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Biomedical subjects

M Hutchinson

Publications and source records attributed to M Hutchinson.

At least 19 recordsLinked to original sources
PubMed1992

Folate deficiency enhances the development of colonic neoplasia in dimethylhydrazine-treated rats.

In patients with ulcerative colitis, epidemiological work has suggested an association between low folate status and an increased risk of colonic neoplasia. The aim of the present study was to determine if experimental folate deficiency increases the likelihood of developing neoplasia in rats treated with the carcinogen dimethylhydrazine. Weanling male Sprague-Dawley rats were fed with an amino acid-defined diet containing either 8 or 0 mg/kg folic acid. After 5 weeks of defined diet, weekly s.c. injections of dimethylhydrazine (20 mg/kg) were administered to both groups. Serum, whole blood, liver, and colonic folate concentrations at the time of sacrifice were significantly lower in folate-depleted animals (P less than 0.001). There were significant differences in the incidence of colonic neoplasia between the two groups after 20 weeks of dimethylhydrazine exposure: folate-deficient rats had a greater incidence of dysplasia (6 of 7 versus 2 of 7 animals; P less than 0.05) and carcinoma (6 of 7 versus 1 of 7 animals; P less than 0.01). Furthermore, a significantly greater proportion of folate-replete rats than folate-deficient rats were free of neoplastic lesions (5 of 7 versus 0 of 7 animals; P less than 0.05). These results suggest that, in this animal model, folate deficiency increases the risk of malignancy when there is an underlying predisposition to colorectal cancer.

Animals↗
PubMed1992

Bilateral paramedian thalamic infarction: a distinct but poorly recognized stroke syndrome.

Six patients with bilateral paramedian thalamic infarction were seen in a general hospital over a 4 year period. This distinct stroke syndrome was recognized by the features of disturbed vigilance, often episodic, with vertical gaze disorder. Other signs included an amnesic syndrome, convergence difficulty, third nerve palsies, eyelid retraction, dysarthria, ataxia and involuntary limb movements. Diagnosis was confirmed by CT brain scan or magnetic resonance imaging. A variety of risk factors for stroke were present. All patients improved but two had significant residual disabilities.

Adult↗
PubMed1991

Increased DNA synthesis and repair-enzyme expression in lymphocytes from patients with chronic lymphocytic leukemia resistant to nitrogen mustards.

Resistance to the nitrogen mustards in patients with chronic lymphocytic leukemia (CLL) correlates with an enhanced removal of melphalan-induced DNA interstrand cross-links. This finding suggests that DNA repair enzymes may be involved in this process. The activity of 3-methyladenine-DNA glycosylase, which can release altered bases, including adducts at the N-7 position of guanine, was increased significantly in lymphocytes from patients with resistant CLL compared with those from untreated CLL patients. Since glycosylase activity varies with cell proliferation, the amount of [3H]thymidine incorporated into DNA was determined and found to be elevated almost threefold in lymphocytes from patients with resistant CLL. The ratio of glycosylase activity to level of thymidine incorporation did not differ between these two groups of patients. Northern blot analysis of ERCC1 gene (a putative DNA repair enzyme involved in nucleotide excision repair) expression in lymphocytes from patients with CLL revealed multiple gene transcripts (1.1, 3.4, and 3.8 kilobases). In addition, analysis of two samples revealed the presence of a 2.6-kilobase transcript. The 2.6-kilobase transcript was recognized by specific RNA probes that hybridize to antisense ERCC1 transcripts. Levels of expression of the 1.1-kilobase protein encoding transcript in lymphocytes from patients with resistant CLL were increased twofold to threefold above those of untreated patients with CLL. These results indicate that increased expression of ERCC1 and increased activity of 3-methyladenine-DNA glycosylase occur with the development of resistance to the nitrogen mustards in patients with CLL, suggesting a role for enhanced DNA repair in this process.

Aged↗
PubMed1991

Acute cerebrovascular episodes in systemic lupus erythematosus.

Twelve patients with systemic lupus erythematosus (SLE) who developed major acute cerebrovascular episodes are described. All patients were female, with a mean age of 43.3 years and they had suffered from SLE for between 1 month and 22 years (mean 9.3 years) at the time of stroke. All patients had multiple clinical and laboratory features of systemically active SLE. Stroke was the initial neurological feature in nine patients. Cerebral infarction was confirmed in eight patients and cerebral haemorrhage in two; the two remaining patients had convincing clinical evidence of thromboembolic neurological complications. Characteristic clinical and serological features of antiphospholipid antibodies were observed in six patients (50 per cent). Five patients died as a direct result of stroke and two other patients died within one year.

Acute Disease↗
PubMed1991

Cervex-Brush and Cytobrush. Comparison of their ability to sample abnormal cells for cervical smears.

A study was designed to test specimen adequacy and the detection of disease using two new cervical cytologic sampling devices, the Cervex-Brush and Cytobrush plus a modified Ayre spatula. Two clinicians used each device at random. The laboratory was blind to the sampling method, and the results were compared with those from control samples (Ayre spatula with cotton swab or alone). The 567 test samples were compared with 569 age-matched control samples. The Cervex-Brush and Cytobrush plus spatula were comparable in detecting disease, and both were improvements over the control method. Both the Cervex-Brush and Cytobrush plus spatula produced more consistent good smear quality across the age range studied than did the control method, which resulted in a lower percentage of good-quality smears in older women. Use of the Cytobrush plus spatula and the control method produced smear results the quality of which varied considerably with each clinician.

Adolescent↗
PubMed1991

Neurological manifestations of Lyme disease.

Neurological disorder may be the initial manifestation of Lyme disease. Six cases of neurological Lyme disease have been seen in the years 1986-89, five of whom contracted the disease in the West of Ireland. Three presented with a radiculoneuropathy, one with myalgia/fatigue and one with bilateral sixth nerve palsies and ataxia. These cases indicate the spectrum of neurological involvement of Lyme disease in Ireland which reflects that seen in Europe. They also highlight some of the problems in diagnosis which sometimes necessitate treatment while awaiting serological studies. We feel even in the absence of a history of tick-bite or rash, Lyme disease should be considered in the differential diagnosis of many neurological disorders, especially in patients from the West of Ireland.

Adolescent↗
PubMed1990

Progressive multifocal leukoencephalopathy-remission with cytarabine.

A 51-year-old woman who was in complete remission from non-Hodgkin's lymphoma, developed a rapidly progressive dementia. Progressive multifocal leukoencephalopathy (PML) was diagnosed on the basis of a rising antibody titre to JC polyomavirus in cerebro-spinal fluid and serum and the presence of diffuse white matter changes on magnetic resonance imaging. She was treated initially with intravenous cytarabine and showed minimal improvement. Rapid improvement occurred when intrathecal cytarabine was added and the patient is in complete remission from both lymphoma and PML 20 months later.

Cytarabine↗
PubMed1990

Fluctuations in T helper subpopulations in relapsing-remitting multiple sclerosis.

Patients with active multiple sclerosis (MS) have been reported to have a depletion of CD4+ CD45R+ cells, the immature resting CD4+ subpopulation. Using Leu 3a(anti-CD4) and Leu 18(anti-CD45R), the frequencies and absolute numbers of CD4+ CD45R+ and CD4+ CD45R- subsets were measured in 30 patients with MS and 17 healthy controls. These subsets were monitored every 6 weeks over a 6 month period. CD4+ CD45R- cells were found to be increased in relapse compared to remission (p less than 0.005) while CD4+ CD45R+ levels were not significantly altered in relapse. However, the CD4+ subset ratio (CD4+ CD45R-/CD4+ CD45R+) was significantly higher in relapse compared with remission (p less than 0.002). Furthermore, these findings were upheld when data from the same 6 patients in relapse and remission was compared. Increased disease activity was not associated with changes in any of the other parameters measured (total T cells, total CD4+ cells, suppressor cells or activated T cells). These results suggest that relapse in MS is accompanied by the conversion of CD4+ CD45R+ resting cells to CD4+ CD45R- primed cells.

Adult↗
PubMed1989

Evidence for increased alpha MSH receptor binding in the F1 variant of B16 melanoma cells grown in dialyzed fetal calf serum.

The specific binding of an alpha MSH analogue (Ac-[Nle4, D-Phe7] alpha MSH4-11 NH2) was enhanced in the presence of 10% dialyzed fetal calf serum (FCS) as compared with 10% FCS (nondialyzed) in the F1 variant of B16 melanoma cells. The replenishment of dialyzed serum with adrenocorticotrophic hormone (ACTH) or insulin had no effect on the increased level of alpha MSH receptor binding in these cells. However, 10 nM alpha MSH or 1 microM ACTH under identical conditions significantly decreased the level of alpha MSH binding. Competitive binding studies involving the alpha MSH analogue revealed that the specificity of the receptor was restricted to the complete molecule of alpha MSH, our analogue, beta MSH and ACTH1-24, ACTH4-10, which contains the amino acid sequence responsible for biological activity, showed a very low affinity for the receptor. Furthermore, we observed an interesting phenomenon unique to dialyzed FCS in that once the cells were grown to confluence and melanin was produced, the cells were no longer viable. However, in McCoy's medium, which is deficient in tyrosine, the cells did not produce melanin and remained viable.

Animals↗
PubMed1989

Contrast sensitivity in multiple sclerosis measured by Cambridge Low Contrast Gratings: a useful clinical test?

The Cambridge Low Contrast Gratings (CLCG) were used to assess contrast sensitivity (CS) in 39 patients with clinically definite multiple sclerosis and 60 control subjects. CS was determined in both horizontal and vertical orientations and compared with visual evoked responses (VERs) in the same populations. Only 33% of patients had abnormal CS whereas 82% had abnormal VERs. There was no correlation between the degree of abnormalities in CS and VERs. There was no significant difference between CS determined in the vertical and horizontal orientation; however, examination in the vertical orientation increased the number of abnormalities detected by 2 (5%). We conclude that although CS, using the CLCG, is abnormal in a proportion of multiple sclerosis patients its detection is not clinically useful and is insensitive as a measure of subclinical optic neuropathy in multiple sclerosis.

Adult↗
PubMed1988

Transport, metabolism, and DNA interaction of melphalan in lymphocytes from patients with chronic lymphocytic leukemia.

We investigated the transport of [chloroethyl-14C]melphalan with lymphocytes from three groups of patients with chronic lymphocytic leukemia (untreated, treated sensitive, and treated resistant). There was no significant difference in the Km or Vmax of melphalan transport in lymphocytes from the three groups. In addition, there were no significant differences in intracellular melphalan levels after a 35-min incubation with 5.4 microM melphalan among the three groups. There was no evidence of intracellular metabolism of melphalan to dihydroxymelphalan except in lymphocytes from one treated sensitive patient. DL-2-Aminobicyclo[2,2,1]heptane-2-carboxylic acid, a specific analogue of the sodium-independent leucine-preferring amino acid transport system, inhibited the uptake of melphalan to a greater extent in lymphocytes from resistant patients than in those of untreated patients. Glutathione levels were not significantly different in lymphocytes from resistant patients as compared to those of untreated patients. The percentage of DNA cross-links as determined by an ethidium bromide fluorescence assay was 2-5-fold greater in lymphocytes from untreated patients than in those of resistant patients. These results suggest that resistance to the nitrogen mustards in patients with chronic lymphocytic leukemia is secondary to neither a transport defect nor alteration in intracellular melphalan levels but rather due to some other mechanism responsible for decreased DNA cross-links.

Amino Acids↗
PubMed1988

Fast MRI data acquisition using multiple detectors.

We present a novel imaging procedure using multiple receiver coils. This circumvents the sequential acquisition of signals required by conventional imaging strategies. The advantage of this technique over existing subsecond imaging techniques is that (a) contrast can be maintained and (b) there is no magnetic field gradient switching involved.

Computer Simulation↗