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Biomedical subjects

M Thomas

Publications and source records attributed to M Thomas.

At least 541 records · Page 30Linked to original sources

Determinants of the brain-specific expression of the rat aldolase C gene: ex vivo and in vivo analysis.

A 115-bp promoter fragment of the aldolase C gene is sufficient for conferring neural cell specificity on a reporter gene, in cultured PC12 cells and in transgenic mice. In vitro DNase I protection experiments detected two footprints on the promoter, termed boxes A/A', and B. The 5' A/A' box contains overlapping Sp1 and Krox20/Krox24 binding sites; it binds Sp1 in fibroblasts (box A') and a different complex in brain (box A). Any deletion or mutation of this box that impairs protein recognition also suppresses promoter activity. The replacement of box A/A' by a Sp1 consensus binding site results in the loss of the brain specificity of expression in transgenic mice. Further 3', box B is composed of a 5' direct repeat and a 3' GC box consisting of overlapping Sp1 and Krox20/Krox24 binding sites. Mutation of the direct repeat subregion appears to be more deleterious for the promoter activity than mutation of the G+C-rich subregion.

3T3 Cells↗

Programmed lipid peroxidation of biomembranes generating kinked phospholipids permitting local molecular mobility: a peroxidative theory of fluidity management.

The lipid peroxidation profiles in the uterus of mature mice show cyclic alterations during the reproductive cycle. Similarly, during early pregnancy, alterations in lipid peroxidation are evident, keeping close pace with the superoxide anion radical levels and fluidity parameters reported elsewhere. This formulates a theory that a 'controlled' lipid peroxidation of biomembrane terminating at the accumulation of cyclic endoperoxides could rather enhance local molecular mobility because of the increased inter-molecular distance in these 'kinked-species'.

Animals↗

Hospital associated costs of treating patients with AIDS.

AIM: To determine the hospital associated costs of caring for patients with AIDS. METHOD: We reviewed the notes of all 40 patients with AIDS admitted to the Auckland Hospital infectious disease unit during 1988. We used the resource utilisation system (RUS) to determine costs. RESULTS: Costs were maximal in the month of diagnosis of AIDS (ca $3500/month), falling thereafter to ca $1000/month until they rose again in the last months of life. Total costs were dominated initially by inpatient costs but subsequently by the costs of medicines. CONCLUSION: The hospital costs associated with the care of AIDS patients are not spaced evenly throughout the illness. Extended life will not increase costs proportionately.

Acquired Immunodeficiency Syndrome↗

Internal mammary nodal status is a more reliable prognostic factor than DNA ploidy and c-erb B-2 expression in patients with breast cancer.

We evaluated the relationship among DNA ploidy, c-erb B-2 oncoprotein expression, and clinicopathologic prognostic factors, especially axillary and internal mammary node metastases, and their value in estimating the prognosis in 128 patients with operable breast cancer. There were significant correlations between DNA ploidy and clinical stage, tumor size, or axillary or internal mammary lymph node metastases, and between c-erb B-2 expression and clinical stage or axillary lymph node metastases. In a univariate study, overall or disease-free survival was significantly correlated to clinical stage, tumor size, DNA ploidy, c-erb B-2 expression, and axillary and internal mammary node metastases. In a multivariate study, however, only axillary and internal mammary node metastases were recognized as independent factors on overall survival, whereas on disease-free survival, only axillary lymph node metastases were identified as an independent indicator. Since the DNA ploidy status and c-erb B-2 expression were closely correlated with the axillary and/or internal mammary lymph node metastases, they did not appear as independent prognostic factors in this small series.

Adult↗

Risk of internal mammary lymph node metastases and its prognostic value in breast cancer patients.

The risk of an internal mammary lymph node (IMN) metastasis and its prognostic value for patients with invasive breast cancer were assessed by evaluating 142 patients who had either a mastectomy with lymph node dissection or a biopsy of the IMN. By univariate analysis, overall survival significantly correlated with the patient's age, clinical axillary node status, tumor size, and DNA ploidy, as well as histologically confirmed axillary and IMN metastases. By multivariate analysis, however, only the presence of axillary and IMN metastases appeared to be an important independent factor affecting survival. However, the incidence of IMN metastases was associated significantly with age, clinical tumor and axillary node status, tumor size, axillary lymph node metastases, and DNA ploidy. Accordingly, the patient's age, tumor size, DNA ploidy, and axillary lymph node metastases proved to be effective variable for discrimination. Consequently, in predicting the presence of IMN metastases, a diagnostic accuracy of 82%, a sensitivity of 84%, and a specificity of 82% can be achieved by a discriminant function. We conclude that the discriminant function with these four variables is effective in assessing the risk of IMN metastases.

Aneuploidy↗

Risk of bilateral cervical lymph node metastases in papillary thyroid cancer.

We evaluated the risk of bilateral or contralateral cervical lymph node metastases in 135 patients with papillary thyroid cancer who underwent bilateral neck dissection. We confirmed that bilateral jugular lymph node metastases were frequent in patients with obvious carcinoma in both lobes of the gland, in those with cancers arising in the isthmus, in those with clinically detectable bilateral lymphadenopathy, and in those with recurrent thyroid cancer. However, only 24% of the patients who had cancer clinically confined to one lobe with no bilateral or contralateral lymphadenopathy had histologically detected bilateral or contralateral jugular lymph node metastases. But the occurrence of contralateral jugular lymph node metastases was significantly correlated with both clinical lymphadenopathy in the ipsilateral neck and contralateral paratracheal lymph node metastases. Bilateral lymph dissection might be beneficial for these patients.

Adolescent↗

A double-blind, randomized, placebo-controlled trial of n-3 fatty acid based lipid infusion in acute, extended guttate psoriasis. Rapid improvement of clinical manifestations and changes in neutrophil leukotriene profile.

Twenty patients hospitalized for acute psoriasis guttata with a minimum 10% of body surface area involvement (range 10-90%) completed a 10-day trial in which they were randomly allocated to receive daily infusions with either an n-3 fatty acid based lipid emulsion [100 ml/day with 2.1 g eicosapentaenoic (EPA) and 21 g docosahexaenoic acid (DHA)] or a conventional n-6 lipid emulsion (EPA + DHA < 0.1 g/100 ml). The severity of disease was evaluated by scoring daily erythema, infiltration, and desquamation and by a subjective scoring of clinical manifestations offered by the patients. Leukotriene (LT) and platelet-activating factor (PAF) generation were investigated in ionophore-stimulated neutrophils obtained on days 0, 1, 3, 5, 10, and 40. Moderate improvement in clinical manifestations was noted in the n-6 group (changes in score systems between 16-25% from baseline within 10 days). In contrast, the severity of disease markedly decreased in all patients of the n-3 group, with improvements in all score systems ranging between 45% and 76% within 10 days (P < 0.05 for each variable). The difference in response to the two regimens was evident within 4-7 days after onset of lipid infusion. A more than ten fold increase in neutrophil EPA-derived 5-lipoxygenase product formation (LTB5, its omega-oxidation products, non-enzymatic degradation products of LTA5 and 5-hydroxyeicosapentaenoic acid) was noted in the n-3 group but not in the n-6 group. Neutrophil PAF generation increased in the n-6 group but decreased in the n-3 group. In conclusion, modulation of eicosanoid metabolism by intravenous n-3 fatty acid supplementation appears to exert a rapid beneficial effect on inflammatory skin lesions in acute guttate psoriasis.

Acute Disease↗

A comparison of breast cancers detected by mass screening and those found in out-patient clinics.

We evaluated the results of a mass screening study on breast cancer detection by physical examination alone conducted in Ishikawa Prefecture from 1978 to 1990. The number of cases of breast cancer detected by mass screening was then compared with that found in out-patient clinics during the same period. Breast cancer was detected in 88 of 152,969 women by mass screening, the detection rate being 0.06% for the total study: 0.08% at the initial screening and 0.04% at periodic screenings. Early stage breast cancer was more frequently detected during periodic screenings than at the initial screening or in out-patient clinics. Moreover, although the initial screenings may have identified patients with breast cancer at more advanced stages, the survival was not significantly different. The results of this series led us to conclude that mass screening by physical examination alone may have no impact on the mortality rate of breast cancer.

Adult↗

A retrospective study on the clinical and biological prediction of axillary lymph node metastasis in breast cancer.

If axillary lymph node metastases were able to be accurately predicted, dissection could be avoided in some patients with breast cancer whose axillary nodes are clinically negative. In this study, we assessed the relationships between histological axillary lymph node metastases and clinical axillary nodal status, tumor size, DNA-ploidy, c-erbB-2 expression, and the score of the argyrophilic nucleolar organizer region. We then attempted to evaluate their predictive values for axillary lymph node metastasis in 173 patients with invasive breast cancer, retrospectively. The clinical and biological variables were significantly correlated with the presence and degree of axillary lymph node metastases. A metastatic index, calculated from the clinical and biological variables, proved especially useful for predicting axillary lymph node metastases in patients whose axillary nodes were clinically negative. However, the predictive abilities were still limited and thus it was concluded that as yet, only axillary dissection can provide accurate information on axillary lymph node metastases.

Adult↗

DNA ploidy and helix pomatia lectin binding as predictors of regional lymph node metastases and prognostic factors in breast cancer.

This study was designed to evaluate whether DNA ploidy and/or Helix pomatia lectin (HPA) staining would be useful for predicting regional lymph node metastases and patients' prognosis in 106 patients with invasive breast cancer. The combination of DNA ploidy and HPA staining correlated better with regional lymph node metastases than DNA aneuploidy or HPA staining alone. DNA ploidy and HPA staining in combination correlated strongly with overall and disease-free survival by univariate analysis. However, the prognostic significance of DNA ploidy and HPA staining in combination was lost in multivariate analysis when regional lymph node metastases were introduced into the models. This emphasized the relationship in survival between regional lymph node metastases and the combination of DNA ploidy and HPA staining. We therefore concluded that the combination of DNA ploidy and HPA staining might provide prognostic information for breast cancer patients in whom regional lymph node dissection has not been performed.

Adult↗

Caffeine reversal of sleep deprivation effects on alertness and mood.

This study assessed the ability of high doses of caffeine to reverse changes in alertness and mood produced by prolonged sleep deprivation. Fifty healthy, nonsmoking males between the ages of 18 and 32 served as volunteers. Following 49 h without sleep, caffeine (0, 150, 300, or 600 mg/70 kg, PO) was administered in a double-blind fashion. Measures of alertness were obtained with sleep onset tests, the Stanford Sleepiness Scale (SSS), and Visual Analog Scales (VAS). Sleep deprivation decreased onset to sleep from a rested average of 19.9 min to 7 min. Following the highest dose of caffeine tested, sleep onset averaged just over 10 min; sleep onset for the placebo group averaged 5 min. Scores on the SSS increased from a rested mean of 1.6-4.8 after sleep deprivation. Caffeine reduced this score to near rested values. Caffeine reversed sleep deprivation-induced changes in three subscales of the POMS (vigor, fatigue, and confusion) and produced values close to fully rested conditions on several VAS. Serum caffeine concentrations peaked 90 min after ingestion and remained elevated for 12 h. This study showed that caffeine was able to produce significant alerting and long-lasting beneficial mood effects in individuals deprived of sleep for 48 h.

Adolescent↗

Bilateral auditory-evoked potentials in conditions of hypnosis and focused attention.

Brain event-related potentials (ERPs) evoked by auditory stimulation were used to study cerebral hemispheric activity during hypnosis. ERPs were recorded from bilateral central (C3 and C4) and temporal (T3 and T4) scalp locations in response to tone pips in 6 medium-high and 6 low-susceptible subjects in three conditions: baseline (tones only), hypnosis (tones plus hypnotic induction), and a focused attention control (tones plus a newspaper story read by the hypnotist). Task asymmetries were individually adjusted for baseline asymmetries. Responses from central locations did not differentiate hypnosis from focused attention for either group. The same was true of temporal locations for the low-susceptible group. The predominant temporal lobe pattern for both conditions and groups was larger left than right responses. The exception was the hypnosis condition for the medium-high susceptible group where there was an increase in responses in the right temporal lobe.

Acoustic Stimulation↗

Influence of hormones on tumor growth, cell kinetics, estrogen receptor and insulin-like growth factor-I-related protein of human breast cancer (MCF-7) cells transplanted in nude mice.

The influence of estrogens and tamoxifen on estrogen receptor (ER)-positive human breast cancer (MCF-7) cells transplanted into athymic nude mice was investigated. The mice were divided into the following three groups: (1) an E2 group with mice receiving 17 beta-estradiol dipropionate; (2) a TAM group with mice receiving tamoxifen; (3) a control group with mice given no hormone. (1) Tumor growth was significantly increased in the E2 group, but significantly decreased in the TAM group compared to control; (2) the tumor contents of insulin-like growth factor-I (IGF-I) and the rate of IGF-I-positive cells were significantly lower in the E2 group, but significantly higher in the TAM groups compared to control; (3) the IGF-I-positive cell rates were in significant inverse correlation with the [3H]thymidine-labeled cell rates in the E2, TAM and control groups. Thus, the tumor contents of IGF-I and the rate of IGF-I-positive cells were inversely correlated to the tumor growth and the [3H]thymidine-labeled cell rate in this in vivo study, although IGF-I is known to be a mitogen for breast cancer cells in vitro. Further studies are necessary to answer the questions as to the in vivo roles of immunoreactive IGF-I in ER-positive breast cancer.

Animals↗

Vitamin D-dependency rickets type II: truncated vitamin D receptor in three kindreds.

Fibroblasts from three patients with vitamin D-dependency rickets type II were used to study mutations in the 1,25-dihydroxyvitamin D3 receptor responsible for this hereditary disease. Normal human fibroblasts contain 43 +/- 13 fmol receptor/mg protein as determined by immunoradiometric assay and 22 +/- 3 fmol/mg by ligand binding assay. The fibroblasts from the rachitic patients contained no receptor detectable by either method. The 1,25-(OH)2D receptor cDNA for cells from each kindred was produced from total RNA using reverse transcription and polymerase chain reaction amplification. When these cDNAs were sequenced, it was found that each cell line contained a nucleotide substitution resulting in a stop codon in the coding sequence. The predicted resultant receptor protein is 69 amino acids long in one family, and 148 and 291 amino acids long in two other families. These truncated proteins have little or no 1,25-dihydroxyvitamin D3-binding domain accounting for 1,25-dihydroxyvitamin D resistance.

Base Sequence↗

Young adult offspring and their families of origin: cohesion, adaptability, and addiction.

This study examined relationships among measures of family functioning (FACES-II), number of family addictions, and risk of alcoholism (Short Michigan Alcoholism Screening Test, SMAST) in a college sample. Multiple regression analyses indicated that the number of family addictions and the additively combined FACES-II scales each predicted scores on the SMAST. Thus, addictions in the family contribute to offspring alcoholism both directly, through their presence, and indirectly, through family functioning. Information on the history of a wide range of family addictions and on the functioning style of the family of origin can be valuable in assessing and addressing addiction risk.

Adaptation, Psychological↗