PubMed HealthSearch

Biomedical subjects

C L Hill

Publications and source records attributed to C L Hill.

At least 19 recordsLinked to original sources

Synthesis, characterization, and biological activity of a new potent class of anti-HIV agents, the peroxoniobium-substituted heteropolytungstates.

The mono- and trisubstituted peroxyniobium polyoxotungstates of formulas [(CH3)3NH]7[Si-(NbO2)3W9O37], Cs7[Si(NbO2)3W9O37], alpha-K5[Si(NbO2)W11O39] and alpha-[(CH3)3NH]5[Si(NbO2)-W11O39], have been prepared, purified, and characterized spectroscopically by 29Si NMR, 183W NMR, and IR. The presence of peroxo groups was verified by the yellow color of the product and quantified by iodometric titration. The potency of both the complexes and the precursor complexes was evaluated in human peripheral blood mononuclear cells (PBMC) acutely infected with human immunodeficiency virus type 1 (HIV-1). Hexaniobate (K7H[Nb6O19]) was the least effective with a median effective concentration (EC50) of > 100 microM, while Cs7[Si(NbO2)3W9O37] was one of the most effective compounds with an EC50 of 1.0 microM. None of the compounds were toxic to uninfected PBMC with the exception of alpha-K8[SiW11O39], which had a median inhibitory concentration (IC50) of 79 microM. The potency and selectivity of the complexes against HIV-1 reverse transcriptase was also evaluated and shown to be quite high (IC50 values from 0.03 to 0.06 microM). The trimethylammonium salts of the complexes were tested for their ability to inhibit the interaction between gp120 and CD4 using a cell-free system. The complex [(CH3)3NH]7[Si(NbO2)3W9O37] inhibited this interaction by 70% at 25 microM.

Antiviral Agents

Synthesis, characterization, and anti-human immunodeficiency virus activity of water-soluble salts of polyoxotungstate anions with covalently attached organic groups.

The cesium and tetramethylammonium (TMA) salts of polyoxotungstate anions with covalently attached organosilyl groups of formula [(RSi)2O]SiW11O39(4-), where R = CH2CH2COCH3, (CH2)3CN, and CH==CH2 (1-R, cesium salt, unless otherwise noted) have been prepared, purified, and spectroscopically characterized. The water solubility (25 degrees C) of these 10 new compounds ranges from 0.14 mM to 2.16 mM. All appear to be stable in aqueous media over a period of several hours as assessed by 1H NMR. The activities (EC50) of the new compounds against human immunodeficiency virus in primary human lymphocytes range from 3.3 microM to 39.0 microM. Their toxicities (IC50) are all greater than 100 microM. The inhibition constants of the new compounds against purified virion-derived HIV-1 reverse transcriptase are in the 1-10 microM range.

Anions

Induction of resistance to 6-thioguanine and cytarabine by a range of anticancer drugs in Chinese hamster AA8 cells.

A mutagenicity assay using AA8 Chinese hamster cells has been used to explore the potential of some currently used clinical anticancer drugs to induce cells resistant to 6-thioguanine and cytarabine. Preliminary experiments gave evidence of a "low dose" and "high dose" resistance to cytarabine, and subsequent work considered only the latter of these events. When ethyl methane sulphonate was used as a reference mutagen, induced resistance to cytarabine developed substantially later and at a lower frequency than resistance to 6-thioguanine. Of the clinical drugs tested, carmustine showed the highest ability to induce either 6-thioguanine or cytarabine resistant cells. Bleomycin, daunomycin and amsacrine showed moderate ability, while vincristine was essentially inactive in these assays. Such information could potentially be used in selecting new drug combinations or timing of drug administration in cancer chemotherapy.

Amsacrine

Anti-HIV-1 activity, toxicity, and stability studies of representative structural families of polyoxometalates.

The anti-HIV-1 activity and toxicity of representative structural families of polyoxotungstates in human lymphocytes was determined. The 21 compounds examined include those derived from the following structural families: [NaSb9W21O86]18- (HPA-23), Xn+W12O40(8-n)- (Keggin), P2W18O62(6-) (Wells-Dawson), W6O19(2-) (Lindqvist), [NaP5W30O110]14- (Preyssler), and W10O32(4-) (decatungstate). The molecular architecture of each of these structural families is constituted principally by a network of bonds between d0 WVI and oxide ions. Of these, 10 show median effective concentration (EC50) values of approximately 1 microM and six have marked toxicity with a median inhibitory concentration (IC50) of less than 50 microM. Only compounds containing more than six metal atoms showed appreciable antiviral activity. Beyond this, however, no marked correlation existed between the molecular size, charge, or charge density of the polyoxometalates and their anti-HIV-1 activity. Examination of an exemplary class of polyoxotungstates, the phosphotungstates of formula A- and B-PW9O34(9-) under physiological conditions (buffered neutral aqueous media), illustrates that both isomers equilibrate rapidly to generate the same distribution of products and that this distribution depends principally on the buffer. These heretofore unappreciated complexities in the chemistry of these compounds under neutral aqueous conditions indicates interpretation or evaluation of these compounds in cell culture and other biological screens must be done with care.

Antimony

The Yale-Brown Obsessive Compulsive Scale. I. Development, use, and reliability.

The Yale-Brown Obsessive Compulsive Scale was designed to remedy the problems of existing rating scales by providing a specific measure of the severity of symptoms of obsessive-compulsive disorder that is not influenced by the type of obsessions or compulsions present. The scale is a clinician-rated, 10-item scale, each item rated from 0 (no symptoms) to 4 (extreme symptoms) (total range, 0 to 40), with separate subtotals for severity of obsessions and compulsions. In a study involving four raters and 40 patients with obsessive-compulsive disorder at various stages of treatment, interrater reliability for the total Yale-Brown Scale score and each of the 10 individual items was excellent, with a high degree of internal consistency among all item scores demonstrated with Cronbach's alpha coefficient. Based on pretreatment assessment of 42 patients with obsessive-compulsive disorder, each item was frequently endorsed and measured across a range of severity. These findings suggest that the Yale-Brown Scale is a reliable instrument for measuring the severity of illness in patients with obsessive-compulsive disorder with a range of severity and types of obsessive-compulsive symptoms.

Adult

The nonluteal porcine ovary as a source of angiogenic activity.

Nonluteal ovarian tissue extracts were tested for their ability to stimulate migration and proliferation of cultured bovine capillary endothelial cells. Stimulation of migratory and proliferative activity was found in the 105,000 X g supernatant of homogenates of either whole nonluteal porcine ovaries or isolated theca (follicular walls). Maximal proliferative and migratory activity was obtained with 1-10 micrograms homogenate protein. Neither follicular fluid nor extracts of granulosa cells showed significant activity when tested over a broad concentration range. The proliferative and migratory activities were associated with a heat-labile, nondialyzable, protease-sensitive fraction that was soluble in 40%, but not 60% (NH4)2SO4. The tissue extracts that effectively stimulated growth and migration of capillary endothelial cells in vitro also stimulated the formation of new capillary blood vessels in an angiogenesis assay performed on chick chorioallantoic membranes.

Allantois

Retromastoid microsurgical approach to vascular compression of the eighth cranial nerve.

In our series of 10 patients, the age ranged between 31 and 69 years. Seven patients were followed for from 1-2 1/2 years. Complaints consisted of tinnitus, vertigo, or both. Vegatative symptoms consisting of nausea or vomiting were minimal or absent. Audiometry revealed a varying neurosensory loss. Vestibular hypoexcitability was a common finding. Good discrimination appeared to indicate a vascular loop rather than hydrops. The neuroradiological work-up was unremarkable. Treatment consisted of neurovascular decompression of the VIIth nerve by microdissection. The approach used was a retromastoid incision with a bony removal limited to 20 mm. Cerebrospinal fluid withdrawal and lateral decubitus positioning permitted visualization of the VIIIth nerve without retraction of the cerebellum. Lack of bleeding, rapidity of procedure and benign postoperative course are emphasized. The results on tinnitus and vertigo were satisfactory. No additional deficit was created by surgery. If the symptoms are significantly disabling, microsurgical exploration is indicated.

Adult

Reticuloendothelial and mesangial function in murine immune complex glomerulonephritis.

The function of the mesangial and reticuloendothelial system was evaluated in normal mice and in mice with nephritis induced by lymphocytic choriomeningitis (LCM) virus infection. Heat-aggregated human immunoglobulin (AlgG) and colloidal carbon served as traceable materials which could be detected in animals' blood and tissues. LCM virus-infected proteinuric (LCM-P) mice, as compared to normal mice or LCM-infected nonproteinuric (LCM) mice, had greater accumulation of AIgG in their glomeruli at all times of examination following i.p. injection of AIgG. The removal rate of AIgG from the kidney, however, was the same in normal and LCM-P mice, indicating an unimpaired mesangial clearing system. This suggested that other mechanisms were responsible for the increased glomerular accumulation of AIgG in LCM-P mice. Reticuloendothelial function was examined directly by i.v. injection of AIgG or colloidal carbon. The data demonstrate that in this model of immune complex glomerulonephritis, colloidal material tested was removed from the blood at a slower rate than it was in normal mice. Deficient clearance of endogenous blood-borne immune complex-like material may be one of the factors playing a role in the accumulation of immune complex-like material in the glomeruli of these nephritic animals.

Albuminuria

Identification of the iron-sulfur center in trimethylamine dehydrogenase.

Trimethylamine dehydrogenase [trimethylamine:(acceptor) oxidoreductase (demethylating), EC 1.5.99.7] from a facultative methylotroph bacterium has a molecular weight of 147,000 and contains two types of prosthetic groups, one a covalently bound organic chromophore of uncertain structure and the other containing iron and labile sulfur (S*). The structure of the Fe-S* center has been investigated by reactions of the enzyme with sodium mersalyl, o-xylyl-alpha,alpha'-dithiol, and p-methoxybenzenethiol in a 4:1 vol/vol hexamethylphosphoramide/water reaction medium, which destabilizes tertiary structure. Mersalyl treatment results in reduction of visible absorbance consistent with the presence of a 4-Fe center of the ferredoxin type. Reaction with thiols effects partial bleaching of the organic chromophore, as established by separate studies of a detached chromophore peptide, and results in removal (extrusion) of the core unit of the Fe-s* center in the form of the complexes [Fe4S*4(S2-o-xylyl)2]n2n- and [Fe4S*4(SC6H4OMe)4]2-, which were identified by absorption spectra. These results, in conjunction with control extrusion reactions of oxidized ferredoxins from spinach and Clostridium pasteurianum, establish that trimethylamine dehydrogenase contains one Fe4S*4 core unit most probably present as a ferredoxin-type, cysteinate-ligated cluster [Fe4S*4(S-Cys)4].

Bacteria

Studies of abluminuria and proteinuria in normal mice and mice with immune complex glomerulonephritis.

Proteinuria is supposedly a frequent and early manifestation of glomerulonephritis. Since albuminuria rather than proteinuria is the hallmark of glomerular disease, the present studies were designed to study the occurrence of albuminuria in normal mice (SWR/J strain) and in mice with a reproducible and predictable immune complex glomerulonephritis induced by chronic infection with lymphocytic choriomeningitis (LCM) virus. A radial immunodiffusion technique, specific for mouse albumin, was employed to quantify the albuminuria. Column chromatography of concentrated urine obtained from normal and nephritic mice demonstrated that albumin excreted in the urine had the same molecular weight as serum albumin and that identifiable fragments of albumin did not appear in the urine. Some albuminuria did occur in normal mice, 0.12 +/- SD. 0.13 mg. per 18 hours for 80 males and 0.13 +/- 0.09 mg. per 18 hours for 55 females. Increased albuminuria, defined as values greater than a normal mean + 2 S.D. (0.40 mg. per 18 hours) occurred in only 25 per cent of nephritic mice, although in more than 600 animals studied, immunofluorescent microscopy invariably demonstrated abnormal accumulation of immune complexes in the glomeruli of SWR/J mice chronically infected with LCM virus. Values of total proteinuria measured by the sulfosalicylic acid method did not correlate with radial immunodiffusion measured albuminuria. The results indicate that measurement of total proteinuria in mice is not a useful parameter of glomerular disease. Albuminuria, while increased in 25 per cent of nephritic animals, was not abnormal even in the presence of marked histologic alterations in 75 per cent of mice, suggesting that abnormal immunopathology may very commonly not be reflected in increased or pathologic albuminuria. Recent observations also suggest that this is the case in humans.

Albuminuria

Surgicenters.

Explore the source record for details and available documents.

Arizona