Bcl11b is required for differentiation and survival of alphabeta T lymphocytes

The gene Bcl11b, which encodes zinc finger proteins, and its paralog, Bcl11a, are associated with immune-system malignancies. We have generated Bcl11b-deficient mice that show a block at the CD4-CD8- double-negative stage of thymocyte development without any impairment in cells of B- or gammadelta T cell lineages. The Bcl11b-/- thymocytes showed unsuccessful recombination of V(beta) to D(beta) and lacked the pre-T cell receptor (TCR) complex on the cell surface, owing to the absence of Tcrb mRNA expression. In addition, we saw profound apoptosis in the thymus of neonatal Bcl11b-/- mice. These results suggest that Bcl11b is a key regulator of both differentiation and survival during thymocyte development.     

Rhythmic motor activity in thin transverse slice preparations of the fetal rat spinal cord

Networks generating locomotor-like rhythmic motor activity are formed during the last week of the fetal period in the rat spinal cord. We investigated the coordinated rhythmic motor activity induced in transverse slice preparations of the lumbar spinal cord taken from fetal rats as early as embryonic day (E) 16.5. In slices as thin as 100 microm, bath-application of 5-hydroxytryptamine (5-HT) induced rhythmic [Ca(2+)](i) elevations in motoneurons labeled with Calcium Green-1 dextran. The rhythmic [Ca(2+)](i) elevations were similar in frequency to that in the intact lumbar spinal cord, although there was no temporal correlation between the activity in the left and right sides of 100-microm slices. Such rhythmic [Ca(2+)](i) elevations were observed in the slices taken from all lumbar segments. Moreover, the rhythmic activity was abolished by simultaneous blockade of glutamate, glycine, and GABA(A) receptors, indicating that synaptic transmission mediated by these receptors is important for the generation of the rhythm in these slices. Synchronous rhythmic activity between the left-right sides was found in slices thicker than 200 microm taken from any segmental level of the lumbar spinal cord. In these preparations, commissural neurons were activated synchronously with ipsilateral motoneurons. These results indicate that the neuronal networks sufficient to generate coordinated rhythmic activity are contained in one-half of a single lumbar segment at E16.5. Such spinal cord slices are a promising experimental model to investigate the neuronal mechanisms and the development of rhythm generation in the spinal cord.     

Lymphokine activity production in graft-versus-host reactions across minor histocompatibility antigen barriers.

Activated T cells responding to murine minor histocompatibility antigens (HA) were characterized according to the patterns of lymphokine activity production. Although B10.D2/nSN and BALB/c are mutually non-reactive in mixed lymphocyte reaction (MLR), graft-versus-host reaction (GVHR) can be induced by the injection of a large amount of B10.D2/nSN lymphoid cells into irradiated BALB/c recipient mice. Spleen cells from such GVHR mice spontaneously produced interleukin 3 (IL-3)-dependent cell-stimulating activity in cultures, but did not produce interleukin 2 (IL-2). Normal B10.D2/nSN spleen cells also produced IL-3-like activity, but not IL-2 in MLR supernatants, in response to irradiated BALB/c splenocytes. In addition, B-cell stimulatory factor-1 (BSF-1)/interleukin 4 (IL-4) and colony-stimulating factor (CSF) activity were detected in MLR supernatants. The properties of the produced lymphokine activities were similar to those produced in syngeneic transplant mice and syngeneic MLR, but a difference in the time course of lymphokine production existed between GVHR and syngeneic transplant mice. These results indicate that T cells may be activated in vivo in allogeneic transplantation when the donor and the recipient are matched for major HA, and are non-reactive in MLR. Also, the character of lymphokine-producing T cells activated by minor HA may not be qualitatively different from those responding to irradiated syngeneic cells.     

Optical monitoring of synaptic summation along the dendrites of CA1 pyramidal neurons

The primary function of neurons is to integrate synaptic inputs and to transmit the results to other cells. Recent studies with somatic whole-cell recordings have shown that separate excitatory inputs to hippocampal or cortical pyramidal neurons are summated non-linearly. In the present study, we examined how postsynaptic potentials (PSPs) are summated along the dendrites employing fast optical voltage imaging techniques. Rat hippocampal slices were stained with a fluorescent voltage-sensitive dye (JPW1114) and optical signals were monitored with a 16 x 16 photodiode array system. Two independent input pathways were stimulated individually or in pairs through glass electrodes such that different locations of the dendrites received separate synaptic inputs. We found that (1) the summation of PSPs was sub-linear along the entirety of dendrites, (2) the blockade of GABA(A) receptors suppressed sub-linearity and (3) further blockade of GABA(B) receptors suppressed sub-linearity of the summation of separate inputs on apical dendrites. Our study demonstrates that pyramidal neurons integrate PSPs linearly along the entirety of dendrites; moreover, GABAergic inputs are responsible for maintaining sub-linear summation in CA1 pyramidal neurons.     

Are cerebrovascular factors involved in Alzheimer's disease?

Recent epidemiological studies have shown that vascular risk factors may be involved in Alzheimer's disease (AD) as well as dementia in general. To investigate the relation between a vascular disorder and AD pathology, current criteria are defective because most depend on exclusion of a cerebrovascular disorder. Epidemiological studies have indicated the possibilities that arteriosclerosis, abnormal blood pressure, diabetes mellitus and smoking may be related to the pathogenesis of AD. As for the mechanism that vascular disorders influence AD, it is presumed that amyloid deposition may be caused by a vascular disorder. Alternatively, a vascular event may cause progression of subclinical AD to a clinical stage. Insulin resistance and apolipoprotein E may also be involved in these mechanisms. Our studies show that ischemia-induced the Alzheimer-associated gene presenilin 1 (PS1) and endoplasmic reticulum-stress, generated from a vascular disorder, may unmask clinical AD symptoms caused by presenilin mutation, suggesting that a vascular factor might be involved in the onset of familial AD.     

Mesenteric lymphadenitis of swine caused by Rhodococcus sputi.

Rhodococcus sputi caused tuberculosislike lymphadenitis of mesenteric lymph nodes in swine. This is the first study reporting that R. sputi can be a pathogen in swine.     

AMYLASE IN THYROID TISSUES FROM NORMAL AND VARIOUS THYROID DISEASES

Amylase activity was measured in thyroid tissues of various thyroid diseases and was analysed electrophoretically. Normal thyroid tissues contained significant amounts of amylase (mean ± SD; 2.71 ± 1.15 lU/g of tissue), and their amylase isozyme was composed of a majority of salivary type isoamylase and other peculiar isoamylase. The statistical decrease of amylase activities in tissues of Graves' disease under hyperthyroldism, thyroid carcinoma, and most of thyroid adenomas were found (Graves' disease; 1.04 ± 0.41, carcinoma; 1.49 ± 1.10, adenoma (except five cases with high activity); 0.88 ± 0.49 IU/g tissue). Five of 18 cases of adenoma showed strikingly higher amylase activity in their tissues. Electrophoretical patterns of amylase isoenzymes in these five adenoma tissue were different from those of normal thyroid tissues. The cellular localization of amylase in the normal thyroid tissues and the adenoma tissues was also demonstrated immunohlstochemically.     

Liver metastasis from rectal cancer with prominent intrabile duct growth

Intrabiliary growth of liver metastases from colorectal cancer has rarely been studied. A surgically resected case of a metastatic liver tumor with prominent intrabiliary growth derived from rectal cancer is reported. The patient was a 62-year-old man who had received a low anterior resection for rectal cancer in March 2000. He was re-admitted due to obstructive jaundice in January 2003, and was diagnosed with hepatic malignancy in segment II of the liver with an intrabiliary tumor extending from the intrahepatic bile duct of segment II to the common hepatic duct. He underwent a left hepatectomy, a partial resection of segment VI, and an extrahepatic bile duct resection with reconstruction of the biliary tract. In the resected specimen, there were whitish tumors of 3 cm and 1.5 cm in diameter in segments II and VI, respectively, and an intrabiliary tumor originating from the main tumor in segment II extended to the common hepatic duct. Both the liver tumors and the intrabiliary tumor consisted of a well- to moderately differentiated adenocarcinoma, which showed the same histological features as the rectal cancer. The immunohistochemical findings strongly supported that these tumors, including the intrabiliary growth, were liver metastasis from the rectal cancer. The intrabiliary invasion and growth of metastatic liver tumors has generally been overlooked, notwithstanding their frequently observed biological behavior. The present case is informative, and further investigation into this type of metastatic liver tumor may be warranted.     

Differentiation of clara cells and pneumocytes of the rat by means of enzyme- and immunohistochemistry

Localization of non-specific esterases, Cu-Zn superoxide dismutase and dehydropeptidase-I, in rat lung was investigated enzymecytochemically or immunohistochemically. Esterase was demonstrated in Clara cells, type II pneumocytes, and septal cells (or vitamin A-storing lung cells), to a somewhat lesser extent in type I pneumocytes and ciliated epithelial cells of the bronchioles, and to a minor extent in interstitial fibroblasts of the alveolar septum. Large amounts of esterase reaction product were deposited in the rough endoplasmic reticulum and the nuclear envelope in Clara cells, type II pneumocytes, and septal cells, in addition to smaller amounts in other organelles. No reaction product was found in macrophages (histiocytes) in alveolar septi and alveolar macrophages, except for the primary lysosomes or phagolysosomes and trace amounts in the Golgi vesicles, and none in endothelial cells of alveolar blood capillaries, except for primary lysosomes. Immunolocalization of Cu-Zn superoxide dismutase was generally limited to a particular area of Clara cells. A constriction occurred in the apical cytoplasm of Clara cells between an immunoreactive dome-like protrusion and the non-immunoreactive cytoplasm of the supranuclear area, and the dome-like protrusion appereared to be pinched off in a ball-like or oval from. Immunolocalization of dehydropeptidase-I was demonstrated in a dome-like protrusion or supranuclear area of Clara cells or throughout the cytoplasm and in the surface plasma membrane of mesothelial cells. The presence of these enzymes in Clara cells suggests a contribution to the detoxification system of the lung, together with cytochrome p-450-dependent monooxygenase systems. © 1994 Wiley-Liss, Inc.