Cryopreserved autologous bone marrow transplantation in patients with acute nonlymphoid leukemia: chemotherapy before harvesting is the main factor in delaying hematological recovery

We analyzed the kinetics of hematological recovery after autologous bone marrow transplantation in 13 patients with acute nonlymphoid leukemias (ANLL). A comparison was made with 31 patients with non-Hodgkin's lymphoma (NHL) whose bone marrow was harvested and cryopreserved, either at diagnosis or after intensive chemotherapy. Hematological recovery of ANLL patients was similar to that of pretreated NHL patients and significantly slower than that of untreated NHL patients. We suggest that chemotherapy before harvest (more than the possible decreased stem cell marrow potentiality resulting from the underlying disease) appears to be the main factor responsible for delayed recovery after autologous bone marrow transplantation in ANLL.     

Clinical significance of fibrinopeptide A in acute lymphocytic and non-lymphocytic leukaemia

Fibrinopeptide A (FPA) was systematically investigated in 74 patients with acute leukaemia at different stages of the disease (50 with non-lymphocytic leukaemia, ANLL; 24 with lymphocytic leukaemia, ALL). At diagnosis, 75% of the cases had high FPA levels (86% in ANLL and 54% in ALL) with significantly higher levels in ANLL than in ALL (13.4 vs 4.4 ng/ml; p less than 0.001). Patients with DIC (20 cases in ANLL and 1 case in ALL) had significantly higher levels (p less than 0.001). FPA levels were neither correlated with fibrinogen or FDP levels nor with blast cell count. During chemotherapy, median FPA did not show significant changes whereas, at the end of therapy, a return toward normality was generally observed both in ALL and ANLL apart from the group of patients with acute promyelocytic leukaemia. Among the 24 patients who entered post-remission follow-up (13 ANLL and 11 ALL), 10 cases out of the 11 relapsing (6/6 with ANLL and 4/5 with ALL) had increased FPA 1 to 2 months before the ascertainment of the relapse. However, 16% and 9% of the samples obtained on different occasions, respectively from ANLL and ALL cases in maintained first remission, showed FPA above the normal limit. This study demonstrates that subclinical activation of blood coagulation, as indicated by high FPA level, is common both in lymphocytic and non-lymphocytic leukemia and suggests that this phenomenon is related to disease activity.     

Abnormalities in the fine structure of the spermatids of rats injected with cadmium

The degenerative changes in the spermatids as measured by changes in fine structure abnormalities increased with time following injection of Cd²⁺ into rat testis. The spermatids in the twelve hours group appear as peculiarly club shaped and elongated structures with one or two small but perceptible vacuoles. The subacrosomal area and the space between the nucleus and the middle piece are seen abnormally dilated. In the 30 day group, the central filaments are the most susceptible unit of 9+2 axoneme complex. The plasma membrane, the cytoplasmic matrix, the mitochondria of the middle piece and the fibrous sheath appear shrunken, discontinuous and degenerative.     

The Insulin-Like Growth Factor System and Neurological Complications in Diabetes

The IGF system plays vital roles in neuronal development, metabolism, regeneration and survival. It consists of IGF-I, IGF-II, insulin, IGF-I-receptor, and those of IGF-II and insulin as well as IGF-binding proteins. In the last decades it has become clear that perturbations of the IGF system play important roles in the pathogenesis of diabetic neurological complications. In the peripheral nervous system IGF-I, insulin, and C-peptide particularly in type 1 diabetes participate in the development of axonal degenerative changes and contributes to impaired regenerative capacities. These abnormalities of the IGF system appear to be less pronounced in type 2 diabetes, which may in part account for the relatively milder neurological complications in this type of diabetes. The members of the IGF system also provide anti-apoptotic effects on both peripheral and central nervous system neurons. Furthermore, both insulin and C-peptide and probably IGF-I possess gene regulatory capacities on myelin constituents and axonal cytoskeletal proteins. Therefore, replenishment of various members of the IGF system provides a reasonable rational for prevention and treatment of diabetic neurological complications.     

Effect of quinolinic acid on neurons in dissociated cultures of cells of different structures of the brain

Using neurohistological and cytochemical methods in the living cells, the peculiarities of the action of endogenous neurotoxin, quinolinic acid (QUIN), on the neurons developing in the cell cultures of the hippocamp, neocortex and septum have been investigated in 17-19-day-old mouse embryos. The addition of 500 microM of QUIN on the 21st--22nd day into the nutrition medium in vitro resulted in the rapid destruction of neurons localized in glioneuronal aggregates, while the isolated nervous cells as well as septal cholinergic neurons remained intact. At earlier stages of cultivation (up to 2 weeks) QUIN did not provoke degenerative changes in the cultivated neurons. The comparison of our results with the literary data suggests that in nervous cell cultures QUIN, having mature synaptic connections with afferent nervous fibers, causes destruction of neurons.     

Association of matrix metalloproteinase-9 and Purkinje cell degeneration in mouse cerebellum caused by Angiostrongylus cantonensis

Angiostrongylosis is a neurological disorder caused by invasion of the central nervous system by developing larvae of Angiostrongylus cantonensis. Purkinje cells in infected mouse cerebellums are small and irregular with degenerative atrophy or partial loss. Ultrastructural changes in degenerative cells included enlarged vacuolar structures and swollen mitochondria within the cytoplasm. The matrix metalloproteinase-9 mRNA which is low in normal cerebellums was expressed in A. cantonensis-infected mice cerebellum prior to Purkinje cell degeneration. Matrix metalloproteinase-9 protein level and enzyme activity increased when the Purkinje cells appeared degenerated. Using immunohistochemistry, matrix metalloproteinase-9 was localised within degenerative Purkinje cells. In addition, when the specific matrix metalloproteinase inhibitor, GM6001, was added, matrix metalloproteinase-9 enzyme activity was reduced by 41.6%. The numbers of degenerative Purkinje cells increased significantly upon establishment of infection but subsided upon inhibition. These results suggested that the expression of matrix metalloproteinase-9 may be associated with degeneration of Purkinje cells in mouse cerebellum infected by A. cantonensis.     

Effects of systemic administration of 6-hydroxydopamine on the circumventricular organs in nonhuman primates

6-Hydroxydopamine (6-OH-DA) has been shown to produce degenerative changes in noradrenergic nerve terminals and preterminals in the CNS following intracisternal, intraventricular or direct injection into the brain parenchyma. Systemic injection of 6-OH-DA is known to result in degenerative changes in noradrenergic terminals in the peripheral nervous system. However, only a few studies have been carried out on the effects of systemic injections of 6-OH-DA on noradrenergic terminals in the CNS. In the present study cynomolgus and squirrel monkeys were injected intravenously on two successive days with total doses of 350 mg/kg and 150 mg/kg of 6-OH-DA, respectively, and sacrificed at 2 and 24 h following the second injection. Degenerative changes in the area postrema (AP) neurons in all injected animals were characterized by a generalized increase in electron density of cytoplasmic elements in axonal terminals and preterminals. Multilamellar bodies, clusters of clear and dense core vesicles, increased numbers of secondary lysosomes, and an increase in the number of glycogen increased markedly in injected animals, but no other glial alterations were observed. The number of mast cells in the AP was greater in injected than in noninjected animals, both in the perivascular spaces (PVS) and in parenchymal locations. Cell processes in the PVS were occasionally observed to contain electron dense bodies, and degenerative changes were seen in supraependymal processes in some injected animals.     

Clinical implications of chromosome abnormalities in acute non-lymphocytic leukemia: current status.

Data currently available on banded chromosome studies on patients with ANLL suggest that the presence of a chromosome abnormality in such patients indicates a poor prognosis, and that different treatment strategies need to be developed for these patients. However, patients with at least one normal metaphase survive nearly as long as those with only normal metaphases. A specific chromosome abnormality in APL [t(15;17)], an unusual association of a translocation [t(8;21)] in association with loss of a sex chromosome, and a rare association of thrombocytosis and a chromosome insertion (3;3 ins), suggest that some chromosome changes in ANLL are specific.     

Ultrastructural changes in erythrocytes and thrombocytes in patients with severe thermal burns of the skin in the burn shock period

The data obtained show that a great amount of deformed red blood cells, i.e. ovalocytes, cristate-shaped cells appear in the peripheral blood of patients with severe cutaneous burns during shock. In the most severe shocks a dramatic increase in degenerative forms of red blood cells in the blood has been observed. These are spheroids and spheroechynocytes frequently with impaired matrix structure. A correlation has been established between the progressing shock severity and the number of degenerative forms of red blood cells in the blood. Reversible changes of platelet fine structure were also noted.     

Ultrastructural reactions of spinal ganglia to tri-ortho-cresyl-phosphate: Effects of neurotoxicity

Summary The ultrastructure of neurons in spinal ganglia of the domestic fowl poisoned with tri-ortho-cresyl-phosphate (TOCP) shows characteristic changes. The light neurons react to TOCP by a marked increase in the number of neurofilaments. These neurons also contain mitochondria in various degenerative stages. Several of the altered mitochondria show an increasing osmiophilia. Some of the darker neurons display a hypertrophy of the endoplasmic reticulum or a relative increase of neurofilaments. The mitochondria in some of these cells show early stages of degeneration. These changes appear 13 days after TOCP ingestion.     

中枢疲劳研究与思考

中枢疲劳既可以作为独立疾病影响人们的日常工作和学习,又可以作为症状出现于多种慢性疾病,其定义和机制国内外说法不尽相同。中枢疲劳是由于中枢神经系统发生退行性或其他不良变化,从而导致躯体、神经、包括心理一系列的疲劳样反应。其机制涉及到中枢神经系统和外周传导系统等多个维度、多个节点的变化,充分把握中枢疲劳的概念本质及潜在生物学机制对其临床防治有着重要理论和实践意义。此外,动物模型作为基础研究的前提和必要工具是中枢疲劳研究过程中又一重要问题。本文在文献整理的基础上,先从定义的角度出发由疲劳引申到中枢疲劳,将现阶段对中枢疲劳的不同概念阐述做一分析,并从机制和动物模型两个方面展开对国外研究进展进行综述。     

The mei-P26 gene encodes a RING finger B-box coiled-coil-NHL protein that regulates seizure susceptibility in Drosophilia

Seizure-suppressor mutations provide unique insight into the genes and mechanisms involved in regulating nervous system excitability. Drosophila bang-sensitive (BS) mutants present a useful tool for identifying seizure suppressors since they are a well-characterized epilepsy model. Here we describe the isolation and characterization of a new Drosophila seizure-suppressor mutant that results from disruption of the meiotic gene mei-P26, which belongs to the RBCC-NHL family of proteins. The mei-P26 mutation reduces seizures in easily shocked (eas) and slamdance (sda) epileptic flies following mechanical stimulation and electroconvulsive shock. In addition, mutant mei-P26 flies exhibit seizure thresholds at least threefold greater than those of wild type. The mei-P26 phenotypes appear to result from missense mutation of a critical residue in the NHL protein-protein interaction domain of the protein. These results reveal a surprising role for mei-P26 outside of the germline as a regulator of seizure susceptibility, possibly by affecting synaptic development as a ubiquitin ligase.     

Proteinase-activated receptors in the nervous system

Recent data point to important roles for proteinases and their cognate proteinase-activated receptors (PARs) in the ontogeny and pathophysiology of the nervous system. PARs are a family of G-protein-coupled receptors that can affect neural cell proliferation, morphology and physiology. PARs also have important roles in neuroinflammatory and degenerative diseases such as human immunodeficiency virus-associated dementia, Alzheimer's disease and pain. These receptors might also influence the pathogenesis of stroke and multiple sclerosis, conditions in which the blood-brain barrier is disrupted. The diversity of effects of PARs on neural function and their widespread distribution in the nervous system make them attractive therapeutic targets for neurological disorders. Here, we review the roles of PARs in the central and peripheral nervous systems during health and disease, with a focus on neuroinflammatory and degenerative disorders.     

Early detection of inherited muscular dystrophy in chickens

Summary New Hampshire chickens, homozygous for inherited muscular dystrophy, display clinical manifestations at an early age. A fine structural examination of embryos from this strain shows marked degenerative changes four days prior to hatching. The Z bands appear to dissolve progressively to the point where finally the myofibrils become uniformly dense with no detectable banding patterns.     

Cytochemical maturation index for the prognostication of adult acute nonlymphocytic leukaemia

76 adult acute nonlymphocytic leukaemias (ANLL) were characterized by cytochemical markers and placed in a coordinate system. The position of each ANLL was determined on the basis of the peroxidase and nonspecific esterase reactivity of the blast cells. This classification numerically identifies the maturation tendency and heterogeneity of individual ANLL cases according to its position in the coordinate system. 49 ANLL patients were treated with TAD protocol and the response rate seemed to be in a conspicous correlation with the position of the individual ANLL cases in the modified arrangement. Cases exhibiting a strong peroxidase maturation, i.e. the cytochemical maturation index being 80% or more had a considerable higher complete remission rate and longer duration of remission than those with low (less than 80%) maturation index. Age profoundly influenced even this figure.     

The development of connections in the tecto-thalamo-telencephalic visual system of the brain in 13-day-old chick embryos

Light and electron microscopic studies have been made on degenerative changes in the nervous tissue induced by experimental destruction of the median brain bulb at the 5th day of incubation, in parts of the tecto-thalamo-telencephalic visual system in 13-day chick embryos (in the visual tectum, round nucleus of the thalamus and ectostriatum of the telencephalon). It was shown that to this period tecto-thalamic connections are already formed in the visual system, whereas thalamo-telencephalic connections are, presumably, indirect ones.     

Changes in the blood vessels, spinal cord neurocytes, pia mater and spinal ganglia in chronic stimulation of the sympathetic trunks

Taking into account the data concerning disturbances in blood supply of the spinal cord as a response to irritation of the sympathetic trunks, the experimental morphological investigation has been performed on rabbits. By means of the injection technique and staining of neurocytes, changes in the spinal cord, in the spinal nodes and in the pia mater have been studied at chronic irritation of the lumbar nodes of the sympathetic trunk. Certain degenerative changes have been revealed in nervous cells and also phenomena of the spinal cord ischemia, decreasing contacts between the nervous cells and the capillaries surrounding them. As the authors believe, these data can be used by clinicians for revealing pathological mechanisms of the spinal cord ischemia as a result of chronic irritation of the sympathetic trunk.     

Morphologic changes in the nervous apparatus of the pharynx, esophagus and stomach of cats following a single gravitational stress]

Under investigation were the pharynx, oesophagus and stomach of 23 cats subjected to a single maximum endurable gravitation stress. The material was treated after Bielschowski-Gross. It has been established that as early as within 48--72 hours after gravitation effects there appear changes of different elements of the nervous apparatus of the organ under study such as increased argirophilia of nervous structures and reactive changes of different sensory nerve terminations. Motor animal nerve terminations do not change. Most of myelinated afferent fibres and non myelinated vegetative fibres undergo reactive changes. Within 7 days there appear certain myelinated fibres which are in the stage of granular desintegration,     

Prediction of advanced puberty by height velocity in children with acute lymphoblastic leukemia.

Pubertal development was retrospectively evaluated in 58 children with cancer, mostly acute lymphoblastic leukemia (ALL), who are in complete remission and off chemotherapy. Six girls [5 patients with ALL, and 1 with malignant lymphoma (NHL)] showed advanced puberty (25.0%, 6 of 24 female patients with ALL and NHL) through the evaluation of their growth velocity. No evidence for advanced puberty was seen in the males. All 6 girls had received cranial irradiation for central nervous system prophylaxis and systemic chemotherapy including glucocorticoid. The mean age at onset of the pubertal growth spurt in these 6 girls was significantly lower than for girls with a solid tumor [6.90 +/- 0.10 and 9.00 +/- 0.77 (mean +/- SD) years, respectively (p < 0.01)]. By simply evaluating the height velocity, we could predict advanced puberty which was ultimately associated with short stature.