Severe leukopenia and dysregulated erythropoiesis in SCID mice persistently infected with the parvovirus minute virus of mice

Parvovirus minute virus of mice strain i (MVMi) infects committed granulocyte-macrophage CFU and erythroid burst-forming unit (CFU-GM and BFU-E, respectively) and pluripotent (CFU-S) mouse hematopoietic progenitors in vitro. To study the effects of MVMi infection on mouse hemopoiesis in the absence of a specific immune response, adult SCID mice were inoculated by the natural intranasal route of infection and monitored for hematopoietic and viral multiplication parameters. Infected animals developed a very severe viral-dose-dependent leukopenia by 30 days postinfection (d.p.i.) that led to death within 100 days, even though the number of circulating platelets and erythrocytes remained unaltered throughout the disease. In the bone marrow of every lethally inoculated mouse, a deep suppression of CFU-GM and BFU-E clonogenic progenitors occurring during the 20- to 35-d.p.i. interval corresponded with the maximal MVMi production, as determined by the accumulation of virus DNA replicative intermediates and the yield of infectious virus. Viral productive infection was limited to a small subset of primitive cells expressing the major replicative viral antigen (NS-1 protein), the numbers of which declined with the disease. However, the infection induced a sharp and lasting unbalance of the marrow hemopoiesis, denoted by a marked depletion of granulomacrophagic cells (GR-1(+) and MAC-1(+)) concomitant with a twofold absolute increase in erythroid cells (TER-119(+)). A stimulated definitive erythropoiesis in the infected mice was further evidenced by a 12-fold increase per femur of recognizable proerythroblasts, a quantitative apoptosis confined to uninfected TER-119(+) cells, as well as by a 4-fold elevation in the number of circulating reticulocytes. Therefore, MVMi targets and suppresses primitive hemopoietic progenitors leading to a very severe leukopenia, but compensatory mechanisms are mounted specifically by the erythroid lineage that maintain an effective erythropoiesis. The results show that infection of SCID mice with the parvovirus MVMi causes a novel dysregulation of murine hemopoiesis in vivo.     

棉籽蛋白发泡粉生产工艺及其应用的研究

研究了植物蛋白起泡剂的生产原理及工艺路线,对其影响因素和产品的实际应用作了探讨。结果表明：利用此工艺方法生产的棉籽蛋白发泡性达９００ｍｌ／２００ｍｌ２％溶液,其中包含游离棉酚质量分数小于０．００２％。     

Phosphofructokinase from mantle tissue of Mytilus galloprovincialis. Purification and effects of phosphorylation on the enzymatic activity

Phosphofructokinase purified from mantle tissue of the sea mussel Mytilus galloprovincialis, was phosphorylated "in vitro" by the catalytic subunit of cyclic AMP-dependent protein kinase. The incorporation of phosphate gave rise to an activation of the enzyme by increasing its affinity for fructose-6-phosphate, by decreasing its sensitivity to the inhibition by ATP and by enhancing the effect of allosteric activators (5'-AMP and fructose-2,6-bisphosphate). In addition, the effects of phosphorylation on the catalytic activity are pH-dependent.     

Imported measles. A potential control problem

From Dec 23, 1978, through Jan 31, 1979, an outbreak of five laboratory-confirmed cases and four clinical cases of measles occurred in a Vietnamese refugee population living in a single housing complex in Albuquerque, NM. The index cases were in two refugee siblings in whom measles was incubating on arrival in the United States. Despite spread through three subsequent generations of disease transmission within the Vietnamese population, there was no additional spread into the general Albuquerque population. Responsible factors included the age distribution of susceptible persons, the social isolation of the refugee population, and the physical structure of the housing complex. There is a need to identify the problem of imported measles in "ethnic islands" in need of vaccination.     

Endoscopic sclerotherapy is useful in Dieulafoy's disease

1.5% Capsaicin (Cap) or Vehicle was respectively used to treat the right or left sciatic nerve in 20 Sprague-Dawley rats. On the seventh day, the 20 rats were at random divided into electroacupuncture (EA) group and non-EA group, the spinal cord corresponding to the afferent segments of sciatic nerve was taken out for observing the changes of acetylcholinesterase (AChE) activity and [3H]-quinuelidinylbenzylate (QNB) binding sites in the spinal dorsal horn (SDH). The results were as follows: (1) EA "Huantiao" could enhance AChE activity in the SDH and decrease [3H]-QNB binding sites; (2) Cap treating sciatice nerve could weaken AChE activity in the SDH and merease [3H]-QNB binding sites; (3) Cap treatment could inhibit or partially inhibit the actions of EA as above. The results indicated that ACh participated in the primary afferent of acupuncture information and might exist in Cap-sensitive neurons.     

Sleep-induced breathing instability. University of Wisconsin-Madison Sleep and respiration Research Group

We present a view of the neuromechanical regulation of breathing and causes of breathing instability during sleep. First, we would expect transient increases in upper airway resistance to be a major cause of transient hypopnea. This occurs in sleep because a hypotonic upper airway is more susceptible to narrowing and because the immediate excitatory increase in respiratory motor output in response to increased loads is absent in non-REM sleep. Secondly, sleep predisposes to an increased occurrence of ventilatory "overshoots", in part because abruptly changing sleep states cause transient changes in upper airway resistance and in the gain of the respiratory controller. Following these ventilatory overshoots, breathing stability will be maintained if excitatory short-term potentiation is the prevailing influence. On the other hand, apnea and hypopnea will occur if inhibitory mechanisms dominate following the ventilatory overshoot. These inhibitory mechanisms include: a) hypocapnia-if transient, will inhibit carotid chemoreceptors and cause hypopnea, but if prolonged will inhibit medullary chemoreceptors and cause apnea; b) a persistent inhibitory effect from lung stretch; c) baroreceptor stimulation, from a transient rise in systemic blood pressure immediately following termination of apnea or hypopnea may partially suppress the accompanying hyperpnea; d) depression of central respiratory motor output via prolonged brain hypoxia. Once apneas are initiated, reinitiation of inspiration is delayed even though excitatory stimuli have risen well above their apneic thresholds, and these prolonged apneas are commonly accompanied by tonic EMG activation of expiratory muscles of the chest wall and upper airway.     

Two modes of ligand binding in maltose-binding protein of Escherichia coli. Electron paramagnetic resonance study of ligand-induced global conformational changes by site-directed spin labeling

Binding of ligands to the maltose-binding protein (MBP) of Escherichia coli often causes a global conformational change involving the closure of its two lobes. We have introduced a cysteine residue onto each of these lobes by site-directed mutagenesis and modified these residues with spin labels. Using EPR spectroscopy, we examined the changes, caused by the ligand binding, in distance between the two spin labels, hence between the two lobes. The binding of both maltose and maltotetraose induced a considerable closure of the N- and C-terminal lobes of MBP. Little closure occurred upon the binding of maltotetraitol or beta-cyclodextrin. Previous study by fluorescence and UV differential absorbance spectroscopy (Hall, J. A., Gehring, K., and Nikaido, H. (1997) J. Biol. Chem. 272, 17605-17609) showed that maltose and a large portion of maltotetraose bound to MBP via one mode (R mode or "end-on" mode), which is physiologically active and leads to the subsequent transport of the ligands across the cytoplasmic membrane. In contrast, maltotetraitol and beta-cyclodextrin bound to MBP via a different mode (B mode or "middle" mode), which is physiologically inactive. The present work suggests that the B mode is nonproductive because ligands binding in this manner prevent the closure of the two domains of MBP, and, as a result, the resulting ligand-MBP complex is incapable of interacting properly with the inner membrane-associated transporter complex.     

Activation of a retroviral membrane fusion protein: soluble receptor-induced liposome binding of the ALSV envelope glycoprotein

Cellular aspects of remodeling in intact arteries have not been fully investigated, mainly due to the lack of an appropriate methodology that allows for simple measurements. The aim of this study was to develop a method based on laser scanning confocal microscopy (LSCM), compare it with previous methodology, and apply it to the study of remodeling in hypertension. The morphology of mesenteric resistance arteries from stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto rats (WKY) was determined with wire myography on one segment with a standardized diameter setting (0.9[d100]) and with perfusion myography on a second segment from the same artery at the calculated equivalent pressure. The second segments were stained with the nuclear dye Hoechst 33342 (live tissue) or propidium iodide (fixed tissue) and measured with LSCM and MetaMorph software. Compared with wire myography, perfusion myography showed similar differences from those previously reported. Compared with LSCM, perfusion myography showed a similar lumen but significantly smaller wall thickness in both live and fixed tissue, probably due to measurement underestimation. In the study with LSCM, arteries from SHRSP compared with those from WKY showed (1) reduced lumen, (2) altered cell density that was significantly increased in the adventitia, decreased in the media, and unchanged in the intima, (3) significantly increased medial volume, (4) significantly smaller endothelial cell nuclei, and (5) adventitial-like cells in the media. We conclude that (1) LSCM is a reliable and straightforward method to study morphology in intact vessels, (2) it provides new information on the cellular changes in remodeling, (3) adventitia might play an active role in the process of remodeling in hypertension, and (4) endothelium "remodels" in hypertension.     

Hippocampal N-acetyl aspartate in unaffected siblings of patients with schizophrenia: a possible intermediate neurobiological phenotype

BACKGROUND: Shared neurobiological characteristics of patients with schizophrenia and their siblings may represent "intermediate phenotypes" that may more closely reflect the genetic susceptibility underlying this illness. We sought evidence of such phenotypes using magnetic resonance spectroscopy based on previously described regional abnormalities in levels of the neuronal marker N-acetyl-aspartate (NAA) in the hippocampal area and dorsolateral prefrontal cortex of patients with schizophrenia. METHODS: We studied 47 schizophrenics, 60 unaffected siblings, and 66 healthy control subjects with long echo time multislice proton magnetic resonance spectroscopic imaging, primarily measuring NAA, creatine plus phosphocreatine (CRE), and choline-containing compounds. RESULTS: Both patients and their unaffected siblings had significant reductions in hippocampal area NAA/CRE as compared with control subjects. As exploratory analyses, estimates of heritability were performed. Although quantitative correlation of hippocampal NAA between patients and sibs was low (likely reflecting measurement noise), qualitatively defined "low hippocampal NAA/CRE phenotypes" yielded relative risk estimates (lambda s) of between 3.8 and 8.8, suggesting this characteristic is heritable. CONCLUSIONS: Our finding adds to the evidence that hippocampal abnormalities are associated with schizophrenia and may represent a novel biological phenotype for genetic studies of schizophrenia.     

Influence of protective isolation on outcome of allogeneic bone marrow transplantation for leukemia

Most of the previously published surgical series of suprasellar meningiomas have two disadvantages: (1) patients involved were treated within a relatively long time period, making analysis more difficult, (2) radiographic long term follow-up examinations with either CT- or MRI-scans were not performed. Both disadvantages were overcome in our retrospective clinical study, consisting of 50 consecutive patients with suprasellar meningiomas treated between 1982 and 1991. Radiological, ophthalmological, and neurological investigations were performed preoperatively, postoperatively and at long term follow-up (mean: 5.7 years). A radiologically confirmed radical tumour removal could be achieved in 84% of patients. Both, the peri-operative mortality (2%) and serious operative morbidity (6%) were low. However, 12% of patients developed late onset epilepsy. At long term follow-up, visual function was improved in 67%, unchanged in 9% and worsened in 24%. In more than 50% of patients the vision showed recovery over a longer time period than the first 10 days after operation. Radiographic control examinations revealed tumour recurrences in 2 patients (both asymptomatic) and progress of residual tumour in 5 patients (2 symptomatic, 3 asymptomatic). Since introduction of modern neurosurgery, a clear improvement in the surgical treatment of suprasellar meningiomas can be observed. However, the still long delay in diagnosing these tumours correctly prevents a further improvement of the ophthalmological results at long-term follow-up. Due to a relatively high rate of late onset epilepsy, anticonvulsive prophylaxis for 6 months seems to be justified. Regarding present preoperative diagnostic measures, ia-DSA seems only be indicated in patients with CT/MRI-scans, suspicious for tumourous narrowing or invasion of major cerebral arteries. In addition, we recommend radiographic control examinations at regular time intervals to confirm radical tumour removal and to detect the "ideal" point of time for renewed treatment.