Reduced expression of aquaporin 4 in human muscles with amyotrophic lateral sclerosis and other neurogenic atrophies

Aquaporin 4 (AQP4) is a water channel protein that is widely distributed in human tissues. However, the precise functional role of AQP4 in skeletal muscle tissue has not yet been determined. Expression of AQP4 was reported to be reduced in muscle tissue from Duchenne muscular dystrophy patients. In the regenerating phase of skeletal muscle, AQP4 expression was reduced when nerve supply was not present. However, in diseased human muscles with neurogenic atrophy including amyotrophic lateral sclerosis, there has been no data on the changes in AQP4 expression. In the present study, we investigated the expression of AQP4 at mRNA and protein levels in human muscles with neurogenic atrophy. The mean level of AQP4 mRNA was significantly lower in muscles with neurogenic atrophy than that in muscles from normal controls. The myofiber surface immunostaining with anti-AQP4 antibody in muscles with neurogenic atrophy was reduced on the surface of scattered myofibers, small angulated myofibers, and myofibers in small- and large-group atrophy despite the presence of dystrophin. Based on the present findings, we conclude that the expression of AQP4 is affected by nerve supply and is down-regulated in human muscles with neurogenic atrophy.     

Ultrastructural localization of aquaporin 4 and alpha1-syntrophin in the vascular feet of brain astrocytes

Aquaporin 4 (AQP4) is a recently discovered membrane bound water-selective channel and has been described at the light microscopic level to be predominantly expressed in the astrocytes of the brain, especially at the perivascular astrocyte endfoot processes. Alpha1-syntrophin, a member of dystrophin-associated protein, has also been reported at the light microscopic to be expressed level in the same site of astrocytes as AQP4 and interacts with other molecules through its PDZ domain. AQP4 expression has been reported to be absent at the sarcolemma and the perivascular astrocyte endfoot processes of alpha1-syntrophin knockout mice. Based on these observations, the molecular association between AQP4 and alpha1-syntrophin could be speculated. To test this hypothesis, we investigated the ultrasturctural localization of AQP4 and alpha1-syntrophin in the brain astrocytes by using double immunogold labeled electron microscopy. The results showed that AQP4 and alpha1-syntrophin colocalized frequently at the astrocyte membrane, especially at the perivascular astrocyte endfoot processes and suggested the presence of linkage between AQP4 and alpha1-syntrophin at the astrocyte plasma membrane.     

DPC-4 (Smad-4) and K-ras gene mutations in biliary tract epithelium in children with anomalous pancreaticobiliary ductal union

Background/Purpose: Recent studies have found that anomalous pancreaticobiliary ductal union (APBDU) is a substantial risk factor for biliary tract cancer at a younger age. DPC-4 (Smad-4) is a new tumor suppressor gene frequently inactivated in pancreatic and bile duct adenocarcinoma. To clarify carcinogenesis in APBDU, the authors investigated possible DPC-4 and K-ras mutations in 35 pediatric patients. Methods: DNA was extracted from biliary tract epithelial cells, which were resected surgically and histologically purified using microdissection. Polymerase chain reaction (PCR) primers were designed specifically for exons 8-11 of DPC-4 (18q21.1) and exons 1-2 of the K-ras oncogene (12p12.1). DNA sequences were determined using the direct DyeDeoxy Terminator Cycle method. Results: Of 35 children, 30 had wild-type DPC-4 and K-ras genes. K-ras mutations were detected in 5 patients, 4 of whom showed epithelial hyperplasia or metaplasia. In a 12-year-old girl with adenocarcinoma arising from a choledochal cyst, K-ras and DPC-4 (homozygous deletion) mutations were identified simultaneously. Conclusions: These results suggest that carcinogenesis in the biliary tract epithelium in APBDU is accompanied by multistep genetic mutational events; K-ras gene mutation occurs early in epithelial hyperplasia or metaplasia, whereas inactivation of the DPC-4 gene accumulates late in the progression of biliary tract adenocarcinoma. J pediatr Surg 38:694-697. [copy ] 2003 Elsevier Inc. All rights reserved.     

Two types of VIP neuronal components in rat suprachiasmatic nucleus

Vasoactive intestinal peptide (VIP) neurons constitute a large group in the suprachiasmatic nucleus (SCN) and it is thought that they are involved in the generation and entrainment of circadian rhythm. We have characterized these VIP-expressing neurons in rat SCN by their ability to induce the mammalian Period1 (Per1) gene in response to light exposure, innervation of retinal afferents, day-night variations in VIP mRNA, and coexpression of gastrin releasing peptide (GRP). VIP neurons in the ventrolateral SCN (SCNVL) were subdivided into two groups, light-evoked Per1-inducible main SCNVL (SCNVLmain) and non-Per1-inducible medially located SCNVL (SCNVLmed). Retinal innervation was abundant in the SCNVLmain but nearly absent in the SCNVLmed. Day-night variation in VIP mRNA expression level was observed in the SCNVLmain but not in the SCNVLmed. GRP mRNA was seen in rarely SCNVLmed but abundant in SCNVLmain, where some neurons coexpressed VIP mRNA. These findings indicate that VIP neurons in the SCN can be divided into two topographically and functionally distinct groups.     

Partial characterization of an intra-acrosomal protein, human acrin1 (MN7)

Acrin1 (MN7), a 90-kd glycoprotein, is localized in the sperm acrosome of several rodents. The purpose of this study was to determine the molecular size and subcellular localization of acrin1 (MN7) in human sperm, and its organization in spermatids during spermiogenesis. Immunocytochemical and biochemical analyses revealed that acrin1 (MN7) is localized in the anterior acrosome and its molecular size is 90 kd, the same as in rodents. Based on molecular size, acrin1 (MN7) is likely to be a novel human acrosomal protein. During spermiogenesis, acrin1 (MN7) is initially localized in the head-cap portion of spermatids from the cap phase to the end of the acrosomal phase, and then relocates from the posterior to the anterior region of the acrosome in the maturation phase in spermatids. Such a morphological organization mechanism is also basically the same as that in rodents. Thus, acrin1 (MN7) is a common acrosomal protein of 90 kd in rodents and humans.     

Oscillator representations and systems of ordinary differential equations

Using representation-theoretic methods, we determine the spectrum of the 2 x 2 system. Q(x, D(x)) = A- partial differential(2)(x)2 + x(2)2 + Bx partial differential(x) + 1/2, x in, with A, B in Mat(2)(R) constant matrices such that A = (t)A > 0 (or <0), B = -(t)B not equal 0, and the Hermitian matrix A + iB positive (or negative) definite. We also give results that generalize (in a possible direction) the main construction.     

Hypercalcemia in a Case of Childhood Acute Lymphoblastic Leukemia

Severe hypercalcemia (serum calcium, 4.25–5.25 mmol/l),in association with osteolytic bone lesions, was found in agirl aged 2 yr 7 mo with common acute lymphoblastic leukemia(ALL). Hormonal studies excluded the possibility of the hypercalcemiabeing caused by primary hyperparathyroidism or ectopic parathyroidhormone secretion. Increased plasma prostaglandinE₂ (PGE₂).Jlevels (130 ng/l), probably produced by leukemic cells, wereconsidered to be one of the pathogenic mechanisms responsiblefor the occurrence of hypercalcemia in this patient. Both thehypercalcemia and the abnormal plasma PGE₂ level returned tonormal after chemotherapy.