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Biomedical subjects

E M Walker

Publications and source records attributed to E M Walker.

At least 55 records · Page 3Linked to original sources
PubMed1988

Selective release of the Treponema pallidum outer membrane and associated polypeptides with Triton X-114.

The effects of the nonionic detergent Triton X-114 on the ultrastructure of Treponema pallidum subsp. pallidum are presented in this study. Treatment of Percoll-purified motile T. pallidum with a 1% concentration of Triton X-114 resulted in cell surface blebbing followed by lysis of blebs and a decrease in diameter from 0.25-0.35 micron to 0.1-0.15 micron. Examination of thin sections of untreated Percoll-purified T. pallidum showed integrity of outer and cytoplasmic membranes. In contrast, thin sections of Triton X-114-treated treponemes showed integrity of the cytoplasmic membrane but loss of the outer membrane. The cytoplasmic cylinders generated by detergent treatment retained their periplasmic flagella, as judged by electron microscopy and immunoblotting. Recently identified T. pallidum penicillin-binding proteins also remained associated with the cytoplasmic cylinders. Proteins released by Triton X-114 at 4 degrees C were divided into aqueous and hydrophobic phases after incubation at 37 degrees C. The hydrophobic phase had major polypeptide constituents of 57, 47, 38, 33-35, 23, 16, and 14 kilodaltons (kDa) which were reactive with syphilitic serum. The 47-kDa polypeptide was reactive with a monoclonal antibody which has been previously shown to identify a surface-associated T. pallidum antigen. The aqueous phase contained the 190-kDa ordered ring molecule, 4D, which has been associated with the surface of the organisms. Full release of the 47- and 190-kDa molecules was dependent on the presence of a reducing agent. These results indicate that 1% Triton X-114 selectively solubilizes the T. pallidum outer membrane and associated proteins of likely outer membrane location.

Bacterial Outer Membrane Proteins↗
PubMed1987

Chelating-agent suppression of cadmium-induced hepatotoxicity.

The administration of sodium N-methyl-N-dithiocarboxy-D-glucamine (NaG) at 500 mg/kg, i.p., or sodium calcium diethylenetriaminepentaacetic acid (DTPA) at 632.5 mg/kg, i.p., reduces the serum enzyme levels characteristic of hepatic damage following the intravenous administration of cadmium chloride (3.5 mg CdCl2.2.5H2O/kg). Some effect on serum enzyme levels was found even when the interval between administration of cadmium chloride and that of the antagonist was as great as 4 h. The enzymes examined included aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), alanine aminotransferase (SGPT), and alkaline phosphatase (AP). A histopathological examination of the livers of such animals also reveals the presence of a significant protective action.

Alanine Transaminase↗
PubMed1987

Mortality and morbidity in infants born between 20 and 28 weeks gestation.

Of 149 infants with ultrasound evidence of gestational age, born in Ninewells Hospital at between 20 and 28 weeks gestation over a 5-year period, 50 were alive at birth. Of these infants, 21 died within 1 week, a further three died within 1 month and a further two within 18 months. Of the 24 survivors, 8 (33%) have significant handicap. The obstetric factors leading to delivery and the mode of delivery are discussed.

Delivery, Obstetric↗
PubMed1987

Effects of diethyldithiocarbamate and structural analogs in mice with systemic candidal infections.

Three different substituted dithiocarbamates: sodium diethyldithiocarbamate (DDTC), sodium dimethyldithiocarbamate (DmDTC), and sodium N-methyl-D-glucamine dithiocarbamate (NMG-DTC) were evaluated for their ability to combat the growth and development of three human pathogenic strains of Candida albicans, in vitro and in vivo, in mice. DDTC and DmDTC produced marked growth inhibition on agar plates, in vitro, of three different strains of Candida albicans, while NMG-DTC displayed little inhibitory effect. Low, nontoxic doses of each compound administered to immunosuppressed mice exhibited impressive therapeutic effects in treating candidiasis. NMG-DTC showed the best consistent therapeutic antifungal effect against Candida albicans in mice immunosuppressed with Solu-Medrol. Combinations of low doses of DDTC and Amphotericin-B appeared to be effective in treating systemic candidal infections, and the results suggested that these combinations may offer therapeutic advantages over those produced by the use of either agent alone.

Amphotericin B↗
PubMed1987

Dithiocarbamate inhibition of cadmium-induced changes in spermatozoan acetyltransferases.

The administration of sodium N-methyl-N-dithiocarboxy-D-glucamine (NaG) subsequent to the administration of CdCl2.2.5H2O to male rats, inhibits the cadmium-induced decreases in spermatozoan acetyltransferase (AT) levels and provides marked protection against the cadmium-induced morphologic testicular changes in the cauda and corpus and partial protection against the changes in the caput.

Acetyltransferases↗
PubMed1987

Acetaminophen-induced hepatotoxicity: antagonistic action of caffeine in mice.

Studies of interactions in mice between acetaminophen (ACM) and caffeine (CAF) revealed that CAF given immediately after ACM antagonized the acute toxicity of ACM and reduced the severity of ACM-induced hepatic necrosis as assessed grossly and microscopically. It also attenuated the elevations of SGOT and SGPT levels following ACM administration. CAF reduced significantly the magnitude of ACM-induced mobilization of cadmium from hepatic cadmium-metallothionein stores and the extent of binding of 3H-ACM to hepatic proteins. CAF did not restore hepatic GSH levels toward control values in ACM-treated mice; administration of CAF alone led to a reduction of hepatic GSH concentrations. It was concluded that the antagonistic action by CAF of ACM toxicity in mice is not mediated through a salutary effect on endogenous hepatic sulfhydryl levels. The significance of these observations was discussed in terms of possible interactions at the level of ACM and CAF biotransformation and the potential for interactions of CAF with other xenobiotics.

Acetaminophen↗
PubMed1986

Does mild atypia on a cervical smear warrant further investigation?

228 women referred to a colposcopy clinic over a 10-year period with mildly atypical cervical cytology had a histological diagnosis established by colposcopically directed biopsy. Of the 187 women (82.0%) who had dyskaryosis on the referral smear, 129 (69%) had cervical intraepithelial neoplasia (CIN) grade II or III on histology, as did 12 (29.2%) of the 41 women without dyskaryosis. 27.6% of smears taken at the time of colposcopy had normal cytology, although a third of these women had CIN II or III diagnosed on histology at that time. The poor correlation between mildly atypical cervical cytology and histology suggests that the practice of relying on cytology alone for the surveillance of women who have already had an atypical smear should be discouraged.

Adult↗
PubMed1986

Effects of acetaminophen on cadmium metabolism in mice.

Acetaminophen (ACM) administration to mice of the (C57BL/6 X DBA/2)F1 strain produced a typical hepatic centrilobular necrosis similar to that observed in rodents and humans. To determine the effects of this drug-induced necrosis on cadmium (Cd) metabolism, mice were given a sublethal dose of CdCl2 . 2.5 H2O containing 109CdCl2 and maintained for a period of time sufficient for Cd-metallothionein (Cd-MT) to be synthesized and distributed. Subsequent administration of ACM ip or po evoked a marked redistribution of Cd from livers to kidneys of mice, and increased the amount of Cd excreted in urine and feces. There were only minimal or no effects on Cd concentrations in other organs assessed. The effect of ACM on Cd redistribution was antagonized by administration of cysteine, a glutathione precursor, and was enhanced by pretreatment with phenobarbital, a potent inducer of the cytochrome P-450 mixed-function oxidase system. Pretreatment of mice with ACM 6 or 24 hr prior to Cd administration caused aberrations of the normal Cd distribution pattern, but no effect was noted when Cd administration was delayed for 48 hr after ACM injection, indicating recovery of the mechanisms of Cd-MT synthesis and sequestration. Sephadex G-75 gel filtration chromatography of serum from ACM-treated mice showed that most of the Cd was associated with high-molecular-weight proteins, and only a minor portion was present as Cd-MT. Cd excreted in urine was predominantly in a low-molecular-weight form, but there was evidence of two minor components of higher molecular weight, neither of which eluted as Cd-MT. Cd excreted in feces was insoluble following homogenization in 0.25 M sucrose solution. Cd in livers and kidneys of ACM-treated mice eluted as Cd-MT. It was concluded that persons who have a moderately high Cd burden may be at risk of Cd nephrotoxicity if they incur hepatic necrosis subsequent to ACM abuse.

Acetaminophen↗
PubMed1986

Comparative antidotal effects of diethyldithiocarbamate, dimercaptosuccinate, and diethylenetriaminepentaacetate against cadmium-induced testicular toxicity in mice.

The compounds diethyldithiocarbamate (DDTC, Dithiocarb), 2,3-dimercaptosuccinic acid (DMSA), and diethylenetriaminepentaacetic acid (DTPA) were evaluated for effectiveness in protecting mouse testes following administration of an LD100 dose of CdCl2 X 2.5 H2O (Cd). Toxicologic responses were assessed by light microscopic techniques. DTPA gave the most effective testicular protection of the three compounds when given within 30 minutes prior to Cd, but only DDTC was effective when given 30 minutes or longer after Cd. Degenerative changes were minimal when DDTC was given as late as three hours after Cd, and were mild following a four-hour interval. However, the changes were marked, but less severe than in mice receiving Cd only, when DDTC was administered five hours after Cd.

Animals↗
PubMed1986

Effects of caffeine on acetaminophen-induced hepatotoxicity and cadmium redistribution in mice.

When caffeine (CAF) was given ip to BDF1 mice immediately after an otherwise hepatotoxic dose of acetaminophen (ACM), the hepatotoxic action of ACM was abolished and there was no concomitant redistribution of previously-administered cadmium (Cd) from livers to kidneys as occurred in mice which received ACM only. These observations were not in accord with the recently reported enhancement of ACM hepatotoxicity by CAF following coadministration in rats (Toxicology 34, 95-101, 1985). Conversely, pretreatment of mice with CAF for 3 days followed by ACM injection enhanced the hepatotoxicity of ACM and caused a greater mobilization of Cd from livers to kidneys than was found in mice given ACM alone. The ACM-CAF interaction in mice is thus similar to the ACM-ethanol interaction in rats (Gastroenterology 80, 140-148, 1981; J. Pharmacol. Exptl. Therap. 218, 805-810, 1981). It is proposed that CAF interferes with the metabolism of ACM when administered concomitantly, but induces the microsomal mixed function oxidase system when used in a pretreatment regimen, leading to a more rapid rate of formation of the hepatotoxic arylating ACM biotransformation product.

Acetaminophen↗
PubMed1985

An investigation into in vitro methods for the detection of chlorhexidine resistance.

During an outbreak of catheter-related urinary tract infection, due to Proteus mirabilis, it was suggested that the epidemic strain was resistant to chlorhexidine. In this study, the minimum inhibitory concentrations (MICs) of chlorhexidine to the epidemic Pr. mirabilis and other laboratory isolates were tested in different media. Results were compared with killing times using 1/4 strength Ringers solution, normal human urine and the in vivo killing times in two patients' catheter bags. It was found that the MIC test was unreliable in the assessment of chlorhexidine resistance as it was dependent on the medium used, the inoculum size, and the age of the culture. The test which gave results closest to the in vivo experiments was the killing curve in normal human urine. It is concluded that chlorhexidine resistance is a complex phenomenon which is difficult to evaluate. If in vitro tests are to be used to evaluate the clinical relevance of reduced sensitivity to chlorhexidine, they must mimic the in-use conditions as closely as possible.

Chlorhexidine↗
PubMed1985

The action spectrum for benzanthrone photosensitization of mouse macrophages.

An in vitro method for determination of the phototoxic action spectrum of benzanthrone was established using a cover slip-test tube culture system with mouse peritoneal macrophages. The action spectrum peaked between 380 and 400 nm with abrupt fall-off to either side. These findings correlate closely with both the absorption spectrum of benzanthrone and the clinical action spectrum of phototoxicity in humans.

Animals↗
PubMed1984

Comparative effects of N,N-disubstituted dithiocarbamates and dimercaptosuccinate on mobilization of methylmercury in mice.

Diethyldithiocarbamate (DDTC) and five of its N,N-disubstituted analogs were compared with dimercaptosuccinate (DMSA) for effectiveness in mobilizing and promoting excretion of methylmercury (MeHg) following administration of a sublethal dose of MeHg labeled with Me203Hg. The previously reported effectiveness of DMSA was confirmed. Of the dithiocarbamates assessed, only di(carboxymethyl)-dithiocarbamate (DCDC) was active in mobilizing MeHg, and its activity on a molar dose basis was less than that of DMSA. The disparate structural requirements of dithiocarbamates as antagonists of MeHg and of cadmium were discussed.

Aged↗
PubMed1984

Effects of substituted dithiocarbamates on the testicular toxicity of cadmium.

Five substituted dithiocarbamates were evaluated for effectiveness in protecting mouse testes following administration of an LD100 dose of CdCl2 X 2.5 H2O (Cd). Toxicologic responses were assessed by light microscopic, electron microscopic, and computerized image analysis techniques. Diethyldithiocarbamate (DDTC) was the most effective antagonist. N-ethyl-N-hydroxyethyldithiocarbamate (EHDC), N-methyl-N-hydroxyethyldithiocarbamate (MHDC), and dimethyldithiocarbamate (DMDC) were moderately to minimally effective, while di-(hydroxyethyl)dithiocarbamate (DHDC) afforded no protection. Degenerative changes increased progressively in severity as the time interval between administration of Cd and DDTC was increased, but remained minimal when DDTC was given as late as two hours after Cd.

Animals↗
PubMed1984

Heterocyclic N-dithiocarboxylates as cadmium antagonists: 4-hydroxypiperidine- and 4-carboxamidopiperidine-N-dithiocarboxylate.

Sodium 4-hydroxypiperidine-N-dithiocarboxylate(HP-N-DTC) and sodium 4-carboxamidopiperidine-N-dithiocarboxylate (CAP-N-DTC) were synthesized by the reaction of each piperidine analog with CS2 in the presence of NaOH. Following isolation and characterization, each dithiocarboxylate (DTC) when added to an aqueous solution of CdCl2 formed a water-insoluble complex with Cd which was shown by elemental analyses to consist of DTC:Cd in a 2:1 molar ratio. HP-N-DTC was a highly effective antagonist of acute Cd toxicity in mice, while CAP-N-DTC was less effective. When seven equimolar doses of each DTC were administered to mice which had received a non-lethal dose of CdCl2 along with 1.0 microCi of 109CdCl2 50 days earlier, both effected marked reductions of renal Cd levels. CAP-N-DTC was much more effective than HP-N-DTC in reducing the whole body Cd burden, apparently due to its more rapid depletion of hepatic Cd accompanied by an enhanced rate of Cd excretion. The data illustrate that subtle structural modifications of this class of heavy metal binding agents can yield compounds with impressive differences in pharmacologic activity.

Animals↗
PubMed1983

Automated erythrocytopheresis for relief of priapism in sickle cell hemoglobinopathies.

Priapism, a complication of male patients with sickle hemoglobinopathies, has been managed by a variety of surgical and nonsurgical forms of therapy that often are unsuccessful. The application of automated erythrocytopheresis (red blood cell exchange) by continuous-flow and semicontinuous-flow procedures appears to offer distinct advantages in the treatment of complications resulting from sickle hemoglobinopathies. The successful application of erythrocytopheresis for the relief of priapism in a patient with hemoglobin SC disease is presented and probably represents the first case reported on the use of automated red blood cell exchange procedures in the treatment of this condition. Data and results of automated erythrocytopheresis in 4 additional patients are presented. The advantages and disadvantages of erythrocytopheresis in the treatment of priapism (and other complications of sickle hemoglobinopathies) are discussed and the method is compared to other modes of therapy.

Adult↗
PubMed1983

A retrospective review of cervical cytology in women developing invasive squamous cell carcinoma.

The records of 93 women who presented with invasive squamous cell carcinoma were searched for evidence of cervical cytology during the years preceding this diagnosis; a search was also made through the files of local laboratories and contact was made with general practitioners and relevant hospital departments. Only 26 (28%) of these 93 women had had a cervical smear at any time before the diagnosis of invasive cancer, and only 11 (12%) had had regular cytological surveillance. Fifteen (60%) had had a smear taken and reported as negative within the previous 5 years, six (6%) within the previous year. Eleven of these 15 slides were obtained for review: three were regarded as positive and three more were re-classed as too scanty for conclusive assessment. In nine of the 67 women who had never had a smear, a gynaecological or obstetric examination was known to have been performed or indicated within the previous 5 years, thereby representing a missed opportunity for screening. In three patients cytological abnormalities had been reported within the previous 3 years but no action had been taken.

Adult↗