Case of minocycline-induced pneumonitis with bilateral pleural effusion]

A 51-year-old man was admitted to our hospital with fever, dry cough and dyspnea. He had taken minocycline for 11 days because of urinary tract infection. Chest X-ray on admission showed diffuse reticular shadows in bilateral lung fields with bilateral pleural effusion. Cessation of minocycline led to spontaneous improvement of symptoms and radiographic findings. The lymphocyte stimulation test for minocycline with peripheral blood and pleural effusion were negative. After provocation test with minocycline, he developed fever and dry cough and bilateral ground glass opacity appeared on his chest X-ray. He was diagnosed as minocycline-induced pneumonitis and recovered rapidly following corticosteroid therapy.     

Influence of acute-phase proteins on the activity of natural killer cells

The effects of ₁-antitrypsin ( ₁,-AT), ₁,-acid glycoprotein ( ₁AGP), and haptoglobin (Hp), the main constituents of-globulin and which belong to acute phase proteins, on NK activity were examined using K562 cells as the NK target cells. Among the three proteins, ₁,-AT and ₁AGP had inhibitory effects on NK activity for fast target K562 cells. The,-AT preparations having the same protein concentration and a different trypsin inhibitory capacity (TIC) had an equal effect. Although ₁AT and ₁,-AGP equally reduced the NK activity, the mechanism involved in the reduction differed, in that the effect of ₁,-AT directed toward NK cells reduced their binding capacity with the target cells, ₁,-AGP probably interacts with a cytotoxic factor secreted from NK cells following effector-target interaction. These studies suggest that each of the acute-phase proteins, which increase following inflammation, inhibits NK cell function by two distinct mechanisms.     

Active matrix metalloproteinases in the tear fluid of individuals with vernal keratoconjunctivitis

Corneal epithelial lesions distinguish vernal keratoconjunctivitis (VKC) from other ocular allergic diseases. Such lesions result from degradation of the corneal epithelial basement membrane, which comprises mostly type IV collagen and laminin. Matrix metalloproteinase 2 (MMP-2) and MMP-9 catalyze the degradation of these 2 extracellular matrix proteins. The possible role of MMP-2 and MMP-9 in the pathogenesis of corneal lesions associated with VKC was investigated by assaying tear fluid for the presence of these enzymes. Tear fluid was collected from 6 eyes of 6 patients with active VKC, 14 eyes of 14 patients with active allergic conjunctivitis, and 6 eyes of 6 nonallergic healthy volunteers. Gelatin zymography revealed that the tear fluid of healthy volunteers contained inactive proforms of both MMP-2 and MMP-9 but not the active forms of these enzymes. Active forms of MMP-2 or MMP-9 were detected in a minority of patients with allergic conjunctivitis. However, with the exception of one individual for whom active MMP-9 was not detected, tear fluid from all patients with VKC contained both proforms and active forms of MMP-2 and MMP-9. These results implicate MMP-2 and MMP-9 in the pathogenesis of corneal epithelial disorders associated with VKC.     

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.     

Parkin localizes to the Lewy bodies of Parkinson disease and dementia with Lewy bodies

Mutations in alpha-synuclein (alpha S) and parkin cause heritable forms of Parkinson disease (PD). We hypothesized that neuronal parkin, a known E3 ubiquitin ligase, facilitates the formation of Lewy bodies (LBs), a pathological hallmark of PD. Here, we report that affinity-purified parkin antibodies labeled classical LBs in substantia nigra sections from four related human disorders: sporadic PD, inherited alphaS-linked PD, dementia with LBs (DLB), and LB-positive, parkin-linked PD. Anti-parkin antibodies also detected LBs in entorhinal and cingulate cortices from DLB brain and alphaS inclusions in sympathetic gangliocytes from sporadic PD. Double labeling with confocal microscopy of DLB midbrain sections revealed that approximately 90% of anti-alpha S-reactive LBs were also detected by a parkin antibody to amino acids 342 to 353. Accordingly, parkin proteins, including the 53-kd mature isoform, were present in affinity-isolated LBs from DLB cortex. Fluorescence resonance energy transfer and immunoelectron microscopy showed that alphaS and parkin co-localized within brainstem and cortical LBs. Biochemically, parkin appeared most enriched in cytosolic and postsynaptic fractions of adult rat brain, but also in purified, alpha S-rich presynaptic elements that additionally contained parkin's E2-binding partner, UbcH7. We conclude that parkin and UbcH7 are present with alphaS in subcellular compartments of normal brain and that parkin frequently co-localizes with alpha S aggregates in the characteristic LB inclusions of PD and DLB. These results suggest that functional parkin proteins may be required during LB formation.