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Biomedical subjects

H J Williams

Publications and source records attributed to H J Williams.

At least 109 records · Page 6Linked to original sources
PubMed1988

Site-directed mutagenesis and high-resolution NMR spectroscopy of the active site of porphobilinogen deaminase.

The active site of porphobilinogen (PBG)1 deaminase (EC 4.3.1.8) from Escherichia coli has been found to contain an unusual dipyrromethane derived from four molecules of 5-aminolevulinic acid (ALA) covalently linked to Cys-224, one of the two cysteine residues conserved in E. coli and human deaminase. By use of a hemA- strain of E. coli the enzyme was enriched from [5-13C]ALA and examined by 1H-detected multiple quantum coherence spectroscopy, which revealed all of the salient features of a dipyrromethane composed of two PBG units linked head to tail and terminating in a CH2-S bond to a cysteine residue. Site-specific mutagenesis of Cys-99 and Cys-242, respectively, has shown that substitution of Ser for Cys-99 does not affect the enzymatic activity, whereas substitution of Ser for Cys-242 removes essentially all of the catalytic activity as measured by the conversion of the substrate PBG to uro'gen I. The NMR spectrum of the covalent complex of deaminase with the suicide inhibitor 2-bromo-[2,11-13C2]PBG reveals that the aninomethyl terminus of the inhibitor reacts with the enzyme's cofactor at the alpha-free pyrrole. NMR spectroscopy of the ES2 complex confirmed a PBG-derived head-to-tail dipyrromethane attached to the alpha-free pyrrole position of the enzyme. A mechanistic rationale for deaminase is presented.

Ammonia-Lyases↗
PubMed1988

Identification of a cysteine residue as the binding site for the dipyrromethane cofactor at the active site of Escherichia coli porphobilinogen deaminase.

The dipyrromethane cofactor of Escherichia coli porphobilinogen deaminase was specifically labelled with 13C by growth of the bacteria in the presence of 5-amino[5-13C]levulinic acid. Using 13C-NMR spectroscopy, the structure of the cofactor was confirmed as a dipyrromethane made up of two linked pyrrole rings each derived from porphobilinogen. The chemical shift data indicate that one of the pyrrole rings of the cofactor is covalently linked to the deaminase enzyme through a cysteine residue. Evidence from protein chemistry studies suggest that cysteine-242 is the covalent binding site for the cofactor.

Aminolevulinic Acid↗
PubMed1988

One-year experience in patients treated with auranofin following completion of a parallel, controlled trial comparing auranofin, gold sodium thiomalate, and placebo.

Following a 21-week double-blind trial that compared the effects of treatment with auranofin (AUR), gold sodium thiomalate, and placebo in 193 patients, 147 patients entered a 1-year, open-label study of treatment with AUR (6 mg/day). Results of this open-label study suggest that AUR has a long-term use profile similar to that of other slow-acting antirheumatic drugs. AUR appears to be capable of sustaining an initial response to gold sodium thiomalate. The withdrawal rate remains relatively high: Nearly half of the study patients had discontinued AUR by the end of 1 year.

Adolescent↗
PubMed1988

A controlled trial comparing sulfasalazine, gold sodium thiomalate, and placebo in rheumatoid arthritis.

One hundred eight-six patients with active rheumatoid arthritis were evaluated in a double-blind, randomized study that compared treatment with sulfasalazine (SSZ) (2 mg/day), gold sodium thiomalate (GST) (50 mg/week), and placebo (PBO). The 37-week course of therapy was completed by 109 patients. While marked improvement was seen in all 3 treatment groups, the only statistically significant differences between SSZ or GST and PBO were in a decreased erythrocyte sedimentation rate and increased grip strength in the right hand. GST is known to be superior to PBO, and the response of the GST-treated group was similar to that seen in other trials. The response of the PBO group, however, was much greater than in other placebo groups we have studied. SSZ was similar in efficacy to injectable gold, but was better tolerated. Because of adverse drug reactions (most commonly, rash, stomatitis, and proteinuria), 41% of patients were withdrawn from the GST treatment. Untoward drug effects (most frequently, rash and gastrointestinal distress) caused 16% of patients to be withdrawn from SSZ therapy.

Adolescent↗
PubMed1988

In vivo and solid state 13C nuclear magnetic resonance studies of tyrosine metabolism during insect cuticle formation.

1. Tyrosine metabolism during pupation can be followed in living Heliothis virescens larvae using nuclear magnetic resonance spectroscopy. 2. Loss of 13C signals from a label at the C-3 position of tyrosine during pupation indicates uptake of tyrosine into solid cuticle. 3. Solids 13C NMR spectroscopy of cuticle formed by insects injected with 3-13C labelled tyrosine indicates that little change in chemical shift occurs during cuticle hardening, indicating that the side chain is probably not involved in protein cross-linking.

Animals↗
PubMed1988

Cervical spine management in patients with rheumatoid arthritis. Review of the literature.

Rheumatoid arthritis of the cervical spine is a well-recognized source of neck pain. Discussion of the potential effects of various treatment interventions on the tissues of patients with rheumatoid arthritis of the cervical spine, however, has been scarce in the physical therapy literature. Physical therapists should understand the implications of this type of inflammatory arthritis when treating patients with rheumatoid arthritis. The end-stage results of the inflammatory process and the mechanical forces on the cervical spine can cause atlantoaxial subluxation, atlantoaxial impaction, and subaxial subluxation. The purpose of this article is to review the literature on several aspects of rheumatoid arthritis of the cervical spine: 1) pathological anatomy, 2) clinical findings, 3) surgical management, 4) management with cervical orthoses, and 5) physical therapy management.

Arthritis, Rheumatoid↗
PubMed1988

Comparisons of sulfasalazine to gold and placebo in the treatment of rheumatoid arthritis.

Studies comparing sulfasalazine to gold or placebo are few in number. Two controlled trials have been conducted comparing sulfasalazine and placebo, and 2 uncontrolled trials have compared sulfasalazine and gold sodium thiomalate. A controlled trial conducted by the Cooperative Systematic Studies of Rheumatic Diseases compared enteric coated sulfasalazine, gold, and placebo. These studies suggest that sulfasalazine is superior to placebo but is associated with significant side effects, particularly gastrointestinal. These studies also suggest that sulfasalazine is similar in efficacy to gold, but with lesser and milder toxicity. Additional comparison studies are indicated.

Arthritis, Rheumatoid↗
PubMed1988

Nonoperative management of blunt hepatic trauma in adults.

Although well accepted in pediatric patients, nonoperative management of blunt hepatic trauma in adults remains controversial. From January 1981 through May 1987, 66 adults were identified with blunt hepatic trauma that had been confirmed by abdominal exploration or abdominal computed tomography (CT): 46 underwent immediate operation, and 20 were initially managed nonoperatively. Patients were considered for nonoperative management only if they were hemodynamically stable and had no significant peritoneal irritation. CT criteria for nonoperative management included contained subcapsular or intrahepatic hematoma, unilobar fracture, absence of devitalized liver, minimal intraperitoneal blood, and absence of other significant intra-abdominal organ injuries. The predominant CT pattern in the 17 patients successfully managed nonoperatively included unilobar right-lobe fracture or intrahepatic hematoma. A small amount of blood in either gutter or in the pelvis did not portend failure of nonoperative management. No delayed complications were noted during an average follow-up of 27 months. Nonoperative management of blunt hepatic injury based on abdominal CT findings is a useful alternative in a select group of hemodynamically stable patients.

Accidents, Traffic↗
PubMed1988

Gynecomastia as a complication of auranofin therapy.

Gynecomastia was found in a patient taking 12 mg of auranofin (AF) daily. The gynecomastia was noticed after AF was increased to this dose and resolved after the drug was discontinued. The patient refused rechallenge.

Adult↗
PubMed1987

Membrane phenotype and response to deoxycoformycin in mature T cell malignancies.

The adenosine deaminase inhibitor deoxycoformycin was used in low doses to treat 19 patients with clinically aggressive T cell malignancy with a mature membrane phenotype. The patients comprised eight with prolymphocytic leukaemia, two with chronic lymphocytic leukaemia, four with adult T cell leukaemia-lymphoma, three with Sézary syndrome, and two with T cell lymphoma. Two thirds of the patients had been resistant or minimally responsive to combination chemotherapy. Complete remission was obtained in five patients (two with prolymphocytic leukaemia and one each with chronic lymphocytic leukaemia, adult T cell leukaemia-lymphoma, and Sézary syndrome) and partial remission in two others. Unmaintained complete remission lasting more than one year was seen in three patients. Responses were obtained only in patients with CD4+,CD8-membrane markers (seven out of 10), and no responses were recorded in any of the nine patients with a different phenotype. In this series remission appeared to correlate with the membrane phenotype of the neoplastic cell and not with the cytopathological diagnosis. Future studies should establish the biochemical basis for the greater sensitivity of CD4+ lymphoid cells to deoxycoformycin.

Adult↗
PubMed1987

Arthritis in hereditary hemochromatosis.

Seven pedigrees with 45 members were evaluated for arthropathy associated with hereditary hemochromatosis (HC). Patients with symptomatic extraarticular disease were compared with asymptomatic patients who had evidence of HC on laboratory findings, and with normal subjects. Patients who were homozygous for HC were compared with heterozygous patients and normal subjects. HC arthritis does not appear to be an early predictor of disease, and chondrocalcinosis is a late manifestation of HC arthropathy.

Adult↗
PubMed1987

Percutaneous renal calculus removal in an extracorporeal shock wave lithotripsy practice.

The introduction of extracorporeal shock wave lithotripsy and transurethral ureteroscopy have altered markedly the incidence of standard surgical and percutaneous stone removal procedures. To help define the present role of percutaneous procedures in our practice we evaluated our indications, results and the clinical course of 143 patients who were treated primarily with percutaneous methods during 1 year in which extracorporeal shock wave lithotripsy also was available. The complexity of these residual percutaneous cases necessitated repeat endoscopic or fluoroscopic stone removal procedures in 20 per cent and ancillary extracorporeal shock wave lithotripsy in 22 per cent, and led to a slightly higher complication rate than in our previous percutaneous series. Despite the effectiveness of extracorporeal shock wave lithotripsy, percutaneous methods still are necessary for comprehensive therapy of upper tract urolithiasis.

Body Height↗
PubMed1987

Benign postoperative biliary strictures: dilation with fluoroscopic guidance.

Benign postoperative biliary strictures in 74 patients were dilated percutaneously with balloon catheters. In all cases, dilation was performed with fluoroscopic guidance in a radiology suite. Lasting patency following removal of biliary stents occurred in 73% of 49 patients with biliary-enteric anastomotic strictures and in 88% of 25 patients with primary ductal strictures, for an overall success rate of 78%. A successful outcome was more likely if the interval between the last biliary tract surgery and balloon dilation exceeded 2 years. Stricture patency was more easily achieved in patients with primary ductal strictures than in those with biliary-enteric anastomotic strictures. Serious, procedure-related complications were encountered when strictures were dilated transhepatically; these included sepsis in 18 of 65 patients and bleeding due to arteriobiliary communications in seven. No serious complications occurred when strictures were dilated via a T tube track, making this the preferred route if available. Surgeons should be encouraged to leave T tubes in place if postoperative biliary stricture is suspected. Balloon dilation should be strongly considered in patients with benign postoperative strictures in whom surgical repair is difficult.

Adult↗
PubMed1986

Diagnosis and treatment of jaundice.

1. CT and sonography are helpful in distinguishing between an obstructing lesion and hepatocellular disease as the cause of jaundice. 2. CT and sonography can demonstrate the level and extent of an obstructing lesion, and can define its nature if a mass more than 1-2 cm is present; sonography is usually the preferred screening study because of its availability, relatively low cost and lack of radiation hazard. 3. PTC or ERCP is useful in the evaluation of jaundice when sonography and CT are equivocal, fail to provide information necessary to establish proper therapy, or are at variance with the clinical impression of obstructive jaundice; in addition to defining obstructions these techniques can detect atrophy, sequestra, stones, abscesses, fistulas, primary sclerosing cholangitis, etc. 4. PBD offers an expedient alternative to surgical decompression in patients with obstructive jaundice, since most cancers that cause biliary obstruction are not resectable for cure at the time of diagnosis.

Adenoma, Bile Duct↗