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Biomedical subjects

D B Myers

Publications and source records attributed to D B Myers.

At least 19 recordsLinked to original sources

Temporal changes to uterine collagen types I, III and V in relation to early pregnancy in the rat.

Uterine tissues of pregnant rats were extracted to define any changes to the proportions of collagens types I, III and V. The total concentration of extracted collagen was determined in tissue samples from implant and adjacent non-implant (NI) sites. Extracts were also subjected to polyacrylamide gel electrophoresis (PAGE), immunoblotting and gel densitometry to define the collagen types and to determine their relative proportions. By relating the proportions to the collagen concentrations in the extracts, type I was found to be the predominant collagen in both tissue regions although the concentration in the implant sites was lower than that in the NI sites. The concentration of Type I collagen decreased significantly over the period of observation in both implant and NI sites. Although the concentrations of collagen type III and type V also decreased in the implant sites, they did not alter in the NI sites. The results demonstrate that shortly after the initiation of implantation the uterus responds to the presence of the implanting embryo by decreasing the concentration of all three types of collagen. This indicates that their metabolism may, in part, be regulated by similar mechanisms. Furthermore, it was evident that a decrease in the concentration of collagen type I was initiated in uterine areas that, at the time of sampling, were not directly involved with implantation. During the study, it was found that the alpha 1 chain of collagen type V separated into two distinct bands when run on gels containing 3.8 M urea.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Collagen concentrations in dissected tissue compartments of rat uterus on days 6, 7 and 8 of pregnancy.

Implantation and non-implantation sites were dissected into myometrial and stromal components; a decidual/embryonic region was obtained on Days 7 and 8 of pregnancy. The concentration of collagen (as a percentage of the dry weight of tissue), measured by hydroxyproline analysis, was significantly lower in the implantation regions than in the non-implant regions in all areas studied. The concentrations in the antimesometrial myometrium and stroma of the implantation region remained the same over the days studied. In contrast, the mesometrial collagen concentration in the implantation region declined from Day 6 to Day 8 of pregnancy. Collagen concentration was low within the decidual/embryonic tissue on Days 7 and 8 of pregnancy. Remodelling of collagen within the embryonic area appears to be an important feature of the uterine response to implantation in rats.

Animals

Decreased collagen concentration in rat uterine implantation sites compared with non-implantation tissue at days 6-11 of pregnancy.

Collagen concentrations at implantation sites in the rat uterus were found to be significantly decreased compared with concentrations in adjacent non-involved uterine tissue in early pregnancy (75% by Day 11). The decrease in collagen was most marked in primary decidua and was also observed to a lesser extent (20%) in myometrium at the implantation site. There was a decrease of 20% in the concentration of total proteins at Day 7 (as measured by the ninhydrin method) and a slight increase in water content (2%) at Days 6 and 7. The differences in total protein and water content were transient, but the difference in collagen was maintained throughout early pregnancy. The localized changes in collagen content observed in this study, along with previously reported morphological changes in fibrillar and basement-membrane collagens in the uterus, give support to a theory of remodelling in early pregnancy involving simultaneous synthesis and degradation of extracellular proteins during decidualization.

Animals

Production of peptides inducing chemotaxis and lysosomal enzyme release in human neutrophils by intestinal bacteria in vitro and in vivo.

Low molecular weight (Mr 200-1500) N-formylated peptides that stimulate many leucocyte functions, including chemotaxis and lysosomal enzyme release, have previously been isolated from Escherichia coli cultures. We have used high-performance liquid chromatography and bioassay techniques to study production of such peptides by intestinal bacteria in vitro and their activity in intestinal luminal contents, obtained by in vivo dialysis methods. Bioactivity was detected in culture supernatants of all 11 species of bacteria so far investigated, was resistant to digestion with aminopeptidase, but was destroyed by carboxypeptidase, confirming that bioactive moieties were amino-terminal-blocked peptides. By similar isolation procedures, pronase-sensitive bioactive factors have been demonstrated in human rectal dialysates from normal subjects and patients with Crohn's disease. In the patients, bioactivity in dialysates was not observed after treatment with broad-spectrum poorly absorbed antibiotics. The gut may be a reservoir or source of bacterial peptides that could promote an inflammatory response should they cross the 'mucosal barrier'.

Bacteria

Heat shrinkage of extraocular muscle tendon.

We have designed and employed a bipolar heating device to shorten extraocular muscles. Treatment involves placing the unidirectional heating device on the sclera with the active surface beneath the tendinous portion of the extraocular-muscle. When power is applied, visible tissue shrinkage occurs. Heat-induced extraocular muscle shrinkage was performed on live rhesus monkeys. Two months later, thermal tendinoplasty-treated extraocular muscles were surgically isolated and evaluated for strength. Biopsies were then performed on these muscles. It was our clinical impression that treated tissues retained their strength, while histologic and electron-microscopic evaluation of heat-treated tendon revealed evidence of shrinkage and compaction of collagen bundles. Thermal tendinoplasty may offer a sutureless method of correcting strabismus by shortening and thereby strengthening extraocular muscles.

Animals

The cored sponge model of in vivo leucocyte chemotaxis.

A method has been developed for the in vivo measurement of leucocyte chemotaxis in response to the bacterial chemotactic peptide F-met-leu-phe (FMLP). Polyurethane sponges were pre-treated with FMLP and implanted subcutaneously in rats and after a suitable interval removed for determination of leucocyte influx. In vivo concentration gradients of chemotactic factors within intact sponges were shallow and leucocyte accumulation unsatisfactory. Accordingly a cored sponge model was developed in which the cylindrical core only was treated with chemotactic factor and the sponge reassembled prior to subcutaneous implantation. Steep concentration gradients were established within the outer sponge matrix with marked effects on leucocyte accumulation, permitting studies of the time course of in vivo chemotaxis. With cored sponges test to control cell number ratios were maximal at 4 hours using both free and albumin-bound FMLP. This model of in vivo chemotaxis may prove useful in several areas of inflammation research.

Animals

Proximal and distal changes in collagen content of peripheral nerve that follow transection and crush lesions.

Collagen content of rat sciatic nerve was measured 10 weeks after either nerve transection or nerve crush. Nerve transection led to a significant increase in fascicular collagen in nerve segments 2.5 mm proximal and distal to the injury site. Remote from the transection, fascicular collagen was also significantly increased, this effect being most marked distally. Nerve crush by comparison resulted in only a small increase in fascicular collagen, significantly less than after transection. The greater amount of fascicular collagen far distal to the nerve injury could relate to a predominantly caudal endoneurial flow of inflammatory or growth factors. Differences in the amount of fascicular collagen formed after nerve transection compared with nerve crush are clearly due to factors other than axonal degeneration, and may relate to collagen synthesis by denervated Schwann cells or to the severity of the nerve injury.

Animals

Morphological and biochemical comparison of convex and concave articular surfaces from adult subtalar and midtarsal joints.

Convex and concave articular cartilage from adult subtalar and midtarsal joints showed depressions over surface chondrocytes and linear arrays of surface fibres when examined by scanning electron microscopy (SEM). Full-thickness cartilage from concave surfaces contained significantly less collagen than cartilage from convex surfaces (40.8% vs. 47.4%, p less than 0.05). Plano-concave surfaces contained 44.7% collagen. Water and uronic acid content did not differ significantly for the different shapes. A higher collagen content in convex surfaces is consistent with the hypothesis that collagen networks in these surfaces are subjected to higher tensile stress under load than are those in concave ones.

Adult

Diurnal and sequential grip functions in normal subjects and effects of temperature change and exercise of the forearm on grip function in patients with rheumatoid arthritis and in normal controls.

Rate of grip development (power), time to reach maximum grip strength and fatigue were not affected by the diurnal variation known to influence maximum grip strength and work during grip formation in normal subjects. Rheumatoid hands were less affected by exercise or temperature change of the forearm than were normal hands. Cold more consistently produced change in hand function than did warmth or exercise. Environmental changes affected the dynamic (rates of grip development and release and power) more than the static parameters (maximum grip strength and work) of grip. Measurement of power, fatigue and rate of grip release provide additional parameters useful in the assessment of hand function in patients with arthritis.

Adaptation, Physiological

Ibuprofen and diflunisal in rheumatoid arthritis: a double-blind comparative trial.

Both diflunisal (750 mg/day) and ibuprofen (1600 mg/day) were shown to be superior to placebo in the treatment of rheumatoid arthritis in a double-blind cross-over trial. Neither drug affected lymphocyte transformation to plant mitogens. Diflunisal scored better than ibuprofen at the dose levels chosen but the differences did not reach significance.

Arthritis, Rheumatoid

A single-blind crossover trial of the anti-inflammatory drug sodium meclofenamate and placebo, including an evaluation of hand grip and of lymphocyte responsiveness.

A single-blind crossover trial was carried out in 21 patients with active rheumatoid arthritis to assess the effectiveness and tolerance of sodium meclofenamate (300 mg per day) compared with placebo. After a 1-week washout period patients had two periods of active medication, each of 2 weeks, separated by 1 week on placebo. Morning stiffness, walking speed, pain score, patient impression of response, joint tenderness and power, work and maximum grip strength achieved by hand grip were all improved by sodium meclofenamate and an anti-inflammatory effect of the drug was demonstrated, with some reduction in the swelling of PIP joints. There was no advantage in assessing pain on full movement of the small joints of the hands in addition to direct tenderness. Power, work and rate of grip release achieved during hand grip provided more information about hand function than maximum grip strength alone. Lymphocyte transformation to non-specific mitogens was enhanced by the drug. Twelve patients had some form of gastro intestinal complaint during the study and it is suggested that diarrhoea is likely to prove to be the major limiting factor of acceptance by some patients.

Adult

Subcellular particles in synovial fluids and synovial cells.

Membranous particles of mycoplasma-like appearance (100 to 300 nm in diameter) and non-membranous particles which are viral-like (20 to 80 nm in diameter) were observed in negatively-stained preparations of synovial fluid pellets from patients with rheumatoid arthritis (RA), osteoarthrosis (OA) or psoriatic arthritis (PA). The incidence of positive fluids were: membranous particles--22/28 (RA), 7/11 (OA), 1/3 (PA); non-membranous particles--12/28 (RA), 1/11 (OA), 1/3 (PA). Eight of the RA fluids, one OA and one PA fluid were positive for both types of particle. The observation of an increased frequency of viral-like particles in RA synovial fluids compared to OA and PA fluids is of possible aetiological interest. Viral-like particles were also observed in the nuclei of rheumatoid synovial macrophage syncytia by electron microscopy of ultra-thin sections of cultured cells.

Arthritis