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Biomedical subjects

J Francis

Publications and source records attributed to J Francis.

At least 127 records · Page 7Linked to original sources

Joint contractures and diabetic retinopathy.

It has been suggested that joint contractures may be an early marker of microangiopathy, especially retinopathy, in diabetic patients. To investigate this possibility, the prevalence of contractures of the finger joints, as assessed by the painted hand technique, was compared in 106 diabetic patients without, and 105 with retinopathy (proliferative in 66%). There was an increased prevalence of contractures in those with diabetes (25.2%) as compared with an age-matched control of 106 subjects (7.5%, P less than 0.01). The prevalence of contractures was similar in those diabetics with and without retinopathy (29.5% v. 20.8%, P less than 0.1), and did not vary with the type of retinopathy. The contracture prevalence rate was also similar in those with a diabetes duration of 5 or more years (retinopathy 29.3%, no retinopathy, 30%) or of similar diabetic duration (retinopathy 20.8%, no retinopathy, 25%). Diabetic control, as assessed by HbA1, was similar in retinopathic patients with or without contractures. We conclude that although finger joint contractures are more prevalent in adult diabetic patients, they are not necessarily a reliable early indicator of the development of retinopathy of any specific type.

Adult↗

Effects of dibutyryl cyclic adenosine 3':5'-monophosphate on the growth of cultured human small-cell lung carcinoma and the specific cellular activity of L-dopa decarboxylase.

High activity of L-dopa decarboxylase separates small (oat)-cell from non-small-cell lung cancer in cell culture. The present study investigates relationships between the specific cellular activity of this enzyme and: (a) cell growth kinetics of an established line (O-H-1) of human small cell lung carcinoma, and (b) responses of these cells to treatment with cyclic adenosine 3':5'-monophosphate and sodium butyrate. The O-H-1 cells, as for most other established small-cell lines, grow as suspended cell aggregates. During growth, the specific cellular activity of L-dopa decarboxylase parallels levels for [3H]thymidine labeling index and the ratio of cells in G2-M to those in G1-G0 phases of the cell cycle. Each of these parameters is 2- to 3-fold higher during exponential versus stationary growth. Continuous treatment with dibutyryl cyclic adenosine 3':5'-monophosphate (dcAMP; 0.1 or 1 mM) and 1 mM theophylline produces simultaneous cessation of cell growth and an increase in cellular L-dopa decarboxylase activity. During this period, analyses of DNA histograms reveal an increase in the number of cells in the G2-M phase; the rate of increase in the ratio of G2-M to G1-Go cells paralleled the rate of increase in specific activity of the enzyme. The effects of the dcAMP were promptly reversible; release of the apparent G2-M block preceded regrowth of the cells and was accompanied by a return of L-dopa decarboxylase activity to base-line levels. The changes in enzyme activity were specific for cyclic adenosine 3':5'-monophosphate; another cyclic adenosine 3':5'-monophosphate analogue, 8-bromo adenosine cyclic 3':5'-monophosphate yielded similar increases in L-dopa decarboxylase to those seen with dcAMP, while 0.01 to 1 mM butyrate alone produced the inhibition of cell growth but no changes in specific activity of L-dopa decarboxylase or percentage of cells in the different phases of the cell cycle. We conclude that the specific activity of L-dopa decarboxylase, a key neuroendocrine marker for cultured small-cell lung carcinoma, is highest during proliferative growth and/or when these cells are in the G2M phase of the cell cycle. The differential effects of dcAMP and sodium butyrate offer potential for exploring neuroendocrine differentiation in this important lung cancer and related endocrine neoplasms.

Aromatic-L-Amino-Acid Decarboxylases↗

The comparative tuberculin test in guinea pigs using PPD extracts prepared from mycobacteria killed with phenol.

Purified-protein-derivative (PPD) extracts were prepared from Mycobacterium tuberculosis (PPD-S), M. bovis (PPD-BS), M. avium (PPD-A) and M. kansasii (PPD-K), after killing the cultures with phenol. The reactions were assessed in guinea pigs sensitised to a range of mycobacteria, with a view to selecting a suitable pairing of the extracts to distinguish sensitivity due to M. tuberculosis or M. bovis from that due to other mycobacteria. Sensitisation induced by M. bovis was best distinguished from others using PPD-S and PPD-A; for sensitisation by atypical mycobacteria, PPD-BS was better than PPD-S, used with either PPD-K or PPD-A. PPD-BS was more specific than PPD-S. Using PPD-BS, PPD-A and PPD-K in a comparative test, 3 groups were recognised: those sensitive to M. bovis or M. tuberculosis (greatest reaction was to PPD-BS); those sensitive to M. avium, M. intracellulare and M. scrofulaceum (greatest reaction was to PPD-A); those sensitive to M. kansasii, M. marium, M. gordonae and M. fortuitum (greatest reaction was to PPD-K).

Animals↗

Evidence for papillomaviruses in ocular lesions in cattle.

Negatively stained preparations of various ocular lesions, generally considered to be precursors to bovine ocular squamous cell carcinoma, were subjected to electron microscopic examination for viruses. Lesions examined included five conjunctival plaques, an acanthotic lesion from an eyelid, 15 conjunctival papillomas, two papillomas of the eyelid and two keratinised elongated proliferative lesions of the eyelid (cutaneous horns). Eight lesions contained particles that resembled papillomaviruses. These consisted of a conjunctival plaque, five conjunctival papillomas, a papilloma of the eyelid and one of the samples of cutaneous horn. The particles were present in small numbers and were found only after prolonged search. The finding of these particles suggests that papillomavirus may be involved in the aetiology of bovine ocular squamous cell carcinoma.

Animals↗

Lateral hypothalamic lesions: effects on Pavlovian cardiac and eyeblink conditioning in the rabbit.

Rabbits received either bilateral lesions of the far lateral hypothalamus (LH), or sham-operate lesions. After recovery from surgery the animals were exposed to Pavlovian conditioning in which eyeblink (EB), electromyographic (EMG), and heart rate (HR) conditioned responses (CRs) were recorded. Adaptation, acquisition and extinction training were studied. Subsequent to conditioning, free-field activity, paraorbital electric shock thresholds, and HR unconditioned responses (URs) were measured. At the end of behavioral testing forebrain norepinephrine (NE), dopamine (DA), an serotonin (5-HT) concentrations were assessed. Animals with LH lesions did not differ from controls on EB responding during either adaptation or acquisition. However, lesioned animals revealed more EB CRs during extinction than control animals. EMG CRs were minimal in both groups of animals. Lesioned animals showed smaller HR changes than control animals during all phases of training, although HR CRs tended to consist of bradycardia in all animals. No differences were observed in either shock thresholds or open field activity as a result of LH lesions. Cortical and hippocampal 5-HT and NE concentrations were significantly depleted in lesioned as compared to control animals. These findings were interpreted within the framework of the phasic control of attention by midbrain modulation of forebrain structures; however, the interruption of downward going fibers which mediate brain stem cardiac control cannot be ruled out.

Animals↗

Salmonella in the intestinal tract and associated lymph nodes of sheep and cattle.

The distribution of salmonellas along the gastrointestinal tract and in associated lymph nodes were studied in 100 sheep and 100 cattle at slaughter. Animals were chosen from those slaughtered on the first day of the week, since this meant that they were likely to have been held at the abattoir for several days and thus to be at high risk of salmonella infection. The contents of the rumen, abomasum, ileum, caecum and rectum were sampled, together with the lymph nodes draining each of these sites. Of the cattle, 77 were carrying salmonellas, including 61 with infected lymph nodes, whereas only 43 sheep were infected, 14 of them with infections in the nodes. The lower prevalence in sheep than in cattle might be explained by a shorter time between leaving the property and slaughter. In both species, within the gastrointestinal tract salmonellas were most frequently found in the caecum and rectum and least frequently in the abomasum. In cattle salmonellas were frequently present, usually in large numbers, in the lymph nodes draining the ileum, caecum and colon, but rarely in the ruminal and abomasal nodes; however this difference was not apparent in sheep. Over 70% of infected animals yielded more than one serotype, the maximum number isolated from any one animal being ten.

Animals↗

Specificity of purified protein derivative extracts from cultures of mycobacteria killed by phenol.

Purified protein derivative (PPD) extracts were prepared from Mycobacterium bovis, M tuberculosis, M kansasii, M marinum, M avium, M intracellulare, M gordonae and M fortuitum. The cultures were killed with phenol before extraction and were not subjected to heat. They were tested in guinea pigs sensitised with killed cultures of homologous or heterologous species of mycobacteria. The most specific extract was from M fortuitum. M bovis and M tuberculosis were closely related, with M bovis PPD the more specific of the two. A close relationship was shown between M scrofulaceum, M avium and M intracellulare.

Animals↗

Substrate-dependent irreversible inactivation of cytochrome P-450: conversion of its haem moiety into modified porphyrins.

2-Allyl-2-isopropylacetamide and other drugs containing either an allyl, a vinyl or an ethynyl unsaturated side chain are metabolized by liver cytochrome P-450 to reactive derivatives that irreversibly inhibit the haemoprotein by a suicidal type of inactivation. The main target is the haem moiety of cytochrome P-450 which is converted into abnormal porphyrins. These have been isolated from the liver of treated rats, extensively purified and compared with model porphyrins. The abnormal porphyrins incorporate metal ions in vitro much more readily than does their parent porphyrin, protoporphyrin. They are also much more basic than protoporphyrin, and on titration with a strong acid they readily give rise to a porphyrin monocation which then requires relatively large amounts of acid for conversion to the porphyrin dication. In all these respects and also in the intensity of their bathochromic shifts these abnormal porphyrins closely resemble N-alkylated porphyrins and they markedly differ from porphyrins that are substituted at one of their meso-carbon positions or which bear electron-withdrawing substituents at the beta-positions of the pyrrole rings. This suggests strongly that reactive derivatives of the unsaturated drugs act as electrophilic reagents and alkylate one of the pyrrole nitrogen atoms of cytochrome P-450. A model centred on the apoprotein of cytochrome P-450 is considered for the degradation of liver haem caused by unsaturated drugs. The apocytochrome may accept exchangeable pools of liver haem for degradation, leading to a state of haem depletion and to activation of delta-aminolaevulinate synthase.

Acetamides↗