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Biomedical subjects

R S Williams

Publications and source records attributed to R S Williams.

At least 109 records · Page 6Linked to original sources
PubMed1995

Granulomatous lobular mastitis.

Two cases of benign lobular granulomatous mastitis, both clinically felt to be carcinoma, are reported. One patient was cured by local excision of the mass while the other was cured by oral prednisolone, demonstrating the variable ways to treat this entity. The clinical and histological features were similar to those noted in previous reports. Immunological studies revealed predominantly stromal T lymphocytes and only duct intra-epithelial T lymphocytes.

Administration, Oral↗
PubMed1995

Lack of plasma complement activation in severe acute alcoholic hepatitis.

To investigate whether complement pathway activation contributes to the clinical and histological features of acute alcoholic hepatitis, we studied the activation of the classical and alternative pathways in patients with alcoholic hepatitis (n = 20), inactive alcoholic cirrhosis (n = 8), heavy drinkers without alcoholic liver disease (n = 10), patients with liver disease of nonalcoholic etiology (n = 11), and healthy control subjects (n = 18). Complement activation was evaluated in the alcoholic hepatitis patients by its correlation with a number of clinical and laboratory features indicative of the severity of liver injury, as well as by comparison of the patient groups. There was no significant difference in circulating C3 [1.02 g/liter, confidence interval (CI) = 0.76-1.28] or C4 (0.25 g/liter, CI = 0.17-0.33) in patients with alcoholic hepatitis when compared with the four control groups. Factor B levels (0.24 g/liter, CI = 0.21-0.27) were higher in the alcoholic hepatitis patients than the control groups (p < 0.01). However, activation of complement (given by the ratios C3d/C3, C4d/C4, and Ba/factor B) was not different in alcoholic hepatitis patients when compared with the control groups. Univariate analysis of a wide range of clinical and laboratory features in the alcoholic hepatitis subjects showed a positive correlation between plasma C3 and serum alkaline phosphatase (r = 0.68, p = 0.0014), AST (r = 0.55, p = 0.015), and gamma-glutamyltranspeptidase (r = 0.47, p = 0.035), but no correlation with clinical or laboratory features associated with high morbidity or mortality. There is no relationship between clinical or laboratory indicators of disease severity and complement activation, and it is unlikely that complement activation contributes to the clinical and histological features of alcoholic liver disease.

Acute Disease↗
PubMed1995

Synergistic interactions between heterologous upstream activation elements and specific TATA sequences in a muscle-specific promoter.

Previous investigations have defined three upstream activation elements--CCAC, A/T, and TATA sequences--necessary for muscle-specific transcription of the myoglobin gene. In the present study, we demonstrate that these three sequences elements, prepared as synthetic oligonucleotide cassettes, function synergistically to constitute a cell-type-specific transcription unit. Previously, cognate binding factors that recognize the CCAC and TATA elements were identified. In this study we determine that the A/T element binds two nuclear factors, including myocyte enhancer factor-2 (MEF-2) and an apparently unknown factor we provisionally termed ATF35 (A/T-binding factor, 35 kDa). Mutations that alter in vitro binding of either MEF-2 or ATF35 to this site diminish promoter function in vivo. Functional synergism between factors binding the CCAC and A/T elements is sensitive to subtle mutations in the TATA sequence, recapitulating the unusual preference for specific TATA variants exhibited by the native myoglobin promoter. These results provide new insights into mechanisms that underlie the distinctive pattern of myoglobin gene regulation in mammalian muscle development and lay a foundation for further studies to elucidate general principles of transcriptional control of complex mammalian promoters through combinatorial actions of heterologous transcriptional factors.

Animals↗
PubMed1995

Nuclear responses to depletion of mitochondrial DNA in human cells.

The derivation of human cell lines devoid of mitochondrial (mt) DNA (rho 0) provides an opportunity to study nuclear responses to a chronic impairment of mitochondrial oxidative phosphorylation. Expression of several nuclear genes is induced in human rho 0 cells, including those encoding integral proteins of the mitochondrial inner membrane, intermediate filaments, and ribosomes. In contrast to conditions in which mitochondrial respiration is altered acutely, expression of heat shock proteins and immediate early genes is not induced. Mitochondria from rho 0 cells maintain a transmembrane electrochemical potential and are distributed within the cytoplasm of these cells in a manner indistinguishable from that of wild-type cells. We conclude that a chronic deficiency of mitochondrial oxidative phosphorylation produced by elimination of mtDNA is associated with a different pattern of gene induction than that provoked by other acute or subacute conditions that impair mitochondrial respiration or create energy demands in excess of mitochondrial respiratory capacity.

Base Sequence↗
PubMed1995

Effect of skeletal muscle fiber type on the pressor response evoked by static contraction in rabbits.

The purpose of this study was to determine whether the reflex hemodynamic responses to static contraction of predominately glycolytic muscle are greater than the changes elicited by primarily oxidative muscle. Low-frequency electrical stimulation (continuous 21 days) of the tibial nerve of one hindlimb of adult rabbits converted the metabolic characteristics of the predominately glycolytic gastrocnemius to a muscle that was primarily oxidative. After 21 days of stimulation, the rabbits were decerebrated, and static contraction of the glycolytic muscle (unstimulated gastrocnemius) initially decreased heart rate (HR; -16 +/- 3 beats/min) and mean arterial pressure (MAP; -17 +/- 3 mmHg). Thereafter, MAP increased 13 +/- 3 mmHg above baseline. Static contraction of the oxidative muscle (stimulated gastrocnemius) produced similar decreases in HR and MAP (-12 +/- 4 beats/min and -12 +/- 3 mmHg, respectively). However, the subsequent increase in MAP (8 +/- 3 mmHg; above baseline) was less than that evoked by contraction of the glycolytic muscle. The responses evoked by stretch of each muscle and high-intensity electrical stimulation were the same, indicating that the afferents from the muscle were not destroyed by the chronic-stimulation technique. These results support the hypothesis that metabolic by-products play a role in the pressor response to static contraction of skeletal muscle. In addition, these data confirm that contraction of predominately oxidative muscle can evoke a reflex pressor response, albeit smaller than the change elicited from primarily glycolytic muscle.

Analysis of Variance↗
PubMed1994

Ethanol augments pre-emptive analgesia produced by nitrous oxide in the formalin test in the rat.

Experimental evidence suggests that the introduction of analgesia prior to a painful stimulus can reduce the subsequent pain (preemptive analgesia). Using the formalin test model, previous studies have demonstrated that general volatile anesthetics reduce the pre-emptive analgesia produced by nitrous oxide administration in the rat. The present study compared the influence of halothane and ethanol on the response to formalin injection in rats previously exposed or not exposed to nitrous oxide. Nitrous oxide decreased second phase licking behavior by approximately 70% from controls. Halothane decreased second phase licking by 37% from sham animals and, when administered with nitrous oxide, mitigated the suppression of licking seen with nitrous oxide alone. Ethanol reduced the licking response in both early and late phases following formalin injection. In contrast to halothane, ethanol failed to attenuate the analgesia produced by nitrous oxide administration alone. Thus, ethanol provides apparent analgesia following formalin injection and, unlike halothane, augments the preemptive analgesia produced by nitrous oxide.

Analgesics↗
PubMed1994

Nitrate reductase of the ascomycetous fungus, Leptosphaeria maculans: gene sequence and chromosomal location.

The nitrate reductase (niaD) gene was isolated from the phytopathogenic loculoascomycete Leptosphaeria maculans by screening a genomic DNA library with the Aspergillus nidulans niaD gene. The L. maculans niaD gene is the first protein-encoding gene characterised from this fungus. It encodes a predicted protein of 893 amino acids and contains four putative introns at positions in the gene equivalent to those of four of the six introns in the A. nidulans niaD gene. Mutants defective in niaD and molybdenum cofactor gene(s) of L. maculans have been isolated. Transformation of a L. maculans niaD mutant with a 3.8 kb SacII fragment containing the L. maculans niaD gene restored wild-type growth on nitrate as a sole nitrogen source. The niaD gene is present as a single copy on a chromosome which ranges in size from 2.6 to 2.8 Mb between the different L. maculans isolates examined.

Amino Acid Sequence↗
PubMed1994

Comparison of antibiotic release from polymethylmethacrylate beads and sponge collagen.

The rates of elution of tobramycin in vitro were compared for polymethylmethacrylate beads impregnated with the powder form and an alternative biodegradable substance, sponge collagen. The impregnated polymethylmethacrylate beads initially had a lower zone of inhibition, but the rate of release was slow in comparison with that of the impregnated sponge collagen. The sponge collagen delivered a higher dose faster and with a shorter duration than the polymethylmethacrylate beads with the same antibiotic concentration in vitro, but the beads delivered a therapeutic concentration for longer periods. Because it deteriorates rapidly, sponge collagen may be unsatisfactory as an agent of antibiotic delivery in patients who have chronic osteomyelitis; however, it may be useful for patients who have acute trauma with highly contaminated bone or soft tissue, or during hemiarthroplasty revision, to deliver a high local concentration of antibiotic for a short period of time.

Anti-Bacterial Agents↗
PubMed1994

Neem oil inhibits two-cell embryo development and trophectoderm attachment and proliferation in vitro.

PURPOSE: The in vitro effect of neem oil was studied on the development of mouse two-cell embryos and trophectodermal cell attachment and proliferation. METHOD: Female mice were primed with gonadotropins for superovulation and caged with male mice. Early embryos, at the two-cell and the blastocyst stages, were recovered at 40 and 88 hr post-hCG from the oviducts and the uteri, respectively. In the first experiment, two-cell embryos were exposed to culture medium containing different concentrations of neem oil for 1, 12, and 24 hr and then grown in neem oil-free culture medium and assessed for the formation of total and hatching blastocysts at 96 hr. In the second experiment, partially hatching blastocysts were cocultured with human endometrial stromal cell monolayers in culture medium containing different concentrations of neem oil and assessed for the attachment and proliferation of trophectodermal cells at 96 hr. RESULTS: Exposure of two-cell embryos to neem oil concentrations of 0.050-0.500% for 1 hr, 0.010-0.250% for 12 hr, and 0.005-0.100% for 24 hr caused significant inhibition of the formation of total and hatching blastocysts, in a dose-dependent manner. Neem oil at 0.050-0.100% concentrations inhibited, in a dose-dependent manner, the in vitro attachment and proliferation of trophectodermal cells of partially hatching blastocysts cocultured with human endometrial stromal cells monolayers. CONCLUSION: Neem oil inhibits the development of two-cell embryos and attachment and proliferation of the trophectodermal cells of partially hatching blastocysts in vitro. The study encourages the use of this herbal product as a postcoital contraceptive that warrants further research.

Animals↗
PubMed1994

Long-term effects of polytetrafluoroethylene injected into the rat bladder submucosa.

OBJECTIVE: The use of polytetrafluoroethylene (PTFE) paste in the lower urinary tract for the treatment of vesicoureteral reflux or urinary incontinence is increasing. Its use remains controversial and the long-term consequence of this substance injected into the lower urinary system of humans is largely unknown. When injected into the bladder submucosa, PTFE paste has been shown to elicit a foreign body reaction with chronic inflammation and possibly granuloma formation. Whether these inflammatory changes result in neoplastic changes over the long term has yet to be determined. The purpose of this study was to evaluate histologically the potential for submucosal PTFE paste to induce bladder neoplasia in a rodent model, realizing that others have shown an increased tendency for such alloplastic materials to produce sarcomas in these animals. METHODS: Sixteen experimental animals and 4 control animals were sacrificed at various time intervals and evaluated for systemic and local tumor formation following submucosal injection of PTFE paste in the bladder. A time well beyond the equivalent of the latency period believed to be necessary for the induction of tumors in humans (15 months) was evaluated. RESULTS: On sacrifice, histologic changes consistent with encapsulation and chronic inflammation were evident, but there was no evidence of either epithelial or sarcomatous tumor formation. CONCLUSIONS: A quiescent foreign body reaction occurs when injecting PTFE into the bladder submucosa of rodents. Urologic use of PTFE has never been proven to induce tumors in humans or animals.

Animals↗
PubMed1994

Methemoglobin levels during prolonged combined nitroglycerin and sodium nitroprusside infusions in infants after cardiac surgery.

Nitroglycerin (NTG) and sodium nitroprusside (SNP) are routinely used perioperatively in infants with congenital heart defects. In this study, NTG and SNP were infused in the operating room to increase venous capacitance, reduce systemic and pulmonary afterload, facilitate weaning off cardiopulmonary bypass, stabilize hemodynamics for transport to the intensive care unit (ICU), and reduce the fluid resuscitation needed upon arrival in the ICU. Because of the risk for accumulation of methemoglobin (MetHb) and cyanmethemoglobin (cyan-MetHb) during prolonged continuous infusion of NTG and SNP, it was decided to (1) quantify ICU use, (2) measure % MetHb at 12-hour intervals, and (3) look indirectly for the accumulation of cyan-MetHb by comparing simultaneous pulse oximetry (SpO2) (Nellcor N-100 [Nellcor, Haywood, CO]) and CO-oximetry (SaO2) (Corning 270 [Corning, Medfield, MA]). A total of 69 arterial samples were obtained from 16 infants (median age 4.4 months) following cardiac surgery with bypass. Median doses of NTG, 6.0 mg/kg (range 0.7 to 27.5), and SNP, 3.3 mg/kg (range 0.6 to 33.4), were infused over a median of 64.5 hours (range 12 to 183) (N = 16 patients). The median MetHb was 0.6% (range 0.0 to 1.5) after infusions of NTG, 1.8 micrograms/kg/min (range 0.5 to 4), and SNP, 1.3 micrograms/kg/min (range 0.3 to 8.4) (N = 69 measurements). Regression analysis of oximetry data yielded the equation: SpO2 = 1.04 SaO2 - 3.7%, r = 0.97. The mean difference between SpO2 and SaO2 data pairs was 0.0% (bias) with a SD (precision) of +/- 2.3%.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Surgical Procedures↗
PubMed1994

Identification of epidermal growth factor, transforming growth factor-alpha, and epidermal growth factor receptor in surgically induced pelvic adhesions in the rat and intraperitoneal adhesions in the human.

OBJECTIVE: Our purpose was to determine the presence and cellular distribution of epidermal growth factor, transforming growth factor-alpha, and epidermal growth factor receptor in surgically induced pelvic fibrous adhesions in rat uterine horns subjected to burn, crush, and debridement injury and intraperitoneal fibrous adhesions formed to various organs in the human. STUDY DESIGN: A total of 15 injured and five uninjured rats were used in this study, and fibrous adhesions and intact peritoneum were removed for processing 2 weeks after surgery. Fibrous adhesions formed to uterine, ovarian, and oviductal tissues and the peritoneal wall from eight patients who had gynecologic surgery were also collected. The tissues were processed for immunohistochemical localization of epidermal growth factor, transforming growth factor-alpha, and epidermal growth factor receptor with specific antibodies to human and rat epidermal growth factor and transforming growth factor-alpha and the extracellular binding domain of the epidermal growth factor receptor. RESULTS: All the cell types in the rat fibrous adhesion immunostained for epidermal growth factor, transforming growth factor-alpha, and epidermal growth factor receptor. The highest immunostaining intensity for epidermal growth factor was associated with inflammatory cells infiltrated into the fibrous adhesion, followed by arteriole endothelial and smooth muscle cells, fascial striated muscle, and fibroblasts of the fibrous adhesion. In the uterine tissue at the site of injuries myometrial smooth muscle cells, in addition to inflammatory cells that migrated among stromal cells, also immunostained for epidermal growth factor. Fibrous adhesions also immunostained for transforming growth factor-alpha with three separate polyclonal antibodies to the amino and carboxy termini of transforming growth factor-alpha precursor and the mature transforming growth factor-alpha, with no substantial differences in their intensity and pattern compared with epidermal growth factor. The pattern and cellular distribution of epidermal growth factor receptor was similar to that seen for epidermal growth factor and transforming growth factor-alpha. Fibrous adhesions from patients with intraperitoneal adhesions immunostained for epidermal growth factor, transforming growth factor-alpha, and epidermal growth factor receptor with a pattern and intensity similar to that observed in fibrous adhesions in the rats. CONCLUSIONS: The data suggest that epidermal growth factor and transforming growth factor-alpha may play a key role both in normal mechanism of peritoneal repair after injury and formation and maintenance of fibrous adhesions.

Animals↗
PubMed1994

Subcellular partitioning of MRP RNA assessed by ultrastructural and biochemical analysis.

A small RNA encoded within the nucleus is an essential subunit of a RNA processing endonuclease (RNase MRP) hypothesized to generate primers for mitochondrial DNA replication from the heavy strand origin of replication. Controversy has arisen, however, concerning the authenticity of an intramitochondrial pool of MRP RNA, and has called into question the existence of pathways for nucleo-mitochondrial transport of nucleic acids in animal cells. In an effort to resolve this controversy, we combined ultrastructural in situ hybridization and biochemical techniques to assess the subcellular partitioning of MRP RNA. Cryosections of mouse cardiomyocytes were hybridized with biotin-labeled RNA probes complementary to different regions of MRP RNA and varying in length from 115 to 230 nucleotides, followed by immunogold labeling. In addition, we transfected mouse C2C12 myogenic cells with constructs bearing mutated forms of the mouse MRP RNA gene and compared the relative abundance of the resulting transcripts to that of control RNAs within whole cell and mitochondrial fractions. In the former analysis we observed preferential localization of MRP RNA to nucleoli and mitochondria in comparison to the nucleoplasm and cytoplasm. In the latter series of studies we observed that wild-type MRP RNA partitions to the mitochondrial fraction by comparison to other RNA transcripts that are localized to the extramitochondrial cytoplasmic space (28S rRNA) or to the nucleoplasm (U1 snRNA). Deletions within 5' or 3' regions of the MRP RNA gene produced transcripts that remain competent for mitochondrial targeting. In contrast, deletion of the midportion of the coding region (nt 118 to 175) of the MRP RNA gene resulted in transcripts that fail to partition to the mitochondrial fraction. We conclude that an authentic intramitochondrial pool of MRP RNA is present in these actively respiring cells, and that specific structural determinants within the MRP RNA molecule permit it to be partitioned to mitochondria.

Animals↗
PubMed1994

Emphysematous cholecystitis can cause pneumoperitoneum.

A case of emphysematous cholecystitis with gall-bladder perforation, resulting in free intraperitoneal gas, is presented. It adds to only nine previous reports. A successful outcome was achieved by early surgery, combined with appropriate antibiotic therapy.

Aged↗
PubMed1994

Myocyte nuclear factor, a novel winged-helix transcription factor under both developmental and neural regulation in striated myocytes.

A sequence motif (CCAC box) within an upstream enhancer region of the human myoglobin gene is essential for transcriptional activity in both cardiac and skeletal muscle. A cDNA clone, myocyte nuclear factor (MNF), was isolated from a murine expression library on the basis of sequence-specific binding to the myoglobin CCAC box motif and was found to encode a novel member of the winged-helix or HNF-3/fork head family of transcription factors. Probes based on this sequence identify two mRNA species that are upregulated during myocyte differentiation, and antibodies raised against recombinant MNF identify proteins of approximately 90, 68, and 65 kDa whose expression is regulated following differentiation of myogenic cells in culture. In addition, the 90-kDa form of MNF is phosphorylated and is upregulated in intact muscles subjected to chronic motor nerve stimulation, a potent stimulus to myoglobin gene regulation. Amino acid residues 280 to 389 of MNF demonstrate 35 to 89% sequence identity to the winged-helix domain from other known members of this family, but MNF is otherwise divergent. A proline-rich amino-terminal region (residues 1 to 206) of MNF functions as a transcriptional activation domain. These studies provide the first evidence that members of the winged-helix family of transcription factors have a role in myogenic differentiation and in remodeling processes of adult muscles that occur in response to physiological stimuli.

Amino Acid Sequence↗
PubMed1994

Biphasic induction of immediate early gene expression accompanies activity-dependent angiogenesis and myofiber remodeling of rabbit skeletal muscle.

Sustained contractile activity of skeletal muscle promotes angiogenesis, as well as transformation of contractile protein isoforms and mitochondrial proliferation within myofibers. Since the products of immediate early genes such as c-fos, c-jun, and egr-1 function in many signaling pathways governing cellular responses to external stimuli, we sought to determine whether sustained contractile activity induces their expression in skeletal muscle. Low voltage electrical stimulation was applied to the motor nerve innervating rabbit tibialis anterior muscles for periods ranging from 45 min to 21 d. Northern and Western analysis demonstrated marked but transient inductions of c-fos, c-jun, and egr-1 mRNA and protein within the first 24 h. Longer durations of stimulation were associated with a secondary and sustained rise in the abundance of c-fos, c-jun, and p88egr-1 protein that, surprisingly, was not accompanied by detectable changes in mRNA. Immunohistochemistry demonstrated c-fos immunoreactivity within myofiber and vascular cell nuclei during both early and late phases of this response. These findings reveal a complex pattern of c-fos, c-jun, and egr-1 expression in response to nerve stimulation and suggest that these proteins could function in regulatory pathways that modify muscle phenotype.

Animals↗
PubMed1994

Human uterine tissue throughout the menstrual cycle expresses transforming growth factor-beta 1 (TGF beta 1), TGF beta 2, TGF beta 3, and TGF beta type II receptor messenger ribonucleic acid and protein and contains [125I]TGF beta 1-binding sites.

The use of isoform-specific transforming growth factor-beta (TGF beta) primers, 35S-labeled 40-mer oligonucleotide probes and polyclonal antibodies, reverse transcription-polymerase chain reaction, in situ hybridization, and immunohistochemical observations has revealed that human uterine tissue at various reproductive stages expresses TGF beta s and TGF beta type II receptor messenger RNAs (mRNAs) and proteins. The reverse transcription-polymerase chain reaction revealed the predicted 443-, 310-, 524-, and 431-basepair fragments for TGF beta 1, TGF beta 2, TGF beta 3, and TGF beta type II receptor, respectively, in both endometrial and myometrial tissues, which were further verified by restriction enzyme analysis. In situ hybridization and immunohistochemical observations indicated that all uterine cell types express TGF beta s mRNAs and proteins. In the functionalis region, endometrial luminal and glandular epithelial cells are the primary cell types expressing TGF beta s mRNAs and proteins, with lesser expression in stromal cells, whereas in the basalis region, they are equally expressed in both cell types. In myometrium, TGF beta mRNA and protein expression in smooth muscle cells occurs at a substantially lower level than in endometrial tissue. In endometrial tissue, the highest level of TGF beta mRNA and protein expression appeared in the late proliferative and early to midsecretory phases of the menstrual cycle, with a considerable reduction during the late secretory and postmenopausal periods. The pattern and cellular distribution of TGF beta type II receptor protein were similar to those seen with TGF beta isoforms in both endometrial and myometrial tissues. Quantitative autoradiography (net grain density per 100 microns 2) of specific binding of [125I]TGF beta 1 for different uterine cell types indicated that the stromal cells contain a higher grain density than other uterine cell types (P < 0.05), without a significantly different density in the proliferative, compared with the secretory, phase of the menstrual cycle. These data suggest that TGF beta s acting through their specific receptors may play an important role in a variety of uterine functions in an autocrine/paracrine manner, and ovarian steroids may also regulate their expression in endometrial tissue.

Adult↗