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Biomedical subjects

W G Humphreys

Publications and source records attributed to W G Humphreys.

At least 37 records · Page 2Linked to original sources
PubMed1990

Comparison of the DNA-alkylating properties and mutagenic responses of a series of S-(2-haloethyl)-substituted cysteine and glutathione derivatives.

The mutagenicity of 1,2-dibromoethane is highly dependent upon its conjugation to glutathione by the enzyme glutathione S-transferase. The conjugates thus formed can react with DNA and yield almost exclusively N7-guanyl adducts. We have synthesized the S-haloethyl conjugates of cysteine and glutathione, as well as selected methyl ester and N-acetyl derivatives, and compared them for ability to produce N7-guanyl adducts with calf thymus DNA. The cysteine compounds were found to be more reactive toward calf thymus DNA and yielded higher adduct levels than did the glutathione compounds. Adduct levels tended to be suppressed when there was a net charge on the compound and were not affected by substitution of bromine for chlorine, as expected for a mechanism known to involve an intermediate episulfonium ion. Sequence-selective alkylation of fragments of pBR322 DNA was investigated. The compounds produced qualitatively similar patterns of alkylation, with higher levels of alkylation at runs of guanines. The compounds were also tested for their ability to act as direct mutagens in Salmonella typhimurium TA98 and TA100. None of the compounds caused mutations in the TA98 frameshift mutagenesis assay. In the strain TA100, where mutation of a specific guanine by base-pair substitution produces reversion, all compounds were found to produce mutations, but the levels of mutagenicity did not correlate at all with the levels of DNA alkylation. The ratio of mutations to adducts varied at least 14-fold among the various N7-guanyl adducts examined.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkylating Agents↗
PubMed1990

Subungal melanoma.

Subungal melanoma is a rare condition accounting for 1-3% of all melanomas. It has been associated with a poor prognosis, with a 10-30% 5 year survival usually attributed to the delay in diagnosis. Early biopsy of suspicious lesions followed by amputation of the digit in those proving positive is the treatment of choice.

Aged↗
PubMed1990

DNA-glutathione adducts derived from vic-dihaloalkanes: mechanisms of mutagenesis.

The conjugation of the prototype dihaloalkane ethylene dibromide (EDB) with glutathione (GSH) yields S-(2-bromoethyl)GSH, which gives rise to S-[2-(N7-guanyl)ethyl]GSH as the major DNA adduct (greater than or equal to 95%). All reaction steps have SN2 character. Another minor DNA and RNA adduct is S-[2-(N1-adenyl)ethyl]GSH, formed in vitro and in vivo. These adducts have similar half-lives in vivo. Enhancement of GSH conjugation or inhibition of cytochrome P-450 IIE1 oxidation enhances DNA adduct levels in vivo and GSH depletion lowers levels. The mercapturic acid N-acetyl-S-[2-(N7-guanyl)ethyl]cysteine is excreted in urine and may find use as a biomarker. A series of compounds of the general structure RSCH2CH2Cl has been used to alkylate Salmonella typhimurium TA100. The ratio of (guanyl) base-pair mutations to N7-guanyl adducts varies dramatically, with S-(2-chloroethyl)GSH apparently producing the most potent guanyl adduct. This mutagenicity is not due to SOS response or alkylation specificity. Physical studies with modified oligonucleotides indicate that the N7-guanyl substitution weakens G-C pairing but does not in itself alter the selectivity of pairing to C in an isolated oligomer.

Alkylation↗
PubMed1990

Crohn's disease in Northern Ireland--a retrospective study of 440 cases.

The incidence of Crohn's disease in the community is thought to be changing, with conflicting evidence for increases, decreases or steady state situations being described. A retrospective study, using strict criteria for diagnosis, for a 16 year period in Northern Ireland demonstrated an increasing incidence of Crohn's disease, with a distribution in the population similar to that described in previous studies.

Adolescent↗
PubMed1990

Impact of community violence on the workload of a district general hospital.

Clinical observation suggests that deliberate violence against the person is increasing in both incidence and severity in the community. Over a six-year period there was a trend towards an annual increase in the number of attendances at the Waveney Hospital as the result of assaults. A retrospective study for a six-month period (August 1987 to January 1988) defined the pattern of attendance, injuries and treatment for 284 cases. Most of the victims were young males who presented outside normal working hours with superficial injuries. Admission was required in 12% of patients.

Adolescent↗
PubMed1990

Gastric paraganglioma: an immunohistological and ultrastructural case study.

This is a report of the immunohistochemical and ultrastructural features of a case of paraganglioma of the stomach in a 61-year-old woman who presented with melaena. The typical 'Zellballen' arrangement of epithelial cells with granular cytoplasm was present and the tumour was highly vascular. The polygonal epithelial cells stained strongly for neuron specific enolase and the intervening elongated sustentacular or support cells were positive for S100 protein and vimentin. Many dense core granules were present within the epithelial cells while the elongated support cells contained plentiful diffuse intermediate filaments. No hybrid cells or ganglion cells were present in the tumour. This is the sixth recorded case of gastric paraganglioma and the first to be studied in detail by immunostaining and electron microscopy.

Female↗
PubMed1990

Disseminated intravascular coagulation complicating Ender's nailing of a pathologic fracture in prostatic carcinoma. A case report.

Disseminated intravascular coagulation (DIC) occurred after closed Ender's pinning of a pathologic fracture of the humerus in a 58-year-old man with metastatic prostatic carcinoma. A review of the oncologic and urologic literature revealed that coagulopathy can be associated with prostatic carcinoma. This association seems not to have been previously reported in the orthopedic literature.

Bone Nails↗
PubMed1988

The effects on tubulin polymerization and associated guanosine triphosphate hydrolysis of aluminum ion, fluoride and fluoroaluminate species.

The effects of aluminum ion, fluoride, and fluoroaluminate species on the assembly of tubulin in the presence of guanine nucleotides and the consequences of these ions on the associated GTPase of microtubules was investigated. Combinations of GDP and fluoroaluminate species were incapable of activating tubulin for polymerization, in contrast to other guanine nucleotide binding proteins, in which these species produce a functional GTP equivalent. Fluoride alone has an effect on GTP-magnesium-promoted microtubule assembly, causing an increased amount of polymer formation and a reduced rate of associated GTP hydrolysis. It is concluded that aluminum ion and fluoroaluminate species possess distinct mechanisms in inhibiting GTP hydrolysis of GTP-binding proteins and that subpopulations of GTP-binding proteins must exist based on differential sensitivities to these ions.

Aluminum↗
PubMed1988

Some clinical aspects of Crohn's disease in Northern Ireland: an aid to earlier diagnosis?

A retrospective epidemiological study of Crohn's disease in Northern Ireland between 1966 and 1981 has been carried out. Using strict diagnostic criteria 440 cases were identified and aspects of the clinical presentation of the disease at initial diagnosis were examined. This paper describes the clinical pattern of the major symptoms of the disease and highlights the delay in diagnosis. One-third of cases (32.7%) were not diagnosed until more than a year after the onset of symptoms and 7.5% of cases were not diagnosed for more than five years. Colicky abdominal pain, one of the classical diagnostic symptoms of Crohn's disease was not present at initial diagnosis in 28.6% of cases nor were altered bowel habits found in 24.5% of cases. Only 17.7% of cases had an abdominal mass, just over half had an elevated erythrocyte sedimentation rate or lowered haemoglobin level and only 39.8% had rectal bleeding.Increased awareness by general practitioners of the delay in diagnosis of Crohn's disease may lead to earlier investigation and diagnosis of the condition which in this community occurs with an incidence of 2.34 new cases per 100 000 of the population per year.

Adolescent↗
PubMed1987

Promotion of tubulin assembly by aluminum ion in vitro.

It has been proposed that aluminum ion is a contributing factor in a variety of neurological diseases. In many of these diseases, aberrations in the cytoskeleton have been noted. The effects of aluminum ion on the in vitro assembly of tubulin into microtubules has been examined by determining the association constants for the metal ion-guanosine triphosphate-tubulin ternary complex required for polymerization. The association constant for aluminum ion was approximately 10(7) times that of magnesium ion, the physiological mediator of microtubule assembly. In addition, aluminum ion at 4.0 X 10(-10) mole per liter competed effectively with magnesium ion for support of tubulin polymerization when magnesium ion falls below 1.0 millimole per liter. The microtubules produced by aluminum ion were indistinguishable from those produced by magnesium ion when viewed by electron microscopy, and they showed identical critical tubulin concentrations for assembly and sensitivities to cold-induced depolymerization. However, the rate of guanosine triphosphate hydrolysis and the sensitivity to calcium ion-induced depolymerization, critical regulatory processes of microtubules in vivo, were markedly lower for aluminum ion microtubules than for magnesium ion microtubules.

Aluminum↗
PubMed1986

The presentation and management of presacral tumours.

Twenty cases of presacral tumours are presented, nine males and eleven females being affected. Malignancy occurred in 50 per cent of adults and was commoner in men than in women. Diagnosis depends on a careful rectal examination. Computerized axial tomography is the single most useful investigation; however, should it not be available, plain X-rays and ultrasonography give considerable information. For lesions less than 10 cm in size a local parasacral approach is often feasible but for larger lesions an abdominal approach or combined approach should be considered.

Adolescent↗
PubMed1985

Closed abdominal trauma in a child causing avulsion of the common bile duct and gastric stasis.

A case of closed abdominal trauma causing complete transection of the supraduodenal common bile duct and gastric stasis in an 8-year-old boy is described. Surgical management involved re-establishment of biliary-enteric continuity and later gastric drainage to overcome gastric stasis. It is postulated that this child had sustained a traumatic vagotomy resulting in failure of gastric emptying. The literature does not report this complication of blunt abdominal injury.

Abdominal Injuries↗
PubMed1984

A plea for judgment in management of thoracolumbar fractures and fracture-dislocations. A reassessment of surgical indications.

Until basic knowledge of fracture anatomy and stability includes experiments with comminuted anterior column injuries, posterior column injuries, and these injuries in combination with ligament and capsular injuries, and until the long-term implications of the long fusion in an otherwise healthy patient are fully known, clinicians making decisions about individual patients must assemble all the variables that bear on the patient's ability to heal and become fully functional again before making a decision about surgical stabilization of the thoracolumbar fracture. An assessment of plain roentgenograms, tomograms, and CAT scans and an understanding of the anatomy of the fracture site provide essential but insufficient data for clinical decisions about patients.

Fracture Fixation, Internal↗