to the HSL-L for their biological effects in the conscious normovolemic rat (n = 6 - 11). HSL-L induced hypotension (-25 +/- 3 mmHg, P less than 0.01), tachycardia (+88 +/- 11 beats/min, P less than 0.01), decrease in cardiac index (-33 +/- 4%, P less than 0.01), and elevation of the total peripheral resistance index (+0.450 +/- 0.003 mmHg/ml/min/kg, P less than 0.01). The hematologic responses to HSL-L were: leukocytosis (+6,070 +/- 1,064/microliters, P less than 0.01), hemoconcentration (+4.0 +/- 0.1%, P less than 0.01), 0.01), and thrombocytopenia (-160 +/- 18 X 10(3)/microliters, P less than 0.01). Plasma thromboxane B2 (TXB2) was elevated to 30.4 +/- 5.6 pg/100 microliters (P less than 0.01). In contrast, the only effects induced by sDSPC-L were slight tachycardia (+37 +/- 9 beats/min, P less than 0.05) and a marginal increase in plasma TXB2 to 9.7 +/- 3.3 pg/100 microliters (P less than 0.05). All effects, except for those related to cardiac output and peripheral resistance, were transient. These data underscore the importance of pure synthetic DSPC in improving the biological effects of liposomes and suggest sDSPC-L as a promising vehicle for encapsulating hemoglobin.     

胰腺多房性潴留性囊肿1例

0　引言　胰腺多房性潴留性囊肿极为罕见,我科收治1例,报道如下.1　病例报告　患者,男,29岁,因发现右上腹包块11d入院,缘于11d前无明显诱因感右上腹痛,仅局限于右上腹部,无肩背部放散痛,伴间歇性发热,体温最高达38.3℃,经抗炎,对症治疗无效.并逐渐可触及右上腹有一肿块,在当地医院行穿刺检查为脓血性液体.镜检发现炎性细胞,B超示:胆囊窝下方及右肾内侧及腹腔动脉,下腔静脉外前方可见异常区,大小约9.1cm×6.6cm×7.6cm,边界清楚,形态不规则,内呈蜂窝状,可见多个大小不等的液性暗区,CT示:右上腹部上腔静脉前方6.0cm×9.0cm肿块和周围组织粘…     

Aging trends: Indonesia

The authors discuss causes and consequences of aging trends in Indonesia. Aspects considered include median age and support ratios; life expectancy; marital status and living arrangements; health, mobility, and disability; education; and work and income.     

IMPACTED RIGHT UPPER CENTRAL INCISOR AND TRANSPOSITION OF TWO OTHER ANTERIOR TEETH ON THE SAME SIDE (A Case Report)

A young boy presented with an uncommon finding of impaction of upper right central incisor and transposition of canine and lateral incisor on the same side. Esthetic management of his cosmetic problem which included fixed appliance therapy followed by light cure restorations is discussed.KEY WORDS: Impaction, Transposition     

Which organic acids does hemofiltrate contain in the presence of acute renal failure?

It is not generally possible to measure most organic acids in the serum of critically ill patients, due to rapid metabolism and methodological problems. Only the regular measurement of lactic acid and the arterial ketone body ratio (acetoacetate/beta-hydroxybutyrate, AKBR) have been introduced in clinical practice, but these parameters can represent only a part of the disturbed metabolism. In pediatric patients, a chromatographical urine analysis has been established for detection of inborn errors of metabolism, which allows the determination of more than 50 organic acids simultaneously (gas chromatographic (GC) analysis in combination with mass spectrometry (MS)]. In continuous treatment of acute renal failure, hemofiltrate is always available, but it contains only low protein concentrations and after the filtration process, metabolism is rapidly stopped. The sieving coefficient of lactic acid is nearly one in hemofiltration. The aim of our study was to compare results of the regular and CG/MS methods in blood and hemofiltrate for lactic acid, and to find other organic acids of possible clinical importance. We investigated serum (lactic acid) and hemofiltrate of 40 critically ill patitens, similar to the urine analysis method for infants. All patients suffered from acute renal failure and were treated by continuous veno-venous hemofiltration (CVVH). The conditions of treatment were standardized (spontaneous ultrafiltration in the first hour), and the material (blood/hemofiltrate) was taken one hour after the beginning of extracorporeal circulation. Statistical methods included correlation analysis, nonparametric ANOVA with Wilcoxon scores (ranks of data), and stepwise discriminant analysis. Regular and GC/MS methods in hemofiltrate showed a good correlation for lactic acid. The best correlation with lactic acid was found for 4-hydroxy-phenyllactic acid (n=20, r=0.866), 2-hydroxy-valeric acid (n=22, r=0.7491) and 2-hydroxybutyric acid (n=32, r=0.5148). Age, sex, diagnosis, and APACHE II score play a subordinate role, but the presence of glyceric and citric acid possibly have prognostic importance [nonparimetric ANOVA with Wilcoxon scores (ranks of data)], as does the combination of 3-hydroxypropionic acid, glyceric acid, and threonic-acid-4-lacton (stepwise discriminant analysis). It can be concluded that in acute renal failure, the measurement of lactic acid and AKBR can reflect only a small part of disturbed metabolism. Hemofiltrate can be a useful medium in describing metabolic processes in critically ill patients with acute renal failure. Some inherited metabolic diseases in infants (phenylketonuria, maple syrup disease) and ketoacidosis show similar metabolic modifications.