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Biomedical subjects

J D Williams

Publications and source records attributed to J D Williams.

At least 91 records · Page 5Linked to original sources
PubMed1996

The impact of legislation to improve coordination of services to children with serious emotional disturbance.

OBJECTIVE: This study evaluated the impact of state legislation in Indiana mandating establishment of local coordinating committees to prevent inappropriate placement of children and youth with serious emotional disturbance out of the home and to facilitate the development of communitybased initiatives. METHODS: In the first stage of the study, a survey was sent to the directors of mental health, welfare, education, and probation agencies of each county to estimate the extent that the structure and processes mandated by law were in place. In the second stage, structured interviews were conducted with the directors of key agencies in seven representative counties. RESULTS: Stage 1 produced 310 completed surveys from all 92 counties; 73 counties had functioning committees. Improved coordination among providers was the most frequently cited reason for the committee's success; half of the respondents felt that the committee resulted in better services. More than half reported that too few service options were available. Other problems cited were rigid funding opportunities that limited options and lack of staff time to attend and prepare for meetings. Interviewees in the second stage noted that the committee too often formalized already-made decisions, that consideration of individual cases came too late in the process, and that in many cases less restrictive options had already been tried unsuccessfully. They also noted that the committee process had not achieved its major objective of pooling resources to address the needs of particular children. CONCLUSIONS: Adequate funding and a fiscal strategy to support coordination and staffing of local coordinating committees are critical to their successful implementation.

Affective Symptoms↗
PubMed1996

Evaluation and management of the lingual thyroid gland.

Lingual thyroid gland is a rare clinical entity that is due to failure of descent of the gland anlage early in the course of embryogenesis. It may present with symptoms of dysphagia, upper airway obstruction, or even hemorrhage at any time from infancy through adulthood. We present two illustrative cases of lingual thyroid gland along with a protocol for diagnosis and management of the condition. Elements in the diagnostic and therapeutic evaluation are described with attention to the clinical findings, laboratory tests, and radiographic imaging studies employed in confirming the diagnosis and planning appropriate treatment. The natural history of the condition is reviewed and a treatment strategy is outlined that focuses on the use of suppressive doses of thyroid hormone as the initial therapy. Surgical excision of the gland is reserved for more advanced cases of gland enlargement resulting in airway compromise, severe dysphagia that limits oral intake, or ongoing hemorrhage.

Adult↗
PubMed1996

Establishment and functional characterization of human peritoneal fibroblasts in culture: regulation of interleukin-6 production by proinflammatory cytokines.

The functional and morphologic integrity of the peritoneal membrane is of major importance for the successful treatment of patients with chronic peritoneal dialysis. This study aimed at the establishment and functional characterization of human peritoneal fibroblasts (HPFB) in cell culture. HPFB were isolated from human omentum by enzymatic digestion and cultured. Confluent HPFB could be identified as spindle-shaped cells, growing in parallel arrays and whorls which stained positive for vimentin and negative for factor VIII, cytokeratin 18, and desmin. Maximum cell growth was observed after 24 h in medium supplemented with 10% fetal calf serum. HPFB could be growth arrested and maintained in fetal calf serum-depleted medium (0.1%) for > 48 h without loss of cell viability as evaluated by intracellular ATP determination. Stimulation of resting HPFB for 0.5 to 48 h with increasing doses of interleukin (IL)-1 beta and/or tumor necrosis factor-alpha (1 to 10,000 pg/mL) resulted in a dose- and time-dependent induction of IL-6 messenger RNA and an increase in immunoreactive IL-6 protein secreted into HPFB supernatants, which was significant with IL-1 beta or tumor necrosis factor-alpha doses as low as 1 pg/mL. HPFB IL-6 production could be inhibited by both actinomycin D or cycloheximide, which suggests that the induction of IL-6 occurs both on a transcriptional and a post-transcriptional level. In summary, this cell culture model is expected to facilitate further investigation of the potential role of the HPFB in the peritoneal cytokine network of patients treated with chronic peritoneal dialysis.

Cell Cycle↗
PubMed1996

Adherence of neutrophils to human peritoneal mesothelial cells: role of intercellular adhesion molecule-1.

Peritonitis is accompanied by a massive influx of polymorphonuclear leukocytes (PMN) into the peritoneal cavity, little is known, however, about the process of neutrophil transmigration across the peritoneal membrane. The study presented here, therefore, investigates the adherence of human PMN to human peritoneal mesothelial cell monolayers and examines the importance of intercellular adhesion molecule-1 (ICAM-1) in the process. Human peritoneal mesothelial cells (HPMC) constitutively expressed ICAM-1 protein and mRNA. Stimulation with IL-1 beta or TNF alpha resulted in time- and dose-dependent upregulation of ICAM-1 mRNA transcript and increased cell-surface immunoreactive protein expression. Peak surface expression of ICAM-1 occurred between 12 and 24 h after cytokine stimulation when the level of expression was increased by on average threefold above control. The adherence of PMN to HPMC after stimulation with either IL-1 beta or TNF alpha was both dose- and time-dependent. Peaks of PMN binding to HPMC occurred at 2 and 12 h after stimulation. After 12 h, the number of PMN binding to HPMC increased from 71.3 +/- 12.5 in control cells to 180 +/- 36.5 and 125 +/- 23.6 (x 10(3) PMN), after IL-1 beta (100 pg/mL) and TNF alpha (1000 pg/mL), respectively (z = 2.52 and 2.38, N = 6, P < 0.02 versus control for both). The roles of HPMC ICAM-1 and the PMN counter receptor LFA-1 (CD11a/CD18) in the adherence of PMN to HPMC were confirmed by using anti-CAM Fab2' fragments, and anti-integrin antibodies, all of which significantly reduced the adherence of PMN to both control and cytokine-treated HPMC. These data suggest that ICAM-1 expression by HPMC may be one mechanism by which neutrophils adhere to the mesothelium during their transmigration into the inflamed peritoneal cavity.

Antigens, CD↗
PubMed1996

In vitro effects of bicarbonate and bicarbonate-lactate buffered peritoneal dialysis solutions on mesothelial and neutrophil function.

The inclusion of bicarbonate in the formulation of peritoneal dialysis solutions may avoid the in vitro impairment of certain cell functions seen with acidic lactate-based fluids. The supranormal physiological levels of HCO3- and PCO2 inherent in such formulations may, however, not be biocompatible. This study compared the in vitro biocompatibility of a pH 5.2 lactate-based formulation with formulations containing either 40 mM lactate at pH 7.4, 38 mM HCO3- at pH 6.8 (PCO2 at approximately 240 mm Hg) or 7.4 (PCO2 at approximately 60 mm Hg), and 25 mM HCO3- plus 15 mM lactate at pH 6.8 (PCO2 at approximately 160 mm Hg) or 7.4 (PCO2 at approximately 40 mm Hg). Significant release of lactate dehydrogenase or decreases in ATP content by human peritoneal mesothelial cells (HPMC) and human peripheral polymorphonuclear leukocytes (PMN) after a 30-min exposure to each test solution was only seen with the pH 5.2 lactate-based fluid. The ATP content of HPMC exposed to this fluid returned to control levels after 30 min of recovery in M199 control medium but showed a trend toward decreasing ATP content at 240 min. Similarly, interleukin (IL)-1 beta-induced IL-6 synthesis by HPMC was also only significantly reduced by the pH 5.2 lactate solution. PMN chemiluminescence was unaffected by 30-min exposure to all test solutions except for the pH 5.2 lactate formulation. Staphylococcus epidermidis phagocytosis was reduced to between 46 to 57% of control with all test solutions except the pH 5.2 lactate solution, which further suppressed the chemiluminescence response to 17% of control. These data suggest that short exposure to supranormal physiological levels of HCO3- and PCO2 does not impair HPMC or PMN viability and function. Furthermore, neutral pH lactate-containing solutions show equivalent biocompatibility to bicarbonate-based ones.

Adenosine Triphosphate↗
PubMed1996

Laminins 2 and 4 are expressed by human decidual cells.

During pregnancy, the resident stromal cells of the endometrium differentiate to become decidual cells and produce a pericellular basement membrane. We used immunofluorescence and Western blotting with a panel of monoclonal Ab specific for various laminin subunits to examine the composition of decidual laminin. The stromal cell basement membrane contained subunits alpha 2 (M), beta 1 (B1), beta 2 (S), and gamma 1 (B2). Low levels of alpha 1 could also be detected. The glandular and vascular basement membranes of decidual tissue contained subunits alpha 1 (A), beta 1, and gamma 1. An extract was produced from decidual extracellular matrix. Western blots of nonreducing gels showed the presence of high molecular weight complexes containing alpha 2, beta 1, beta 2, and gamma 1. These data indicated that laminins 2 and 4 are coexpressed by decidual cells. Laminin 1 was present in the extract as a minor component. In contrast, cultured stromal cells expressed laminin 1 as the major secreted variant. Immunolocalization was carried out using tissue from various stages of the nonpregnant cycle. The alpha 2 chain polypeptide was absent in the proliferative phase of the cycle but present in late secretory phase in perivascular areas where predecidual differentiation occurs. Reverse transcriptase-PCR experiments confirmed the presence of alpha 2 chain mRNA in decidua but showed that this transcript is detectable throughout the nonpregnant cycle. The results showed that laminins 2 and 4 are hormonally regulated products of decidual cells. The composition of the vascular and epithelial basement membranes remained constant throughout the cycle.

Blotting, Western↗
PubMed1995

Comparative efficacy of oral doses of clindamycin and erythromycin in the prevention of bacteraemia.

Two antibiotics, clindamycin and erythromycin, were compared in a double-blind trial to test their efficacy in the prevention of post-dental extraction bacteraemia with streptococci in a group of 40 healthy patients. Tolerance to the oral doses was tested by questionnaire. Levels of drug in the serum were estimated using a microbiological assay. An in-vitro blood culture system was used as an analogy of the persistence of a bacteraemia in the presence of high levels of antibiotic. Isolates of streptococci were identified to species level. Minimum inhibitory concentrations of clindamycin and of erythromycin for each isolate were estimated. Results showed satisfactory levels of antibiotics in the blood for activity against oral streptococci. Clindamycin was slightly more effective than erythromycin in the prevention of post-extraction streptococcal bacteraemia but that efficacy was only 45%. Clindamycin as a single oral dose of 600 mg was well tolerated by patients compared with erythromycin 1.5 g.

Abdominal Pain↗
PubMed1995

A new antibody capture enzyme linked immunoassay specific for transforming growth factor beta 1.

Previous studies which examined Transforming Growth Factor beta 1 (TGF-beta 1) generation have relied on the identification of TGF-beta 1 mRNA or measurement of TGF-beta 1 by bioassay. Quantitation of TGF-beta 1 message alone however is inadequate since the regulation of TGF-beta 1 synthesis is often post-transcriptional. TGF-beta 1 is poorly immunogenic, and sensitive and specific immunoassays for this peptide have proved difficult to develop. Bioassays depend on stimulation or inhibition of cell proliferation in a TGF-beta 1 dependent manner, and are very rigid in their requirements for optimal performance. The aims of this work was therefore to develop a sensitive and reproducible immunoassay for TGF-beta 1. Microtitre plates were coated with human recombinant TGF-beta 1, unbound protein was discarded from the wells prior to blocking with bovine serum albumin. Chicken anti-human TGF-beta 1 antibody was incubated with the test solution overnight at 4 degrees C and then added to the coated wells. Bound antibody was detected with alkaline phosphatase conjugated anti-chicken antibody. The assay is sensitive to 0.2 ng/ml with a range to 100 ng/ml. The assay detects the mature form of human recombinant TGF-beta 1, natural platelet extracted TGF-beta 1, and TGF-beta 1 derived from human monocytes stimulated with Phorbol myristate acetate (PMA). Active TGF-beta 1 is measured directly and latent TGF-beta 1 can be measured indirectly following acid activation of samples. Inter-assay precision ranged from 4.3 to 9.6%, (coefficient of variation, %CV) and intraassay precision ranged from 2.8 to 8.6% (CV).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Metalloproteinase generation by human glomerular epithelial cells.

In the present study cultured human glomerular epithelial cells (HGEC) were used to examine the potential role for these cells in the turnover of the glomerular basement membrane (GBM) through the secretion of matrix metalloproteinases. The cells were shown by substrate gel electrophoresis to secrete gelatinase activity of molecular weights 72 kDa and 92 kDa. The gelatinolytic activity was inhibited by EDTA (10 mM), and by both TIMP-I and TIMP-II, but was not inhibited by PMSF (2.5 mM), indicating that the enzymes belonged to the metalloproteinase family. The identity of the enzymes was confirmed by the use of specific antisera to gelatinase A and gelatinase B. In addition, reverse transcription polymerase chain reaction (RT PCR) amplification of HGEC mRNA using specific primers to the two enzymes yielded single bands of amplified DNA and served to verify the identity of the enzymes. In supplementary experiments using both specific antiserum and PCR primers it was shown that HGEC express message and secrete both the specific metalloproteinase inhibitors TIMP-I and TIMP-II. These results indicate that the synthesis and secretion of degradative enzymes and their controlling inhibitors by HGEC have the potential to be involved in the turnover of the extracellular matrix.

Base Sequence↗
PubMed1995

Tumor necrosis factor-alpha augments the pro-inflammatory interaction between PMN and GBM via a CD18 dependent mechanism.

Acute glomerulonephritis is frequently associated with intraglomerular neutrophil (PMN) accumulation and the intensity of the inflammatory reaction is correlated with elevated concentrations of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF alpha). PMN are thought to damage glomeruli due to a combination of reactive oxygen species and proteolytic enzymes. Using an in vitro model of anti-GBM nephritis the effects of TNF alpha on GBM damage by PMN were evaluated. The interaction of GBM and PMN resulted in a low grade respiratory burst that was significantly augmented by the addition of TNF alpha. Luminol dependent chemiluminescence (LCL) was increased from 2.4 x 10(6) to 48.1 x 10(6) (P < 0.05). The GBM induced LCL could be > 85% inhibited by blocking with monoclonal antibodies (mAbs) to the common beta chain of the PMN beta 2 integrin family (CD18), but was unaffected by mAbs to CD11a or CD11b subunits. Degradation of GBM, however, was not influenced by either TNF alpha priming of PMN or anti-beta 2 integrin mAbs. When PMN were incubated with GBM-anti-GBM IgG complex they underwent an increase in LCL from 2.4 x 10(6) to 31.1 x 10(6). They also degraded more GBM than controls (10.1% vs. 1.8%). These aspects of PMN activation were Fc receptor mediated, dependent upon anti-GBM IgG being bound to GBM and inhibited by mAb to the PMN Fc receptor. These studies show that TNF alpha can modulate the inflammatory response of PMN in contact with GBM in a CD18 dependent manner. In contrast, Fc receptor mediated events are uninfluenced by TNF alpha.

Basement Membrane↗
PubMed1995

Effect of lactate-buffered peritoneal dialysis fluids on human peritoneal mesothelial cell interleukin-6 and prostaglandin synthesis.

The present study focused on the evaluation of constitutive and cytokine-stimulated human peritoneal mesothelial cell (HPMC) IL-6 and 6-keto-PGF1 alpha release following pre-exposure to peritoneal dialysis fluid (PDF). Exposure of HPMC to PDF pH 5.2 resulted in a time-dependent increase in cell cytotoxicity [as assessed by lactate dehydrogenase (LDH) release] and concomitant inhibition of constitutive and IL-1 beta stimulated IL-6 and 6-keto-PGF1 alpha synthesis. After 15 minutes of exposure to PDF constitutive and IL-1 beta stimulated IL-6 release were reduced by 32.0 +/- 9.7% and 76.0 +/- 7.4% (N = 6, P < 0.046 and P < 0.027, respectively). PCR amplification of reverse transcribed mRNA from HPMC pre-exposed to PDF pH 5.2 demonstrated suppression of IL-1 beta stimulated IL-6 and cyclooxygenase (Cox-1 and Cox-2) transcripts. In order to mimic the dialysis cycle in vivo, an in vitro dialysis system was established. HPMC were exposed first to control medium, PDF pH 5.2 or PDF 7.3 for 15 minutes and then sequentially to pooled spent peritoneal dialysis effluent for up to four hours. The cells were subsequently allowed to recover in control medium for 12 hours in the presence or absence of IL-1 beta or TNF-alpha (both at 1000 pg/ml). There was no evidence of significant cell toxicity as assessed by LDH release during either the 'in vitro dialysis' or 'recovery' phases. Under these conditions short term exposure to PDF pH 5.2 followed by 'in vitro dialysis' resulted in significant inhibition of cytokine stimulated IL-6 (69.6 +/- 18.2 vs. 96.7 +/- 27.9 pg/microgram, N = 13; P < 0.020 for IL-1 beta) and 6-keto-PGF1 alpha (197.5 +/- 89.2 vs. 289.6 +/- 114.5 pg/microgram, N = 13; P < 0.020 for IL-1 beta) and 6-keto-PGF1 alpha (197.5 +/- 89.2 vs. 289.6 +/- 114.5 pg/microgram, N = 13; P < 0.003) release when compared to cells incubated in control medium. Adjustment of the pH of PDF to 7.3 reversed its inhibitory effects. We conclude that short-term exposure to PDF pH 5.2 significantly inhibits HPMC cytokine and prostaglandin release, an effect which appears to be related to its initial pH. Repeated exposure to nonphysiological PDF might impair mesothelial cell function and thus modulate intraperitoneal inflammatory processes.

6-Ketoprostaglandin F1 alpha↗
PubMed1995

Influence of follicular maturation on inhibition of luteinizing hormone-, cyclic 3',5'-adenosine monophosphate-, and forskolin-stimulated progesterone production in chicken ovarian granulosa cells exposed to bursal anti-steroidogenic peptide.

Previously, we demonstrated that a peptide from chicken bursa of Fabricius, bursal anti-steroidogenic peptide (BASP), inhibited LH-stimulated progesterone biosynthesis by granulosa cells from the two largest preovulatory follicles of the chicken ovary. In the present study, we investigated the influence of follicular maturation on the ability of BASP to inhibit granulosa cell steroidogenesis. Granulosa cells from the largest (F1), third largest (F3), and fifth largest (F5), preovulatory follicles of the laying hen were exposed to BASP in the presence or absence of ovine LH, forskolin, or dibutyryl-cAMP (db-cAMP). BASP (0.125 or 0.25 bursal equivalents [BEQ]) suppressed basal progesterone production in F5, but not in F1 or F3, granulosa cells. BASP suppressed LH-stimulated progesterone production in F1, F3, and F5 granulosa cells in a concentration-dependent manner; however, the lowest level (0.06 BEQ) did not suppress progesterone production in F5 granulosa cells. All levels of BASP suppressed forskolin-stimulated progesterone production in F1 granulosa cells, but only the highest level (0.25 BEQ) inhibited forskolin-stimulated steroidogenesis in F3 and F5 granulosa cells. Similar results were obtained with db-cAMP-stimulated granulosa cells. The inhibitory effects of BASP on F1, F3, and F5 granulosa cells were directly compared on a percentage basis. In the presence of each secret-agogue, the lowest level (0.06 BEQ) of BASP effectively suppressed progesterone synthesis in F1 and F3 but not F5 granulosa cells. At higher levels, there was no consistent difference in the ability of BASP to suppress stimulated progesterone production in granulosa cells at different stages of maturation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Psychophysiological correlates of dynamic imagery.

Brain Electrical Activity Maps were recorded from 20 subjects whilst performing: (a) the Vandenberg & Kuse Mental Rotation Test (MRT) and: (b) the Isaac, Marks & Russell Vividness of Movement Imagery Questionnaire (VMIQ), and under control conditions. Subjects were classified as good or poor imagers, first on the basis of their VMIQ scores, and secondly on their MRT scores. Alpha, beta 1 and beta 2 at different cortical regions were compared between groups and between task performance and control conditions. During MRT significant reductions in alpha amplitude were found over both right and left parietal areas and over the left frontal region. In beta 1 non-significant trends in the same direction were observed in the same regions found to be significant in alpha. Non-significant trends in beta 2 were observed over the right parietal and frontal regions. No differences in amplitude at any frequency band were found between good and poor VMIQ scorers but subjects with high MRT scores showed greater alpha amplitude at many sites in the parietal, parieto-occipital and frontal areas than subjects with low MRT scores. During VMIQ testing the VMIQ high imagers showed a non-significant trend towards higher alpha amplitude at frontal regions and some scattered parietal and occipital sites and significantly higher levels of beta 2 in the left frontal region. However, no differences were found between imagery and control conditions. The results confirm the involvement of motor as well as spatial processes in dynamic imagery.

Adult↗