Potential function of TGF-β isoforms in maturation-stage ameloblasts

Objectives

To investigate potential functions of transforming growth factor-beta (TGF-β) isoforms in maturation-stage ameloblasts during amelogenesis.

Non-viral in vivo thrombomodulin gene transfer prevents early loss of thromboresistance of grafted veins.

OBJECTIVE: Immediate loss of thrombomodulin activity in the endothelium of vein grafts has been demonstrated during 90 min exposure to arterial circulation; this loss of activity is ascribed as an important cause of early thrombosis. Conventional ex vivo gene transfection after vein harvest cannot cover this acute period immediately after implantation. We have established a highly efficient non-viral gene therapy protocol utilizing modified transferrin receptor-facilitated gene transfer. Using this technique, we examined whether in vivo thrombomodulin gene therapy, directed to the endothelium of rat veins 2 days prior to grafting, may prevent thromboresistance impairment of vein grafts under simulated arterial circulation. METHODS: Abdomen of SD rat was opened and cationic liposome:transferrin:thrombomodulin gene complexes or the vector without DNAs were applied to the inferior vena cava of rats while blood flow was reduced by proximal and distal clamping. After 2 days, the transfected veins were harvested and thrombomodulin expression and thromboresistance properties determined before and after exposure to an artificial circuit. RESULTS: The trial of gene transfection using variable doses of DNAs confirmed that 7.5 microg of total DNAs was the most efficient quantity for thrombomodulin gene transfection to IVCs, although accompanying an increase of gene expression in other downstream organs. By transfection of the thrombomodulin gene in IVCs, the generation capacity of activated protein C in venous endothelium increased three-fold compared with veins treated with vector alone (P<0.01). Under simulated arterial circulation, perfusion of veins treated with vector alone decreased thrombomodulin activity to 36% of preperfused levels (P<0.01), whereas transfected grafts preserved the activity at normal vein endothelium levels even after perfusion. Consequently, the increase in endothelial thrombin activity induced by simulated arterial circulation was markedly attenuated in transfected veins (P<0.01), while immunohistochemistry confirmed the preservation of endothelial lining. CONCLUSIONS: Transferrin receptor-facilitated in vivo gene transfer to the inferior vena cava resulted in sufficient thrombomodulin gene expression immediately after graft implantation and subsequent maintenance of thromboresistance even after exposure to arterial pressure. Although further studies are needed, the present results suggest the possibility of gene therapy targeting acute phases of vein graft disease.     

Pancreatic insulinoma combined with glucagon positive cell: A case report

We present a 70-year-old man who was referred for surgery with uncontrollable hypoglycemia. Ultrasonography and abdominal contrast computed tomography revealed a hypervascular tumor of 1 cm in diameter in the pancreatic tail. With a diagnosis of insulinoma, we performed a distal pancreatectomy. The patient showed a good postoperative course without any complications. The patient’s early morning fasting hypoglycemia disappeared. The respective levels of C-peptide and insulin dropped from 14.9 ng/mL and 4860 μIU/mL preoperatively to 5.3 ng/mL and 553 μIU/mL after surgery. A histopathological examination demonstrated that the tumor was a pancreatic neuroendocrine tumor, grade 1. Immunostaining was negative for insulin and positive for CD56, chromogranin A, synaptophysin and glucagon. These findings suggested that the tumor was clinically an insulinoma but histopathologically a glucagonoma. Among all insulinoma cases reported between 1985 and 2010, only 5 cases were associated with independent glucagonoma. In this report, we characterize and discuss this rare type of insulinoma by describing the case we experienced in detail.     

Reoperative surgery in cholelithiasis

From 1965 to 1980, reoperations for residual or recurrent stones were performed on 78 out of 962 Japanese patients with cholelithiasis. The majority of patients who required reoperation had intrahepatic stones. Most of the causes of reoperation were residual stones due to incomplete removal or the non-detection of intrahepatic stones at the previous surgery. Very careful examination of the intrahepatic biliary trees should be done in patients with biliary tract diseases, because in many, the first operation was done during their youth. To remove the intrahepatic calculi completely, hepatic lobectomy should be considered as a final procedure. The causes of reoperation of common duct stones were residual in 60 per cent and recurrent in 40 per cent. Definitive surgery should be done at the first or at least the second operation to avoid irreversible hepatic disorders which have untoward effects on the prognosis. It is important not only to remove the stones but also to relieve the bile stasis in the biliary tract.     

Clinicopathological studies of minimal thyroid and oridinary thyroid cancers

Clinicopathological studies were carried out on 27 patients with minimal thyroid cancer and 56 with ordinary thyroid cancer at Kanazawa University, from April, 1979 to December, 1982. There was a significant difference in the rate of preoperative diagnosis between the minimal and the ordinary cancer groups. Subtotal thyroidectomy with modified neck dissection was usually performed in both groups. The histological types in minimal cancer group included 16 papillary carcinomas, 7 nonencapsulated sclerosing carcinomas, one follicular carcinoma, one anaplastic carcinoma with squamous cell metaplasia and two multiple mixed carcinomas. There was no significant difference in the rates of intrathyroidal and lymph node metastases between the two groups. While the metastatic lesions of sclerosing carcinoma were localized to the central cervical lymph nodes, the ordinary cancer in general and the papillary variant of minimal cancer metastasized not only to the central cervical lymph nodes but also to the ipsilateral and even to the contralateral jugular lymph nodes.     

Coronary arterial remodeling in differing clinical presentations of unstable angina pectoris--an intravascular ultrasound study

BACKGROUND: Coronary arterial remodeling influences the clinical presentation of ischemic heart disease; however, there is little information on the relationship between coronary arterial remodeling and the type of angina pectoris that patients manifest. HYPOTHESIS: The study was undertaken to determine the difference of coronary arterial remodeling in patients with different types of angina pectoris. METHODS: We analyzed 100 patients with ischemic heart disease using intravascular ultrasound (IVUS). Intracoronary IVUS images of proximal reference (PR), distal reference (DR), and target lesion were recorded, and intraluminal area (LA) and external elastic membrane (EEM) were measured. We defined a remodeling index as 100 x (lesion EEM - [PR-EEM + DR-EEM]/2) / ([PR-EEM + DR-EEM]/2). Cases were classified into three groups according to the clinical history (Group 1a: de novo unstable angina pectoris, Group 1b: accelerating unstable angina pectoris, and Group 2; stable angina pectoris). RESULTS: The remodeling index in Group 1a was significantly larger than that in Groups 1b and 2 (18.6 +/- 28.5 vs. 5.3 +/- 27.1 and 18.6 +/- 28.5 vs. -2.7 +/- 17.6, p = 0.0347 and p = 0.0005, respectively), but there was no statistical difference in remodeling index between Groups 1b and 2. CONCLUSIONS: Our results indicate that positive coronary arterial remodeling is more prevalent in patients with new onset of angina pectoris. The specific type of coronary arterial remodeling may affect the clinical presentation of patients with coronary artery disease.     

Effect of <Emphasis Type="Italic">Kaempferia parviflora</Emphasis> extract on knee osteoarthritis

Knee osteoarthritis (OA) is becoming more prevalent worldwide due to increases in the numbers of elderly and obese patients. Currently, pharmaceutical medicines used for the treatment of OA are for symptomatic therapy and therefore new therapeutic agents are needed. Kaempferia parviflora (KP) is a plant growing naturally in Southeast Asia and has various pharmacological effects including an anti-inflammatory effect, but no effect on OA has yet been reported. We therefore conducted a search for the effects KP and the active components of KP extract (KPE) exert on OA as well as its mechanism of action. Results from a study of KPE using the monoiodoacetic acid rat OA model revealed that KPE reduced the pain threshold and severity of osteoarthritic cartilage lesions. The mechanism of action and active components were then investigated using IL-1β-treated human knee-derived chondrocytes. KPE, as well as 5,7-dimethoxyflavone and 5,7,4′-trimethoxyflavone, which are key constituents of KPE and highly absorbable into the body, reduced the expression of matrix metalloproteinases (MMPs), which are the main extracellular matrix enzymes that degrade collagen within cartilage. As mentioned above, KPE acted to suppress OA and 5,7-dimethoxyflavone and 5,7,4′-trimethoxyflavone were shown to be involved as part of KPE’s mechanism that inhibits MMPs.     

Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (2003). I. Susceptibility distribution

The bacterial strains isolated from 565 patients diagnosed as having urinary tract infections (UTIs) in 14 institutions in Japan were collected between August 2003 and July 2004. The susceptibilities of them to many kinds of antimicrobial agents were investigated. Of them, 701 strains were estimated as prophlogistic bacteria and used for the investigation. The strains consisted of 258 Gram-positive bacterial strains (36.8%) and 443 Gram-negative bacterial strains (63.2%). Against Staphylococcus aureus, vancomycin (VCM) showed the strongest activity and prevented the growth of all strains with 2 microg/mL. Against Streptococcus agalactiae, ampicillin (ABPC), cefozopran (CZOP), imipenem (IPM), and clarithromycin (CAM) showed a strong activity and the MIC90 was 0.125 microg/mL or less. Against Enterococcus faecalis, VCM, ABPC, and IPM showed a strong antibacterial activity. The antibacterial activity of cephems to Escherichia coli was generally good, and especially CZOP and cefpirome (CPR) showed the strongest activity (MIC90: < or = 0.125 microg/mL). Quinolone resistant E. coli [MIC of ciprofloxacin (CPFX): > or =4 microg/mL] was detected at frequency of 15.7%, which was higher than that in the last year. Against Klebsiella pneumoniae, meropenem (MEPM) showed the strongest activity and next, the antibacterial activity of CRMN and CZOP was good. The antibacterial activity of the other cephems, however, significantly decreased, compared with that evaluated in last year. Against Serratia marcescens, MEPM had the strongest antibacterial activity. Against Proteus mirabilis, MEPM and CRMN showed the strongest activity and prevented the growth of all strains with 0.125 microg/mL or less. Nest, cefmenoxime (CMX), ceftazidime (CAZ), cefixime (CFIX), cefpodoxime (CPDX), CPR, CZOP, and cefditoren (CDTR) showed a strong activity. The antibacterial activity of the drugs to Pseudomonas aeruginosa was generally low, and MIC90 of all the drugs was ranged from 32 to < or = 256 microg/mL except IPM and amikacin (AMK) having 16 microg/mL. The antibacterial activity of CZOP was relatively good (MIC50: 2 microg/mL).