Biomedical subjects

J McGeachie

Publications and source records attributed to J McGeachie.

At least 19 recordsLinked to original sources

PubMed2000

Vertebral arteries and neck rotation: Doppler velocimeter interexaminer reliability.

The purpose of this study was to test the interexaminer reliability of Doppler ultrasound (US) velocimeter examination of vertebral arteries during contralateral cervical rotation. Vertebral arteries from 20 adults were insonated using a bidirectional Doppler velocimeter at the suboccipital portal (standard technique) and C2 transverse process level (new technique) during contralateral cervical rotation. The data obtained by two examiners, regarding persistence or major reduction in Doppler signals, were compared. There was 93% agreement between the data from the two examiners, and the kappa score was 0.78 at p = 0.05. These results provide evidence to support the interexaminer reliability of bidirectional Doppler velocimeter examination for the purpose of assessing the effects of contralateral rotation on vertebral artery blood flow.

Adolescent↗

PubMed2000

Myotube formation is delayed but not prevented in MyoD-deficient skeletal muscle: studies in regenerating whole muscle grafts of adult mice.

We compared the time course of myogenic events in vivo in regenerating whole muscle grafts in MyoD(-/-) and control BALB/c adult mice using immunohistochemistry and electron microscopy. Immunohistochemistry with antibodies to desmin and myosin revealed a striking delay by about 3 days in the formation of myotubes in MyoD(-/-) autografts compared with BALB/c mice. However, myotube formation was not prevented, and autografts in both strains appeared similar by 8 days. Electron microscopy confirmed myotube formation in 8- but not 5-day MyoD(-/-) grafts. This pattern was not influenced by cross-transplantation experiments between strains examined at 5 days. Antibodies to proliferating cell nuclear antigen demonstrated an elevated level of replication by MyoD(-/-) myoblasts in autografts, and replication was sustained for about 3 days compared with controls. These data indicate that the delay in the onset of differentiation and hence fusion is related to extended proliferation of the MyoD(-/-) myoblasts. Overall, although muscle regeneration was delayed it was not impaired in MyoD(-/-) mice in this model.

Animals↗

PubMed1998

Vascular tissue adaptations in end-to-end autologous arterial grafts in rats: a morphometric analysis.

Autologous vein grafts are employed extensively to bypass stenoses in the arterial circulation. More recently arterial segments have been used for such bypass surgery. In this study the adaptation of regenerating vascular tissues in experimental autologous artery grafts (4 mm long and 1 mm in diameter) in 20 adult male Wistar rats was analysed. At 1, 2, 4, 8 and 16 wk after insertion, 4 grafts per time interval were removed, processed for high resolution light microscopy and the thicknesses of the media and neointima, as well as the area fractions of smooth muscle cells, were analysed morphometrically. All grafts were reendothelialised by 2 wk. Neointimal hyperplasia (a subendothelial layer of smooth muscle cells) developed in all grafts and reached its maximal thickness (40.4 +/- 4.7 microns) at 2 wk. The area fraction of smooth muscle cells in the neointima of the artery grafts did not change significantly at any time from 2 to 16 wk. The media underlying the neointima of the artery grafts remained relatively constant throughout the 16 wk duration of the experiment. Whilst the total wall thickness of the grafts reduced significantly between 2 and 4 wk after insertion, at all times the grafts were thicker than the host artery.

Analysis of Variance↗

PubMed1997

Low-dose oral type I interferons reduce early virus replication of murine cytomegalovirus in vivo.

Immunity to viral infections involves both innate and antigen-specific immune responses. The antiviral properties of interferons (IFNs) are part of the innate immune response. Low doses of type I IFNs (IFN-alpha and IFN-beta) administered daily (10 IU per mouse) by the oral route significantly reduced the early replication of murine cytomegalovirus (MCMV) in both the spleen and liver of MCMV-infected susceptible BALB/c mice. Significant inhibition of virus replication was observed for two different inoculum doses of virus (2 x 10(4) pfu per mouse [0.6 LD50] and 2 x 10(4.12) pfu per mouse [0.8 LD50]). Analysis of IFN retention, using [35S]-labeled IFN-alpha1 compared with the nonreceptor binding mutant IFN-alpha1 (R33M) administered orally to mice, revealed binding of wild-type IFN-alpha1 to several tissues. In particular, IFN was retained by tissues proximal to lymphoid regions, including the posterior nasal cavity, posterior tongue, small intestine, and rectum. These findings suggest that type I IFNs may inhibit MCMV replication by distal binding of the orally administered IFN to various tissues, which in turn augment the primary immune response to virus infection.

Administration, Oral↗

PubMed1997

Growth factors and their implications for clinicians: a brief review.

Growth factors play a vital role in both homeostasis and disease. In recent years considerable research has revealed the importance of growth factors in biology and they are now becoming incorporated in the clinical literature. Growth factors are peptides (protein fractions) that transmit signals within and between cells. They were discovered in the early 1960s as growth stimulants in tissue culture. It is now evident that growth factors play a comprehensive role in the modulation of tissue growth and development. The modes of action of growth factors are discussed with examples pertinent to clinical dentistry.

Animals↗

PubMed1997

Neo-intimal hyperplasia in vascular grafts and its implications for autologous arterial grafting.

With the advent of modern microsurgical procedures and an improved understanding of the cellular dynamics of vascular graft adaptation, arterial grafts are being used more frequently in surgical practice. In this article the structure and development of neointimal hyperplasia in vascular grafts, both venous and arterial, are reviewed briefly. The underlying biology of venous graft adaptation is now well understood. However, in addition to venous grafts, many different arterial conduits are now being used; these include the radial artery, internal mammary (thoracic) and gastroepiploic arteries. The different clinical outcomes of these arterial grafts and the underlying cell biology of their adaptation to the grafted environment are also reviewed.

Arteries↗

PubMed1996

Autogenous vein grafts in hypertensive (SHRSR) rats have increased smooth muscle cell hyperplasia in the graft neo-intima, compared with grafts in normotensive rats.

This study examined the effects of raised intralumenal blood pressure on smooth muscle cell hyperplasia in the neo-intimal layer of experimental vein-to-artery grafts in rats. Autogenous vein grafts 1 mm in diameter and 4 mm long were inserted microsurgically into the left common iliac arteries of 24 genetically hypertensive (SHRSR) rats. At 2, 4, 6, 12, and 26 weeks after insertion, the grafts and contralateral unoperated iliac arteries were perfused at constant pressure and removed for histological and morphometric analyses. Neo-intimal thicknesses of the grafts and the intima-plus-media thicknesses of the contralateral arteries in the same rats were measured and compared statistically. From previous studies it is clear than in normotensive rats the neo-intima stabilises once it reaches the equivalent thickness of the contralateral arterial intima-plus-media, about 4 weeks after graft insertion. In the SHRSR rats the graft neo-intima developed at a similar rate (over the first 4 weeks) to that seen in previous studies in normotensive rats, but the development continued to occur over a longer period (6 weeks); therefore the neo-intima became significantly thicker. The graft neo-intima in SHRSR rats also became much thicker than the functionally equivalent intima-plus-media of the contralateral unoperated iliac arteries in the same rats. It was hypothesised that higher intralumenal blood pressure to SHRSR rats stimulates neo-intimal hyperplasia, resulting in the development of a thicker graft neo-intima, compared with that in normotensive rats.

Animals↗

PubMed1996

Long-term structural alterations to endothelial cells in vein-to-artery grafts: a quantitative electron microscopic study.

The intracellular structure of endothelium lining vein-to-artery grafts in rats was analysed, using transmission electron microscopy and morphometry, to determine the ultrastructural adaptations of endothelial cells in this altered vascular environment. Autogenous 4-mm sections of iliolumbar veins were inserted microsurgically into the left common iliac arteries of 16 male Wistar rats. At 3, 6, 26 and 52 weeks the cytoplasmic-vesicular, mitochondrial and rough endoplasmic reticular contents of endothelial cells lining the grafts, the opposite iliac arteries and the remaining ilio-lumbar veins were analysed morphometrically. There was a significant increase in the amount of all these cytoplasmic structures in endothelial cells at 3, 6 and 26 weeks, at 52 weeks there was also a significant increase in the volumes of mitochondria and cytoplasmic vesicles, but not in rough endoplasmic reticulum. It was concluded that the ultrastructure of endothelial cells lining these grafts is changed chronically after graft insertion, and we propose that this may be attributable to altered haemodynamic stresses within the graft.

Animals↗

PubMed1992

Reaction of skeletal muscle to small implants of titanium or stainless steel: a quantitative histological and autoradiographic study.

Small wire implants of titanium or stainless steel were inserted into mouse leg muscles to test the reaction of regenerating skeletal muscle. Muscle fibres regenerated rapidly, starting at 3 d; by 2 wk all implants were encapsulated in thin (10 microns) fibrous tissue capsule surrounded by myotubes for 15-20 microns. Quantitatively there were no detectable differences in muscle regeneration between the two metals. The initiation of myoblast precursor cell replication was determined in regenerating muscle next to the implants. Tritiated thymidine was injected 18-156 h after implant insertion and labelled myotube nuclei in the regenerated muscle indicated that their precursors had started DNA synthesis 24 h after implant insertion. This is similar to myogenesis in many other muscle lesions and indicated that neither titanium nor stainless steel retarded muscle regeneration.

Animals↗

PubMed1990

Transverse or longitudinal arteriotomies in end-to-side microvascular anastomoses for small vessels (1-2 mm).

This investigation quantitatively compared lumenal dimensions of 1 mm end-to-side anastomoses with longitudinal or transverse arteriotomies into host arteries 1.5-2 mm in diameter. In 27 rats, 6-7 mm sections of iliac arteries (1 mm in diameter) were sutured as small bypasses onto abdominal aortae (1.5-2 mm in diameter). Half the anastomoses were performed on transverse. and half on longitudinal arteriotomies. Between 1 and 20 weeks following surgery intravascular methacrylate casts were made of the aortae and bypasses, and detailed measurements taken from the casts. The success rate (patency) of the bypasses was 78%; 18 successful casts (36 anastomotic sites) were analysed; 6 failed due to stenosis (3 other successful bypasses were used to develop the techniques). From these, five sites developed small dilations ("aneurysms"), which did not occur preferentially on either longitudinal or transverse arteriotomy sites. Despite a trend towards a greater diameter in the transverse compared with the longitudinal arteriotomies, they were not statistically different. Therefore, the authors recommend for technical reasons that for small end-to-side vascular anastomoses the transverse arteriotomy is preferable: it produces a simple incision which opens the artery and facilitates suturing. With a longitudinal arteriotomy in such small vessels it is often necessary to remove an elliptical area of tissue, which may produce an excessive defect.

Anastomosis, Surgical↗

PubMed1987

The effect of nicotine on aortic endothelium. A quantitative ultrastructural study.

This study used quantitative electron microscopy to assess ultrastructural features of endothelial injury occurring with exposure to nicotine. Fourteen mice were given nicotine in their drinking water for 5 weeks. The dose (5 mg/kg body wt/day) was equivalent to a human smoking 50-100 cigarettes/day. A control group of mice was unexposed to nicotine over the same period. Stereological analysis of electron micrographs of endothelium from both groups revealed that the nicotine-exposed endothelium showed greater cytoplasmic vacuolation, mitochondrial swelling and subendothelial oedema than the control endothelium. In addition the intercellular cleft morphology was significantly (P less than 0.005) less complex than in the control endothelium. This difference in cleft morphology suggests the nicotine-exposed endothelium is more permeable than the control endothelium. The ultrastructural differences noted in this study are indicative of endothelial damage, and provide structural evidence to support the hypothesis that nicotine contributes to the pathogenesis of arterial disease in smokers.

Animals↗

PubMed1986

Quantitation of the relationship between aortic endothelial intercellular cleft morphology and permeability to albumin.

The aortic endothelial intercellular cleft (AEC) is a determinant of permeability to macromolecules. This study compared the surface density and frequency of AEC profile types between areas of rat aorta that were permeable/impermeable to albumin-bound Evans Blue dye (EBD). Five adult male Wistar rats were given saturating i.v. doses of EBD and 30 min later were perfusion, fixed and their aortae excised. Samples of impermeable (White) and permeable (Blue) areas were prepared for EM. Sections were coded randomly and all AEC profiles observed were assigned to 4 different morphological classes. Ten to 15 micrographs per sectioned sample, per area, per rat were taken to determine the surface density of AEC's relative to the endothelial cell layer. The frequency distribution of AEC profile types from Blue areas was significantly (P less than 0.01) different from that of the White areas. The Blue regions had relatively more AEC profiles of a less complex structure than did the White areas. The majority of cleft profiles in the Blue areas were of the simple 'overlap' type, whereas the commonest in the White areas were the 'mortise' type. The mean surface density of the AEC's in Blue areas was 0.066 +/- 0.002 micron-1, which was significantly (P less than 0.05) less than in White areas (0.11 +/- 0.002 micron-1). These findings confirm earlier qualitative observations and indicate that AEC's in areas permeable to macromolecules, such as albumin, are less complex in structure and of lower surface area than those in areas relatively impermeable to such macromolecules.

Albumins↗

PubMed1985

The effect of nicotine on aortic endothelial cell turnover. An autoradiographic study.

Endothelial injury and increased mitotic activity are early features in the pathogenesis of intimal thickening in arteries. This study examines the effect of systemic nicotine on mitotic activity in endothelial cells. Nine adult mice were given nicotine in their drinking water for 5 weeks. The dose (5 mg/kg body wt/day) was equivalent to a human smoking 50-100 cigarettes/day. A group of 8 similar mice, not exposed to nicotine, was the control. At the end of the exposure period all mice were injected with [3H]thymidine (1 microCi/g body wt) and were killed 24 h later. After perfusion fixation, en-face preparations of aortic endothelium were processed for autoradiography. In nicotine-affected endothelium 0.46 +/- 0.11% (SEM) of cells were labelled, which was significantly higher (P less than 0.01) than in controls (0.14 +/- 0.06%). However, there was no difference in cell density between the groups. On this evidence it was concluded that the rate of cell loss, or cell turnover, was greater in nicotine-affected endothelium. Because other studies have shown that increased mitotic activity and cell loss are established features of endothelial injury, the present findings provide evidence in support of the hypothesis that nicotine contributes to the pathogenesis of arterial disease in smokers.

Animals↗

PubMed1984

Vein to artery grafts. An experimental study of reinnervation of the graft wall.

Iliolumbar vein to iliac artery grafts were placed in 21 rats by microsurgical techniques. Graft innervation was examined at five time intervals between 1 and 32 weeks after surgery. Nerve fibers were demonstrated microscopically by formaldehyde-induced fluorescence of catecholamines. The morphology and degree of graft innervation were assessed, semiquantitatively, relative to the contralateral iliac artery (control) within each animal. Nerves were seen in the graft region as early as 2 weeks, but it was not until 4 weeks that they were present along its length (5 mm). The formation of a nerve plexus in the adventitia surrounding the graft was evident at 8 weeks. By 16 weeks the degree of innervation in the graft had increased to a level that was greater than the control iliac artery in three of four animals examined. Grafts at 32 weeks were also hyperinnervated. However, the morphology of this innervation was different from the control arteries; nerve fibers were finer, not varicosed, and were located at a greater distance from the outer layer of smooth muscle cells. The origin of the nerves appeared to be collateral sprouts from nerves supplying the adjacent iliac vein and also from invading vasa vasorum. The host iliac artery nerve plexus did not contribute to graft innervation.

Animals↗

PubMed1983

Block staining with p-phenylenediamine for light microscope autoradiography.

A study was designed to test the suitability of p-phenylenediamine (pPd) as a block stain for light microscope autoradiography. This was done to obviate the conventional method of staining through the emulsion with histological stains after exposure and development. Ten rats were injected with 3H-thymidine and 1 to 3 days later were perfused with glutaraldehyde. Tissue samples were processed by three different schedules: 1) direct embedding in Araldite-Epon; 2) postfixation in OsO4 before embedding; 3) postfixation in OsO4 and staining in 1% pPd before embedding. Autoradiographs of these tissues showed that pPd-treated tissues were well stained with clearly defined cellular detail. The nuclear region was pale-staining, which highlighted the overlying silver grains. There was no evidence of chemography and the nuclear labeling intensity did not differ significantly from the fixed and post-fixed tissues. It was concluded the pPd is a most useful block prestain to use for light microscope autoradiography.

Animals↗

PubMed1982

Arterial vasa vasorum: a quantitative study in the rat.

This study was designed to quantitate the vasa vasorum of common iliac arteries in 20 rats. The number of vasa vasorum per mm2 of arterial wall was extremely variable - from 0 to 124, the mean being 33 . 95 +/- 29 . 86 (S.D.). There was no significant difference in the vasa vasorum vascularity between the right and left common iliac arteries. The mean wall thickness of these arteries was 0 . 085 +/- 0 . 015 (S.D.) mm and 60 +/- 8% (S.D.) of this was made up by the tunica media. Arterial tissue in this study was shown to have approximately 10% of the vascularity of muscle tissue. By relating these data to the 'critical depth' hypothesis, on the nutritional supply of large arteries, it was concluded that the vasa vasorum in the common iliac arteries in rat (major arteries in small animals) probably play an insignificant role in the nutrition of the arterial wall.

Animals↗

PubMed1981

Vein to artery grafts. A quantitative study of revascularization by vasa vasorum and its relationship to intimal hyperplasia.

Iliolumbar vein to iliac artery grafts were placed in 40 rats by microsurgical technique. Groups of animals were perfused with fixative at eight intervals between one and 20 weeks after operation, and sections of the graft and control arteries (the opposite iliacs) were analyzed microscopically. The revascularization of the graft by capillaries commenced within the first postoperative week. The level of vascularity (capillaries per cross-sectional mm2) increased during the first four weeks, maintained a constant level and declined after week 16. The grafts of the 17--20 week group were substantially less vascular than the earlier groups. Intimal thickening commenced at three to four weeks after operation, i.e. during the period of increasing graft vascularity. The mean intimal proportion of the graft was 14% at four to five weeks and at 17--20 weeks was 35% of the cross-sectional area of the graft wall. However, the actual thickness of the intima did not increase significantly with time, rather the whole graft wall tended to become thinner. At 17--20 weeks grafts which showed a high degree of intimal thickening had significantly fewer capillaries within their walls. Quantitative evidence is presented to suggest that the continued growth of the graft intima may not be supported by a similar increase in the number of vasa vasorum. Therefore, it is suggested that the reduced level of vascularity in grafts with hyperplastic intimae may form an ischemic basis for degenerative changes which are known to take place in some long-term grafts.

Animals↗

PubMed1978

Cell proliferation in skeletal muscle following denervation or tenotomy. A series of autoradiographic studies.

Autoradiographic experiments using 3H-thymidine were designed to analyse cell proliferation which occurs in skeletal muscle after denervation and after tenotomy. In mouse tibialis anterior and tongue muscles during the first 24 h after denervation or tenotomy labelling levels were low and did not differ significantly from sham operated control muscles. By 48 h after denervation and tenotomy of tibialis anterior muscles, increased levels of labelling occurred in both muscle and connective tissue nuclei. Daily pulse labelling for 7 days after denervation produced a labelling level which was 8 times that of sham operated controls, 25--30% of the total nuclear population being labelled. Denervated muscles had twice the level of labelling compared to tenotomised muscles. These results provide conclusive evidence that both denervation and tenotomy stimulate cell proliferation in skeletal muscle and it is suggested that the increased numbers of labelled muscle nuclei are likely to be the result of mitotic activity in muscle satellite cells.

Animals↗