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Biomedical subjects

M J Russell

Publications and source records attributed to M J Russell.

At least 37 records · Page 2Linked to original sources
PubMed1994

[FeS/FeS2], a redox system for the origin of life (some experiments on the pyrite-hypothesis).

The FeS/FeS, redox system, whose importance is stressed in recent theories on the origin of life, has been tested experimentally. In this paper it is demonstrated by thermodynamical calculations as well as by experiments, that cyclohexanone, which served as model compound, can be reduced by the aforementioned redox system. Reactions were carried out in methanol and DMF at 25 degrees C and at 100 degrees C. Besides products that were synthesised in both solvents, like cyclohexanethiol and dicyclohexydisulphide, special compounds were obtained in methanol and in DMF, because of the involvement of the respective solvent in the reaction. Yields of reduced compounds were lower in methanol owing to compound that hindered the reduction (cyclohexylketal). With increasing temperature and duration the amount of reduced compounds increased. Further experiments have shown that 1,1-cyclohexanedithiol is likely to be a necessary intermediate for the reduced products. The experiments give evidence to the 'pyrite hypothesis', which postulates that the FeS/FeS2, redox system was of importance for the origin of life.

Cyclohexanones↗
PubMed1994

Pharmacological properties of the cloned alpha 1A/D-adrenoceptor subtype are consistent with the alpha 1A-adrenoceptor characterized in rat cerebral cortex and vas deferens.

1. The pharmacological characteristics of cloned mammalian alpha 1A/D-, alpha 1B- and alpha 1C-adrenoceptor subtypes expressed in rat 1 fibroblasts were determined in comparison to the binding and functional properties of these subtypes in rat tissues. 2. Analysis of [3H]-prazosin binding to membrane homogenates from rat 1 fibroblast cells expressing each of the alpha 1-subtypes indicated high affinity binding to a single population of binding sites. Binding affinities were similar for alpha 1A/D-, alpha 1B- and alpha 1C-subtypes (Kds: 0.13, 0.10 and 0.15 nM respectively) although a higher density of alpha 1B- and alpha 1C-receptors (Bmax: 4068 and 10,323 fmol mg-1 protein respectively) were expressed in comparison to alpha 1A/D (838 fmol mg-1). 3. Displacement of [3H]-prazosin from membranes expressing cloned alpha 1-adrenoceptor subtypes revealed that 5-methyl-urapidil, WB 4101, benoxathian and phentolamine displayed high affinity and selectivity for alpha 1A/D- over alpha 1B-subtypes. These compounds also had high affinity and selectivity for alpha 1C- over alpha 1B-subtypes. 5-Methyl-urapidil showed selectivity for alpha 1C (Ki 0.60 +/- 0.16 nM) over both alpha 1A/D (Ki, 9.8 +/- 2.8 nM) and alpha 1B (Ki 57.2 +/- 12 nM) subtypes. Prazosin and doxazosin were not subtype selective. 4. In comparison to [3H]-prazosin a similar pharmacological profile was obtained with [125I]-HEAT using cloned alpha 1A/D-, alpha 1B- and alpha 1C-adrenoceptors expressed in rat 1 fibroblasts. 5. The affinities of prazosin, WB 4101, 5-methyl-urapidil, phentolamine and benoxathian at cloned alpha 1A/D-receptors were consistent with alpha 1A affinities determined with chlorethylclonidine-treated rat cortical membranes. Affinities at cloned XIB-receptors were consistent with alpha 1B affinities determined with rat liver membranes.6. Using the epididymal rat vas deferens as a functional measure of alpha 1A affinity, prazosin (pA29.23 +/- 0.28), WB 4101 (pA2 9.58 +/- 0.12), phentolamine (pKB 7.90 +/- 0.16), benoxathian (pKB 9.21 +/- 0.21)and 5-methyl-urapadil (pKB 8.51 +/-0.16) were potent antagonists of noradrenaline-induced contractions.7. At present, evidence from cloning studies suggests the existence of at least three alpha 1-adrenoceptor subtypes. In contrast to the recent proposal for alpha l-adrenoceptor classification, the pharmacology of the cloned alpha 1A/D (or alpha lD)-adrenoceptor is more consistent with that of an alpha 1A-adrenoceptor characterized in rat cerebral cortex and vas deferens.

Adrenergic alpha-Antagonists↗
PubMed1993

Perineuronal satellitosis in the human hippocampal formation.

A previously unreported example of perineuronal satellitosis in the medial CA1 and adjacent subiculum in the human hippocampal formation is described. This phenomenon is characterized by a clustering of glial cells in relation to the perikarya of a subpopulation of neurons in the deep pyramidal layer and around most neurons scattered in the stratum oriens and subcortical white matter. Most of the perineuronal satellite glia were identified as oligodendrocytes based on their nuclear chromatin patterns and antigenic properties. Satellite oligodendrocytes were mostly of the medium dense variety. A type of satellite glia with nuclear features of the dark oligodendrocyte could not be identified unequivocally using the antigenic criteria employed in this study.

Adult↗
PubMed1993

Life span changes in the verbal categorization of odors.

An odor description task was used to explore age-related change in odor perception based on 1.19 million U.S. and Canadian respondents (ages 10-90 years) to the National Geographic Smell Survey. Respondents sampled six microencapsulated odorants and selected 1 of 11 descriptors to characterize each smell. Four odors were characterized by strong consensus endorsement of a single descriptor. This consensus weakened with advancing age, and nonmodal descriptors were endorsed more frequently. Nonmodal responses were neither randomly selected, nor systematically biased across odors. Rather, they showed odor-specific patterns of change. Together, these results suggest a marked change in odor categorization across the life span. Odor descriptor profiles were used to generate age-specific multidimensional scaling maps. Stimulus configurations were stable from the third through fifth decades. Those from the sixth through ninth decades showed major displacements for two odors, and suggest that the sweet dimension of odor quality may be particularly variable with maturation.

Adolescent↗
PubMed1992

Familial influence on plaque formation in the beagle brain.

Aged canines exhibit central neuropathological changes strikingly similar to those seen in patients with Alzheimer's disease. In this study, brain tissue from pure bred beagles raised in a controlled environment were examined for Alzheimer-like pathology. The mean age of the animals was 15.6 years. The incidence of plaques among these 29 dogs was 65.5%. Of the 19 samples that demonstrated Alzheimer-like pathology, 18 were characterized as diffuse and one as neuritic. Plaque density was found to be independent of age. Plaque numbers were highest in the perirhinal cortex and the adjacent temporal cortex. Familial influence on plaque development is supported by congruence within 15 of the 16 litters examined (p < 0.001). In this environmentally controlled group the diffuse plaques were rarely converted to the dense neuritic plaques found in Alzheimer's disease.

Aging↗
PubMed1990

Long-term survival of neural transplants to senescence in rats.

A critical issue for clinical and research applications of transplant techniques is the long-term survival of transplanted tissue and its effect on the host brain. In this study, entorhinal cortices from donor embryos were transplanted into the lesioned angular bundle of juvenile male Sprague-Dawley rats. Animals were maintained for 2 years and then sacrificed for histological and histochemical examinations. The results indicate that entorhinal transplants survive to old age and that both the host and transplant tissues maintain morphological features consistent with those of short-term neural grafts. An unexpected finding of this experiment was the persistence in the transplanted tissue and adjacent host cortex of a pattern of AChE staining which is typical of early postnatal development.

Acetylcholinesterase↗
PubMed1988

Advances in platinum cancer chemotherapy. Advances in the design of cisplatin analogues.

In the past 4 years substantial progress has been made in the development of platinum cancer chemotherapy. A number of drug candidates have undergone clinical trials and one 'second generation' platinum drug, carboplatin, has been approved for use in the treatment of ovarian and small cell lung cancer. This review covers the major developments since the last international conference on Platinum Chemotherapy in Vermont, and attempts to highlight the primary factors that appear to be influencing the synthesis and screening of potential third generation platinum drugs. A predominant feature in the evaluation of analogues has been the emphasis on chelating diamine complexes, in particular those of diaminocyclohexane, which show activity in L1210 tumours that are resistant to cisplatin, and the use of a wide range of carboxylate ligands as a means of circumventing solubility and toxicity problems inherent in the parent compounds. There has also been an increased effort in studies relating to complexes containing mixed amines and functionalised amines, building on the assumption, which remains valid to date, that two amines are a necessary requirement for anti-tumour activity. Efforts have also been made to address the use of complexes containing biologically active ligands, and the concept of targeting compounds to specific organs and formulating drugs to achieve more specific activity or controlled release of drugs with lower toxicities. These may provide a viable route to drugs that can be administered more easily, for example by an oral route, or show a different spectrum of activity. However, it may prove difficult to adequately characterise these more complex systems. The major problem encountered in evaluating cisplatin analogues, as with other prospective cancer drugs, is finding reproducible anti-tumour screens that are predictive of the behaviour of the drugs in the clinic. Progress is being made in the development of sensitive and resistant human tumour xenograft lines and this area should be monitored with interest, as it may provide a key to the development of a future platinum drug, hopefully with a wider range of activity than either cisplatin or carboplatin.

Cisplatin↗
PubMed1988

An autoimmune aetiology for hypothyroidism following interferon therapy for breast cancer.

Alpha-interferon has been administered as an adjuvant treatment for women with loco-regional relapse of breast cancer. During the course of treatment 5/10 (50%) of women receiving interferon developed de novo thyroid autoantibodies. Three patients became clinically myxoedematous, with biochemical evidence of hypothyroidism which responded to thyroxine replacement therapy. The leucocyte alpha-interferon preparations used in the trial enhanced Class I but not Class II MHC antigens on thyrocytes in vitro. These data strongly suggest that patients receiving alpha-interferon therapy should be closely monitored for the possible development of thyroid dysfunction and that thyroid antibody determination can greatly help to predict overt thyroid clinical abnormalities.

Autoantibodies↗
PubMed1988

A prospective study of the relationship between serum vitamins A and E and risk of breast cancer.

In an 8 year prospective study (1977-1985) on breast cancer, blood was taken from 5,086 women resident in Guernsey, and the serum stored at -20 degrees C. During this period 30 women developed the disease and their serum samples were analysed for vitamins A and E, and for retinol-binding protein (RBP). A further 288 age-matched control sera (up to 10 per pre-cancer case) were similarly analysed. No relationship was found between any of these substances and subsequent development of breast cancer. A significant correlation between increasing age and vitamin A (r = 0.46, P less than 0.001) and RBP (r = 0.36, P less than 0.001) concentrations was observed. There was also a trend for increased blood concentrations of vitamin E with age, but this was not significant. Serum RBP and vitamin A concentrations were highly correlated (r = 0.91, P less than 0.0001).

Adult↗
PubMed1986

Thyroid function and the incidence of breast cancer in Hawaiian, British and Japanese women.

Serum-free thyroxine (FT4) concentrations are lower in Hawaiian and Hawaiian Caucasian women than in Hawaiian Japanese, Hawaiian Filipino, Hawaiian Chinese, and English and Japanese mainland women. There is a high inverse correlation between FT4 and risk of breast cancer in these ethnic groups. Thyroid-stimulating hormone (TSH) concentrations, which are inversely correlated with FT4, generally show the same relationship.

Adult↗
PubMed1984

Urinary androgen and 17-hydroxylated corticosteroid metabolites and their relation to recurrence rates in early breast cancer.

The amounts of urinary androsterone and etiocholanolone are highly correlated with recurrence rates in patients with early breast cancer after treatment by mastectomy. A more efficient means of predicting the clinical course of the disease is obtained by using a ratio of these compounds to the amounts of individual 17-hydroxycorticosteroids in the urine. For instance, the ratio of androsterone to alpha-cortolone is particularly effective in identifying women with a high rate of recurrence, and this is largely independent of pathological stage and tumor grade.

17-Hydroxycorticosteroids↗
PubMed1983

Thyroid function in early breast cancer.

Serum 'free thyroxine' was measured as a thyroid function index (TFI) in 238 women with early breast cancer and 107 normal controls. The mean TFI was significantly lower in the cases compared with controls. The TFI was not related to pathological stage but correlated with histological grade, with the highest values found in well-differentiated (grade I) and the lowest in anaplastic tumours (grade III). A similar result was obtained with the urinary and androsterone:aetiocholanolone (5 alpha:5 beta) ratio in that the ratio was significantly lower in patients with grade III than in those with grade I tumours. These results indicate that thyroid hormones may be involved in tumour cell differentiation. Patients with low 5 alpha/5 beta ratios had significantly faster recurrence rates than those with high ratios. A similar trend was found for the TFI. The TFI decreases after mastectomy and at 12 months after operation is still below the pre-operative basal level.

Adult↗
PubMed1981

Knowledge of stimulus timing attenuates human evoked cortical potentials.

To determine whether or not knowledge of stimulus timing influences the amplitude and latency of evoked cortical potentials, we have studied the evoked potentials of 24 adults under two contrasting conditions in which people knew or did not know the timing of tone stimuli by means of numerical perceptual cuing. Results demonstrated markedly smaller amplitude and significantly faster latency for the late components of vertex potentials evoked by stimuli whose timing subjects knew in advance. The cognitive act of knowing when auditory stimuli will occur attenuates the amplitude and facilitates the poststimulus timing of cortical evoked potentials.

Acoustic Stimulation↗
PubMed1980

Olfactory influences on the human menstrual cycle.

Two groups of women were compared for the timing of the onset of their menstrual cycles. One group was rubbed on the upper lip (directly beneath the nose) with a mixture of alcohol and underarm perspiration collected from a single female donor. The other group was rubbed with plain alcohol. The group which received the perspiration showed a significant shift in the timing of their menstrual cycles which conformed closely with the donor's monthly cycle. This is a preliminary study which supports the hypothesis that the time of menstrual onset may be modified by olfactory cues.

Adult↗
PubMedDate not supplied

Beta-amyloid accumulation in aged canine brain: a model of early plaque formation in Alzheimer's disease.

We characterized eight aged beagles (maintained from birth in a laboratory colony) and one black Labrador using Bielschowsky's, thioflavine S, and Congo red staining, and antibodies to the beta-amyloid peptide, dystrophic neurites, and other plaque components. All plaques within these canine brains were of the diffuse subtype and were neither thioflavine S- nor Congo red-positive. The majority of plaques in the entorhinal cortex contained numerous neurons within them while plaques in the dentate gyrus did not. beta-Amyloid immunoreactivity was also present within select neurons and neuronal processes and was detected as a diffuse linear zone corresponding to the terminal fields of the perforant path. There was no significant correlation between extent of beta-amyloid accumulation and neuron number in entorhinal cortex. Neither tau-1, PHF-1, nor SMI-31-immunostaining revealed dystrophic fibers, confirming the classification of these plaques as diffuse. Canine plaques did not appear to contain bFGF- or HS-positive immunostaining. This may explain why neuritic involvement was not detected within these canine plaques. It is possible that the beta-amyloid within the canine brain has a unique primary structure or may not be in an assembly state that adversely affects neurons.

Adolescent↗
PubMedDate not supplied

Carboxy terminal of beta-amyloid deposits in aged human, canine, and polar bear brains.

Immunocytochemistry, using antibodies specific for different carboxy termini of beta-amyloid. A beta 40 and A beta 42(43), was used to compare beta-amyloid deposits in aged animal models to nondemented and demented Alzheimer's disease human cases. Aged beagle dogs exhibit diffuse plaques in the absence of neurofibrillary pathology and the aged polar bear brains contain diffuse plaques and PHF-1-positive neurofibrillary tangles. The brains of nondemented human subjects displayed abundant diffuse plaques, whereas the AD cases had both diffuse and mature (cored) neuritic plaques. Diffuse plaques were positively immunostained with an antibody against A beta 42(43) in all examined species, whereas A beta 40 immunopositive mature plaques were observed only in the human brain. Anti-A beta 40 strongly immunolabeled cerebrovascular beta-amyloid deposits in each of the species examined, although some deposits in the polar bear brain were preferentially labeled with anti-A beta 42(43). beta-amyloid deposition was evident in the outer molecular layer of the dentate gyrus in the aged dog, polar bear, and human. Within this layer, A beta 42 was present as diffuse deposits, although these deposits were morphologically distinct in each of the examined animal models. In dogs, A beta 42 was cloud-like in nature; the polar bear demonstrated a more aggregated type of deposition, and the nondemented human displayed well-defined deposits. Alzheimer's disease cases were most frequently marked by neuritic plaques in this region. Taken together, the data indicate that beta-amyloid deposition in aged mammals is similar to the earliest stages observed in human brain. In each species, A beta 42(43) is the initially deposited isoform in diffuse plaques.

Aged↗