Regulation of proliferation, motility, and contractility of human endometrial stromal cells by platelet-derived growth factor

To evaluate the involvement of platelet-derived growth factor (PDGF) isoforms (PDGF-AlphaAlpha, PDGF-AB, and PDGF-BB) on endometrial tissue remodeling during the perimenstrual period, we investigated the effects of PDGF on the proliferation, motility, invasiveness, and contractility of cultured human endometrial stromal cells (ESC) using a modified methylthiazoletetrazolium assay, a 5-bromo-2'-deoxyuridine incorporation assay, an in vitro wound repair assay, a chemotactic migration assay, a Transwell invasion assay, and a collagen gel contraction assay. All three isoforms of PDGF significantly enhanced the cell proliferation, DNA synthesis, and in vitro wound repair of ESC. Chemotactic migration assay, Transwell invasion assay, and collagen gel contraction assay demonstrated that the PDGF isoforms significantly stimulated both the motility of ESC and the collagen gel contractility of ESC. PDGF-BB showed the strongest effects on these cellular functions of ESC. The present study suggested that PDGF isoforms may promote endometrial tissue repair by enhancing the proliferation and expansion of ESC, stimulating ESC migration, and stimulating the contraction of the collagen gel matrix by ESC. By regulating ESC function during the perimenstrual period, PDGF may help to protect the endometrium from extensive fibrosis and scarring.     

RP105-lacking B cells from lupus patients are responsible for the production of immunoglobulins and autoantibodies

OBJECTIVE: We previously reported that B cells lacking the RP105 molecule, which proved to be highly activated B cells, are increased in the peripheral blood of patients with systemic lupus erythematosus (SLE). In the present study, we attempted to determine whether RP105-negative B cells obtained from SLE patients would be capable of producing autoantibodies as well as immunoglobulins. METHODS: RP105-positive and RP105-negative B cells, sorted by cell sorter, were cultured for 5 days without stimulation, or were stimulated with Staphylococcus aureus Cowan 1 strain (SAC) or recombinant interleukin-6 (IL-6). For the assay of autoantibodies, RP105-positive and RP105-negative B cells were cultured separately for 10 days with anti-CD3 antibody-stimulated T cells. The production of immunoglobulins and autoantibodies was determined by enzyme-linked immunosorbent assay. RESULTS: We demonstrated that RP105-negative B cells, but not RP105-positive B cells, obtained from SLE patients could spontaneously produce IgG and IgM in vitro until day 5. SAC and IL-6 enhanced production of IgG and IgM by RP105-negative B cells but failed to induce such production by RP105-positive B cells. The latter cells, however, when cocultured with activated T cells in the presence of IL-10, produced IgG, although the amount was very small compared with that produced by RP105-negative B cells. Most important, under these conditions, anti-double-stranded DNA antibodies were produced only by the RP105-negative B cells obtained from SLE patients. CONCLUSION: These data indicate that RP105-negative B cells, constituting a subset of B cells in SLE patients, are highly activated and may be responsible for the production of autoantibodies as well as polyclonal immunoglobulins.     

Re-entry circuit in ventricular tachycardia due to focal fatty-fibrosis in a patient with myotonic dystrophy

A 69-year-old man with a recurrent ventricular tachycardia (VT) was admitted. The patient was diagnosed as myotonic dystrophy type 1 (DM1) and DNA analysis revealed 1,800 CTG-repeat expansion in the myotonic dystrophy protein kinase (DMPK) gene. Ultrasonic cardiogram (UCG), left ventriculogram (LVG) and magnetic resonance imaging (MRI) did not show any abnormal sign including fatty infiltration. But, endomyocardial biopsy obtained from ventricular outflow tract revealed severe fatty infiltration and interstitial fibrosis. Radiofrequency catheter ablation at the biopsy site could eliminate VT, so it was strongly suggested that the re-entry circuit was formed by focal fatty-fibrosis. Careful observation should be continued for a long period.     

Squamous cell carcinoma of the liver originating from non-parasitic cysts after a 15 year follow-up

Squamous cell carcinoma is an extremely rare primary liver tumour. A 42-year-old man presented at our hospital on 19 February 1986, with pain in the right upper quadrant of the abdomen and general fatigue, and reported an 8 year history of this complaint. Ultrasonography showed four cystic masses in the liver with a maximum diameter of 15 cm, one of which contained a solid component. A computed tomography (CT) scan confirmed a huge, predominantly cystic, mass in the liver with a small solid component and irregular wall. Calcifications were seen in the solid components. On 22 April 1986, a laparotomy was performed but the masses were too large to be removed. During 15 years of follow-up after the laparotomy, there had been no change seen in his abdominal CT scan. He subsequently arrived at our hospital again on 10 July 2001 with loss of appetite and of body weight. A CT scan showed a cyst in the liver of 25 cm in diameter with calcification that had a large solid part invading the liver. A post-mortem pathological dissection showed multiple cysts, the largest of which was 25 cm in diameter. They had large solid parts with calcification invading the liver. There were widespread metastatic lesions. Microscopic examination showed the tumour to be a well differentiated squamous cell carcinoma. To the best of our knowledge, this is the first report of a squamous cell carcinoma arising from 15 multiple non-parasitic hepatic cysts after a 15 year follow-up. Furthermore, 23 years had passed since the patient's symptoms appeared for the first time.     

Homozygous familial hypercholesterolemia mutant with a defect in internalization of low density lipoprotein.

During studies on binding of low density lipoprotein (LDL) to fibroblasts from patients with the homozygous form of familial hypercholesterolemia (FH), a unique line was derived from subject M.N. This line could bind as much LDL as normal cells, or even more. However, like fibroblasts from other patients with the homozygous form of FH, it failed to show regulation of cholesterol synthesis. Analyses of the LDL receptors showed that this line could not mediate internalization of receptor-bound LDL. Studies on the fibroblasts of the parents of this subject showed that the inability to internalize LDL was hereditary and that the subject was a pure homozygote for this defect. The plausibility of this finding was supported by the fact that her parents were first cousins. The possible existence of a homozygous state of this defect was predicted by Goldstein et al. [Goldstein, J. L., Brown, M. S. & Stone, N. J. (1977) Cell 12, 629-41], but an actual case of the internalization defect in a pure homozygous form had not been found. There were no differences from normal cells in the nature of the LDL binding activity of this line, such as in its specificity, affinity, or Ca2+ requirement.     

Assessment of adenosine-induced coronary steal in the setting of coronary occlusion based on the extent of opacification defects by myocardial contrast echocardiography

The authors examined the ability of real-time myocardial contrast echocardiography (MCE) to assess adenosine-induced coronary steal in the setting of coronary artery occlusion. The left anterior descending (LAD) coronary artery was occluded in 8 open-chest dogs. Real-time MCE was performed during LAD occlusion, and the extent of opacification defects from MCE was measured without and with adenosine infusion. Microsphere-derived myocardial blood flow (MBF) was measured in the LAD and left circumflex (LCx) coronary artery beds, and the LAD/LCx ratio of MBF was calculated. The LAD/LCx ratio of MBF decreased in response to adenosine administration (without adenosine: 0.66, with adenosine: 0.43, p < 0.01). The extent of opacification defects from MCE increased in response to adenosine administration (without adenosine: 18%, with adenosine: 22%, p < 0.01). Thus, real-time MCE allows for the detection of adenosine-induced coronary steal as changes in the extent of opacification defects in the setting of occlusion of 1 coronary artery accompanying another normally patent coronary artery.     

A case of Vietnamese immigrant with tuberculous mediastinopericarditis

A case of vietnamese immigrant with tuberculous mediastinopericarditis was reported and the literature was reviewed. A 39 year-old man was admitted to our hospital with chief complaints of dyspnea and weakness. Blood chemistry suggested the existence of congestive liver dysfunction. Chest X-ray film revealed marked cardiomegaly and a abnormal mass in the anteriorly superior area which was confirmed as anterior mediastinum on CT scan. Echocardiogram disclosed a large volume of pericardial effusion and thickened pericardium. Tuberculin test was positive. Firstly, this mediastinal mass was believed to be malignant tumor and the pericardial effusion had originated from it. Finally, tuberculous mediastinopericarditis was diagnosed by detecting tuberculous mycobacterium from the cultured pericardial effusion and also the biopsied lymph nodes. Although occurrence of tuberculous mediastinopericarditis is rare at the present time in Japan, this disease has not been exterminated and should be kept in mind.     

Pancreaticobiliary maljunction: retrospective and nationwide survey in Japan

Pancreaticobiliary maljunction (PBM) is a congenital anomaly defined as a union of the pancreatic and biliary duct that is located outside the duodenal wall. The Japanese Study Group on Pancreaticobiliary Maljunction and the Committee for Registration enrolled and analyzed 1627 patients with PBM who had been diagnosed and treated from January 1, 1990 to December 31, 1999 at 141 hospitals throughout the country. There were 1239 patients with dilatation of the bile duct (group A) and 388 patients without dilatation (group B). The average age was 24 years in group A and 47 years in group B; the age was significantly higher in group B. The type of confluence between the terminal choledochus and the pancreatic duct has been classified into three types (type a, right-angle type; type b, acute-angle type; and type c, complex type). In group A, type a accounted for 57.9% and was significantly more frequent compared with the other types (type b, 32.4%; type c, 5.6%). In group B, type b accounted for 60.8%, being significantly more frequent compared with the other types (type a, 29.4%; type c, 7.2%). Subjective symptoms, preoperative complications (e.g., liver dysfunction and acute pancreatitis), pancreatic stone, and pancreatic duct morphological abnormality were significantly more frequent in group A. However, the amylase levels in the bile and gallbladder were significantly higher in group B, and the presence of gallstone and morphological abnormality of the gallbladder was significantly more frequent in group B. The occurrence rate of cancer in the biliary tract was 10.6% in group A and 37.9% in group B, being significantly higher in group B. In group A, cancer of the extrahepatic bile duct was seen in 33.6% and cancer of the gallbladder was seen in 64.9%, but gallbladder cancer was present significantly more frequently in the patients with diffuse or cylindrical dilatation, and bile duct cancer was present significantly more frequently in the patients with cystic dilatation. In group B, 93.2% of the patients had gallbladder cancer, and bile duct cancer was found in as few as 6.8%. Against this background Japanese surgeons regard cholecystectomy, resection of the extrahepatic bile duct, and hepaticojejunostomy as standard operations for PBM with dilatation of the bile duct. However, opinion on whether or not the bile duct should be removed in the treatment of PBM without dilatation of the bile duct has been divided among Japanese surgeons. A randomized controlled trial is necessary.