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PubMed2005

Loss and recovery of voluntary hand movements in the macaque following a cervical dorsal rhizotomy.

The recovery of manual dexterity was analyzed in the macaque following a cervical dorsal root section that abolished cutaneous feedback from selected digits of one hand. Monkeys were trained to retrieve a target object from a clamp using thumb and index finger opposition. Dorsal rootlets containing electrophysiologically identified axons projecting from the thumb and index finger were then cut in two monkeys (Group 1). In four others (Group 2), additional rootlets shown to innervate the middle finger and thenar eminence were also transected. Three performance parameters were analyzed before and following the rhizotomy: 1) percentage of successful retrievals; 2) digital stratagem (the pattern of digit opposition); and 3) contact time (duration of digit contact with the object before its retrieval). During the first postoperative week, hand function was severely impaired in all monkeys. Over the following weeks, Group 1 monkeys recovered the ability to retrieve the object by opposing the index finger and thumb in >80% of trials. Group 2 monkeys also regained some function in the impaired hand: each monkey adopted a stratagem for grasping the target, using digits that were incompletely deafferented. In the terminal experiment, hand representation in the contralateral somatosensory cortex was electrophysiologically mapped to define hand deafferentation and cortical reactivation further. There was a close correspondence between the cortical map and digit use. Our data imply that the recovery of precision grip using the thumb and index finger depends on the survival of afferents innervating these digits, as well as the proliferation of their central terminals.

Afferent Pathways↗
PubMed1987

The chandelier cell of the human visual cortex: a Golgi study.

The size, location, distribution, and spatial orientation of the chandelier cell of the human visual cortex are described for the first time. The rapid Golgi method has been utilized to study the structural features of these inhibitory interneurons. The human chandelier cell is a small stellate interneuron with prominent idiodendritic and idioaxonic arborizations. These arborizations are distributed within a narrow rectangular tissue slab that measures approximately 300 X 200 X 100 microns. This relatively small and narrow functional territory is oriented perpendicular to the pial surface and to the long axis of the gyrus. The territory of distribution of its axon is larger than and encloses that of its dendrites. The number of specific axonic terminals (candles) per chandelier cell is also relatively small, ranging from 60 to 80 units. These axonic terminals represent the functional units of the neuron and reflect the number of pyramidal cell axons contacted by it. The chandelier cell of the human visual cortex possibly represents the smallest neuron of this kind described to date. The size of its functional territory and the number of its specific axonic terminals are among the smallest of any neuron of this kind thus far described. It is postulated herein that in the course of mammalian phylogeny the chandelier cell shows a tendency toward a progressive reduction in the size of its functional territory and in the number of its functional units (candles), as well as a tendency toward a more "idio" pattern of distribution for its axonic and dendritic arborizations. Perhaps, these progressive evolutionary modifications could reflect a tendency of this type of interneuron toward an increasing specialization. The possible existence of a relationship between the progressive transformation of the chandelier cell and the increasing visual acuity, dexterity, and skillfulness in the course of mammalian phylogeny should be explored.

Female↗
PubMed1990

Descending pathways to the spinal cord, IV: Some factors related to the amount of cortex devoted to the corticospinal tract.

In the companion paper to this one (Nudo and Masterton: J. Comp. Neurol. 296:559-583, '90), we have presented data indicating that in each of 22 mammals, there are either 2 or 3 separate regions of neocortex contributing corticospinal fibers. In this paper, we describe the variation in the absolute size of these cortical regions, the total amount of neocortex contributing corticospinal fibers (CST cortex), and the total amount of neocortex (total cortex) in each of the animals. We then use strict statistical tests to examine the relationships between these measures and several other quantitative measures or descriptions of the animals' size, ancestral heritage, motor prowess, and ecological adaptation. The results show that the absolute amount of CST cortex is more closely related to the total amount of neocortex than to any other quantitative measure available. The further variation--that is, the variation in the amount of CST cortex relative to total neocortex--appears to have been random over the inferred ancestral lineages of most animals in the sample, but seems to have been almost absent along the anthropoid lineage. Because this constancy in the relative amount of CST cortex over a very long period of anthropoid ancestry is apparently unusual if not unique among mammals, it may contain a clue to the special role of the corticospinal tract among primates. Finally, the distribution of the CST among the 3 cortical regions in primates was found to be more closely related to their particular mode of ecological adaptation than to their particular combination of digital dexterity and hand-eye coordination.

Animals↗
PubMed2005

Intermolecular electronic excitation transfer in a confined space: a first-principles study.

The process of intermolecular electronic excitation transfer (EET) in a monodimensional supramolecular arrangement of molecules in confined space has been modelled and investigated by means of first-principles molecular dynamics simulations. The chosen model system consists of a wire of chlorine molecules hosted in the noncrossing channels of the zeolite bikitaite. The time evolution of the system in its first excited singlet state has been described by the restricted open shell Kohn-Sham formalism. Simulation results have highlighted that excitation, initially localized on a guest molecule, is transferred to an adjacent moiety in the molecular wire on the picosecond scale via a collision-induced Dexter-type short range EET. Analysis of the modifications of the electronic structure of the system brought about by EET has given insight into the microscopic details of the process.

Journal Article↗
PubMed1987

Immunoglobulin heavy chain gene diversification in the long-term bone marrow culture of normal mice and mice with severe combined immunodeficiency.

The change of immunoglobulin heavy (H) chain gene configuration during the differentiation of B cells from their early precursors was investigated in long-term cultures of bone marrow cells (LTBC). Hemopoietic stem cells are maintained in LTBC described by Dexter et al. (J. Cell. Physiol. 1977. 91: 335; LTBC-D), which supports the differentiation of myeloid lineage cells but not B lineage cells. By simply shifting the culture condition to that devised by Whitlock and Witte (Proc. Natl. Acad. Sci. USA 1982. 79: 3608; LTBC-B) to support the development of B lineage cells, surface IgM-bearing (sIgM+) B cells became detectable by the 2nd week after the shift and the number quickly increased thereafter, while the number of polymorphonuclear cells and granulocyte-macrophage colony-forming cell (CFU-c) decreased rapidly. H chain gene configuration of the developing cells in the culture was examined by Southern blot analysis of Eco RI-digested DNA with a JH probe. Whereas rearranged JH gene configuration was not detectable in the DNA from LTBC-D cells, it first appeared 2 weeks after the shift, and the level of the rearrangement rapidly increased thereafter as the intensity of JH band of germ-line configuration decreased. Almost all the cells in the culture had undergone H chain gene rearrangement in both chromosomes by the 6th week after the shift. During 2 to 4 weeks after the shift, a cluster of bands spanning around 4.5-5.5 kb appeared dominant among the rearranged configurations of JH gene and then it decreased in intensity as the pattern of JH band became a more homogeneous smear. The distribution of rearranged JH bands observed during 3-4 weeks after the shift was strikingly similar to that observed in normal spleen B cells. By semi-quantitative analysis of the intensity of JH and DSP2 bands remaining in germ-line configuration, it was found that the loss of germ-line JH band was far more rapid than that of germ-line DSP2 bands in the developing B cells in vitro. This result is consistent with the conclusion obtained in B cell tumor lines that D to J assembly occurred first and was followed by V to DJ assembly in this culture system. Taken together, it is likely that the process of H chain gene diversification in this culture system may represent the actual process during B cell differentiation in vivo. Differentiative capacity of bone marrow stem cells from mouse with severe combined immunodeficiency (SCID) was also analyzed in the same culture system.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Cytofluorometric and cytomorphologic analysis of human bone marrow cells derived from stromal cultures stimulated by granulocyte-macrophage colony-stimulating factor, interferon-gamma and splenopentin pentapeptide.

We studied the influence of human recombinant granulocyte-macrophage colony-stimulating factor (hrGM-CSF), human recombinant interferon-gamma (hrIFN-gamma) and splenopentin pentapeptide (Sp-5), either alone or in combination, on the proliferation and differentiation of human bone marrow cells in modified Dexter's cultures. After 10, 14 and 21 days cells were analyzed by classical staining according to Pappenheim and by cytofluorometry with a set of different monoclonal antibodies. IFN-gamma inhibited the proliferation of progenitor cells and provided signals promoting monocytic differentiation, whereas GM-CSF induced the proliferation of blastoid elements which expressed HLA-DR and M2 (VIM-2 monoclonal antibody), but progressively lost surface CD34. Furthermore, an increase of CD15+ cells was also observed. When GM-CSF was tested in combination with IFN-gamma, it abolished the inhibitory effect of IFN-gamma and both cytokines synergized to promote the expression of CD11c, CD14 and M2 surface antigens. Sp-5 alone had only a marginal activity, but it potentiated the effects of GM-CSF. These findings suggest that GM-CSF may induce the transition from stem cells to committed myeloid progenitors. In contrast to IFN-gamma, Sp-5 can serve as an additional proliferative signal with negligible effects on cell maturation.

Amino Acid Sequence↗
PubMed1996

Vascular cell adhesion molecule-1 expression by hematopoiesis-supporting stromal cells is not essential for lymphoid or myeloid differentiation in vivo or in vitro.

Binding of myeloid and lymphoid precursors to stromal cells in bone marrow has been suggested to be mediated through alpha 4 integrins (alpha 4) and vascular cell adhesion molecule-1 (VCAM-1) expressed on hematopoietic progenitors and stromal cells, respectively. It has not been shown, however, how essential the VCAM-1/ alpha 4 interaction is for hematopoiesis in vivo and whether or not other adhesion pathways can provide similar functional binding between stromal cells and hematopoietic progenitors. We addressed this issue by analyzing myeloid and lymphoid differentiation in vivo in mice with VCAM-1-null or -hypomorphic mutations and in vitro in long-term hematopoietic cultures with stromal cell clones from wild-type mice, which express or do not express VCAM-1. Mice bearing VCAM-1 mutations had no gross hematopoietic insufficiencies in the myeloid or lymphoid compartments and the distribution of myeloid progenitors between bone marrow and periphery was normal. In Dexter type long-term bone marrow cultures from mutant mice, the formation of supportive stromal cell layers and myeloid proliferation and differentiation were not affected by the absence of VCAM-1. Long-term maintenance and proliferation of clonable pre-B cells, cobblestone formation and differentiation to IgM-secreting, mature B cells was equally possible on VCAM-1+ and VCAM-1- stromal cell clones. We conclude from our data that VCAM-1 is not essential for the functional interaction between hematopoietic progenitors and stromal cells required for myeloid and B-lymphoid development in vivo or in vitro.

Animals↗
PubMed1987

Lack of interaction between cimetidine and buspirone.

Simultaneous administration of cimetidine and many benzodiazepine anxiolytics has resulted in decreased body clearance and marked prolongation of the half-life of these agents. The pharmacokinetic interaction of buspirone, a new nonbenzodiazepine anxiolytic, and cimetidine was studied in 10 healthy male volunteers. Each received, in order, buspirone 45 mg/day (days 1-7), no drug (days 8-14), cimetidine 1 g/day (days 15-21), buspirone 45 mg/day plus cimetidine 1 g/day (days 22-28), and cimetidine 1 g/day (days 29-31). Buspirone and 1-pyrimidinyl piperazine (1-PP), an active metabolite, pharmacokinetics, urinary excretion of cimetidine, a manual dexterity test, the Stroop color-word interference test, and a visual analog mood scale were evaluated on each treatment. There were no significant (p greater than 0.05) differences among treatments for any measurement except for a slight (31%) but significant (p less than 0.05) increase in the 1-PP Cmax value. These results suggest that within the normal therapeutic dosage ranges for both drugs, it is unlikely that a clinically significant interaction between them will occur.

Adult↗
PubMed1991

Long-term marrow cultures: human and murine systems.

The intramedullary control of marrow cell production has been a difficult area to approach experimentally. The introduction by Dr. Dexter and colleagues of long-term stromal dependent culture systems for murine marrow and the adaptation of these systems to human marrow growth have allowed for in-vitro studies of stromal dependent hemopoiesis. Despite some controversy in this area, most studies appear to show that adherent murine or human stromal cells are capable of producing a relatively large number of hemopoietic growth factors including G-CSF, GM-CSF, CSF-1, IL-6 and, at least by PCR analysis, IL-3. Other work indicates that the most primitive hemopoietic cells which appear to be multifactor responsive adhere directly to these stromal cells presumably through mediation of various adherence proteins. An early acting, multilineage factor termed hemolymphopoietic growth factor-1 (HLGF-1) has been isolated from a murine stromal cell line and may be identical to the recently described ligand for the c-kit receptor. This may represent an important early survival/maintenance factor for stem cells in this system. Studies on primitive stem cells, especially the high proliferative potential colony forming cell (HPP-CFC), indicate that they are responsive to varying combinations of growth factors and that with increasing numbers of growth factors, as studied in serum-free systems, decreasing concentrations of the factors may be biologically active. These observations altogether suggest that intramedullary hemopoiesis may be regulated by the positioning of early multifactor responsive stem cells via adherent proteins in juxtaposition to synergistically acting combinations of growth factors attached to stromal cell surfaces or the extracellular matrix.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Culture perfusion schedules influence the metabolic activity and granulocyte-macrophage colony-stimulating factor production rates of human bone marrow stromal cells.

The metabolic function and GM-CSF production rates of adherent human bone marrow stromal cells were investigated as functions of medium and serum feeding rates. A range of medium exchange schedules was studied, ranging from a typical Dexter culture protocol of one weekly medium exchange to a full media exchange daily, which more closely approximates what bone marrow cells experience in situ. Glucose consumption was found to be significantly higher at full daily exchange rate than at any other exchange schedule examined. However, the lactate yield on glucose was a constant, at 1.8 mol/mol, under all conditions considered. Differential serum vs. medium exchange experiment showed that both serum supply and medium nutrients were responsible for the altered behavior at high exchange rates. Glutamine consumption was found to be insignificant under all culture conditions examined. A change in exchange schedule from 50% daily medium exchange to full daily medium exchange after 14 days of culture was found to result in a transient production of GM-CSF and a change in metabolic behavior to resemble that of cultures which had full daily exchange from day one. These results suggest that both stromal cell metabolism and GM-CSF production are sensitive to medium exchange schedules. Taken together, the data presented indicate that attempts to model the function of human bone marrow in vitro may be well served by beginning with medium exchange schedules that more closely mimic the in vivo physiologic state of bone marrow.

Adult↗
PubMed1995

Hematopoietic-promoting activity of the murine stromal cell line MS-5 is not related to the expression of the major hematopoietic cytokines.

As an approach for characterizing the molecules involved in the proliferation and differentiation of hematopoietic stem cells we have compared the ability of four murine stromal cell lines, MS-5, MS-K, both derived from Dexter cultures, BMS1 and BMS2 both derived from Whitlock-Witte cultures, to sustain murine long term hematopoiesis and to express the major hematopoietic cytokine genes. As opposed to the three other cell lines, MS-5 supports the maintenance of stem cells for up to 4-5 weeks. However, reconstituting stem cell output was reduced while clonogenic cell (day 12 and day 8 spleen colony-forming units, granulo-macrophagic, and erythroid progenitor cells) output was markedly increased. This hematopoietic-promoting activity is at least in part mediated by soluble molecules since medium conditioned with MS-5 cells was able to partially complement the nonsupportive cell line BMS1. The comparative study of the cytokine gene expression in MS-5 and in the nonsupportive cell lines included Northern blot and reverse transcriptase-polymerase chain reaction analysis of messenger RNA for interleukin-1, -3, -6, granulo-macrophage-colony-stimulating factor (GM-CSF), granulocyte-CSF, macrophage-CSF, stem cell factor, transforming growth factor-beta, tumor necrosis factor-alpha, macrophage inflammatory protein-1 alpha, and leukemia inhibitory factor. None of these molecules or their association were found to clearly confer to the MS-5 cell line its hematopoietic-promoting activity raising the possibility that uncharacterized molecule(s) would be involved in the proliferation and differentiation of stem cells.

Animals↗
PubMed2006

Free vascularized fibular grafting for reconstruction after tumor resection in the upper extremity.

BACKGROUND: Limb salvage is viable in the majority of patients with malignant bone tumors, but especially in case of extensive tumors and bad soft tissue conditions, it is challenging in upper extremity. OBJECTIVES/METHOD: The clinical and radiological results of 21 patients, who had free vascularized fibular grafts (VFG), for diaphyseal (14), and epipyseal (7) defect reconstruction of the upper extremity, are presented. The indications for VFG were resection after osteosarcoma (9 cases), Ewings sarcoma (9 cases), chondrosarcoma (1 case), rhabdomyosarcoma (1 case), and 1 case of fibrous dysplasia. The 20 malignant tumors were staged as follows: 2a (1), 2b (18), 3 (1). The mean follow-up was 43.6 months (min 6.0-max 131.9). Functional results were described and graded quantitatively according to the MSTS-score. RESULTS: Results were satisfactory with regard to pain, emotional acceptance, manual dexterity, and function. Lifting ability was decreased in two patients. Hypertrophy index was 31% (min 13%-max 71%). Main complications were fracture (5), pseudoarthrosis (4), prolonged wound healing (4), temporary nerve irritation (2), and deep infection (1). Re-operation was required in eight patients (12 operations). CONCLUSION: VFG offers a good possibility for biological reconstruction of large skeletal defects, with an acceptable complication and re-operation rate. When conservative treatment of complications was not successful, further surgery led to recovery in the majority of cases.

Adolescent↗
PubMed1980

Induction and long-term maintenance of Thy-1 positive T lymphocytes: derivation from continuous bone marrow cultures.

In the present study we investigated the presence of T-lymphocyte progenitors in the long-term murine bone marrow culture system described by Dexter: mature Thy-1 antigen-bearing T lymphocytes are lost in these cultures after a few days. By culturing nonadherent cells from such cultures in the presence of a supernatant of concanavalin A-stimulated spleen cells, a source of T-cell growth factor, we found that Thy-1 positive blast cells proliferated together with a second population of Thy-1 negative cells. These two populations of cells have been maintained in long-term in vitro cultures by passaging the cells in fresh conditioned medium at regular intervals. Moreover, we have been able to establish pure cultures of the Thy-1 bearing blast cells after separating them from the non-T cells using their adherence property to plastic surfaces. Long-term cultures of T lymphocytes can thus be established from long-term marrow cultures as well as from the spleen, thymus or fresh bone marrow.

Animals↗
PubMed2002

Acupuncture therapy for the symptoms of Parkinson's disease.

Interest in alternative medical treatments, including acupuncture, is increasing. Alternative treatments must be subjected to the same objective standards as all medical treatments. A non-blinded pilot study of the safety, tolerability, and efficacy of acupuncture (ACUPX) for the symptoms of (PD) was performed. Twenty PD patients (mean age, 68 years; disease duration, 8.5 years; Hoehn and Yahr [H&Y] stage, 2.2; Unified Parkinson's Disease Rating Scale score [UPDRS], 38.7) each received acupuncture treatments by a licensed acupuncturist. All patients were treated with two acupuncture treatment sessions per week. The first seven patients received 10 treatments and the last 13 patients 16 treatments. Patients were evaluated before and after ACUPX with the Sickness Impact Profile (SIP); UPDRS; H & Y; Schwab and England (S & E); Beck Anxiety Inventory (BAI); Beck Depression Inventory (BDI); quantitative motor tests, including timed evaluations of arm pronation supination movements, finger dexterity, finger movements between two fixed measured points, and the stand-walk-sit test; and a patient questionnaire designed for the study. Following ACUPX, there were no significant changes in the UPDRS, H&Y, S&E, BAI, BDI, quantitative motor tests, total SIP or the two SIP Dimension scores. Analysis of the 12 SIP categories not corrected for multiple comparisons revealed a post-ACUPX improvement in the sleep and rest category only (P = 0.03). On the patient questionnaire, 85% of patients reported subjective improvement of individual symptoms including tremor, walking, handwriting, slowness, pain, sleep, depression, and anxiety. There were no adverse effects. ACUPX therapy is safe and well tolerated in PD patients. A range of PD and behavioral scales failed to show improvement following ACUPX other than sleep benefit, although patients reported other discrete symptomatic improvements. A broad battery of tests in PD patients suggested that ACUPX resulted in improvement of sleep and rest only. This finding needs to be verified using more in-depth and controlled evaluation of ACUPX for PD-related sleep disturbance.

Activities of Daily Living↗
PubMed2003

Manual transport in Parkinson's disease.

We analyze hand dexterity in Parkinson's disease patients (PD) and control subjects using a natural manual transport task (moving an object from one place to another). Eight PD patients and 10 control subjects carried out the task repeatedly at maximum speed both in off and on medicated status. The movement parameters and the grip and load forces were recorded. Using the force and velocity signals, 10 subsequent phases of the transport movement were defined and their durations were measured. The difference between the control group and the test group in off and on was established statistically using non-parametric methods. There was slowed reaching and a striking disturbance of establishing the precision grip in PD. The transport capabilities were impaired differentially. Although acceleration and reaching sufficient height of the lift were disturbed in PD subjects, transport of the object toward the target position was almost normal. A partial disturbance was observed when cancelling the grip. Dopaminergic medication improved only specific hand skills, especially establishment of the precision grip and one of the four transport phases. A long movement path was more sensitive for movement disturbance in Parkinson's disease than a short one.

Aged↗
PubMed2005

Corticobasal syndrome with novel argyrophilic glial inclusions.

A 42-year-old, left-handed woman first noted impaired dexterity of the dominant hand, soon followed by dysarthria and cognitive decline. Over a 4-year period, she developed severe left-sided apraxia with eventual neglect of the left arm and progressive extrapyramidal signs. Cognitive testing showed progressive executive, visuospatial, fluency, and naming impairment with relative preservation of memory. Single-photon emission computed tomography demonstrated asymmetric right posterior frontal and superior parietal hypoperfusion. The clinical impression was corticobasal degeneration. At autopsy, severe atrophy was seen in the perirolandic and frontal regions. There was marked neuronal loss and gliosis in the posterior frontal and precentral regions and less severe pathology in prefrontal, temporal, and parietal areas. Mild to moderate gliosis and neuronal loss were also seen in the putamen, globus pallidus, subthalamic, and dentate nuclei. Gallyas silver stain revealed numerous inclusions adjacent to oligodendrocyte nuclei in white and gray matter of affected cortical and subcortical regions. The gracile inclusions were wavy, slender, and stained positively with antibodies to ubiquitin and alphaB-crystallin but not to microtubule-associated proteins (tau, MAP1B, MAP2), tubulin, neurofilaments, glial fibrillary acidic protein, or alpha-synuclein. The argyrophilic inclusions identified in this case are distinct from those previously described in neurodegenerative diseases.

Adult↗
PubMed2005

Throat clicking as the initial symptom of Parkinson's disease.

The presenting manifestations of Parkinson's disease (PD) are variable, but a majority of patients note tremor as the initial symptom. Others complain of slowing of movements, loss of dexterity, fatigue, or changes in handwriting as initial symptoms. We describe a patient who developed an unusual clicking sound emanating from his throat as the initial manifestation of PD.

Aged↗
PubMed2006

Neuropsychological profile of DYT1 dystonia.

The common belief that primary dystonia is a purely motor disorder has recently been challenged. We examined separately the cognitive profiles of symptomatic (SYM) and nonsymptomatic (N-SYM) groups of carriers of DYT1 mutation using a comprehensive neuropsychological test battery. Self-report inventories of anxiety, depression, and pain levels were also administered, as well as manual motor dexterity assessment. Each group was matched with healthy controls by age, sex, mother tongue, and education. No significant differences between the SYM group to its control group were found on cognitive tests evaluating verbal and nonverbal abstract abilities, attention, information processing speed, and spatial organization. However, the SYM group showed increased verbal memory retroactive interference. Interestingly, the patients also showed higher semantic fluency performance. No significant differences between the N-SYM group to controls were found. It was concluded that symptomatic DYT1 mutation carriers do not suffer the distinctive cognitive decline that is seen in other primary degenerative extrapyramidal disorders.

Adult↗