A novel missense mutation (I344K) in the SPG4gene in a Korean family with autosomal-dominant hereditary spastic paraplegia

 Hereditary spastic paraplegia (HSP) is a group of clinically and genetically heterogeneous neurodegenerative disorders characterized by slowly progressive spasticity and weakness of the lower extremities. Among eight loci linked with autosomal-dominant (AD)-HSP, the SPG4 locus on chromosome 2p22 accounts for about 40% of all patients. Recently, mutations in a new member of the AAA protein family, called spastin, have been identified as responsible for SPG4-linked AD-HSP. Here, we describe a novel missense mutation (c.1031T>A; I344K) in exon 7 of the SPG4 gene identified in a Korean family with typical clinical features of pure AD-HSP. The mutation affects the third amino acid of the highly conserved AAA cassette domain, which is the most fore part of the domain altered by a missense mutation reported so far. Clinical presentations of affected individuals carrying the I344K mutation were not different from those of pure AD-HSP with SPG4 mutations reported previously. However, it is noteworthy that neither urinary dysfunction nor involvement of upper extremities was noticed in this family. To our knowledge, this is the first report of genetically confirmed AD-HSP in Korea. Received: February 20, 2002 / Accepted: May 21, 2002     

Detection of reactive oxygen species (ROS) and apoptosis in human fragmented embryos

In human in-vitro fertilization (IVF)-embryo transfer, the in-vitro culture environment differs from in-vivo conditions in that the oxygen concentration is higher, and in such conditions the mouse embryos show a higher concentration of reactive oxygen species (ROS) in simple culture media. ROS are believed to cause damage to cell membranes and DNA fragmentation in somatic cells. This study was conducted to ascertain the level of H2O2 concentration within embryos and the morphological features of cell damage induced by H2O2. A total of 62 human oocytes and embryos (31 fragmented, 15 non-fragmented embryos, 16 unfertilized oocytes) was obtained from the IVF-embryo transfer programme. The relative intensity of H2O2 concentrations within embryos was measured using 2',7'-dichlorodihydrofluorescein diacetate by Quanti cell 500 fluorescence imaging and DNA fragmentation was observed with transmission electron microscopy and an in-situ apoptosis detection kit. The H2O2 concentrations were significantly higher in fragmented embryos (72.21 +/- 9.62, mean +/- SEM) compared to non-fragmented embryos (31.30 +/- 3.50, P < 0.05) and unfertilized oocytes (30.75 +/- 2.67, P < 0.05). Apoptosis was observed only in fragmented embryos, and was absent in non-fragmented embryos. Electron microscopic findings confirmed apoptotic bodies and cytoplasmic condensation in the fragmented blastomeres. We conclude that there is a direct relationship between increased H2O2 concentration and apoptosis, and that further studies should be undertaken to confirm these findings.      

Immunohistochemical labeling for the Dpc4 gene product is a specific marker for adenocarcinoma in biopsy specimens of the pancreas and bile duct.

We immunohistochemically labeled 72 biopsy specimens from the extrahepatic biliary tree and pancreas for Dpc4 protein and correlated expression with histologic diagnosis and patient follow-up. Specimens were classified histologically as follows: nonneoplastic, 35; neoplastic, 22; atypical, 15. Loss of expression of Dpc4 protein was identified in 12 specimens; 11 were histologically diagnostic of carcinoma. The 12th specimen was from a patient whose biopsy specimen initially was diagnosed as "atypical," but clinical follow-up revealed adenocarcinoma. Of the 12 atypical biopsy specimens with intact expression for Dpc4, follow-up later revealed that 10 were adenocarcinoma. Loss of expression of Dpc4 protein was never identified in a benign specimen. Immunohistochemical labeling for the Dpc4 gene product is a specific marker of carcinoma in biopsy specimens of the pancreas and extrahepatic bile ducts and is marginally helpful in classifying atypical specimens. The sensitivity for carcinoma is low. This latter finding is not unexpected, because the DPC4 tumor suppressor gene is inactivated in only about half of pancreatic and biliary malignant neoplasms. Importantly, loss of Dpc4 expression has been reported in in situ carcinomas, suggesting that loss of expression should not be equated with invasive carcinoma.     

Caspase-3/CPP32 immunoreactivity and its correlation with frequency of apoptotic bodies in human prostatic carcinomas and benign nodular hyperplasias

AIMS: Apoptosis is mediated by apoptosis-specific genes, certain oncogenes and tumour suppressor genes. Caspase-3, a group of cystein proteases, is involved in the induction of apoptosis and has been considered to correlate with apoptosis. The aim of this study was to determine whether caspase-3 is expressed in prostatic carcinoma and benign prostatic hyperplasia, and correlated with the apoptosis. METHODS AND RESULTS: We studied the apoptotic index and caspase-3 immunoreactivity in 40 cases of benign nodular hyperplasia (BPH) and 40 cases of prostate carcinoma (PCA) by in-situ labelling and immunohistochemistry. The mean number of apoptotic bodies in cases with BPH was not significantly different from cases with PCA I (Gleason score 2-4), but samples from patients with PCA II (Gleason score 5-7) and PCA III (Gleason score 8-10) showed a significantly higher apoptotic number than cases with BPH. Positive staining for caspase-3 was seen in 42.5% (17/40) of the BPH, and 27.5% (11/40) of the PCA: PCA I was 41.7% (5/12), PCA II 14.3% (2/14) and PCA III was 28.6% (4/14). CONCLUSIONS: Based on our results, the number of apoptotic bodies was not correlated with the caspase-3 expression and there was no relationship between caspase-3 expression and Gleason score. However, the number of apoptotic bodies was significantly higher in cases with intermediate (Gleason score 5-7) and high-grade (Gleason score 8-10) PCAs than cases with BPH and low-grade PCAs (Gleason score 2-4).     

Flat depressed early colon cancer--a case report.

A flat depressed early colon cancer (FDEC) is characterized by non-polypoid growth pattern, no association of adenomatous tissues and a tendency of even small lesions toward submucosal invasion and lymph node metastasis. It supports de novo carcinogenesis of colorectal cancer, although most colorectal cancers arise in pre-existing adenoma (adenoma-carcinoma sequence). There have been few reports of small depressed cancers because of the difficulty in colonoscopic detection and the rapid development to ulcerating advanced cancers. We report a case of flat depressed early colon cancer confined to mucosa detected by indigo carmine contrast colonoscopy.     

Congenital cytomegalovirus infection in Korean population with very high prevalence of maternal immunity.

In order to asses congenital cytomegalovirus (CMV) infection in Korea, five hundred and seventy five pregnant women (mean age 29.5 +/- 3.8 yrs., mean gestational age at test 37.5 +/- 6.7 weeks) visiting the prenatal clinic at Severance Hospital, Seoul, Korea were studied. CMV IgG antibody was present in 96% (552/575) and IgM antibody was present in 0.7% (4/575) of the pregnant women by the third trimester. Four of 445 cord sera were positive for CMV IgM antibody (0.9%). Urine samples from 514 newborns were tested for the evaluation of congenital CMV infection. Six (1.2%) of 514 newborns excreted CMV in their urine. All the congenitally infected infants had subclinical involvement at birth and during the 12 months of the follow-up period. These results indicate that Korean pregnant women were highly immunized against CMV by the third trimester. Furthermore this study suggests that the rate of congenital CMV infection is relatively as high as rates previously reported from other countries, although there is a very high prevalence of maternal immunity. The incidence of maternal primary infection during pregnancy seems to be rare and therefore most congenital infections in Korea might be following by maternal reactivation or reinfection.     

The changing epidemiology of hepatitis A in children and the consideration of active immunization in Korea

Currently, Korea is a low endemicity country for HAV, especially in children. However, recent reports of hepatitis A outbreaks show that there has been a shift of disease incidence to adolescents and young adults, with 2 cases of acute liver failure in one reported outbreak. We need to study the immune status for HAV in order to provide information for the establishment of preventive measures and possible consequences of HAV in Korea. A total of 334 infants, children and adolescents less than 20 years of age living in rural areas of Kyonggi Province, Korea were evaluated for anti-HAV immune status in 1996. Five hundred and eighty-four primary school children living in the same area were separately evaluated for the natural seroconversion rate between 1993 and follow-up samples taken in 1996. Anti-HAV IgG antibody was measured by enzyme immunoassay (HAVAB EIA kit, Abbott Laboratories, Chicago, Illinois, USA). In comparison with previous reports of seroprevalence rates, our data confirmed a dramatic drop in seroprevalence rates among children and adolescents under 20 years of age living in rural areas, from over 63.8% two decades ago to 4.6% in 1996. Natural acquisition of HAV antibody in primary school children rarely occurs, registering only 0.5% during three years. Several outbreaks in young adults during 1996-1998 suggested that immunity against HAV in this population is so low that massive outbreaks are unavoidable. Teenagers and young adults, especially soldiers, who are likely to be exposed to contaminated food or water, would also have a greater risk of hepatitis A. Immunizing children with HAV vaccine as a routine schedule should also be considered in Korea in the future, particularly if the disease burden could be estimated and the cost-effectiveness of the vaccine could be proved.     

Impact of Dissection after Drug-Coated Balloon Treatment of De Novo Coronary Lesions: Angiographic and Clinical Outcomes

PurposeDissection after plain balloon angioplasty is required to achieve adequate luminal area; however, it is associated with a high risk of vascular events. This study aimed to examine the relationship between non-flow limiting coronary dissections and subsequent lumen loss and long-term clinical outcomes following successful drug-coated balloon (DCB) treatment of de novo coronary lesions.Materials and MethodsA total of 227 patients with good distal flow (Thrombolysis in Myocardial Infarction flow grade 3) following DCB treatment were retrospectively enrolled and stratified according to the presence or absence of a non-flow limiting dissection. The primary endpoint was late lumen loss (LLL) at 6-month angiography, and the secondary endpoint was target vessel failure (TVF, a composite of cardiac death, target vessel myocardial infarction, target vessel revascularization, and target vessel thrombosis).ResultsThe cohort consisted of 95 patients with and 132 patients without a dissection. There were no between-group differences in LLL (90.8%) returning for angiography at 6 months (0.05±0.19 mm in non-dissection and 0.05±0.30 mm in dissection group, p=0.886) or in TVF (6.8% in non-dissection and 8.4% in dissection group, p=0.799) at a median follow-up of 3.4 years. In a multivariate analysis, the presence of dissection and its severity were not associated with LLL or TVF. Almost dissections (93.9%) were completely healed, and there was no newly developed dissection at 6-month angiography.ConclusionThe presence of a dissection following successful DCB treatment of a de novo coronary lesion may not be associated with an increased risk of LLL or TVF (Impact of Drug-coated Balloon Treatment in de Novo Coronary Lesion; {"type":"clinical-trial","attrs":{"text":"NCT04619277","term_id":"NCT04619277"}}NCT04619277).     

The fate of the rectal segment after diversion of the fecal stream in Crohn's disease: its implications for surgical management

Diverting the fecal stream has been considered to benefit the course of Crohn's disease. Clinical signs and symptoms have not, however, been distinguished previously from the objective inflammatory changes in the distal segment. We reviewed the course of 16 consecutive patients with Crohn's disease in whom sigmoidoscopy showed normal mucosa at the time of diversion and who underwent an ileostomy or colostomy, the rectal segment being left in place. As early as 3 months after diversion, all 16 patients showed progressive friability, ulceration, and exudation in the retained rectum. Stricture occurred in four and lead to abdominoperineal resection in three. Four of eight patients with only moderate inflammation on sigmoidoscopy underwent reanastomosis which was followed by a return to a normal-appearing rectal mucosa. The rectal segment inflammed after diversion rarely shows the histological characteristics of Crohn's disease when resected. This leads us to suspect that the disorder of nonspecific "diversion colitis" might account for this phenomenon entirely, or at least it may accelerate the Crohn's disease process. Continuity of the intestinal tract should be maintained in the course of Crohn's disease surgery if feasible. If a diversion is clinically warranted, reanastomosis should be considered as early as possible despite progressive inflammation of the rectal mucosa.