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T J Sims

Publications and source records attributed to T J Sims.

At least 19 recordsLinked to original sources
PubMed2001

Anabolic effect of long-term estrogen replacement on bone collagen in elderly postmenopausal women with osteoporosis.

Estrogen has been shown to stimulate osteoblasts in cell culture and increase bone formation in animal models. Such an anabolic effect of estrogen replacement therapy (ERT) would be beneficial to postmenopausal women with osteoporosis. Hence, we assessed the total collagen content and collagen crosslink maturity in iliac crest bone biopsy from 18 such women before and after 6 years of higher-dose ERT. These results were compared with the serum estradiol level and bone mineral density (BMD). Total collagen content of both cortical and cancellous bone increased, showing a median (95% CI) percent change of 6.7 (0.3-14.2) and 25.6 (13.5-33.8), respectively. Increase in collagen synthesis was supported by a rise in intermediate crosslinks in both cortical and cancellous bone, and mature crosslinks in cortical bone only. At the same time, BMD showed a substantial rise both at the lumbar spine and proximal femur with a median (95% CI) percent change of 28.6 (19.8-37.3) and 14.5 (8.4-20.7), respectively. Serum estradiol and BMD results correlated with cortical bone collagen levels. Our results suggest that long-term higher-dose ERT has a therapeutic role due to its anabolic effect on bone in postmenopausal women with osteoporosis.

Absorptiometry, Photon↗
PubMed2001

Immunoglobulin G response of periodontitis patients to Porphyromonas gingivalis capsular carbohydrate and lipopolysaccharide antigens.

Porphyromonas gingivalis clonal types that participate in periodontal infections express serologically distinct surface antigens. This investigation sought to determine whether serum antibodies titers against the serotype-specific capsular carbohydrate K antigen and lipopolysaccharide antigens of P. gingivalis might reveal which serotypes are most likely to be responsible for subgingival infections in subjects with adult periodontitis. Immunoglobulin G (IgG) titers to purified K antigen and lipopolysaccharide from different P. gingivalis strains were measured by ELISA for 28 healthy controls and 51 patients with periodontal pockets known to be infected with genetically and serologically distinct P. gingivalis clonal types. Titers to purified K antigen from strains W50, HG184, A7A1-28, 49417, HG1690 and HG1691, representing serotypes K1-K6, respectively, and lipopolysaccharide from strains 381, HG1691 and W50, representing serotypes O1-O3, respectively, were measured for all subjects. Chi-square likelihood ratios, Mann-Whitney tests and receiver-operating characteristic sensitivity-specificity plots were used to compare the accuracy with which titer results for different target antigens classified subjects with or without disease. Results from assays targeting K2, K3, K4, K5, O1 and O2 generally gave poor diagnostic accuracy, whether evaluated separately or as summed titer pairs corresponding to the K/O combinations actually expressed by the target antigen parent strains. Exceptions were O3 (from W50) and K5+O2 (both from HG1690), which gave moderate accuracy in classifying subjects. In contrast, highly significant diagnostic accuracy was achieved using individual K1 (W50) and K6 (HG1691) titer data and K1+O3 (W50) and K6+O2 (HG1691) titer sum values. These observations suggest that P. gingivalis clonal types expressing K/O serotypes matching those of W50 (K1/O3) and HG1691 (K6/O2) are more likely than others to participate in periodontal infections in adult periodontitis patients and thus are more likely than others to express relevant virulence factors.

Adult↗
PubMed2001

Treatment outcome for IDDM patients in relation to glutamic acid decarboxylase autoantibodies and serum IgG to periodontal pathogens.

BACKGROUND: Patients with insulin-dependent diabetes mellitus (IDDM) have elevated risk for periodontitis (PD) relative to subjects without diabetes. Whether refractory PD in IDDM patients is related to autoimmunity as indicated by serum glutamic acid decarboxylase autoantibody GAD Ab levels or to host bacterial immunity as reflected by serum antibody titers to periodontal pathogens is unknown. AIMS: To determine if non-surgical periodontal treatment outcome differs between GAD Ab-seropositive and -seronegative IDDM patients by assessing the following parameters: (1) pretreatment serum levels of GAD Ab, (2) pretreatment serum IgG titers to key periodontal pathogens, and (3) changes in periodontal pocket probing depth (PDC) after treatment. METHODS: Before and two months after periodontal treatment of 11 GAD Ab-seronegative and 7 -seropositive subjects, PDC was assessed and serum GAD Ab and IgG to Porphyromonas gingivalis (Pg), Bacteroides forsythus (BJ), and Actinobacillus actinomycetemcomitans (Aa) were studied using established radioligand precipitation and enzyme-linked immunosorbent assays, respectively. RESULTS: The PDC decrease was significantly better for GAD Ab-seronegative subjects than for seropositive subjects (median 1.4 mm+/-0.5 s.d. versus 0.5 mm+/-0.3 s.d., p<0.03, Mann-Whitney). GAD Ab levels and PDC were positively correlated (r=+0.71, p<0.05) for sero-positive subjects but were neutral (r=-0.07) for seronegative subjects. Serum IgG to Pg and GAD Ab levels were positively associated (r2=0.42) in seropositive subjects. Logistic regression analysis confirmed that GAD Ab status was the primary discriminator for PDC (p<0.04). CONCLUSION: Detection of elevated GAD Ab levels in combination with elevated IgG titers to Pg before treatment is indicative of IDDM patients with refractory PD.

Aggregatibacter actinomycetemcomitans↗
PubMed2000

Schwann cell-induced loss of synapses in the central nervous system.

Synaptophysin immunostaining of areas of spinal gray matter occupied by radiation-induced intraspinal Schwann cells revealed a loss of immunoreactivity from the neuropil. In contrast, synaptophysin immunoreactivity was preserved on the somata and proximal dendrites of motor neurons. The present study extended these observations to the ultrastructural level and confirmed the absence not only of synapses but also of astrocytes and small- and medium-sized dendrites. These neural elements were abundant and appropriately organized in contiguous areas of irradiated neuropil not occupied by Schwann cells.

Animals↗
PubMed2000

Identification of an intermediate state in the helix-coil degradation of collagen by ultraviolet light.

Differential scanning calorimetry has revealed the presence of a new denaturation endotherm at 32 degrees C following UV irradiation of collagen, compared with 39 degrees C for the native triple helix. Kinetic analyses showed that the new peak was a previously unknown intermediate state in the collagen helix-coil transition induced by UV light, and at least 80% of the total collagen was transformed to random chains via this state. Its rate of formation was increased by hydrogen peroxide and inhibited by free radical scavengers. SDS-polyacrylamide gels showed evidence of competing reactions of cross-linking and random primary chain scission. The cross-linking was evident from initial gelling of the collagen solution, but there was no evidence for a dityrosine cross-link. Primary chain scission was confirmed by end group analysis using fluorescamine. Electron microscopy showed that the segment long spacing crystallites formed from the intermediate state were identical to the native molecules. Clearly, collagen can undergo quite extensive damage by cleavage of peptide bonds without disorganizing the triple helical structure. This leads to the formation of a damaged intermediate state prior to degradation of the molecules to short random chains.

Animals↗
PubMed2000

Isinglass/collagen: denaturation and functionality.

Isinglass is widely used commercially to clarify alcoholic beverages by aggregation of the yeast and other insoluble particles. It is derived from swim bladders of tropical fish by solubilisation in organic acids and consists predominantly of the protein collagen. The low content of intermolecular cross-links allows ready dissolution of swim bladder compared to bovine hide which is cross-linked by a high proportion of stable bonds and requires enzymic digestion to solubilise. Isinglass is no longer effective as a clarifying agent if thermally denatured hence the collagenous triple helical structure must be maintained. Thermal denaturation of isinglass occurs at 29 degrees C, compared to 40-41 degrees C for mammalian collagens, primarily due to the lower hydroxyproline content. The hydroxyproline is essential for the formation of H-bonded water-bridges through the hydroxyl group and the peptide chain thereby stabilising the triple helix. Based on the lower enthalpy determined by differential scanning calorimetry we have calculated that the thermally labile domain of the isinglass molecule was 41 residues compared to 66 for mammalian collagen. The fining efficiency was unaffected by pH, chelating agents, detergents and removal of surface proteins from yeast cells. Studies on the mechanism of action of isinglass have shown that higher molecular weight aggregates that increase the length of the collagen molecules (trimers, tetramers, etc.) increase efficiency and that their surface charge are important in the clarification process. By chemical modification, we have shown that blocking positively charged groups had no effect on the fining process, whilst negative charges are clearly essential and that increasing the negative charge by succinylation increases its efficacy. Solutions of bovine hide collagen were shown to be equally effective in refining beers and standard yeast preparations. The higher thermal denaturation temperature, ready availability and reproducibility of bovine collagen preparations gives it considerable advantages over isinglass.

Air Sacs↗
PubMed2000

Synaptophysin immunoreactivity in spinal white matter of young adult rats.

Patterns of synaptophysin immunoreactivity were examined in the ventral and lateral funiculi of rat lumbosacral spinal cords. In normal young adults, dendrites from neurons in the spinal gray matter extended into the ventral and lateral white matter as finger-like projections, immunopositive for synaptophysin. These projections appeared to diminish in size as they extended peripherally and, in general, did not reach the surface of the spinal cord, so that the outer one-third to one-fourth of the funiculi contained little or no immunoreactivity. The spinal cords of some of the animals studied were X-irradiated on the third postnatal day. When examined 6 weeks to 5 months later, the pattern of synaptophysin immunoreactivity was found to be markedly altered in these animals. In general, the synaptophysin immunoreactivity in the white matter was less organized than in the non-irradiated rat. As a result, the finger-like projections, particularly into the lateral funiculi, were not as distinct, and the immunoreactivity appeared to be more diffusely distributed in the white matter. Further, the immunoreactivity was present throughout the thickness of the white matter in the irradiated animals and subpial concentrations were evident, especially along the lateral aspect of the spinal cord. Ultrastructural evaluation of the synaptic profiles revealed no differences between irradiated and non-irradiated animals. The synapses occurred on both the shafts of the dendrites and on the spines. In general, both dendrites and axon terminals were covered by astrocyte processes except at synaptic sites, and the synaptic complexes were surrounded by astrocyte processes. Although the mechanisms underlying the altered pattern of synaptophysin immunoreactivity are not yet understood, they may be related to radiation-induced effects on the glial populations previously reported by the investigators and/or to radiation-induced alterations in reorganization or maturation of dendritic trees.

Animals↗
PubMed2000

Antigenic cross-reactivity among Porphyromonas gingivalis serotypes.

The goal of our research program is to develop a Porphyromonas gingivalis vaccine. Vaccine development requires identification of antigenic components shared by the many clonal types of P. gingivalis. The purpose of the present study was to evaluate the extent and nature of antigenic cross-reactivity among serotypes of P. gingivalis and to identify shared antigenic components. Strains selected to represent serotypes A-D were 33277, A7A1-28 W50 and 381, respectively. Using intact cells, antibodies were raised in rabbits. Titers were assessed by enzyme-linked immunosorbent assay (ELISA) using intact cells as antigen, Western blots were prepared and biologic activity was measured as opsonization (chemiluminescence expressed as mV) and enhancement of phagocytosis and killing by polymorphonuclear leukocytes. Extensive cross-reactivity that varied greatly among serotypes was observed by ELISA. The Western blots showed an even greater extent of cross-reactivity, with shared protein components at approximately 140, 130, 37, 32 and 28 kDa and a shared variable molecular mass smear considered to be lipopolysaccharide and other carbohydrate. Additional protein components at 110, 85, 35 and 20 kDa appeared to be shared by some but not all serotypes. In the functional assays, strains 33277 and 381 were equally well opsonized by anti-33277 and anti-381 (500-650 mV) but opsonized to a much lesser extent by anti-A7A1-28 and anti-W50 (roughly 125 mV and 350 mV respectively). A7A1-28 and W50 were opsonized by all four immune sera almost equally but to a much lower extent (roughly 400 mV and 250 mV respectively). Enhancement of phagocytosis and killing in the presence of active complement mirrored opsonization with the exception that 381 was reasonably well opsonized by anti-A7A1-28 (400 mV) and anti-W50 (350 mV), but poorly killed. The protein components at 140, 130, 37 and 28 kDa shared by all of the four serotypes appear to have potential as vaccine candidate antigens.

Animals↗
PubMed2000

Alterations in the organisation, ultrastructure and biochemistry of the myocardial collagen matrix in doberman pinschers with dilated cardiomyopathy.

Remodelling of the collagen matrix of the myocardium has been implicated in the pathogenesis of dilated cardiomyopathy, a major cause of heart failure in Doberman pinschers. The aim of this study was to characterise the myocardial collagen matrix of Dobermans. In clinically normal Dobermans there was evidence of focal fibrosis. Collagen cross-links were altered in both diseased and clinically normal Doberman myocardium as compared with myocardium from control dogs. Extensive remodelling, in the form of a loss of collagen tethers, increased collagen synthesis and alterations in the collagen cross-links, occurs in diseased Doberman myocardium. Changes in the collagenous matrix are also present in apparently normal Dobermans. These changes are likely to be involved in the progression of the disease and may explain the predisposition of this breed to dilated cardiomyopathy.

Animals↗
PubMed2000

Age related changes in the non-collagenous components of the extracellular matrix of the human lamina cribrosa.

AIMS: To investigate age related alterations in the non-collagenous components of the human lamina cribrosa. METHODS: Fibronectin, elastin, and glial fibrillary acidic protein (GFAP) staining were assessed in young and old laminae cribrosae. An age range (7 days to 96 years) of human laminae cribrosae were analysed for lipid content (n=9), cellularity (n=28), total sulphated glycosaminoglycans (n=28), elastin content (n=9), and water content (n=56), using chloroform-methanol extraction, fluorimetry, the dimethylmethylene blue assay, and ion exchange chromatography, respectively. RESULTS: Qualitatively, an increase in elastin and a decrease in fibronectin and GFAP were demonstrated when young tissue was compared with the elderly. Biochemical analysis of the ageing human lamina cribrosa demonstrated that elastin content increased from 8% to 28% dry tissue weight, total sulphated glycosaminoglycans decreased, and lipid content decreased from 45% to 25%. There were no significant changes in total cellularity or water content. CONCLUSION: These alterations in composition may be indicative of the metabolic state of the lamina cribrosa as it ages, and may contribute to changes in mechanical integrity. Such changes may be implicated in the susceptibility of the elderly lamina cribrosa and also its response to glaucomatous optic neuropathy.

Adolescent↗
PubMed1999

Transplantation of sciatic nerve segments into normal and glia-depleted spinal cords.

Although peripheral nerves are used as guides in attempts to enhance regeneration in the central nervous system (CNS), surprisingly little is known about the interface that develops between the host tissue and the transplanted or implanted peripheral nerve. This study examines host-nerve interfaces following transplantation of segments of sciatic nerve into the spinal cord under two differing conditions, one in which the spinal cord contains normal numbers of glia and one in which the glial population is reduced. The depletion of the glial population is achieved by exposing the lumbosacral region of the spinal cord in 3-day-old rats to X-rays, a model developed in this laboratory. Twenty days later, segments of fresh or frozen sciatic nerves harvested from other 3-day-old rats were transplanted into the lumbar region of spinal cord in irradiated animals and in their non-irradiated littermate controls. Following a 20-day postoperative period, the interfaces between host spinal cord and sciatic nerves were examined ultrastructurally, and pronounced differences were noted. A distinct scar composed of multiple layers of astrocyte processes completely enveloped the transplant in non-irradiated host spinal cord and confined Schwann cells and fibroblasts to the area enclosed by the scar. Terminals from axons that appeared to have traversed the transplant during this 20-day period ended blindly in the astrocytic scar. In contrast, a complete astrocytic scar failed to form around the transplant in the irradiated, glia-depleted hosts, and Schwann cells intermingled with host tissue. Some Schwann cells migrated away from the transplant, which was placed in the dorsal funiculus, along a perivascular route and extended into the gray matter. In some instances Schwann cells were observed in the ventral gray surrounding blood vessels and motoneurons. From these observations, it is clear that the formation of a distinct astrocytic barrier at the host-graft interface is greatly reduced irradiated host. The effects of astrocyte reduction on enhanced regeneration within the spinal cord are discussed.

Animals↗
PubMed1999

Age-related changes in the biochemical properties of human cancellous bone collagen: relationship to bone strength.

The metabolism of bone collagen has received little attention in relation to age-related loss of bone mass and strength. The aim of the present study was to analyze bone collagen content and metabolism in human bone with respect to age. The material consisted of iliac crest bone biopsies from 94 individuals: 46 women (ages 18-96, mean age 60.8 years) and 48 men (ages 23-92, mean age 59.5 years). Excluded from the study were all individuals with known osteoporotic lumbar vertebral fractures and renal, hepatic, or malignant diseases. Prior to collagen analysis the biopsies were scanned in a pQCT scanner for density assessment and then tested biomechanically. The results showed a decline in apparent bone density with age (P < 0.0001), a decline in maximum stress, Young's modulus, and energy absorption with age (P < 0.001). Concomittantly, there was an age-related decline in the intrinsic collagen content with age (P < 0.001). However, there were no biochemical modifications of the bone collagen during aging. There were no significant differences between women and men in the slopes of the regressions-curves. When multiple regression analyses were performed, only apparent bone density came out as a significant contributor in the correlation to biomechanical properties. Nevertheless, the decrease in bone collagen content with age might indicate an increase in the mineralization degree (probably due to decreased bone turnover) and thereby a change in material properties of bone. In conclusion, the present study has shown that loss of bone mass plays the major role in loss of bone strength. However, there is also a change in bone composition during normal aging, leading to a decrease in collagen content and an increase in the degree of mineralization. At this skeletal site, in a normal population there was no change in the biochemical properties of bone collagen.

Adolescent↗
PubMed1999

Antigenic variation in Porphyromonas gingivalis ribotypes recognized by serum immunoglobulin G of adult periodontitis patients.

We obtained clinical isolates of Porphyromonas gingivalis of known ribotype from patients diagnosed with adult periodontitis and used Western blot methodology to evaluate profiles of antigens recognized by IgG in heterologous and homologous patient sera. Our aims were to identify isolates belonging to different serogroups, to learn if serogroup membership is related to ribotype to assess variation in IgG responses of patients to antigens is homologous and heterologous ribotypes, and to determine the frequency of shared and variable antigens in different biochemical classes recognized across different serogroups and ribotypes. Blots of separation patterns of 28 isolates were developed in sera from patients and bound IgG was quantified by digital image densitometry. The membership of isolates in different serogroups was determined by correlation and hierarchical cluster analysis of isolate whole-cell IgG binding profiles. Two major isolate clusters, each with two subclusters, were found. Isolates within the same ribotype clustered together in some cases but not others. Homologous isolates ranked high in IgG binding levels relative to those from different patients irrespective of ribotype. Patient subgroups with IgG responses dominant for different ribotypes and serogroups were revealed by correlation analysis. The IgG binding profiles observed for individual protein and proteinase-resistant antigens across both homologous and heterologous isolates were very dissimilar. Furthermore, the frequency of antigens both shared across all ribotypes and recognized by IgG in patient sera was unexpectedly low. Only two protein antigens (Mr 44 kDa and 27 kDa) were strongly recognized across all ribotypes by different sera. We conclude that the IgG response of patients infected with a particular P. gingivalis serotype or ribotype is directed mainly against antigens that are not shared by other potentially infective clonal types.

Adult↗
PubMed1998

Changes in collagen cross-linking in degenerative disc disease and scoliosis.

STUDY DESIGN: Biochemical study of the changes in the collagen cross-link profile of human intervertebral discs collected at surgery from patients with either low back pain associated with disc degeneration or scoliosis. OBJECTIVE: To determine whether changes occur in the collagen cross-link profile in the disc of patients with either low back pain associated with disc degeneration or scoliosis, which may well influence matrix integrity. Such changes in the cross-link profile of a tissue indicates increased matrix turnover and tissue remodeling and may have implications for the progression of these disorders. SUMMARY OF BACKGROUND DATA: The diseases of the intervertebral disc, degenerative disc disease and scoliosis, are both characterized by changes in the extracellular matrix components that will affect the mechanical function of the tissue. The stability of the collagenous components and hence the mechanical integrity of connective tissues such as the disc is dependent on the degree and type of cross-links between the collagen molecules. This article reports results on the distribution of the different cross-links in the disc and the changes that occur with age, degenerative disc disease, and scoliosis. METHODS: Thirty-three discs were obtained from patients with degenerative disc disease and 29 discs from patients with scoliosis. Samples were acid hydrolyzed and the collagen cross-links analyzed by either fractionation on an amino acid analyzer configured for cross-link analysis using ninhydrin postcolumn detection or fractionation by high-pressure liquid chromatography with fluorescence detection. RESULTS: The reducible cross-links and the mature cross-link all increased from the outer anulus fibrosus through into the nucleus pulposus. The highest levels of the mature cross-link were found in the cartilage end-plate. The nonenzymic derived cross-link, pentosidine, in contrast, showed little difference across the disc, but did show the expected age-related increase. In degenerative disc disease, no change in the levels of the reducible or mature cross-links was found, but a decrease was observed in the levels of the age-related cross-link pentosidine in the more severe disease samples. In scoliosis, significantly higher levels of the reducible cross-links were found on the convex than on the concave side of the scoliotic disc. CONCLUSIONS: These changes in the cross-link profile of the intervertebral disc in degenerative disc disease and scoliosis are indicative of increased matrix turnover and tissue remodeling and likely to have implications for the progression of these disorders.

Adolescent↗
PubMed1998

Isolation and characterization of advanced glycation end products derived from the in vitro reaction of ribose and collagen.

An amino acid component, NFC-1, when formed in vitro by the reaction of ribose and protein was shown to comprise a complex mixture of high and low molecular AGE compounds. Two low-molecular-weight components have been successfully isolated and their structure determined. These were alphaNFC-1 [Ndelta-(4-oxo-5-dihydroimidazol-2-yl)-l-ornithine] and betaNFC-1 a 4-imidazolon-2-yl derivative existing in three tautomeric forms. These imidazolone compounds have been shown to originate from the reaction of arginine with glyoxal and methylglyoxal, respectively. A third ninhydrin-positive AGE, gammaNFC-1, was shown to be composed of a number of chromatographically similar compounds which have not yet been characterized.

Animals↗
PubMed1998

Antigenic variation and cross-reactivity in Bacteroides forsythus clinical isolates detected by western blot.

Bacteroides forsythus is one of the etiologic agents of destructive periodontal diseases. Determining which antigenic components of the bacterium are recognized in the immune response of periodontitis patients is an important step in assessing strategies for vaccine development. The aim of this study was to identify the major strain-variable and cross-reactive antigens of B. forsythus clinical isolates recognized by serum IgG from patients with early-onset rapidly progressive periodontitis. Ten patient sera with measurable IgG against antigenic components of the species were identified by Western blot. Positive sera were tested by checkerboard ELISA to identify those most responsive to strain-variable antigens in nine clinical isolates and ATCC strain 43037. Correlation analysis of the ELISA data suggested that different subsets of isolates were preferentially recognized by different sera. Western blots revealed that certain sera also recognized major shared components across all the isolates, but preferential recognition of different isolate subsets by different patients was clearly confirmed. To determine if the variable antigens recognized were nonprotein, proteinase K-digested isolates were compared to undigested controls by Western blot. The main strain-variable antigens were proteinase resistant, while proteins at 200 and 210 kDa were identified as the major shared components. Two-dimensional SDS-PAGE revealed that these proteins are the quantitatively dominant heat-modifiable components of the cell envelope. Even though variable antigens are prominent in the immune response of patients, a cross-protective vaccine based on the shared envelope proteins of B. forsythus seems feasible in light of these observations.

Adult↗
PubMed1998

Schwann cell invasion of ventral spinal cord: the effect of irradiation on astrocyte barriers.

This study examines a radiation-induced invasion and spread of Schwann cells into ventral gray regions of the lumbar spinal cord. The prevalence of these cells within the gray matter and the time course of their appearance in the ventral spinal cord is quite different from the pattern of Schwann cell development in dorsal spinal cord reported previously. The focus is on 2 possible pathways, each involving astrocytic barriers, by which Schwann cells access the ventral gray matter. The first of these is the glia limitans covering the ventral surface of the spinal cord and the possibility that its integrity has been disrupted by the exposure to x-rays. Comparisons of the glia limitans, including its thickness, between irradiated and nonirradiated rats revealed that exposure to radiation did not result in any morphologically discernible alterations. The second barrier examined was the astrocytic covering of blood vessels. In irradiated animals the astrocyte processes that normally surround blood vessels were missing in some instances, and Schwann cells were observed at these sites. The difference between the dorsal and ventral occurrence of Schwann cells is that, whereas Schwann cells primarily follow axons, specifically dorsal root axons, to access the dorsal spinal cord, it appears that the presence of Schwann cells in the ventral portion of the spinal cord where their location is primarily in the gray matter is associated with the vasculature.

Aging↗