The co-expression of VR1 and VRL-1 in the rat vagal sensory ganglia

Immunohistochemistry for two nociceptive transducers, the vanilloid receptor 1 (VR1) and vanilloid receptor 1-like receptor (VRL-1), was performed on the vagal sensory ganglia. In the jugular ganglion, VR1-immunoreactive (IR) neurons were small to medium-sized (range 49.7–1125.6 μm², mean±S.D. 407.7±219.7 μm²), whereas VRL-1-IR neurons were medium-sized to large (range 223.6–1341.1 μm², mean±S.D. 584.3±253.5 μm²). In the nodose ganglion, VR1- and VRL-1-IR neurons were mostly small to medium-sized (VR1: range 148.5–1464.4 μm², mean±S.D. 554.3±207.4 μm²; VRL-1: range 161.7–1166.2 μm², mean±S.D. 541.9±186.2 μm²). The double immunofluorescence method revealed that co-expression of VR1-immunoreactivity among VRL-1-IR neurons was more abundant in the nodose ganglion (63%) than in the jugular ganglion (4%). The present study suggests that co-expression of VR1 and VRL-1 may be more common in visceral sensory neurons than in somatic sensory neurons.     

Intrahepatic arterial chemotherapy with 5-fluorouracil and intramuscular interferon-alpha for a patient with diffuse type of hepatocellular carcinoma

We report a case of diffuse type advanced hepatocellular carcinoma (HCC), which was successfully treated by a combination therapy of interferon-alpha (IFN) and 5-fluorouracil (5-FU). A 74-year-old man underwent distal gastrectomy 6 years ago for gastric cancer. In April 2002, an increased serum alpha-feto-protein (AFP) level was noted and a computed tomography (CT) of the abdomen revealed a diffuse type of HCC. He was treated with a combination therapy of IFN (5x10(6) units/body i.m., days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, 26) and 5-FU (500 mg/body/day i.a., days 1-5, 8-12 continuously). The treatment was repeated every 4 weeks with a maximum of five cycles. After 5 cycles, serum AFP levels fell from 665 ng/ml to a normal level. CT showed a reduced size of the tumor. He has been well and continue to receive IFN (3x10(6) units/body i.m., two times a week) and 5-FU (500 mg/body/day i.a., once a week) at the outpatient clinic for the last 16 months.     

Liver stiffness measured by magnetic resonance elastography as a risk factor for hepatocellular carcinoma: a preliminary case�Ccontrol study

Objective

To examine if liver stiffness measured by magnetic resonance elastography (MRE) is a risk factor for hepatocellular carcinoma (HCC) in patients with chronic liver disease.

Methods

By reviewing the records of magnetic resonance (MR) examinations performed at our institution, we selected 301 patients with chronic liver disease who did not have a previous medical history of HCC. All patients underwent MRE and gadoxetic acid-enhanced MR imaging. HCC was identified on MR images in 66 of the 301 patients, who were matched to controls from the remaining patients without HCC according to age. MRE images were obtained by visualising elastic waves generated in the liver by pneumatic vibration transferred via a cylindrical passive driver. Risk factors of HCC development were determined by the odds ratio with logistic regression analysis; gender and liver stiffness by MRE and serum levels of aspartate transferase, alanine transferase, alpha-fetoprotein, and protein induced by vitamin K absence-II.

Results

Multivariate analysis revealed that only liver stiffness by MRE was a significant risk factor for HCC with an odds ratio (95?% confidence interval) of 1.38 (1.05?C1.84).

Conclusion

Liver stiffness measured by MRE is an independent risk factor for HCC in patients with chronic liver disease.

Key Points

? Magnetic resonance elastography can estimate liver stiffness, a marker of hepatic fibrosis. ? Liver stiffness is an independent risk factor of hepatocellular carcinoma (HCC). ? Liver stiffness seems a better indicator of HCC than tumour markers.     

Energy metabolism and turnover are increased in mice lacking the cholecystokinin-B receptor

Cholecystokinin (CCK) is an important gastrointestinal hormone as well as a neurotransmitter. Two types of CCK receptors, types A and B, have been identified. The CCK-A receptor is involved in satiety, food intake and behavior, whereas the B receptor is involved in anxiety. We recently produced CCK-A, -B and AB receptor knockout mice to study the role of these receptors in energy metabolism. Daily energy intake and expenditure were significantly greater in CCK-BR(-/-) and CCK-AR(-/-)BR(-/-) mice than CCK-AR(-/-) and wild-type [CCK-AR(+/+)BR(+/+)] mice. Relative liver and kidney weights (g/kg body) were significantly greater in CCK-AR(-/-)BR(-/-) mice than in wild-type mice. Energy metabolism and energy turnover were increased in mice with a disruption of the CCK-BR gene, although the underlying mechanism is unknown.     

Association of IL28B gene polymorphism with development of hepatocellular carcinoma in Japanese patients with chronic hepatitis C virus infection

IL28B single nucleotide polymorphisms (SNPs) are associated with spontaneous and treatment-induced elimination of hepatitis C virus (HCV). To assess whether the IL28B rs8099917 SNP also affects the progression of chronic HCV infection, we genotyped 511 Japanese HCV patients, including 69 with hepatocellular carcinoma (HCC). The T/T genotype of rs8099917 was not associated with the development of HCC (p = 0.623), although stepwise logistic regression analysis showed that liver cirrhosis, age greater than 68 years, and serum albumin <4.2 mg/dl were associated with HCC onset. It appears that the IL28B SNP does not directly influence hepatocarcinogenesis in chronic HCV infection.     

Vanilloid receptor 1-like receptor-immunoreactive primary sensory neurons in the rat trigeminal nervous system

Immunohistochemistry for vanilloid receptor 1-like receptor (VRL-1), a candidate transducer for high-threshold noxious heat, was performed on rat trigeminal primary sensory neurons. The immunoreactivity was detected in 14% of the trigeminal ganglion cell bodies, while the neurons in the mesencephalic trigeminal tract nucleus were almost devoid of it (0.5%). The immunoreactive neurons in the trigeminal ganglion were mostly of medium to large size (mean+/-S.D. of 956+/-376microm(2)). Nerve bundles in the tooth pulp, periodontal ligament, facial skin and oral mucosa contained VRL-1-positive smooth nerve fibers. The immunoreactivity could not be traced to the isolated nerve fibers, except in the tooth pulp. In the brainstem trigeminal nuclear complex, a notable concentration of the immunoreactivity was seen in laminae I and II of the medullary dorsal horn. Thirty-seven per cent of the trigeminal ganglion neurons retrogradely labeled from the tooth pulp exhibited VRL-1 immunoreactivity, while the immunoreactivity was detected in only 9% of those labeled from the skin. Co-expression of calcitonin gene-related peptide was common among the VRL-1-immunoreactive tooth pulp neurons (45%) and cutaneous neurons (25%). Moreover, as many as 41% of the VRL-1-immunoreactive tooth pulp neurons co-expressed parvalbumin immunoreactivity. Parvalbumin immunoreactivity was never detected in the VRL-1-immunoreactive cutaneous neurons.From the findings of the present study, we propose that large primary neurons responding to high-threshold noxious heat are abundant in the tooth pulp, but not in the facial skin.     

Efficacy of “Awake ECMO” for critical respiratory failure after pediatric open-heart surgery

A 4-year-old boy with atrioventricular discordance, double-outlet right ventricle, pulmonary stenosis, and mitral regurgitation, was undergoing anatomical repair consisting of Senning, Rastelli, Damus–Kaye–Stansel procedures, and a mitral valve repair, complained of post-operative excessive airway tract secretion, which ultimately developed into acute respiratory distress syndrome (ARDS) 28 days after the operation. The cause of the ARDS was thought to be frequent manual positive pressure recruitment and prolonged inhalation of pure oxygen. At 45 days after the operation, hypercapnia and respiratory acidosis turned out to be irreversible, and therefore, veno-arterial extracorporeal membrane oxygenation (ECMO) was established utilizing the Endumo^®4000 system. Pulmonic interstitial inflammation gradually improved while resting the lung under ECMO support; however, effective ventilation volume decreased critically because a massive pulmonary hemorrhage occurred at 2 and 9 days after the initiation of ECMO. To maximize the effectiveness of respiratory physical therapy, “Awake ECMO” was started and tidal volume dramatically increased with a regained cough reflex. Five days later, he was successfully weaned off from ECMO, and discharged 7 months after the operation without any neurological and physiological sequelae.     

Immunohistochemical demonstration of peptidergic nerve fibers associated with the central lacteal lymphatics in the duodenal villi of dogs.

Immunohistochemical demonstration was made of the peptidergic nerves distributed in the central lacteal lymphatics of the canine duodenal villi. The central lacteal-associating nerve fibers were predominantly immunoreactive for both substance P (SP) and calcitonin gene-related peptide (CGRP). Observation of doubly immunostained sections evidenced that both peptides were located in one and the same nerve fibers. The SP/CGRP-immunoreactive fibers were concentrated in the intermediate portion of the villus height. Ultrastructurally, the SP/CGRP-immunoreactive nerve fibers ran closely beneath the endothelial cells of the lacteal, some of them penetrating into the cytoplasm with knob-like swellings. The immunoreactive products were localized to large-cored vesicles in the sub- and intra-endothelial nerves. The occurrence of SP and CGRP in the nerve fibers distributed in the central lacteals which lack smooth muscles implies that these nerves may be sensory in nature. A mechanoreceptive function of the nerves is proposed on the basis of their peculiar knob-like projection into the lacteal endothelium.     

Low incidence of MYC/BCL2 double‐hit in Burkitt lymphoma

Translocations involving MYC are highly characteristic for Burkitt lymphoma (BL). BCL2 expression has also been found previously in about 10 to 20% of BL cases, and BCL2 translocation is a major mechanism for the deregulation of BCL2 expression in non‐Hodgkin lymphomas. However, we know little about the incidence of MYC/BCL2 double‐hit (DH) in BL. We examined BL cases to determine how frequently they contained BCL2 translocations in combination with MYC translocations using fluorescence in situ hybridization. We also determined the effect of BCL2 expression on clinical outcomes of BL. BCL2 translocations were detected in 3.5% (2/57 cases) of the cases, and BCL2 expression was detected in 33%. Two cases with BCL2 translocation also showed BCL2 expression. The incidence of BCL2 expression was significantly higher in patients 16 years of age and older (46%) than in patients under 16 years of age (6%). Among patients 16 years of age and older, we did not detect significant differences in overall survival with respect to BCL2 expression status. In conclusion, BCL2 translocation is a rare cytogenetic abnormality in BL, and BL probably accounts for only a small fraction of MYC/BCL2 DH lymphomas. BCL2 expression in BL is probably not associated with BCL2 translocations.     

Moyamoya disease complicated with renal artery stenosis and nephrotic syndrome: reversal of nephrotic syndrome after nephrectomy

A 7-year-old boy with moyamoya disease developed sustained hypertension, nephrotic syndrome, hyperreninemia, and occlusion of the right renal artery. After right nephrectomy, hyperreninemia and hypertension improved. Proteinuria was resolved after nephrectomy, in parallel with the decrease in plasma renin activity. Moyamoya disease can cause nephrotic-range proteinuria, which is caused hemodynamically by hyperreninemia.