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Biomedical subjects

J L Williams

Publications and source records attributed to J L Williams.

At least 19 recordsLinked to original sources

The inositol phosphate pathway as a mediator in the proliferative response of rat calvarial bone cells to cyclical biaxial mechanical strain.

Isolated newborn rat calvarial bone cells grown in monolayer on polyurethane membranes in specially constructed culture chambers and subjected to a cyclical biaxial mechanical strain of 0.17% at a frequency of 1 Hz for 30 min demonstrated a 16% increase in DNA synthesis during the subsequent 24 h. The metabolites of the inositol phosphate pathway, shown to be an important second messenger in many cell types, were shown to be elevated using high-performance liquid chromatography to separate and quantitate the various inositol polyphosphates. Inositol 1,4,5-trisphosphate, inositol 1,4-bisphosphate, and inositol 1,3,4,5-tetrakisphosphate reached peak accumulations after 20 s of mechanical strain. Inositol 1,3,4-trisphosphate reached a peak accumulation after 2 min, and inositol 1,2,3,4,5,6 phosphate reached a peak accumulation after 60 min of mechanical strain. Neomycin, an inhibitor of phospholipase C, a membrane-bound enzyme that hydrolyzes phosphatidyl inositol 4,5-bisphosphate to start the inositol phosphate cascade, completely inhibited accumulation of the above inositol phosphates during mechanical straining of the bone cells. Neomycin also completely abolished the increase in DNA synthesis that was seen after a mechanical strain of 0.17%. It is concluded from this study that the inositol phosphate pathway is activated by mechanical strain in bone cells and that this pathway is an important and primary mediator in the transduction of mechanical strain into cellular proliferation in these cells.

Analysis of Variance

The neurotoxic effects of methamphetamine on 5-hydroxytryptamine and dopamine in brain: evidence for the protective effect of chlormethiazole.

Studies were undertaken in mice and rats on the neurotoxic effects of methamphetamine on dopaminergic and 5-hydroxytryptaminergic neurones in the brain and the neuroprotective action of chlormethiazole. In initial studies, mice were injected with methamphetamine (5 mg/kg, i.p.) at 2 hr intervals, to a total of 4 times. This procedure produced a 66% loss of striatal dopamine and a 50% loss of tyrosine hydroxylase activity 3 days later. Chlormethiazole (50 mg/kg, i.p.), given 15 min before each dose of methamphetamine, totally prevented the methamphetamine-induced loss of tyrosine hydroxylase activity and partly prevented the loss of dopamine. Phencyclidine (20 mg/kg, i.p.), given in place of chlormethiazole, also prevented the loss of tyrosine hydroxylase. Administration to rats of 4 doses of methamphetamine (15 mg/kg, i.p.) at 3 hr intervals resulted in a 75% loss of striatal dopamine 3 days later and a similar loss of 5-HT and 5-HIAA in cortex and hippocampus. Chlormethiazole (50 mg/kg, i.p.), given 15 min before each injection of methamphetamine, protected against the loss of dopamine and indoleamine content, in the respective regions. Pentobarbital (25 mg/kg, i.p.) also provided substantial protection but diazepam (2.5 mg/kg, i.p.) was without effect. Confirming earlier studies, dizocilpine (1 mg/kg) also provided substantial protection against the methamphetamine-induced neurotoxicity. Preliminary data indicated that chlormethiazole was not neuroprotective because of a hypothermic action. These data therefore demonstrate that chlormethiazole is an effective neuroprotective agent against methamphetamine-induced neurotoxicity and extend the evidence for the possible value of this drug in preventing neurodegeneration.

Animals

Expression of bone morphogenetic proteins in human prostatic adenocarcinoma and benign prostatic hyperplasia.

There are important interactions between prostatic tumours and bone. This study was designed to examine whether prostatic tissue can express bone inductive factors, in particular, the Bone Morphogenetic Proteins (BMPs). The polymerase chain reaction (PCR) has been used to screen for the expression of BMPs one to six in the prostatic tissue of patients with benign prostatic hyperplasia (BPH), non-metastatic prostatic adenocarcinoma and metastatic prostatic adenocarcinoma. BMPs were expressed in both benign and malignant prostate tissue and in the prostate tumour cell lines, PC3 and DU145. BMPs were also expressed in ocular melanoma tissue, a tissue which rarely metastasizes to bone. BMP-6 expression was detected in the prostate tissue of over 50% of patients with clinically defined metastatic prostate adenocarcinoma, but was not detected in non-metastatic or benign prostate samples or in ocular melanoma tissue. These findings suggest that the BMPs may play a role in the osteoinductive activity of prostate metastases and that the pattern of expression of BMPs may be important in the pathogenesis of osteoblastic metastases associated with prostate adenocarcinoma.

Adenocarcinoma

Effect of atriopeptin on production of cerebrospinal fluid.

We reported previously that intravenous infusion of atriopeptin increases blood flow to the choroid plexus. The first goal of this study was to determine whether blood-borne atriopeptin increases the production of CSF. Ventriculocisternal perfusion was used to measure the production of CSF in anesthetized rabbits. Atriopeptin increased blood flow to the choroid plexus (measured with microspheres) but did not alter the production of CSF. The second goal of the study was to determine whether intracerebroventricular injection of atriopeptin affects the production of CSF. Injection of atriopeptin into the cerebral ventricles increased blood flow to the choroid plexus but produced a small decrease in production of CSF. In summary, blood-borne and intraventricular atriopeptin increase blood flow to the choroid plexus, but do not increase the production of CSF.

Animals

Field tests of an acephate baiting system designed for eradicating undesirable honey bees (Hymenoptera: Apidae).

Field evaluations were made of a baiting system designed for use by regulatory agencies in suppressing populations of undesirable feral honey bees, Apis mellifera L. (e.g., bees posing hazards [especially Africanized bees] and colonies infested with parasitic mites). Bees from feral or simulated feral (hived) colonies were lured with honey and Nasonov pheromone components to feeders dispensing sucrose-honey syrup. After 1-3 wk of passive training to feeders, colonies were treated during active foraging by replacing untreated syrup with syrup containing 500 ppm (mg/liter) acephate (Orthene 75 S). In four trials using hived colonies on Grant Terre Island, LA., 21 of 29 colonies foraged actively enough at baits to be treated, and 20 of the 22 treated were destroyed. In the lower Rio Grande Valley of Texas (two trials at each of two trials), treatments killed 11 of 16 colonies (6 of 10 hived; 50 of 6 feral). Overall results showed that all 11 colonies that collected greater than 25 mg acephate died, whereas 3 of 10 colonies receiving less than 25 mg survived. Delivering adequate doses required a minimum of approximately 100 bees per target colony simultaneously collecting treated syrup. The system destroyed target colonies located up to nearly 700 m away from baits. Major factors limiting efficacy were conditions inhibiting foraging at baits (e.g., competing natural nectar sources and temperatures and winds that restricted bee flight).

Animals

Circulating prostate specific antigen-positive cells correlate with metastatic prostate cancer.

Analytical flow cytometry was used to study circulating prostate specific antigen (PSA)-positive cells in 40 consecutive patients with newly diagnosed, untreated prostate cancer; 25 patients (63%) had metastatic disease confirmed by a positive bone scan. Cell suspensions were prepared for each patient from both the primary tumour and peripheral blood samples. The cells were stained with a monoclonal antibody against PSA, and analysed by flow cytometry; PSA-positive cells were sorted according to their immunofluorescence and light scatter properties. The cellular deoxyribonucleic acid (DNA) content of each specimen was also analysed to establish ploidy status. PSA-positive cells were detected in the peripheral blood of 33 patients (83%). The presence of these cells in the circulation showed a higher degree of sensitivity and specificity in predicting positive bone scans than did serum PSA levels. Circulating PSA-positive cells may represent either a subpopulation of tumour cells with distinct metastatic properties or, alternatively, host immunocytes which take up PSA in an active or passive manner.

Aged

Strain fields on cell stressing devices employing clamped circular elastic diaphragms as substrates.

Solutions are presented for the surface strain fields on inflated elastomeric circular diaphragms used for in vitro cell stressing experiments. It is shown, by using the method developed by Way (1934) to solve the nonlinear von Karman plate equations, that the surface strains due to bending are not negligible and that large negative radial strains arise near the clamped edge for center deflection-to-thickness ratios (w/h) less than 10. The method of Hart-Smith and Crisp (1967) was used for w/h greater than 10 to solve the nonlinear equations for symmetrical deformation of axially symmetrical rubber-like membranes. In the membrane solutions the circumferential strains drop parabolically to zero at the clamped edge of the diaphragm, while the radial strains increase slightly with the radius. The solutions for w/h greater than 10 are compared to optical measurements of in-plane displacements used to calculate the circumferential strains on the diaphragm, yielding excellent agreement with the theory.

Biomechanical Phenomena

Ultrasonic wave propagation in cancellous and cortical bone: prediction of some experimental results by Biot's theory.

Pulse transmission ultrasound was used to determine the longitudinal wave speed along the direction of trabecular alignment in 32 water-saturated anisotropic tibial bovine cancellous bone samples and in one cortical bone sample also from the bovine tibia. These results are compared to published ultrasound wave-speed data obtained from bovine femoral specimens. Nonlinear regression was used to fit Biot's theory to the data. The correlation coefficient for regression analysis between the experimental ultrasound velocities and the velocities predicted by Biot's theory was r = 0.78.

Animals

Osteon morphometry in females with femoral neck fractures.

The authors measured osteon dimensions and number in specimens of cortical bone obtained from the medial femoral neck (calcar) from nine female patients treated with hemiarthroplasty for femoral neck fractures, and from 12 (seven women, five men) age-matched cadavers without fractures. Specimens from the same location in 14 (seven women, seven men) younger patients treated with total hip arthroplasty (THA) for osteoarthrosis were also studied. There were fewer osteons per unit area and the osteons and their Haversian canals were bigger in the fracture group than in the nonfracture or osteoarthritic groups. Patients with femoral neck fractures also exhibited a decreased Singh index and an increased intracortical porosity compared with age-matched normal controls. By contrast, the osteoarthritic group showed no difference in osteon or Haversian dimensions, osteon number per unit area, Singh index, or in porosity compared with the nonfracture group. These morphometric differences found in the cortical bone of the medial femoral neck may play a role in the incidence of fractures.

Aged

Alloreactive T-cell recognition of bovine major histocompatibility complex class II products defined by one-dimensional isoelectric focusing.

T-cell recognition of bovine MHC (BoLA) class II antigens was investigated in relation to BoLA class II polymorphisms defined by one-dimensional isoelectric focusing (1D-IEF). One-way mixed lymphocyte reactions (MLRs), and allospecific cell lines and clones were used. In general, T-cell responses correlated with the 1D-IEF defined haplotypes (EDF types). However, with MLRs some responses appeared to be associated with BoLA class I differences. All combinations of responder-stimulator pairs produced alloreactive T-cell responses both in MLR and in generation of allolines/clones. Thus allospecific lines and clones were generated to all EDF types tested. Splits in the IEF typing were observed with EDF6 and EDF3, indicating that distinct BoLA class II haplotypes are not necessarily distinguished by 1D-IEF alone. Furthermore, the patterns of reactivity with EDF3 expressing cells were complex with the T-cell specificities splitting EDF3 into several distinct types. Also, in some cases it was clear that more than one T-cell specificity per EDF type was detectable. Thus, allospecific lines and clones provide complementary and additional information to the 1D-IEF typing for polymorphism of the BoLA class II complex. This extra information is particularly important in terms of the functional significance of the BoLA complex for antigen presentation and immune response gene effects.

Animals

Cerebral vascular physiology in hypertensive disease.

Experimental advances during the last decade have greatly expanded our knowledge of mechanisms that control cerebral blood flow. In addition to local metabolites, many other factors are important in control of cerebral blood vessels. During chronic hypertension, several mechanisms of cerebral vascular control are altered, with both beneficial and detrimental consequences. The changes should be considered carefully during treatment of chronic hypertension.

Brain

Inhibition of human neutrophil elastase by ICI 200,355.

To examine the pathogenetic role of neutrophil elastase in airway hypersecretion, we have studied the novel inhibitor of this enzyme, [4-(4-bromophenylsulfonylcarbamoyl)benzoyl-L-valyl-L-proline 1 (RS)-(1-trifluroacetyl-2-methylprolyl)amide] (ICI 200, 355). This compound was a potent (Ki = 0.6 +/- 0.22 nM) inhibitor of human neutrophil elastase and a much weaker inhibitor of other hydrolases. ICI 200,355 also inhibited the ongoing destruction of insoluble elastin by human neutrophil elastase. ICI 200,355 produced a concentration-dependent inhibition of the secretory response induced by human neutrophil elastase (10(-8) M), with an IC50 of 1.6 x 10(-8) M. ICI 200,355 had no effect on baseline secretion or on the secretory response to chymase, cathepsin G or Pseudomonas aeruginosa elastase. Thus, ICI 200,355 appears to be a useful tool for investigating the role of human neutrophil elastase in inflammatory disorders associated with hypersecretion, such as cystic fibrosis, chronic bronchitis, and asthma.

Elastin

Administration of interleukin-6 stimulates multilineage hematopoiesis and accelerates recovery from radiation-induced hematopoietic depression.

Hematopoietic depression and subsequent susceptibility to potentially lethal opportunistic infections are well-documented phenomena following radiotherapy. Methods to therapeutically mitigate radiation-induced myelosuppression could offer great clinical value. In vivo studies in our laboratory have demonstrated that interleukin-6 (IL-6) stimulates pluripotent hematopoietic stem cell (CFU-s), granulocyte-macrophage progenitor cell (GM-CFC), and erythroid progenitor cell (CFU-e) proliferation in normal mice. Based on these results, the ability of IL-6 to stimulate hematopoietic regeneration following radiation-induced hematopoietic injury was also evaluated. C3H/HeN female mice were exposed to 6.5 Gy 60Co radiation and subcutaneously administered either saline or IL-6 (1,000 micrograms/kg) on days 1 through 3 or 1 through 6 postexposure. On days 7, 10, 14, 17, and 22, femoral and splenic CFU-s, GM-CFC, and CFU-e contents and peripheral blood white cell, red cell, and platelet counts were determined. Compared with saline treatment, both 3-day and 6-day IL-6 treatments accelerated hematopoietic recovery; 6-day treatment produced the greater effects. For example, compared with normal control values (N), femoral and splenic CFU-s numbers in IL-6-treated mice 17 days postirradiation were 27% N and 136% N versus 2% N and 10% N in saline-treated mice. At the same time, bone marrow and splenic GM-CFC values were 58% N and 473% N versus 6% N and 196% N in saline-treated mice; bone marrow and splenic CFU-e numbers were 91% N and 250% N versus 31% N and 130% N in saline-treated mice; and peripheral blood white cell, red cell, and platelet values were 210% N, 60% N, and 24% N versus 18% N, 39% N, and 7% N in saline-treated mice. These studies demonstrate that therapeutically administered IL-6 can effectively accelerate multilineage hematopoietic recovery following radiation-induced hematopoietic injury.

Animals

Trabecular bone densitometry using interactive image analysis.

Interactive image analysis is a novel application of digital image processing to the densitometry of trabecular bone. Briefly, the exposed surfaces of bleached slices of bone are illuminated so that the trabecular tips are bright in relation to the interstices. The image is then captured by a TV camera and digitized with an interactive image analysis system. A grey scale is then chosen that differentiates the bone at the surface from the background. Finally, a computer program calculates the area fraction of bone within a user-specified box which, by Delesse's principle, is an estimate of the volume fraction of bone. The reproducibility of the technique (expressed as an average SD) is +/- 1.5 vol. % and has surface-discriminating capabilities comparable to the traditional point-counting method but is faster and more precise. Most importantly, the technique permits biomechanical testing of the sample after its density has been determined.

Aged

Production of alloantisera against class II bovine lymphocyte antigens (BoLA) by cross-immunization between class I matched cattle.

This paper describes the production of alloantisera directed against bovine major histocompatibility complex (MHC) (BoLA) class II antigens in animals whose MHC phenotypes had been defined by one dimensional isoelectric focusing. Animals of closely matched BoLA class I types were selected by serology and subsequently typed for class I and class II by 1D-IEF of immunoprecipitated antigens. Those with similar class I type by both methods, but differing at the class II locus, were chosen for reciprocal immunization. Cross-immunization was by two skin implantations 6 weeks apart. The resulting antisera showed low titre after the first immunization and elevated titre 3 weeks after the second immunization. The sera reacted strongly with cells expressing specific BoLA class II antigens. The pattern of reactivity correlated well with IEF class II typing on a panel of animals representing all of the class II IEF types present in the Friesian population.

Animals