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Biomedical subjects

C Wells

Publications and source records attributed to C Wells.

At least 19 recordsLinked to original sources
PubMed1992

Synthesis and antiulcer activity of novel 5-(2-ethenyl substituted)-3(2H)-furanones.

In order to investigate new antiulcer agents, spizofurone 1 (AG-629) was fragmented and reassembled to generate 5-phenyl-2,2-dimethyl-3(2H)-furanone (bullatenone, 2). Because of the antiulcer activity of 2,5-phenyl-substituted 2,2-dimethyl-3(2H)-furanones (3-6) were made and shown to have poor activity. Insertion of an ethenyl link between the furanone and phenyl rings gave 5-(2-phenylethenyl)-2,2-dimethyl-3(2H)- furanone (7). This compound had better activity than 2. Compounds 8-41 were synthesized to evaluate the SAR in 5-(2-ethenyl substituted)-3(2H)-furanones. Electron-withdrawing substituents on the aromatic ring (8, 10, 19, and 20) gave 2-3-fold higher activity. Further increases in the activity were found when the phenyl ring was replaced by heterocyclic nuclei. Compounds that contained a thiophene (29), pyridine (24-26), or quinoline ring (32) had the best activity. Replacement of the methyl group on the furanone ring with a phenyl (34) or p-fluorophenyl (40) substituent in the 2-pyridine series gave compounds with activity that ranked with the best obtained in this study. The best compounds from the above SAR studies were evaluated in the ethanol-necrosis model for duration of cytoprotection action. Compounds 19, 24, and 29, which had the best duration of action, were tested with AG-629 in the acidified aspirin and indomethacin-induced lesion models. Only compound 24 had equivalent activity with AG-629 in both models.

Animals↗
PubMed1992

Effects of phosphatidylserine in Alzheimer's disease.

We studied 51 patients meeting clinical criteria for probable Alzheimer's disease (AD). Patients were treated for 12 weeks with a formulation of bovine cortex phosphatidylserine (BC-PS; 100 mg t.i.d.) or placebo, and those treated with the drug improved on several cognitive measures relative to those administered placebo. Differences between treatment groups were most apparent among patients with less severe cognitive impairment. Results suggest that phosphatidylserine may be a promising candidate for study in the early stages of AD.

Aged↗
PubMed1991

Rapid induction of early osteoarthritic-like lesions in the rabbit knee by continuous intra-articular infusion of mammalian collagenase or interleukin-1.

Aminophenyl mercuric acetate (APMA)-activated collagenase (C) (60 U/ml) obtained from in vitro cultures of human skin fibroblasts or recombinant interleukin-1 beta (IL-1 beta) (200 U/ml) was infused continuously for 7 days into the rabbit knee synovial space by means of an implanted Alzet osmotic pump. In stability studies in vitro, activated C or IL-1 incubated for 7 days at 37 degrees C, showed no significant loss of biological activity. Alterations in knee cartilage morphology and proteoglycan (PG) content were determined histologically, and the incidence of cartilage damage calculated. C or IL-1 vehicles infused for 7 days, caused no damage. Incidences of damage for C or IL-1 (n = 8-9), respectively, were as follows: loss PG: 88% and 100%; chondrocyte disorganization and loss, 50% and 78%, fissures and or fraying, 25% and 78%; and convergence of inflammatory cells, 25% and 66%. These results confirm the important role of C and IL-1 in cartilage damage.

Animals↗
PubMed1991

Pain and allodynia in postherpetic neuralgia: role of somatic and sympathetic nervous systems.

The immediate effects of selective sympathetic and somatic blockades on pain and tactile allodynia in 12 patients with long-standing ophthalmic or high cervical postherpetic neuralgia were compared. For the duration of the somatic blockade, pain was completely abolished in 11 patients and allodynia in 8 patients. In contrast, during the sympathetic blockade only one patient reported total pain relief and three a marginal attenuation of pain while eight remained unchanged; and no patient reported clear alleviation of allodynia. After successful somatic blockade, pain and allodynia reappeared with tactile sensation while thermal sensation was still absent. Pain and allodynia appear to be related to sensory impulses travelling along the large rather than the small diameter fibres; and the sympathetic system may only have a limited role.

Aged↗
PubMed1991

Axonemal dynein from Tetrahymena.

Axonemal dynein from Tetrahymena cilia can be separated on a sucrose gradient into two fractions, at least one of which appears to be polymorphic. We have been using immuno-electron microscopy in order to try and locate the different types of dynein molecules within the axonemal structure.

Animals↗
PubMed1991

Peroperative monitoring during percutaneous thermocoagulation of the Gasserian ganglion for the treatment of trigeminal neuralgia.

A bipolar electrode has been designed to assess the possibility of locating accurately the electrode tip position within a nerve pathway prior to its thermal coagulation without having recourse to a wake-up procedure. By electrically stimulating each of the peripheral divisions of the trigeminal nerve and recording the evoked activity pre-ganglionically from the electrode, using an averaging computer, a clear triphasic response is recorded. The amplitude of this wave is largest when the electrode is within the stimulated division, thereby confirming electrically the anatomical location. By incorporating a thermocouple in the tip of the electrode a precisely controlled thermocoagulation can then be achieved using a radiofrequency generator. A preliminary series of 12 patients with trigeminal neuralgia requiring operative treatment were assessed in this study. In eight cases a clear response was obtained, in two the signal-to-noise ratio was too small, in one stimulus artefact obscured the response and in one a blood vessel was hit.

Electrocoagulation↗
PubMed1991

A comparison of intrauterine insemination, intraperitoneal insemination, and natural intercourse in superovulated women.

In a prospective comparison of IP, IUI, and natural intercourse following superovulation in couples diagnosed as having unexplained infertility, semen factors, or sperm antibodies, pregnancy rates were found to be significantly higher after IP. Pregnancy rates were also higher in the unexplained infertility group when compared with those with semen factors. It was concluded that IP in combination with superovulation offered a simple, inexpensive, safe alternative to GIFT.

Administration, Intravaginal↗
PubMed1990

Necator americanus in the mouse: histopathological changes associated with the passage of larvae through the lungs of mice exposed to primary and secondary infection.

The mouse/Necator americanus model was studied to assess the histopathological changes that occur in the lungs following primary and secondary exposure to infective larvae. Groups of BALB/c mice were infected percutaneously and killed on various days post infection. Parasite numbers were counted, the bronchoalveolar leukocyte response was quantified and histological sections of lung material were examined for evidence of host protective inflammatory reactions. An increase in the inflammatory infiltration was observed between days 5 and 9 in both primary and secondary infections but was considerably more intense in re-infected animals. This involved a marked change in the character of the infiltrate, particularly in the number of eosinophils that were recovered in lavage fluid. More worms were trapped in the lungs of challenged mice, as assessed through their inability to escape from lung material incubated in vitro. Overall, the results were found to be compatible with the development of acquired resistance to N. americanus and the expression of host protective immunity during the development of challenge-infection larvae in the lungs.

Animals↗
PubMed1990

Self-interaction of dynein from Tetrahymena cilia.

The molecular mass (Mr) and enzymic activity of the larger dynein species from Tetrahymena thermophila has been studied in the high (600 mM) to low (40 mM) ionic strength range. The apparent Mr is found to vary with both ionic strength (by sedimentation velocity and quasi elastic light scattering analysis) and with protein concentration at low ionic strength (by sedimentation equilibrium analysis). These data indicate a strong self-interaction, resulting in dimer formation under low salt conditions. There is no evidence for the formation of species of higher than dimeric mass. A molecular mass for the dynein monomer of 1.64 x 10(6) daltons has been determined, a value rather lower than previous published estimates. The ATPase activity of dynein increases with increasing ionic strength. The possible relationship between this effect and the self-association phenomenon is discussed.

Adenosine Triphosphatases↗
PubMed1990

Changes in the rate of crypt epithelial cell proliferation and mucosal morphology induced by a T-cell-mediated response in human small intestine.

The rate of crypt epithelial cell proliferation and mucosal morphology have been studied in vitro in explants of fetal human small intestine in organ culture in which a cell-mediated immune response has been elicited by stimulating lamina propria T cells with pokeweed mitogen or monoclonal anti-CD3 antibodies. Twelve hours after the addition of anti-CD3 or pokeweed mitogen, most lamina propria T cells expressed CD25. By 18 and 24 h after the addition of anti-CD3, there were significantly more crypt cells in the cell cycle than in controls, although villus height and crypt depth are the same in both groups. After 3 days, by dissecting microscopy, the villi appeared shorter in cultures in which the T cells were stimulated than in control cultures, and the mucosal surface was obscured by a layer of extruded enterocytes. Villus atrophy was confirmed by direct measurement of Feulgen-stained, microdissected villi. Crypts were longer in T-cell-stimulated cultures, and the rate of crypt epithelial cell proliferation measured by metaphase arrest was increased 10-fold. By electron microscopy, the microvilli and cellular morphology of the surface enterocytes were normal in T-cell-stimulated cultures. These experiments clearly show that a profound immune-mediated crypt epithelial cell hyperplasia can occur in the absence of damage to surface enterocytes.

Antibodies, Monoclonal↗
PubMed1990

N-phenyl-2-pyridinecarbothioamides as gastric mucosal protectants.

A series of substituted 2-pyridinecarbothioamides was synthesized and evaluated for gastric mucosal protectant activity in the rat. Out of this investigation N-(3,5-difluorophenyl)-2- pyridinecarbothioamide (23, AY-31,574) was identified. This compound was much more potent than sucralfate and ranitidine against ethanol-induced lesions. Compound 23 was equipotent with ranitidine against gastric injury caused by stress. Unlike ranitidine, 23 was found to be devoid of antisecretory activity in the pylorus-ligated rat model, making it a selective mucosal protectant. Such a potent selective mucosal protectant may provide a novel clinical approach in treating ulcers.

Amides↗
PubMed1990

Morphological integrity of the bronchial epithelium in mild asthma.

In severe asthma bronchial epithelial cells are damaged and detached, and it has been proposed that such damage might lead to the bronchial hyperresponsiveness that characterises asthma. To investigate the relation between airway hyperresponsiveness and epithelial damage, biopsy specimens of the bronchial mucus membrane were obtained at fibreoptic bronchoscopy from 11 patients with mild atopic asthma and airway hyperresponsiveness (provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) less than 1.0 mg/ml), and from 17 healthy non-atopic subjects who did not have airway hyperresponsiveness (PC20 methacholine greater than 8.0 mg/ml). Observers who were blind to the presence or absence of asthma examined the biopsy specimens by light and electron microscopy. Epithelial cells, intercellular spaces, and goblet cells were counted. Intercellular junctional complexes were examined, and a semiquantitative assessment was made of ciliary loss, non-parallel central ciliary filaments, and vacuoles in ciliated cells. There were no differences between the asthmatic and healthy groups in any of these measurements. These findings indicate that airway hyperresponsiveness may be present when there is no apparent change in the structure of the bronchial epithelium.

Adult↗
PubMed1989

Peptides related to alpha-melanocyte-stimulating hormone are commonly produced by human pituitary corticotroph adenomas: no relationship with pars intermedia origin.

The presence of immunoreactive (ir)-alpha-MSH has been investigated by immunocytochemistry in 24 pituitary adenomas and one case of corticotroph hyperplasia causing Cushing's disease, in four adenomas causing Nelson's syndrome, and in ten 'silent' corticotroph adenomas. It was found that a high proportion of these adenomas have a population of cells containing ir-alpha-MSH in addition to ir-ACTH. In some instances, these adenomas were clearly not associated with the residual intermediate lobe of the pituitary. Radioimmunoassay of plasma from patients with Cushing's disease or Nelson's syndrome showed elevated levels of ir-alpha-MSH in the majority of cases. Characterization of the ir-alpha-MSH in adenoma cells by immunocytochemistry, using an antiserum selective for acetylated forms of alpha-MSH, suggested that only the desacetyl form was present in each case examined. High-performance liquid chromatography of adenoma tissue extracts revealed material co-eluting with acetylated forms of alpha-MSH in only one of six cases. These results have been compared with corticotroph adenomas in animal pituitary glands, and it is concluded that the presence of alpha-MSH peptides cannot be used as a marker for intermediate lobe tumours, and that desacetyl alpha-MSH is commonly produced by corticotroph adenomas.

Adenoma↗