Clinical Comparison of Distal Pancreatectomy with or without Splenectomy

The spleen may be preserved during distal pancreatectomy (DP) for benign disease. The aim of this study was to compare the perioperative and postoperative courses of patients with conventional DP and spleen-preserving distal pancreatectomy (SPDP) for benign lesions or tumors with low-grade malignant potential occurred at the body or tail of the pancreas. A retrospective analysis was performed for the hospital records of all the patients undergoing DP and SPDP between January 1995 and April 2006. One-hundred forty-three patients underwent DP and 37 patients underwent SPDP. There were no significant differences in age, sex, indications of operation, estimated blood loss, operative time, and postoperative hospital stay between the two groups. Pancreatic fistula occurred in 21 (13.3%) patients following DP and in 3 (8.1%) following SPDP without a significant difference (p=0.081). Portal vein thrombosis occurred in 4 patients after DP. Splenic infarction occurred in one patient after SPDP. Overwhelming postosplenectomy infection was observed in one patient after DP. SPDP can be achieved with no increase in complication rate, operative time, or length of postoperative hospitalization as compared to conventional DP. Additionally, it has the advantage of reducing the risk of overwhelming postsplenectomy infection and postoperative venous thrombosis.     

Autologous primary muscle-derived cells transfer into the lower urinary tract

The goal of these experiments was to establish the basic methodology for future clinical applications of muscle-derived cells (MDC) tissue engineering and gene transfer for the treatment of urological dysfunction. Primary MDC isolated via preplating techniques from adult female SD rats were transduced with retrovirus encoding the expression of beta-galactosidase reporter gene. The MDC were injected into the right and left lateral walls of the bladder and proximal urethra of the autologous animals (n = 6) with a 10 microl Hamilton micro syringe. The amount of injected MDC ranged from 1 to 2 x 10(6) cells. The injected tissue was harvested after 7, 14, and 28 days, sectioned and examined histologically for beta-galactosidase and immunohistochemically for fast myosin heavy chain specific to skeletal muscle. The tissues were also stained for anti-CD4 and anti-CD8 antibodies to assess for cellular immune reaction. We have detected a large number of autologous MDC expressing beta-galactosidase and positively stained for fast myosin heavy chain in the bladder and urethral wall. Many injected myoblasts and myotubes were also seen in the bladder and urethral wall at each time point. Staining of lymphocytes with anti-CD4 and anti-CD8 antibodies was negative after MDC injection at each time point. We have demonstrated the long-term survival of autologous MDC and MDC mediated gene transfer into the bladder and urethral wall. Autologous MDC and MDC mediated gene transfer may be a promising treatment to augment bladder and urethral sphincter function.     

A common mutation in methylenetetrahydrofolate reductase gene among the Japanese population

Summary Hyperhomocysteinemia has been reported as an independent risk factor for atherosclerotic cerebrovascular and coronary heart diseases. 5,10-Methylenetetrahydrofolate reductase (MTHFR) is one of the enzymes responsible for hyperhomocysteinemia. The C to T transition of the MTHFR gene at nucleotide position 677 results in decreasing the enzymatic activity and increasing the plasma homocysteine level. We studied the distribution of the MTHFR gene mutation among the Japanese population. The subjects were 129 Japanese males (aged 40–59 years). The allele frequency of the mutation was 0.38. The frequencies of the three genotypes were as follows: +/+, 11%; +/–, 54%; –/–, 35% (+ and – indicate the presence and absence of the mutation, respectively). We also studied the frequency of the MTHFR gene mutation in the middle-aged Japanese males with hypertension to investigate the possibility that this mutation is related to essential hypertension. The normotensive and hypertensive subjects were identical in the distribution of the mutated allele and the frequencies of the three genotypes. Furthermore, the prevalence of hypertension in each genotype group was same, although the mean diastolic pressure of the group with homozygous mutation was significantly higher than that of other groups (p<0.05).     

Primate cytomegalovirus assembly: evidence that DNA packaging occurs subsequent to B capsid assembly

Results presented here show that when cytomegalovirus (strain Colburn)-infected cells are treated with the DNA synthesis inhibitor hydroxyurea or phosphonoformate, one type of intranuclear capsid accumulates. These particles appeared to contain symmetrically organized internal material, and had a protein composition and sedimentation rate characteristic of B capsids. Radiolabeling experiments provided evidence that a population of B capsids lacking DNA is present during the course of a normal infection. These capsids sedimented slightly slower than the peak of viral DNA in the same region of the gradient, and had a ratio of DNA/protein that was estimated to be sevenfold lower than that of the faster sedimenting C capsids. DNA in both the B and C capsid regions of such gradients was found to be relatively resistant to digestion with DNase. The possibility is considered that herpesvirus B capsids lacking DNA may be counterparts of unexpanded proheads in the bacteriophage assembly pathway.     

Clinical prognostic values of vascular endothelial growth factor, microvessel density,and p53 expression in esophageal carcinomas

Vascular endothelial growth factor (VEGF) is known to play a key role in tumor angiogenesis. The tumor-suppressor gene p53 has been thought to regulate VEGF. We investigated the effect of VEGF on esophageal carcinoma and the correlation between VEGF and p53. Tissue samples were taken from 81 patients with esophageal carcinoma after surgery. VEGF and p53 expressions were examined by immunohistochemical staining. Microvessels in the tumor stained for CD34 antigen were also counted. VEGF and p53 expressions were observed in 51.3% (41/80) and 51.9% (41/79), respectively. The microvessel density was 70.9+/-6.7 (mean+/-SE) in VEGF-positive group and 68.7+/-5.1 in VEGF-negative group. However, no correlation was noted between VEGF and p53 expression. Whereas the tumor size, nodal status, depth of invasions, and tumor stage were associated with poor overall survival, VEGF expression or p53 expression was not. These results indicate that VEGF and p53 are highly expressed in esophageal carcinomas. Since the VEGF expression is not correlated with the p53 expression, microvessel density or clinicopathological findings, further studies with other angiogenic molecules are needed to determine the role in esophageal carcinomas.     

The link between T helper balance and lymphoproliferative disease

Lymphoproliferative disorders comprise a heterogeneous group of neoplasms whose behaviors range from indolent to very aggressive. The increased incidence seen in the context of immunodeficiency provides evidence that the host immune system plays a vital role in their pathogenesis. We believe that T-helper (Th)-2 dominant states favor development of lymphoproliferative disorders, including lymphoma, and conversely T-helper (Th)-1 immunity protects against lymphoproliferative disease. The age distribution of lymphomas favors childhood and post-reproductive senescence, suggesting that exposure to these periods of Th-2 bias constitutes a key risk factor for developing the disease. The tendency of lymphomas to arise in Th-2 biased locations such as mucosal interfaces, immunoprivileged sites, and regions of B-cell differentiation may likewise reflect a corresponding spatial predilection. Various clinical conditions or treatments that shift Th1/Th2 balance, including HIV infection, transplant-related immune suppression, and autoimmune disorders, can also influence the status of lymphoproliferative diseases.     

Duplication of chromosome region 4q28.3-qter in monozygotic twins with discordant phenotypes

We describe monozygotic twins with partially discordant phenotypes who were found to have a duplication of chromosome region 4q28.3-qter. The duplicated region of chromosome 4 resulted from an unbalanced segregation of a balanced maternal (4;22)(q28.3;p13) translocation. Duplication of the long arm of chromosome 4 has been described in >60 patients; however, it usually results from the unbalanced segregation of a parental balanced translocation and has an associated monosomy. Twenty cases of dup 4q without an associated monosomy have been reported, and this is the only case of dup 4q28. 3-qter. All cases of dup 4q are reviewed, and phenotypic aspects are analyzed. Issues of monozygotic twinning and other birth defects also are addressed.     

High level expression of apoptosis inhibitor in hepatoma cell line expressing Hepatitis B virus

The serious result of hepatitis B (HBV) virus infection is development of hepatocellular carcinoma (HCC). However, the reason of development of HCC in HBV infected patients is still unclear. Recently, the suppression of cell apoptosis is found to relate with the development of cell carcinogenesis, therefore, the expression of apoptosis inhibitor in the virus related cancer line such as hepatoma cell line HepG2.215 was investigated. There are at least six Human apoptosis inhibitors (IAP) have been identified now. They are cIAP1, cIAP2, XIAP, NAPI, survivin and pIAP. Using gene-assay technology, we have recently compared the expression of IAPs in the HepG2.215 cells that persistently expresses Hepatitis B virus by integrated HBV genome with its parent cell line HepG2. The results suggest that there was obviously increase of cIAP2 and cIAP1 in the HepG2.215 cells versus HepG2 cells. Those observations imply a possibility of long time HBV infection could induce the over-expressing apoptosis inhibitors, furthermore, causing the liver cancer. The high expression of cIAP1 and cIAP2 in HBV expressing cells was confirmed by RT-PCR and Northern blot analysis. However, we did not find the change of NIAP and suvivin in HepG2.215 cells. In contrast, the expression of XIAP was down in the HepG2.215 cells comparing with HepG2 cells. How HBV triggers the over-expression of apoptosis inhibitor is unclear. Transient transfection of HepG2 cells with the plasmids expressing different HBV proteins such as S, M, L, X and core proteins did not give a decisive conclusion. Further study is going on now.     

Intrapulmonary cystic lymphangioma in a 2-month-old infant.

Lymphangioma is an abnormal collection of lymphatics that are developmentally isolated from the normal lymphatic system. Lymphangioma rarely presents as a solitary pulmonary lesion. We report a rare case of intrapulmonary cystic lymphangioma involving the upper lobe of the right lung, which presented with dyspnea in a 2-month-old infant. High-resolution computed tomography (HRCT) of the chest demonstrated a well-circumscribed, multiseptate, cystic lesion in the upper lobe of the right lung, mimicking the feature of type I congenital cystic adenomatoid mal-formation. The tumor was removed by bilobectomy of the upper and middle lobes of the right lung, and its pathologic examination confirmed the diagnosis of an intra-pulmonary cystic lymphangioma.     

Clinical experiences of bacteremia caused by metallo-beta-lactamase-producing gram-negative organisms.

The emergence of acquired metallo-beta-lactamase (MBL) in gram-negative bacilli is regarded as a therapeutic challenge since such enzymes are capable of hydrolyzing all beta-lactams in vitro except the monobactams. The clinical characteristics and outcome of 8 episodes of gram-negative bacteremia caused by MBL-producing isolates from January 1997 through December 2000 (Klebsiella pneumoniae, 6 isolates; Pseudomonas stutzeri, 4; Pseudomonas aeruginosa, 1; and Pseudomonas putida, 1) were analyzed. The median age of the patients was 61 years (range, 2-95 years). Most patients (n = 6, 75%) had more than 1 comorbid illness or condition and 6 patients acquired bacteremia in the intensive care unit. The median time from admission to the first positive culture was 34.5 days (range, 1-99 days). Pneumonia was the most common site of infection. Five patients (62.5%) received a carbapenem to treat bacteremia. The median time to defervescence was 6 days (range, 2-12 days). No bacteriologic failure was noted during or after antimicrobial therapy. The overall mortality rate from bacteremia caused by gram-negative, MBL-producing organisms was nil at 14 or 28 days.