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PubMed2004

An analysis of globally connected active rotators with excitatory and inhibitory connections having different time constants using the nonlinear Fokker-Planck equations.

The globally connected active rotators with excitatory and inhibitory connections having different time constants under noise are analyzed using the nonlinear Fokker-Planck equation, and their oscillatory phenomena are investigated. Based on numerically calculated bifurcation diagrams, both periodic solutions and chaotic solutions are found. The periodic firings are classified based on the firing period, the coefficient of variation, and the correlation coefficient, and weakly synchronized periodic firings which are often observed in physiological experiments are found.

Action Potentials↗
PubMed1985

The connections of the hippocampal region. New observations on efferent connections in the guinea pig, and their functional implications.

This article deals with the efferent connections of the hippocampal region, and considers the functional implications of these projections. The hippocampus receives indirect sensory information from many structures in the brain. Most of these afferents terminate in the superficial layers (I-III) of the entorhinal area. From cells in layers II and III of entorhinal area projections arise which terminate in hippocampus and fascia dentata, the perforant paths. Internal hippocampal projections constitute a unidirectional system of connections which project back to the deep layers (IV-VI) of the entorhinal area. The efferents from these layers may be divided into cortically terminating efferents, which originate from layer IV, and subcortically terminating efferents, which originate from layers V and VI. The cortically terminating projections end in regions of association cortex, and in limbic cortex. The subcortical projections terminate in the caudate, the putamen, and the accumbens nucleus. A hippocampal influence on these subcortical structures may seem surprising, but is logical when one takes into consideration reports on the functional associations between the striatum and the hippocampus. The findings suggest that the role of the hippocampus may be to gather input from all sensory modalities, to assign priorities continuously between these inputs, and as a result, to modify behavior via its influence on subcortical motor centres.

Afferent Pathways↗
PubMed2001

Distribution of hepatic venous blood in the total cavo pulmonary connection: an in vitro study into the effects of connection geometry.

The total cavo pulmonary connection, or TCPC, is a surgical correction to congenital heart defects. The geometry of this connection has been shown to determine the fluid power loss as well as the distribution of hepatic fluid that enters through the inferior vena cava. In vitro studies were performed to measure the power loss and hepatic fluid distribution in models of the TCPC with four different geometries. It was found that a zero offset straight geometry provided good hepatic fluid distribution but large power loss. A zero offset flared geometry provided low power loss but poor hepatic fluid distribution. The optimal geometry from those tested was found to be the zero offset cowl geometry whereby an enlargement was made on one side of the inferior and superior vena cava. So long as the cowl was directed toward the pulmonary artery of lowest flow rate, low power loss and relatively good distribution of hepatic flow could be obtained.

Blood Flow Velocity↗
PubMed2001

[From the concept of permanent percutaneous connections to that of permanent percutaneous electrical connections].

Percutaneous abutment of an extra-oral implant provides two main functions: support of bone anchored hearing aid (BAHA) and fixing maxillofacial prosthesis (MFP). Further developing this concept, and using available surgical strategies and materials, leads to a new application in extra-oral implantology. We analyzed the evolution of concepts in the field of permanent percutaneous connection (PPC) to the new concept of PPEC (permanent percutaneous electric connection), presenting a clinical case.

Biocompatible Materials↗
PubMed1991

Arrhythmias after the Fontan procedure. Comparison of total cavopulmonary connection and atriopulmonary connection.

Arrhythmia was compared between 40 consecutive patients (pts) undergoing atriopulmonary connection (APC) and 40 undergoing total cavopulmonary connection (TCPC), between 1986 and 1990. Patients were not randomized, and those undergoing APC predominantly had tricuspid atresia (57.5% versus 15%) compared with pts undergoing TCPC who had more varied and complex cardiac defects. Before surgery there was no significant arrhythmia in either group. Hospital mortality was 15/40 and 6/40 for APC and TCPC, respectively (p less than 0.05). Early after APC nine pts developed atrial flutter (AFL) and eight died, while after TCPC only two developed AFL, and neither died (p less than 0.01). Fatal junctional ectopic tachycardia occurred in one pt in each group. During follow-up (38 +/- 8.5 months after APC versus 20 +/- 10 months after TCPC), new arrhythmia was uncommon (two AFL after APC with one death versus two AFL and one supraventricular tachycardia after TCPC with no deaths). Ambulatory ECG during follow-up showed arrhythmia in two APC and six TCPC pts (p = NS). The incidence of early arrhythmia and mortality associated with early arrhythmia appears to be less after TCPC compared with APC.

Arrhythmias, Cardiac↗
PubMed1985

Intrinsic connections of macaque striate cortex: afferent and efferent connections of lamina 4C.

We have studied the intrinsic organization of macaque striate cortex by tracing the pattern of horseradish peroxidase (HRP)-labeled axons and cell bodies produced by microinjections of HRP into single cortical laminae. Both anterograde and retrograde transport results were used to examine: (1) the pattern of projections from lamina 4C to the superficial layers; (2) the projection from lamina 4C to deeper cortical layers; and (3) the projections to lamina 4C from other cortical laminae. Laminae 4C alpha and 4C beta differ in their pattern of projections to the superficial layers of striate cortex. Axons from neurons in lamina 4C beta ascend through lamina 4B without giving off collaterals and terminate in lamina 4A and in the base of lamina 3. By contrast, axons from neurons in lamina 4C alpha terminate in lamina 4B and less densely in the 4A/3B region. The projection from lamina 4C beta to lamina 4A is particularly dense and is distributed in a patchy fashion immediately above each injection site. The projection from lamina 4C beta to lamina 3B appears less dense and more widespread; we estimate that individual 4C beta axons may spread laterally for more than 400 micron. Furthermore, the pattern of HRP-labeled cell bodies in lamina 4C beta following injections into laminae 4A and 3B provides evidence for a subdivision within 4C beta. These injections always produce a large number of labeled neurons in the upper part of lamina 4C beta, whereas the lower portion contains few labeled neurons that are located immediately under the center of the injection site. Both lamina 4C alpha and lamina 4C beta also contribute less dense projections to the deeper layers of cortex. Lamina 4C beta projects mainly to lamina 6, whereas lamina 4C alpha contributes axon terminals to both lamina 5A and lamina 6. Neurons in lamina 6 provide the bulk of the intracortical projections to lamina 4C. The axons of these neurons are fine in caliber and have a delicate side-spine morphology that is quite distinct from lateral geniculate axon arbors. Neurons in lamina 5A also project onto lamina 4C, but the projections of these neurons appear concentrated in lamina 4C alpha. These results confirm or refine many conclusions about intrinsic connections of striate cortex drawn from Golgi material and suggest new patterns of connections not suspected from previous work.

Afferent Pathways↗
PubMed1980

Current concepts in the classification of connective tissue diseases. Overlap syndromes and mixed connective tissue disease (MCTD).

New principles are discussed for the classification of the diffuse collagen diseases, particularly the mixed connective tissue disease (MCTD), with clinical and historical explanation. Emphasis in classification has shifted from a concern with tissue pathology to serologic anomalies, which may involve eleven different antigens, many from human cell nuclei. New serologic tests, such as the ribonucleoprotein (RNP) antibody test, may be superior to the well-known fluorescent antinuclear antibody (ANA) studies for diagnosis and follow-up of diffuse collagen diseases. Functional clinical studies, such as esophageal motility, gas exchange in the lung, and major joint mobility, which may appear early in MCTD, are more important to diagnosis than anatomic studies of late-developing lesions.

Connective Tissue Diseases↗
PubMed1987

Connective tissue activation. XXXI. Identification of two molecular forms of a human mesenchymal cell-derived growth factor, connective tissue activating peptide-V.

We previously identified, in normal urine, a growth factor that stimulated monolayer cultures of human synovial, cartilage, and dermal fibroblasts to synthesize incremental amounts of hyaluronic acid, proteoglycans, and DNA. An isolation procedure guided by bioassays and immunologic methods disclosed 2 anionic bioactive polypeptides with Mr of 28,000 and 16,000, respectively, as judged by single bands with sodium dodecyl sulfate-polyacrylamide gel electrophoresis in reduced and nonreduced samples. Rabbit antibodies raised against each purified protein were shown to react, on immunodiffusion and Western blot, with both antigens. Immunohistochemical and immunobinding studies detected the protein in normal human synovial, dermal, and cartilage fibroblasts and in human saphenous vein endothelial cells. The mesenchymal cell-derived growth factor is now designated connective tissue activating peptide-V (CTAP-V). Monospecific polyclonal anti-CTAP-V antibodies were used in a radial immunodiffusion assay for quantitative determination of the antigen in biologic fluids. In normal human plasma the concentration of CTAP-V was below the limit of detection. The CTAP-V concentration in normal urine was 4.5 +/- 2.0 micrograms/ml, calculated from measurements of 5-18-fold concentrated samples. Joint fluid from patients with rheumatic diseases and normal renal function had CTAP-V levels similar to those found in plasma; 2-15-fold increases were detected in plasma and joint fluid of patients with chronic renal failure. Immunodiffusion or dot-blot analysis revealed a CTAP-V-like material in the plasma or serum of 10 mammalian species. It was not detectable in 2 avian species.

Cartilage↗
PubMed1985

Connective tissue activation: stimulation of glucose transport by connective tissue activating peptide III.

Connective tissue activating peptide III (CTAP III), a human platelet derived growth factor, induced marked stimulation of 2-deoxy[14C]glucose (2dG) uptake in cultures of human synovial cells, chondrocytes, and dermal fibroblasts. Cytochalasin B (2 X 10(-5) M) blocked the mediator-induced increase in 2dG uptake; phlorhizin (8 X 10(-4) M) partially inhibited this process. When cells were exposed to CTAP III (4 X 10(-6) M) for 30 min prior to uptake assay, 2dG uptake was stimulated by 30-110%; greater stimulation (400-800%) occurred following 17-40-h preincubation with the mediator. A 17-h exposure to CTAP III similarly stimulated 3-O-methylglucose uptake by over 400%, suggesting that CTAP III stimulated 2dG uptake is mediated via changes in hexose transport. Cycloheximide clearly prevented the 17-h effects of CTAP III on 2dG uptake. Insulin (3 X 10(-6) M) stimulated 2dG uptake 40-70% after 30-min preincubation with hormone; little effect was seen after 17-h preincubation. These data suggest that CTAP III stimulates glucose transport shortly after addition to target cells; the major stimulation observed after a 17-h incubation is consistent with the synthesis of new glucose transport protein.

Biological Transport, Active↗
PubMedDate not supplied

Down-regulation of connective tissue growth factor and type I collagen mRNA expression by connective tissue growth factor antisense oligonucleotide during experimental liver fibrosis.

Transforming growth factor (TGF)-beta 1 is a major mediator of liver fibrosis. Connective tissue growth factor (CTGF) mediates TGF-beta 1 pro-fibrogenic effects in vitro, but its in vivo role is unknown. Both TGF-beta 1 and CTGF are overexpressed in hepatic stellate cells during liver fibrosis. We have used antisense oligonucleotides to examine the role of CTGF in carbon tetrachloride-induced liver fibrosis in mice. Mice received carbon tetrachloride together with CTGF or TGF-beta 1 antisense oligonucleotides for 2 weeks (preventive model), or carbon tetrachloride for 2 weeks followed by carbon tetrachloride and oligonucleotides for 2 more weeks (curative model). In both models, CTGF and TGF-beta 1 oligonucleotides decreased by more than 50 percent the mRNA expression of their targets. Type I collagen mRNA was also decreased by about 40 percent in the preventive experiment. Tissue inhibitor of matrix metalloproteinase-1 mRNA expression and fibrotic deposition evaluated by Sirius red staining were not modified in any group. In summary, our results suggest that hepatic stellate cells can be targeted in vivo with oligonucleotides, and that reducing CTGF levels can lead to a decrease in fibrogenesis as shown by the reduction in type I collagen expression. The lack of effect on fibrosis may be due to the persistence of high tissue inhibitor of matrix metalloproteinase-1 expression.

Animals↗
PubMed1991

[Herpes zoster in connective tissue diseases: II. Rheumatoid arthritis and mixed connective tissue disease in comparison with systemic lupus erythematosus].

We investigated the incidence of herpes zoster (HZ) and the immunological state to HZ in patients with rheumatoid arthritis (RA) and mixed connective tissue disease (MCTD) in comparison with systemic lupus erythematosus (SLE). HZ occurred in 6 (25%) out of 24 patients with RA and 4 (22%) out of 18 patients with MCTD. One patient had had HZ before the diagnosis of RA. On the other hand, all 4 patients with MCTD had had HZ before the diagnosis of MCTD. The patients with RA and MCTD showed normal or higher antibody titers to varicella zoster virus (VZV) than normal subjects as assayed by both complement fixation technique and neutralization test. However, the antibody levels were not very high compared to those in patients with SLE. On the other hand, only 7 (50%) of 14 patients with RA and 4 (40%) of 10 patients with MCTD showed positive skin reactions to VZV antigen, whereas all 15 normal subjects had positive reactions. Thus, cellular immunity to VZV was thought to be impaired in these diseases. In the patients who were receiving less than 10 mg/day of prednisolone, 7 (64%) of 11 had positive skin reactions in RA patients and 3 (60%) out of 5 patients with MCTD, whereas none (0%) out of 3 patients with RA and 1 (20%) out of 5 patients with MCTD who were receiving 10 mg/day or more prednisolone showed positive skin reactions. These results suggest that the high incidence of HZ in patients with RA and MCTD is probably due to an impaired cellular immunity as in the case of SLE.

Adult↗
PubMed1988

A new long-term in vitro invasion assay using fibrous connective tissue matrices maintaining architectural characteristics of connective tissue.

A long-term invasion assay using fibrous connective tissue matrices was developed. The matrices were prepared by treating murine skin or human dura mater with 25 mM ammonium hydroxide containing proteinase inhibitors at 4 degrees C for 7 days. They could be maintained almost indefinitely without the degeneration and necrosis. Electron micrographs of them revealed the preservation of native collagen fibers, and sequential enzyme digestion showed the presence of glycoprotein in the matrices. Local dissolution of extracellular matrix by cultured human rectal adenocarcinoma cell line, RCM-1, was observed morphologically and confirmed by a quantitative assay using radiolabeled matrices. The destruction of extracellular matrix occurred associated with membrane vesicle-shedding from the cells. Both the advantages and disadvantages of this assay were discussed.

Animals↗
PubMedDate not supplied

[Superposition syndrome of connective tissue diseases: current view with special focus on mixed connective tissue disease].

Attention is called to mixed connective tissue disease which, twenty years after it's original description, has now reached the syndromic individualization with important therapeutic and prognostic implications. In particular the discussion concerns the pulmonary complications (hypertension and fibrosis) responsible frequently for fatal outcome.

Humans↗
PubMed1998

Early undifferentiated connective tissue disease. V. An inception cohort 5 years later: disease remissions and changes in diagnoses in well established and undifferentiated connective tissue diseases.

OBJECTIVE: To review the diagnoses after 5 years in patients who were identified within 12 months of the onset of well established and undifferentiated connective tissue diseases (CTD); to examine death rates and disease remissions in these patients. METHODS: This inception cohort of 410 patients was identified in 10 academic rheumatology practices. They had less than one year of signs and/or symptoms of CTD. Diagnoses of specific well established CTD were made using accepted diagnostic and classification criteria. The diagnoses after 5 years were determined. RESULTS: Patients with well established CTD tended to remain with the original diagnosis. The progression of unexplained polyarthritis to rheumatoid arthritis occurred infrequently. Ten percent of patients with isolated Raynaud's phenomenon progressed to systemic sclerosis (SSc). The 5 year survival was over 90% in all diagnostic categories, with the exception of SSc, in which it was 64%. CONCLUSION: Patients with a well established CTD usually continued with the same diagnosis. Patients with undifferentiated CTD tended to remain undifferentiated or to remit.

Arthritis↗
PubMed1992

Connective tissue activation. XXXV. Detection of connective tissue activating peptide-III isoforms in synovium from osteoarthritis and rheumatoid arthritis patients: patterns of interaction with other synovial cytokines in cell culture.

OBJECTIVE: To determine whether extracts of unincubated osteoarthritis (OA) and rheumatoid arthritis (RA) synovial tissue contain connective tissue activating peptide-III (CTAP-III) isoforms and prostaglandin E2 (PGE2), and whether such extracts have growth-promoting activity, and to determine whether binary combinations of CTAP-III with other cytokines reported to be present in synovial tissue lead to synergistic, additive, or inhibitory effects on growth. METHODS: Acid-ethanol extracts of human synovium were examined for growth-promoting activity by measuring formation of 14C-glycosaminoglycan (14C-GAG) and 3H-DNA in synovial cell cultures; PGE2 was measured by enzyme immunoassay, and CTAP-III isoforms were identified by Western blotting of extracted proteins separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Growth-promoting activity of CTAP-III and other cytokines was tested in synovial cultures treated with the agonists singly and in binary combination, by measuring changes in synthesis of 14C-GAG and 3H-DNA. RESULTS: Platelet-derived CTAP-III and a cleavage isoform with the electrophoretic mobility of CTAP-III-des 1-15/neutrophil-activating peptide-2 (NAP-2) and PGE2 were found in biologically active extracts of synovial samples from patients with RA and OA. Five growth factors (recombinant epidermal growth factor [rEGF], recombinant interleukin-1 beta [rIL-1 beta], basic fibroblast growth factor [bFGF], PGE1, and PGE2) in binary combination with CTAP-III showed synergism in stimulating GAG synthesis; two (recombinant platelet-derived growth factor type BB [rPDGE-BB] and recombinant transforming growth factor beta [rTGF beta]) had an additive effect. In combination with CTAP-III, rEGF and rPDGF-BB had a synergistic effect in promoting DNA synthesis, rTGF beta and rbFGF had an additive effect, and rIL-1 beta, PGE1, and PGE2 were antagonistic. CONCLUSIONS: The results suggest that, in addition to endogenous factors, CTAP-III and other platelet-derived cytokines may play roles in regulating synovial cell metabolism in RA and OA, and that combinations of growth factors may be more significant than single agents in amplification or suppression of important cell functions.

Arthritis, Rheumatoid↗
PubMed1993

Connective tissue activation. XXXVI. The origin, variety, distribution, and biologic fate of connective tissue activating peptide-III isoforms: characteristics in patients with rheumatic, renal, and arterial disease.

OBJECTIVE: To determine the origin, distribution, and biologic fate of platelet-derived connective tissue activating peptide-III (CTAP-III), to define the relative amounts of the antigen forms (CTAP-III, beta-thromboglobulin [beta-TG], neutrophil activating peptide-2 [NAP-2]) in plasma of normal persons and those with rheumatic or end-stage renal disease, and to define the isoforms of CTAP-III in platelets, plasma, transudates, and tissue deposits. METHODS: CTAP-III in plasma was measured by enzyme-linked immunosorbent assay, and growth promoting activity of CTAP-III isoforms was tested in synovial and peritoneal cell cultures by measuring increased synthesis of 14C-glycosaminoglycan (14C-GAG) and 3H-DNA. Isolated CTAP-III was characterized by Western blotting, microsequencing, and mass spectrometry. RESULTS: CTAP-III was the primary isoform of this antigen family in normal platelets and platelet-rich plasma; beta-TG and NAP-2 accounted for < 1% of CTAP-III isoforms. Previously undescribed isoforms, i.e., CTAP-III des 1, des 1-2, des 1-3, and a phosphate adduct of CTAP-III, were observed in varying amounts. Elevated plasma levels of CTAP-III antigen were found in a substantial fraction of rheumatic disease patients: 24% of those with rheumatoid arthritis, 36% of those with systemic sclerosis, and 15% of those with systemic lupus erythematosus. All 10 patients with end-stage kidney disease had marked elevations of plasma CTAP-III levels, which stimulated DNA and GAG synthesis by peritoneal cells in culture. Only large isoforms (such as CTAP-III) were detected in venous plasma of normal subjects, rheumatic disease patients, and patients receiving long-term dialysis. Normal human spleen and kidney contained substantial (micrograms/gm) amounts of CTAP-III and traces of an isoform with the electrophoretic mobility of CTAP-III des 1-15/NAP-2. Liver, lung, and urine contained lesser (ng/gm) amounts of CTAP-III. CONCLUSION: These data show that, among the 10 known isoforms, intact CTAP-III itself was the major circulating isoform (> 90%), and beta-TG was the most rare (0-1%). Deposition of CTAP-III in tissues, such as synovium, spleen, and kidney, is associated with partial processing to NAP-2-like isoforms and the potential to induce neutrophil and fibroblast activation in patients with rheumatic or end-stage renal disease.

Adult↗
PubMed2005

Fiber connections of the anterior preglomerular nucleus in cyprinids with notes on telencephalic connections of the preglomerular complex.

Fiber connections of the anterior preglomerular nucleus (PGa) were studied in carp and goldfish by tracer injection experiments to the nucleus and telencephalon. The PGa received fibers from the central nucleus of semicircular torus, perilemniscular nucleus, anterior tuberal nucleus, and medial pretoral nucleus, all of which are presumed auditory structures. The PGa projected to the dorsal (dDm) and ventral (vDm) regions of medial part of dorsal telencephalic area. The caudomedial region of lateral preglomerular nucleus (PGl) and medial zone of medial preglomerular nucleus (PGm), which also receive auditory toral fibers, projected to the same telencephalic regions as did PGa. These preglomerular structures and the PGa also received in common descending fibers from a rostromedial portion of dDm. The PGa also received fibers from the parvocellular and magnocellular preoptic nuclei, and suprachiasmatic nucleus and projected to the anterior tuberal nucleus and medial inferior lobe, suggesting neurohormonal and circadian control on the PGa and auditory influences on hypothalamic functions. Of other diencephalic nuclei that receive auditory toral fibers, only small numbers of neurons were labeled in the central posterior thalamic nucleus and anterior tuberal nucleus even after large injections to the dorsal telencephalic area. Thus, the PGa and closely related preglomerular regions, not the dorsal thalamus, appear to constitute the major auditory relay station to the dorsal telencephalic area. The rostrolateral region of PGl, rostral and lateral zones of PGm, commissural preglomerular nucleus, and preglomerular tertiary gustatory nucleus, which do not receive auditory toral fibers, also projected to the dorsal telencephalic area.

Animals↗
PubMed1976

Molecular connectivity V: connectivity series concept applied to density.

The concept of the expanded series of the connectivity index, chi, is introduced and applied to a consideration of the density of three classes of molecules. Correlations are found using two terms in the expanded series. A preliminary reflection on the extended series terms is made. It is noted that the regression equation constant in the three studies is close to the phase volume, 0.7402, and the possible significance of this fact is discussed.

Alcohols↗