Constitutional translocation t(4;22) (q12;q12.2) associated with neurofibromatosis type 2

We report on a female patient with bilateral acoustic neurinomas and other tumors in the central nervous system (neurofibromatosis type 2: NF2) and the constitutional translocation, t(4;22) (q12;q12.2). The precise identification of the translocation breakpoint (q12.2) on chromosome 22 implies the refined localization of a gene responsible for NF2, and would provide a clue to its molecular characterization and to the isolation of the gene. Chromosomes of a paraspinal neurinoma from the patient were also analyzed, and the same karyotype as seen in cultured peripheral lymphocytes was found. The patient's father was also a carrier of the translocation, but he had no clinical symptoms of NF2, nor did other relatives. Several explanations are offered for the different expression of the translocation between the patient and her father. © 1992 Wiley-Liss, Inc.     

IL-2-regulated persistent human herpesvirus-6B infection facilitates growth of adult T cell leukemia cells

Human herpesvirus-6B (HHV-6B), a causative agent of exanthem subitum, infects human adult T cell leukemia (ATL) cell lines. We established a persistent HHV-6B infection in an ATL cell line, TaY, in the presence of 20 units/ml interleukin-2 (IL-2). The HHV-6B infected culture proliferated with a constant ratio of infected (1%) to the uninfected (99%) cells. When the IL-2 concentration was reduced to 5 units/ml, the number of infected cells in the culture increased transiently by 60% in 11 days, a new balance of 25% infected cells and 75% uninfected cells was established thereafter. PCR analysis confirmed a 125-fold increase in the amount of viral genome in the culture, while the treatment with ganciclovir reduced the proportion of infected cells, indicating that an efficient replication of virus was induced in the culture. Both of these cultures were maintained in the presence of 20 or 5 units/ml IL-2 over one year without loss of infected cells. Interestingly, we found that cultures containing the infected cells grew significantly faster than the parental uninfected cells at the same concentration of IL-2. The infected culture continued to grow for 7 days even in the absence of IL-2. Because the infection induces cell cycle arrest, these results indicate that the HHV-6B-infected ATL cells stimulate the growth of the uninfected cells during persistent infection in culture.     

Imaging of somatotopic representation of sensory cortex with intrinsic optical signals as guides for brain tumor surgery

OBJECT: Intrinsic optical signals in response to somatosensory stimuli were intraoperatively recorded during brain tumor surgery. In the present study, the authors report on the use of this technique as an intraoperative guide for the safe resection of tumors adjacent to or within the sensorimotor cortex. METHODS: In 14 patients with tumors adjacent to or within the sensorimotor cortex, intrinsic optical signals in response to somatosensory stimuli were recorded by illuminating the brain surface with Xe white light and imaging the reflected light passing through a bandpass filter (605 nm). Results were compared with intraoperative recordings of sensory evoked potentials in all 14 patients and with noninvasive mapping modalities such as magnetoencephalography and positron emission tomography in selected patients. In all but two patients, the somatosensory optical signals were recorded on the primary sensory cortex. Optical signals elicited by stimulation of the first and fifth digits and the three branches of the trigeminal nerve were recorded at different locations on the sensory strip. This somatotopic information was useful in determining the resection border in patients with glioma located in the sensorimotor cortex. CONCLUSIONS: Optical imaging of intrinsic signals is a useful technique with superior spatial resolution for delineating the somatotopic representation of human primary sensory cortex. Furthermore, it can be used as an intraoperative monitoring tool to improve the safety and accuracy of resections of brain tumors adjacent to or within the sensorimotor cortex.     

Prostacyclin does not inhibit rho-kinase: an implication for the treatment of pulmonary hypertension

Primary pulmonary hypertension continues to be a fatal disease. We have recently demonstrated that long-term inhibition of Rho-kinase, an effector of the small GTPase Rho, is effective for the treatment of pulmonary hypertension (PH) in rats and humans. Prostacyclin has been clinically used for the treatment of PH with moderate success. However, it remains to be examined whether Rho-kinase inhibition is involved in its beneficial effects on PH. In an ELISA assay, neither prostacyclin nor its oral analogue, beraprost sodium, inhibited Rho-kinase even at higher concentrations (10(-7) to 10(-5) M, 100 to 10,000 times higher than their clinical concentrations), whereas specific Rho-kinase inhibitors, fasudil and hydroxyfasudil, markedly (approximately 95%) inhibited the Rho-kinase activity at 10(-5) M (near their clinical concentrations). Beraprost sodium did not significantly suppress serotonin-induced vascular smooth muscle cell (VSMC) contractions or Rho-kinase activity of the rat aorta without endothelium, as evaluated by the extent of phosphorylation of the ERM family, a substrate of Rho-kinase, whereas hydroxyfasudil markedly suppressed the VSMC contractions and Rho-kinase activity. These results indicate that prostacyclin lacks direct inhibitory effect on Rho-kinase and suggest that combination therapy with prostacyclin and a Rho-kinase inhibitor could exert further beneficial effects on PH.     

Histological evidence of redox system breakdown caused by superoxide dismutase 1 (SOD1) aggregation is common to SOD1-mutated motor neurons in humans and animal models

Living cells produce reactive oxygen species (ROSs). To protect themselves from these ROSs, the cells have developed both an antioxidant system containing superoxide dismutase 1 (SOD1) and a redox system including peroxiredoxin2 (Prx2, thioredoxin peroxidase) and glutathione peroxidase1 (GPx1): SOD1 converts superoxide radicals into hydrogen peroxide (H₂O₂), and H₂O₂ is then converted into harmless water (H₂O) and oxygen (O₂) by Prx2 and GPx1 that directly regulate the redox system. To clarify the biological significance of the interaction of the redox system (Prx2/GPx1) with SOD1 in SOD1-mutated motor neurons in vivo, we produced an affinity-purified rabbit antibody against Prx2 and investigated the immunohistochemical localization of Prx2 and GPx1 in neuronal Lewy body-like hyaline inclusions (LBHIs) in the spinal cords of familial amyotrophic lateral sclerosis (FALS) patients with a two-base pair deletion at codon 126 and an AlaVal substitution at codon 4 in the SOD1 gene, as well as in transgenic rats expressing human SOD1 with H46R and G93A mutations. The LBHIs in motor neurons from the SOD1-mutated FALS patients and transgenic rats showed identical immunoreactivities for Prx2 and GPx1: the reaction product deposits with the antibodies against Prx2 and GPx1 were localized in the LBHIs. In addition, the localizations of the immunoreactivities for SOD1 and Prx2/GPx1 were similar in the inclusions: the co-aggregation of Prx2/GPx1 with SOD1 in neuronal LBHIs in mutant SOD1-related FALS patients and transgenic rats was evident. Based on the fact that Prx2/GPx1 directly regulates the redox system, such co-aggregation of Prx2/GPx1 with SOD1 in neuronal LBHIs may lead to the breakdown of the redox system itself, thereby amplifying the mutant SOD1-mediated toxicity in mutant SOD1-linked FALS patients and transgenic rats expressing human mutant SOD1.     

Adenocarcinoma complicating Barrett's esophagus: an analysis of cell proliferation

Received: May 9, 2000 / Accepted: July 28, 2000     

Incidence of intraoperative floppy iris syndrome in patients on either systemic or topical alpha(1)-adrenoceptor antagonist

PURPOSE: To evaluate the incidence of Intraoperative Floppy Iris syndrome (IFIS) in relation to the usage of alpha(1)-adrenoceptor antagonists. DESIGN: Prospective, interventional case series. METHODS: In 2,643 consecutive eyes of 1,968 patients undergoing cataract surgery, occurrence of IFIS and use of alpha(1) antagonists were recorded. RESULTS: IFIS was observed in 29 eyes (1.1%) of 25 male patients, all of whom were receiving alpha(1) antagonists. In those receiving systemic tamsulosin, alpha(1A) selective antagonist, IFIS developed in 25 (43.1%) of 58 eyes. In those receiving systemic naftopidil, alpha(1A) and alpha(1D) antagonists, IFIS was found in 4 (19.0%) of 21 eyes. There was no case of IFIS in patients who received other systemic alpha(1) antagonists and in eyes treated with bunazosin eyedrops, a nonselective alpha(1) antagonist. CONCLUSIONS: IFIS occurred in 1.1% of cases treated with systemic alpha(1A)-adrenoceptor antagonists for benign prostatic hypertrophy. Topical nonselective alpha(1) antagonist did not induce IFIS.