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Biomedical subjects

C R Howlett

Publications and source records attributed to C R Howlett.

At least 37 records · Page 2Linked to original sources
PubMed1997

Fracture healing in a rat osteopenia model.

Fracture healing is influenced by mechanical and biologic factors. The capacity for fracture repair has been reported to decrease with age, although the risk of fracture increases with age. Fracture healing in an animal model of postmenopausal osteoporosis or osteopenia would provide a useful technique to evaluate and develop new treatment protocols. The authors examined the tensile and bending properties of healing femoral fractures in normal and ovariectomized rats. Mechanical data from tensile and bending tests indicate ovariectomy impairs fracture healing, which was confirmed through histologic study. Bending and tensile data provide useful information concerning the mechanical properties of the healing fracture. Tensile tests were noted to be sensitive indicators of the properties of the healing fracture.

Animals↗
PubMed1996

A novel technique for quantitative detection of mRNA expression in human bone derived cells cultured on biomaterials.

A nonisotopic and quantitative in situ hybridization technique was adapted to investigate the effect of biomaterials on the cellular expression of mRNA from human bone derived cells (HBD cells). HBD cells were cultured for 24 or 48 h on tissue culture plastic, alumina, and ion modified alumina. Osteocalcin, osteopontin, alkaline phosphatase, type I collagen alpha 1, and type I collagen alpha 2 mRNAs were quantified. Protein expression for collagen types I, III, and V, and for anti-human macrophages CD68 (DAKO-CD68, KP1) and CD68 (PG-M1), and anti-human myeloid/histiocyte antigen (DAKO-MAC 387) were determined immunohistochemically using monoclonal antibodies. At 24 and 48 h, levels of mRNA for alkaline phosphatase and osteonectin were greater than mRNA levels for osteopontin, osteocalcin, collagen type I alpha 1, and collagen type I alpha 2 for cells grown on the three substrata. However, at 48 h mRNA levels for alkaline phosphatase and osteonectin were significantly higher on the modified ceramic substrata relative to the native alumina. HBD cells appear to express CD68-KP1 when cultured for 24 h. The techniques provide a sensitive and reproducible assay to evaluate gene and protein expression of cells grown on different substrata.

Alkaline Phosphatase↗
PubMed1995

Anti-inflammatory effects of kappa-opioids in adjuvant arthritis.

Current therapies for arthritis are unsatisfactory and cause serious side effects and morbidity. It has been postulated that opioid drugs may block inflammatory mediators and attenuate the joint damage in adjuvant arthritis. However, the importance of opioid receptor subtypes involved in inflammation remains to be determined because data are conflicting in this regard. The present investigation was designed to test the effects of both a kappa-agonist, (+/-)U50488H and a kappa-antagonist, MR2266 on the progression of experimental arthritis. To produce adjuvant arthritis, male Lewis rats were inoculated subcutaneously (s.c.) with 0.05 ml of Freund's complete adjuvant (10 mg/ml) into the right hind paw. The kappa-opioid agonist, (+/-)U50488H (20 mg/kg/d s.c.) and the kappa-opioid antagonist, MR2266 (20 mg/kg/d s.c.) were administered for 3 days during the primary inflammatory phase of adjuvant arthritis. There were four treatment groups; group I were non-arthritic controls and received paraffin oil vehicle and opioid injections; group II were arthritic controls and received adjuvant and saline injections; group III received adjuvant and agonist and group IV received adjuvant and antagonist. The progression of adjuvant arthritis from day 0 to 24 was monitored by body weight change, hind limb size (ipsilateral and contralateral) and a total severity score for each clinical observation of gait, coat and limb condition. On day 24 histology and radiography of the contralateral limb was performed. There was less soft-tissue swelling, as judged by time-averaged % change in the volume of the contralateral limb, in both agonist (mean +/- se: 82 +/- 5) and antagonist (77 +/- 4) treated rats compared to untreated arthritic controls (99 +/- 5, p < 0.05). Other clinical measures of severity were not different between untreated and opioid-treated arthritic rats. However, the joint damage as judged by radiography was lower in kappa agonist treated rats (2.6 +/- 0.5, p < 0.05) compared to untreated controls (4.1 +/- 0.5) and antagonist treatment (4.4 +/- 0.5). Microscopic pathological scores were also significantly lower in agonist (2.8 +/- 0.3, p < 0.05) compared to both antagonist treated rats (4.2 +/- 0.1) and vehicle-treated controls (3.6 +/- 0.2). The results of this study show that kappa-opioid receptor agonists but not antagonists attenuate the progression of experimental arthritis. These observations have important implications for the evaluation and use of kappa-opioid agents in the management of arthritis.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1995

Shielding of augmented tendon--tendon repair.

Strength and function of autogenic and xenogenic reconstruction of digital extensor tendons was examined in an ovine model. In this study, tendon-graft junctions were formed by either suture augmented with a woven polyester tube (A), or augmented and shielded from surrounding tissues by chemically-treated bovine pericardium (S). By 12 wk, both A and S sheep had returned to full range of motion. Mechanical strength of both the autograft-host and xenograft-host repair sites was similar, with a pooled strength of 131 +/- 25 N (n = 15). Similarly, the mid-portion xenograft strengths were constant at approximately 366 +/- 97 N (n = 7). In contrast, mid-portion autograft strengths decreased from 380 +/- 110 N (N = 4) to 120 +/- 66 N (n = 4) if shielding was omitted. The loss in autograft strength was attributed to loss of function associated with adhesions. The use of the augmentation device coupled with an adhesion barrier gives higher initial reconstruction strength and improved function during the host repair period up to 12 wk.

Animals↗
PubMed1995

MALToma-like lesions in the murine gastric mucosa after long-term infection with Helicobacter felis. A mouse model of Helicobacter pylori-induced gastric lymphoma.

The long-term consequences of helicobacter infection were observed in an established murine model of human helicobacter infection. Stomachs of specific pathogen-free BALB/c mice infected with Helicobacter felis were examined for inflammation with particular reference to lymphoid cell proliferation and lymphoepithelial lesions. There was little evidence of an inflammatory response in animals sacrificed up to 19 months after infection. In contrast, from 22 months, 38% of infected animals had lymphoid follicles, whereas no lymphoid follicles were found in noninfected control animals. Lymphoepithelial lesions were observed in 25% of infected mice compared with none in controls. Immunostaining confirmed the B-cell nature of the lymphoid infiltrate. The morphology of these lesions closely resemble those seen in human gastric MALToma. This animal model would provide an opportunity to study the pathogenesis of lymphoproliferative disease.

Animals↗
PubMed1994

Measurement of microtomy-induced section distortion and its correction for 3-dimensional histological reconstructions.

The presence of microtomy induced distortion in paraffin sections is a significant hindrance to the accurate alignment of sections for three-dimensional reconstructive techniques. Measurements of section distortion in various rat tissues demonstrated distortions to be present in all sections, with over 85% of such distortions being manifest as expansions when compared to the original distances between a series of eight drilled fiducial marks. Mean percentage dimensional changes in the direction of the cutting stroke and at right angles to this direction were -0.5 +/- 1.5% and 3.7 +/- 1.2% for liver, 7.6 +/- 2.4% and 9.1 +/- 1.2% for kidney, 6.6 +/- 2.3% and 10.5 +/- 1.4% for lung, and 20.3 +/- 6.6% and 8.9 +/- 5.9% for skeletal muscle. Individual sections invariably displayed measurable distortions, with only skeletal muscle showing any consistent pattern, in the form of "barrel" distortion at right angles to the cutting stroke. In addition a method of distortion correction and simultaneous image alignment is presented as a means of section alignment with full distortion correction capability. This method uses a quadratic polynomial transform in a non-linear "unwarping" algorithm, to correct for the rotational and translational misalignment as well as for microtomy and camera aspect ratio distortions. Application of this method to a sequence of 46 serial sections demonstrated an alignment accuracy to within 2.6 +/- 0.8 pixels.

Animals↗
PubMed1994

Mechanism of initial attachment of cells derived from human bone to commonly used prosthetic materials during cell culture.

The suitability of polymeric biomaterials as surfaces for the attachment and growth of cells has often been investigated in cell culture. In this study the contribution that serum fibronectin (Fn) or vitronectin (Vn) make to the attachment and spreading of cells cultured from explanted human bone (bone-derived cells) during the first 90 min of culture was determined for metallic and ceramic surfaces. The requirement for Fn or Vn for attachment and spreading of bone-derived cells onto stainless steel 316 (SS), titanium (Ti) and alumina (Al2O3) and to polyethyleneterephthalate (PET) was directly tested by selective removal of Fn or Vn from the serum prior to addition to the culture medium. Attachment and spreading of bone-derived cells onto SS, Ti and Al2O3 surfaces were reduced by 73-83% when the cells were seeded in medium containing serum from which the Vn had been removed. Cell attachment and spreading on these surfaces when seeded in medium containing Fn-depleted serum (which contained Vn) were not reduced to the same extent as in the medium containing Vn-depleted serum. The bone-derived cells failed to attach to the surfaces to the same extent when seeded in medium containing serum depleted of both Vn and Fn. Our results show that for human bone-derived cells, the attachment and spreading of cells onto SS, Ti and Al2O3 as well as PET during the first 90 min of a cell culture attachment assay are a function of adsorption of serum Vn onto the surface.

Aluminum Oxide↗
PubMed1994

Animal and public health implications of gastric colonization of cats by Helicobacter-like organisms.

The bacterial genus Helicobacter contains a number of species which colonize the gastric mucosa of mammals. Natural and/or experimental gastric pathology has been correlated with colonization in humans and a wide variety of animal species. Historical reports in the literature suggest that a high percentage of cats are colonized by large, spiral, gastric helicobacter-like organisms (GHLOs). One of these bacteria (Helicobacter felis) has been isolated on artificial media and has experimentally caused gastritis in gnotobiotic dogs. This study surveyed the prevalence of helicobacter colonization in random-source cats by using the urease assay. Histologic examination was performed to determine the degree of associated pathology present. GHLOs associated with chronic gastritis were present in 70% of the juvenile and 97% of the adult cats studied. Although further study is needed to determine specifically what role GHLOs play in feline gastrointestinal disease, these results indicate that helicobacter colonization should be considered in the pathogenesis of feline gastroenteropathy. Furthermore, the high prevalence of feline infection is interesting because cats have recently been implicated as a potential reservoir for human infection by helicobacter-like organisms.

Animals↗
PubMed1993

The effect of ion implantation on cellular adhesion.

As there are only a finite number of materials suitable for orthopaedic reconstruction, considerable effort has been devoted recently to investigating ways of altering the surface chemistry of prosthetic materials without altering their bulk properties. Ion beam implantation is one such technique which is appropriate for orthopaedic reconstructive materials. This paper investigates the early effect of ion beam modification on cellular attachment of bone derived cells using a prototype device which measures the strength of attachment of individual cells to a silicon substratum. The results point to several conclusions. (1) There is no evidence that ion beam implantation with nitrogen, phosphorus, manganese or magnesium produces increased adhesion of human bone derived cells. (2) Surface etching with hydrofluoric acid, electron bombardment and thermal oxidation increases the strength of attachment between cells and substrata. (3) There is a correlation between wettability and rate of cellular attachment to oxygen implanted substrata during the first 2 h after cellular seeding. However, the increase in cellular attachment cannot be entirely explained by the change in critical surface tension or via increased fibronectin attachment to the substrata.

Bone Transplantation↗
PubMed1993

Attachment of human bone cells to tissue culture polystyrene and to unmodified polystyrene: the effect of surface chemistry upon initial cell attachment.

Cell culture studies have often been used in the determination of the suitability of biomaterials as surfaces for the attachment and growth of cells. For such studies of surfaces for potential use in bone implants, cells derived from bone may be maintained in culture on tissue culture polystyrene (TCPS). We have determined the contribution that serum fibronectin (FN) or vitronectin (VN) make to the attachment and spreading of cells cultured from explanted human bone (bone-derived cells) during the first 90 min following seeding on culture surfaces. The attachment of bone-derived cells to TCPS was simulated two-fold by the addition of 10% (v/v) fetal bovine serum (FBS) to the seeding culture medium. The roles of FN and VN were determined by selective removal of the FN or VN from the FBS prior to addition to the culture medium. FBS from which the VN had been removed did not have this stimulatory activity. In contrast, the attachment of bone-derived cells onto TCPS from medium containing FN-depleted serum (which contained VN) was the same as when intact FBS was used. There was incomplete attachment of bone-derived cells (27% of cells) when seeded in medium containing FBS depleted of both VN and FN. Our results show that for human bone-derived cells, the attachment onto TCPS of cells planted in medium containing FBS during the first 90 min of culture is principally as a result of adsorption onto the surface of serum VN. As unmodified polystyrene (PS) has also been used previously as a model biomaterial surface, PS was compared to TCPS for attachment of the bone-derived cells. Attachment of bone-derived cells to TCPS was twice that onto PS, both when the medium was serum-free and when it contained FBS. Bone-derived cells attached to TCPS or PS onto which purified VN or FN had been precoated, with VN adsorbed onto PS being as effective as was VN adsorbed onto TCPS. With FN, there was an effect of the polystyrene surface chemistry which was evident in that suboptimal concentrations of FN had a slightly higher potency when adsorbed onto TCPS than did the same concentrations of FN coated onto PS. When preadsorbed onto TCPS, the potency of FN for attachment of bone-derived cells was at least equal to that of VN.

Bone and Bones↗
PubMed1991

Treated xenografts as gliding tendon prostheses in an ovine model.

A model for testing the properties of gliding tendon grafts has been developed that allows anastomoses to be evaluated separately from the mid-portion of the graft. In addition, two different graft materials may be implanted in one sheep foreleg whilst maintaining control (not operated) tendons in both the operated leg and contralateral foreleg. The model has been used to evaluate the response of xenografts made from chemically treated kangaroo tail tendon (KTT) compared with autografts. At 3 month the mid-sections of the glutaraldehyde-fixed xenografts maintained between 57 and 82% of their initial ultimate tensile strength whereas lyophilized KTT dropped to 10% and autografts retained 91% of initial strength. Sterilization by gamma-radiation of wet xenografts did not affect the material and implant properties significantly. Longer term studies are necessary to determine the resorption behaviour of the xenografts. Anastomosis strengths were found to be about the same for all grafts, at about 25% of the strength of the original tendon. Alternatives need to be investigated to improve this strength.

Anastomosis, Surgical↗
PubMed1991

Comparative evaluation of treated bovine pericardium as a xenograft for hernia repair.

Two forms of bovine pericardium (BPC) were assessed as hernia repair materials: non-cross-linked (lyophilized) and cross-linked through treatment with glutaraldehyde (GA). These were compared with polypropylene mesh (Marlex) in a rabbit model. Over 52 wk implantation, the GA BPC grafts developed a strong, stable, fibrous tissue replacement with good incorporation into the abdominal muscle wall. The lyophilized BPC grafts were substantially resorbed within 12 wk of implantation, however the thin, fibrous replacement tissue was inadequate for abdominal wall support. Marlex grafts provided sufficient abdominal support, however these grafts were associated with extensive adhesion formation and, in this model, fat deposition around the perimeter of the graft. Control (ungrafted) rabbit abdominal muscle in the transverse orientation had an ultimate tensile load (UTL) of 11.4 +/- 5.1 N (x +/- s.d.) and a strain at UTL of 35 +/- 12% (n = 169). At 52 weeks the UTL of the repair sites was 7.3 +/- 4.5 N (n = 6), 5.1 +/- 3.5 N (n = 6) and 5.6 +/- 2.7 N (n = 6) for GA BPC, lypophilized BPC and Marlex grafts, respectively.

Animals↗
PubMed1991

Autograft and Leeds-Keio reconstructions of the ovine anterior cruciate ligament.

This study compared the Leeds-Keio prosthesis with grafting of autogeneic patellar tendon for the reconstruction of the ovine anterior cruciate ligament under controlled conditions. Reconstructed knees from six sheep of each group were evaluated at 12, 26, and 52 weeks postreconstruction with respect to clinical assessment, gross pathology, mechanical properties, and histology. Although no difference in clinical assessment (anteroposterior draw, range of motion, and function) was noted between the prosthesis reconstruction and the autograft reconstruction, the prosthesis provided a higher strength initially, which remained relatively constant over the one-year study. However, prosthesis wear was observed, with up to 50% of Dacron fibers ruptured in some cases. Histologic sections indicated that in the ovine model, the Leeds-Keio prosthesis should be considered an artificial device and not a scaffold or stent that supports aligned collagenous growth. The autograft had low strength at 12 weeks, which increased over the study period. Despite acceptable clinical performance and adequate mechanical properties up to one year postimplantation, neither reconstruction approached the clinical or mechanical performance of the normal anterior cruciate ligament in the ovine model.

Animals↗
PubMed1990

Presence of type III collagen in disc attachments of human temporomandibular joints.

Samples of discs and disc attachments were extracted by dissociative methods and the resultant collagenous residues cleaved with cyanogen bromide. Soluble peptides thus released were characterized by their electrophoretic mobility following SDS-PAGE and by Western blot staining with specific antibodies against type I and type III collagens. Type III collagen was identified in samples taken from the posterior discal attachments. This may explain why this disc is prone to detachment and internal derangement and the high incidence of patients with temporomandibular joint dysfunction.

Adult↗
PubMed1989

Dupuytren's contracture. Fine structure in relation to aetiology.

The fine structure of palmar fascia from patients with Dupuytren's contracture (DC) was compared with that from patients with carpal tunnel syndrome (CTS). In contrast to previous assumptions, the ultrastructure of fibroblasts both in vivo and in vitro from DC and CTS appeared identical, indicating that myofibroblasts are not specific to DC. The major differences between DC and CTS were: 1) a sixfold and fortyfold increase in fibroblast density in cord and nodular areas of DC compared with CTS; 2) a more disorganised pattern of collagen fibrils in DC; and 3) markedly narrowed microvessels surrounded by thickened, laminated basal laminae and proliferating fibroblasts in DC compared with CTS. To account for these morphological changes a hypothesis is presented which proposes that oxygen-free radicals cause pericytic necrosis and fibroblastic proliferation. This hypothesis provides a potential avenue for therapy of DC and other fibrotic conditions.

Aged↗
PubMed1989

The effect of silicon nitride ceramic on rabbit skeletal cells and tissue. An in vitro and in vivo investigation.

This article presents a morphologic assessment of the effect of silicon nitride ceramic (Si3N4) on rabbit marrow stromal cells and their differentiation when grown in vitro and in vivo. In vitro marrow stromal cells (MSC) attached initially to upper portions of ceramic discs. However, at four weeks, cells only attached to disc edges. Fresh marrow or first passage MSC, inoculated into diffusion chambers with and without Si3N4, formed cartilage, bone, and fibrous tissue after being implanted intraperitoneally for five weeks. Tissue differentiated adjacent to Si3N4 but not within the pores. In contrast, Si3N4 implants inserted into femoral marrow cavities were surrounded initially by woven bone and within three months by mature bone that had permeated implants with a pore size of 255 +/- 64 microns. Plugs having a pore diameter of 170 +/- 45 microns mainly contained vascularized fibrous tissue with occasional foci of osteoid or bone in the peripheral pores. In a pilot experiment, three femoral segmental Si3N4 endoprostheses were implanted in three adult rabbits, and the osseous reactions were monitored during their natural life. Each implant was enclosed by a stable cuff of bone within four months of implantation and remained unchanged during the rest of the animal's life. Autopsies confirmed these roentgenographic observations, and tissue appositional to each prosthesis was morphologically normal. Si3N4 has the potential of an important ceramic for use in osseous reconstruction.

Animals↗
PubMed1988

Osteogenesis by canine and rabbit bone marrow in diffusion chambers.

Osteogenic activity of canine and rabbit bone marrow and marrow stromal fibroblasts (MSF) derived from marrow cultured in vitro was evaluated using diffusion chambers. Marrow from young dogs and rabbits grown in cell culture produced confluent layers of MSF. Diffusion chambers containing 0.18-7.6 x 10(6) allogeneic MSF were inserted into the peritoneal cavities of 5 dogs and 6 rabbits. Chambers recovered from the dogs (15/16) contained only loose fibrous tissue while chambers from rabbits (9/13) contained membranous bone and cartilage. Diffusion chambers implanted with 1.0-32.4 x 10(7) fresh allogeneic marrow cells suspended in cell culture medium were inserted into the peritoneal cavities of 11 dogs and 9 rabbits for 3-8 weeks, and after recovery examined histologically. Membranous bone was formed in 4/40 chambers containing canine marrow while bone and hyaline cartilage was formed in 21/27 chambers containing rabbit marrow. This apparent species difference in incidence of bone marrow osteogenesis may relate to a lower concentration of osteogenic precursor cells in canine marrow, a failure of osteogenic precursor cells to differentiate to osteoblasts in a somewhat artificial environment in vivo (viz diffusion chambers), a lack of cell-matrix interaction to stimulate cell differentiation, inappropriately short diffusion chamber implantation times post grafting, or a difference in ontogenetic stage of development of marrow donors with rabbit cells being physiologically younger.

Animals↗