Expression of vascular endothelial growth factor-C in human hepatocellular carcinoma

Background/Aims: Vascular endothelial growth factor‐C (VEGF‐C) is thought to be an important factor in tumor angiogenesis/lymphangiogenesis, but its role in hepatocellular carcinoma (HCC) has not yet been fully investigated. Methods: We immunohistochemically examined VEGF‐C expression in surgically resected tissues of 90 HCC. Results: In the 78 HCC with a single histological grade, VEGF‐C expression was significantly stronger in poorly differentiated HCC than in well‐ (P = 0.003) or moderately differentiated HCC (P = 0.0002). A ‘nodule‐in‐nodule’ case presented VEGF‐A expression in the well‐differentiated component and VEGF‐C expression in the moderately–poorly differentiated component. According to nodular diameter, VEGF‐C expression was significantly higher in nodules of 3.0 cm or larger (P = 0.0263). Extrahepatic metastases seen in seven cases expressed VEGF‐C. In 20 of the 28 cases who were able to be followed up, the frequency of intrahepatic recurrence tended to be higher and extrahepatic metastasis was significantly higher in the cases who had VEGF‐C expression in the tumor casts of the intrahepatic portal/hepatic vein branches than other cases without the expression (P = 0.0139). Disease‐free survival time tended to be shorter in cases with VEGF‐C expression in tumor casts of the portal/hepatic vein than in those without VEGF‐C expression (P = 0.053; log–rank test). Conclusions: VEGF‐C expression is related to the progression of HCC, and VEGF‐C expression in tumor casts of the intrahepatic portal/hepatic vein is considered to be a factor indicating recurrence/metastasis sites.     

Effect of N-methylation of selected peptide bonds on the biological activity of insulin. [2-N-Methylisoleucine-A]insulin

Hydrogen bonding involving peptide bonds of the backbone of the insulin molecule may play an important role in insulin-receptor interaction. Our previous work suggested that the A²-A⁸ helical segment of the hormone molecule participates in this interaction. To investigate the possible involvement of peptide bonds of this segment in insulin-receptor interaction the [2-N-methylisoleucine-A]insulin and [3-N-methylvaline-A]insulin ([MeIle²-A]- and [MeVal³-A]insulins) were synthesized. The circular dichroic spectra of the analogues were obtained and their properties were examined in several biological assays. The circular dichroic spectra suggested that the analogues remained monomeric at concentrations at which insulin is predominantly dimeric, and that their A²-A⁸ helical segments are distorted. The in vitro biological activity and the receptor binding affinity of these analogues were compared with that of natural insulin. Both analogues are weak full agonists. [MeIle²-A]insulin displayed a potency of 5.4 ± 0.3% in stimulating lipogenesis and 4.6 ± 2.3% in receptor binding affinity in rat fat cells and rat liver plasma membranes respectively. [MeVal³-A]insulin displayed a potency of 2.1 ± 0.2% in lipogenesis and 1.0 ± 0.3% in receptor binding assays. In radioimmunoassays [MeIle²-A]- and [MeVal³-A]insulins exhibited potencies of 13% and 11% respectively relative to the natural hormone. The substantially decreased biological activity and receptor binding affinity of these analogues may be attributed partly to the change of conformation and partly to the loss of hydrogen bonding capacity of the A²-A⁸ segment brought about by N-methylation of the A¹-A² or A²-A³ peptide bonds.     

Possible Application of Microwave Coagulation Therapy for Recanalising Tumor-occluded Self-expandable Metallic Stents

Abstract: There is no consensus regarding optimal management of tumor ingrowth through self-expandable metallic stents in the biliary system. We investigated the possibility that microwave therapy could be used to treat stent occlusion. We evaluated the thermal properties of a muscle equivalent phantom subjected to microwave energy. The temperature of the phantom was continuously monitored using the probe sensor of a fiberoptic thermometer embedded into the phantom model at different distances from a microwave electrode with and without a stent in place. The temperature of the phantom increased incrementally as the power increased from 30 to 50 watts at distances 2 and 5 mm from the electrode (p<0.01). With the goal of achieving adequate local heating without excessive distant heating, the most effective power was 40 watts. There was a significantly lower rise in temperature with stent in place than that without stent at 2 and 5 mm from the electrode at 40 watts. The temperature increase when the tip of the electrode was kept in contact with the stent was significantly smaller than when the conductor tip was kept apart from the stent (p<0.05). Using this method, the microwave energy did not induce destruction of the stent filament. In a muscle equivalent phantom model, the temperature changes induced by microwave energy were consistent with possible safe and effective application of this modality to recanalization of occluded metallic stents. (Dig Endosc 1999; 11: 158–164)     

A case of obstructive sleep apnoea with anterior cervical osteophytes

Summary  Osteophytes of the cervical spine are usually seen in elderly adults. When prominent, they have been blamed for dysphagia, cough, dysphonia and dyspnoea. This paper reports on an obstructive sleep apnoea (OSA) patient with cervical spinal osteophytes, one cause of airway obstruction. A 75-year-old male complained of pronounced snoring. The diagnosis was mild OSA, apnoea hypopnoea index was 9·4. Patient reported no restrictions in neck movements, experiences of neck pain or neck trauma. Previously, patient underwent a tonsillectomy due to discomfort in the pharyngeal region. A lateral cephalometric image was taken to observe airway before oral appliance therapy. The image revealed the presence of large osteophytes or sclerotic enthesopathy, lying on anterior surfaces from the fourth to seventh cervical vertebrae. A computed tomography (CT) image revealed the relationship of airway position to the spine. In the reconstructed three-dimensional (3D) image, the airway appeared displaced to the right of the craniomandiblar bone, with the hyoid bone similarly displaced in a manner to that of the airway. The spine also appeared displaced to the left side ofcraniomandiblar bone. Additionally, the 3D image revealed calcification of the stylohyoideum ligament and ligamentum nuchae. This present case highlights the necessity of CT examination for OSA patients. There were several ligament calcifications in the head and neck region. Cervical spine osteophytes, as a component of Forestier's or cervical spine disease, have been associated with dysphagia and dysphonia. It was reported that bilateral vocal cord paralysis was caused by osteophytes compressing the post-cricoid area of larynx.     

LONGITUDINAL STUDY OR SERUM THYROID HORMONES, CHORIONIC GONADOTROPHIN AND THYROTROPHIN DURING AND AFTER NORMAL PREGNANCY

Measurements of serum levels of thyroxine (T4), free T4, 3,5,3'-triiodothyronine (T3), free T3, 3,3',5'-triiodothyronine (reverse T3, rT3), thyroxine-binding globulin capacity (TBGcap), chorionic gonadotrophin (hCG) and thyrotrophin (TSH) were carried out prospectively in eight women with uncomplicated pregnancies, in order to examine interrelationships between the thyroid gland and thyroid stimulating hormones during pregnancy. During pregnancy the levels of T4, free T4, T3, rT3 and TBGcap were significantly elevated, and TSH was decreased. It was noted that the elevation of T4 was maintained from the 8th to the 27th week of gestation while the level of TBGcap progressively increased. The levels of free T4 and rT3 in the first and third trimesters were significantly higher than those of age-matched, non-pregnant women. The levels of hCG showed a biphasic variation, with a peak in the 8th to 15th weeks, followed by a decline in the second trimester and a small, secondary elevation in the 32nd to 39th weeks. This later elevation was positively correlated with changes in free T4 and free T3 levels. The increase of serum T4 accompanied by an increase of free T4 in the first trimester appeared due to augmented secretion of T4, rather than being secondary to the elevated levels of TBGcap.     

Conduction Velocity in the Tricuspid Valve-Inferior Vena Cava Isthmus is Slower in Patients With Type I Atrial Flutter Compared to Those Without a History of Atrial Flutter

Slower Conduction in the TV-IVC Isthmus. Introduction : In human type I atrial flutter, the electrophysiologic substrate is unclear. In order to determine if slow conduction is mechanistically important, we evaluated conduction velocity in the tricuspid valve-inferior vena cava (TV-IVC) isthmus, right atriai free wall, and interatrial septum in patients with and without a history of atrial flutter undergoing electrophysiologic study.
Methods and Results : Nine patients with (group 1) and nine without a history of type I atrial flutter (group 2) were studied. Conduction time (msec) in the right atrial free wall. TV-IVC isthmus (bidirectional), and interatrial septum was measured during pacing in sinus rhythm at cycle lengths of 600, 500, 400, and 300 msec from the low lateral right atrium and coronary sinus ostium. Conduction velocity (cm/sec) was calculated by dividing the distance between pacing electrodes and sensing electrodes (cm) by the conduction time (sec). Conduction velocity was slower in the TV-IVC isthmus in group 1 (range 37 ± 8 to 42 ± 8 cm/sec) versus group 2 (range 50 ± 8 to 55 ± 9 msec) at all pacing cycle lengths (P < 0.05). However, conduction velocity was not different in the right atrial free wall or interatrial septum between groups 1 and 2. Conduction velocity was also slower in the TV-IVC isthmus than in the right atrial free wall and interatrial septum in group 1 patients, at all pacing cycle lengths (P < 0.05). Atrial flutter cycle length correlated with total atrial conduction time (r ≥ 0.832, P < 0.05).
Conclusion : Slow conduction in the TV-IVC isthmus may be mechanistically important for the development of human type I atrial flutter.     

The Influence of Morphological Changes in Amplatzer Device on the Atrial and Aortic Walls Following Transcatheter Closure of Atrial Septal Defects

Objective: This study prospectively investigated morphological changes in Amplatzer Septal Occluder (ASO) over time and the influences of these changes on the atrial and aortic walls after atrial septal defect (ASD) closure.
Methods: Between August 2005 and December 2007, 78 patients with ASD were treated with ASO devices and changes in the device shape, the device thickness, and relations of the discs to the atrial and aortic walls over time were evaluated by transesophageal echocardiography immediately and 3–12 months after deployment.
Results: The maximum unstretched ASD diameter was 16.2 ± 4.8 mm and the device diameter selected was 20.6 ± 5.5 mm. At the time of last follow-up, the device thickness decreased by 17–33%, 6 of 26 devices with a flare shape on the aortic side developed a closed shape, and the relations of the discs to the anterior atrial and aortic walls changed from touching to intermittent compression in 14 of the 78 cases. In these 14 cases, the aortic rim was significantly smaller, the number of flared device shapes on the aortic side/the number of closed shapes immediately after deployment was significantly larger, and the maximum device thickness at the middle part was significantly more decreased than those in other cases.
Conclusion: As the device becomes thinner, loses its flexibility, and often changes from a flare-to-closed shape on the aortic side over time, the edges of ASO can start to compress the atrial and aortic walls. However, erosion was not recognized in these cases.     

Papuloerythroderma associated with monoclonal gammopathy of undetermined significance

We describe a 73-year-old Japanese man with papuloerythroderma overlapped with monoclonal gammopathy of undetermined significance (MGUS). Clinically, prominent erythroderma was associated with disseminated pruriginous papules, which were characteristically spared on the axillary and inguinal regions, the cubital and popliteal fossae as well as abdominal and small positional folds. Histopathologically, there was a significant perivascular infiltrate of lymphohistiocytic cells intermingled with eosinophils in the upper dermis. A biochemical profile revealed the presence of immunoglobulin G κ chain type monoclonal protein in the serum but the absence of hematological neoplasms. We diagnosed the patient as papuloerythroderma with MGUS, and treated him with narrow-band ultraviolet B and topical steroid. His skin changes were improved, but the sharp γ-globulin peak remained in the electrophoresis of serum protein. This case suggests an association between papuloerythroderma and MGUS.