Biomedical subjects

R G Mills

Publications and source records attributed to R G Mills.

At least 37 records · Page 2Linked to original sources

PubMed1995

Comparison of the antiviral activities of 3'-azido-3'-deoxythymidine (AZT) and gossylic iminolactone (GIL) against clinical isolates of HIV-1.

3'-Azido-3'-deoxythymidine (AZT) and gossylic iminolactone (GIL) were compared for antiviral activities in vitro against fresh clinical isolates of HIV-1 obtained from 19 subjects on AZT therapy. IC50 values for AZT ranged from 0.015 to 6.7 microM (447-fold range) while IC50 values for GIL ranged from 0.40 to 6.6 microM (16-fold range). There was no correlation between IC50 values for AZT and GIL, suggesting that the anti-HIV activity of GIL does not involve inhibition of reverse transcriptase.

Acquired Immunodeficiency Syndrome↗

PubMed1995

'Ceruminoma'--a defunct diagnosis.

The clinical and pathological features of glandular tumours of the external auditory meatus are presented. Their heterogenous clinical and pathological features make the collective term 'ceruminoma' ambiguous and misleading. The spectrum of pathological behaviour and histological features demonstrated by these interesting tumours necessitate a broader classification system. In our hospital 32 patients presented with tumours of the external auditory meatus over a 30-year period, of which seven were glandular in origin. A review of the histology of these glandular tumours enabled us to reclassify them as adenoma, cylindroma, adenoid cystic carcinoma or ceruminous adenocarcinoma. Together with the less common mucoepidermoid carcinoma and pleomorphic adenoma this subdivision forms a basis for a more meaningful classification system with prognostic and therapeutic implications specific to each tumour type. The term 'ceruminoma' should no longer be used unqualified.

Adenocarcinoma↗

PubMed1994

The solution structure of sarafotoxin-c. Implications for ligand recognition by endothelin receptors.

The solution structure of sarafotoxin-c has been determined using NMR spectroscopy. A total of 112 interproton distance constraints derived from two-dimensional NMR spectra were used to calculate a family of structures using a combination of distance geometry and dynamical simulated annealing calculations. The structures reveal a well defined alpha-helix extending from Glu9 to Cys15 and an N-terminal region (Cys1-Asp8) that is tightly constrained by disulfide bonds to Cys residues in the central helix. In contrast, the C-terminal region (His16-Trp21) does not adopt a defined conformation in the final family of structures. This is consistent with the paucity of NMR-derived structural constraints obtained for this region and leads to the suggestion that the C-terminal region oscillates rapidly between a number of substantially different conformers. It is proposed that differences between the central helix of the endothelin and sarafotoxin isopeptides might be important in binding of these ligands by the G protein-coupled endothelin receptors.

Amino Acid Sequence↗

PubMed1994

Fulminant septicaemia due to Streptococcus milleri infection in a previously healthy adult.

A 59-year-old previously healthy female developed purulent pharyngitis leading rapidly to neck cellulitis, septicaemic shock and fatal cardiac arrest despite appropriate antibiotic therapy. Streptococcus milleri was isolated from a submandibular abscess, cellulitic neck tissue and blood cultures. Fulminant septicaemia due to this group of organisms is relatively uncommon and usually occurs in the immunocompromised or otherwise chronically unwell.

Anti-Bacterial Agents↗

PubMed1994

HIV-1 infection despite immediate combination antiviral therapy after infusion of contaminated white cells.

We present a sixth human case in which primary human immunodeficiency virus (HIV-1) infection occurred, despite antiretroviral prophylaxis, after accidental inoculation of infected blood. In the prior five instances, variables such as large virus dose, late administration of antivirals, viral resistance to zidovudine, and pre-existent immunosuppression, may have played a role in the treatment failure. In this case, high-dosage oral zidovudine was given within minutes of the accident and replaced 2 1/2 days later with interferon alpha and dideoxyinosine (ddl). Despite aggressive treatment, HIV-1 infection was demonstrated in blood, spleen, and brain tissue at autopsy 16 days later. Of the tissues studied, detection of HIV-1 was most prominent in the spleen. Double-label immunocytochemistry confirmed the morphologic impression that while some of the infected spleen cells were CD3-positive T cells, the majority were macrophages. Thus, current single or dual (zidovudine, ddl-interferon) therapies for accidental HIV-1 inoculation may not be effective in preventing early infection. Further trials in animals appear warranted to evaluate protection by other strategies, such as passive immunity or combinations of agents that penetrate the brain and attack HIV-1 viral replication at differing sites.

Aged↗

PubMed1994

Voice changes in acromegaly.

The fundamental frequency of 14 patients undergoing hypophysectomy was studied. Eight patients had acromegaly, 3 had a prolactinoma, and 3 had nonfunctioning adenomas. The fundamental frequency of 22 normal, healthy volunteers was measured for comparison. In addition, the external size of the larynx of all patients and volunteers was measured and a relationship between external laryngeal size and the mean fundamental frequency was identified in the volunteers. The mean fundamental frequency in patients with acromegaly was significantly lower than the other 6 patients undergoing hypophysectomy and, in addition, was also lower than the 22 normal volunteers. Postoperatively the fundamental frequency of the acromegalic patients increased rapidly to within the expected normal range. Patients with acromegaly have a lowered fundamental frequency which is most likely due to altered vocal cord mass and elasticity, which is a reversible change. Patients with acromegaly can expect a rapid and complete return of normal fundamental frequency within 2 weeks of surgery to remove the pituitary adenoma.

Acromegaly↗

PubMed1992

Solution structure of endothelin-3 determined using NMR spectroscopy.

The aqueous solution structure of the 21-residue vasoactive peptide hormone endothelin-3 has been determined using high-resolution NMR spectroscopy. A total of 177 proton-proton distance measurements and 5 chi 1 dihedral angle constraints derived from NMR spectra were used to calculate the structure using a combination of distance geometry and dynamical simulated annealing calculations. The calculations reveal a highly ordered, compact conformation in which a helical region extending from K9 to C15 lies in close apposition with the C-terminal hexapeptide; this interaction seems to be largely driven by hydrophobic interactions. Structure-activity studies are interpreted in terms of the conformational features of the calculated endothelin-3 structure.

Amino Acid Sequence↗

PubMed1992

Prediagnostic malakoplakia presenting as a chronic inflammatory mass in the soft tissues of the neck.

Malakoplakia presenting in the head and neck is very rare. We present a case of an inflammatory mass in the neck, clinically mimicking actinomycosis in a 67-year-old man. Repeated culture of E. coli and histological and electron microscopic examination of biopsy material showed an infiltration of granular macrophages and intracellular gram negative bacilli, but no classical Michaelis-Gutmann bodies. The clinical and pathological findings and criteria for the diagnosis of malakoplakia are discussed.

Aged↗

PubMed1992

Early viral brain invasion in iatrogenic human immunodeficiency virus infection.

We report a 68-year-old man who received an IV inoculation of WBCs for an indium radionuclide scan containing 600 to 700 tissue culture infectious doses of human immunodeficiency virus type 1 (HIV-1) from an HIV-1-infected individual. The recipient immediately received zidovudine, then was switched to dideoxyinosine and interferon-alpha, but died of hepatorenal syndrome and hepatic encephalopathy 15 days later. HIV-1 cultures were positive from the recipient's blood on day 14 but not days 0, 1, and 8. At autopsy, cultures of parietal lobe isolated HIV-1. HIV-1 nucleic acid was present in several brain areas, but not in several other organs, by two independent laboratories using the polymerase chain reaction. The brain showed mild perivascular cuffing and a mild lymphocytic meningitis, but there was no evidence of glial nodules, giant cells, or white matter abnormalities. HIV-1 pg41 viral antigen was seen by immunoperoxidase staining in rare infiltrating cells within perivascular and subpial spaces. Thus, HIV-1 was isolated from brain 15 days after mistaken HIV-1 inoculation and 1 day after virus was first recovered from blood.

Aged↗

PubMed1991

Conformation of sarafotoxin-6b in aqueous solution determined by NMR spectroscopy and distance geometry.

The solution structure of sarafotoxin-6b in water has been determined using high-resolution NMR spectroscopy. 127 proton-proton distance measurements and three phi dihedral angle constraints derived from NMR spectra were used to calculate the solution structure using a combination of distance geometry and restrained molecular dynamics. The major structural feature of the resulting family of five structures was a right-handed alpha-helix extending from K9 to Q17. In contrast, the C-terminal region of the peptide appears not to adopt a preferred conformation in aqueous solution. The present structure is compared with those previously determined for endothelin peptides in non-aqueous solvents.

Amino Acid Sequence↗

PubMed1991

Transport complexes associated with slow axonal flow.

Cytoskeletal proteins--neurofilament polypeptides, tubulin and actin--are transported along axons by slow transport. How or in what form they are transported is not known. One hypothesis is that they are assembled into the cytoskeleton at the cell body and transported as intact polymers down the axon. However, recent radiolabeling and photobleaching studies have shown that tubulin and actin exist in both a mobile phase and a stationary phase in the axon. Consequently, it is more likely that cytoskeletal proteins move along the axon in some form of transport complex and are assembled into a cytoskeleton which is stationary. In this overview we discuss these topics and consider the evidence for the existence of transport complexes associated with slow axonal flow. Such evidence includes the slow transport of particulate complexes containing tubulin and neurofilament polypeptides along reconstituted microtubules in vitro, and the coordinate slow transport of actin with actin-binding proteins in vivo.

Actins↗

PubMed1991

Response to beta-blockers in maternal and fetal rat hearts in vitro.

The effects of beta-blockers on maternal and fetal heart rates have been assessed by comparing isoprenaline concentration-heart rate relationships of hearts isolated from pregnant rats. The normal and maximal heart rates obtained for the maternal and fetal hearts were similar to published data. A slightly but significantly higher concentration of isoprenaline was required to produce 50% of the maximal response of fetal hearts than maternal hearts, suggesting that fetal hearts were less sensitive to isoprenaline than the maternal hearts. The beta-blockers used (propranolol, labetalol, metoprolol and atenolol) all showed a lower affinity to the beta-receptors of fetal hearts than those of maternal hearts, as indicated by significant differences in the pA2 values. Given the similar effects of the beta-blockers in the maternal and fetal hearts it is concluded that pharmacokinetic considerations and beta-blocker selectivity should be used as the basis of choice when treating maternal hypertension during pregnancy.

Adrenergic beta-Antagonists↗

PubMed1991

Inhibition of human immunodeficiency virus type I replication by derivatives of gossypol.

Gossypol (I) and its derivatives gossylic nitrile-1,1'-diacetate (II), gossylic iminolactone (III) and gossylic lactone (IV) inhibit the replication of human immunodeficiency virus type 1 in vitro in the order III greater than I greater than II,IV, indicating that derivatives of gossypol can retain antiviral activities. All of the derivatives are less cytotoxic than gossypol.

Antiviral Agents↗

PubMed1990

Effects of electrical stimulation and tetrodotoxin paralysis on antigenic properties of acetylcholine receptors in rat skeletal muscle.

To examine the role of muscle activity in the expression of fetal- and adult-type acetylcholine receptors (AChRs), we studied the effects of muscle stimulation in cell culture and of tetrodotoxin (TTX)-induced paralysis and denervation in adult rat muscles. The AChR content of these muscles was determined using [125I]alpha-bungarotoxin and the proportion of fetal-type receptors was estimated using a radioimmunoprecipitation assay with a myasthenic serum that was highly specific for fetal-type receptors. We found that both stimulated, aneural muscle cells in vitro and inactive muscles in vivo produced predominantly fetal-type AChRs. However the TTX-paralysed muscles had a lower proportion of fetal-type receptors than the denervated muscles. We conclude that neither muscle activity nor innervation alone, but a combination of both, is required for full regulation of AChR antigenicity.

Animals↗

PubMed1990

Does progeria provide the best model of accelerated ageing in humans?

Studies of the causes of ageing are often obscured by the complexity of this phenomenon, hindering investigations in this area. In particular, the variable characteristics of ageing complicate analysis at a molecular level. It is proposed that to gain insight into ageing, the problem must first be simplified by restricting studies to an aspect of the ageing processes. It is suggested that progeria, which presents a less complicated etiology and phenotype than other accelerated ageing diseases, allows research to focus on a regulation site involved in development and ageing.

Aging↗

PubMed1989

Glucose inhibition of human fibroblast proliferation and response to growth factors is prevented by inhibitors of aldose reductase.

Diabetes mellitus is associated with premature senescence of cultured dermal fibroblasts. The present study investigated the effect of elevated glucose concentrations on cultured human fibroblasts from normal donors. Mean population doubling times, population doublings until senescence, saturation density at confluence (cells/cm2), tritiated thymidine incorporation, and response to platelet-derived growth factor (PDGF) were inhibited with the increasing glucose concentrations (11.0, 22, 44, or 55 mM glucose) (P less than 0.05). Replicative life span was markedly diminished by multiple passages in high glucose medium (5.5 mM glucose: 62.4 +/- 7.9 population doublings; 22 mM glucose: 22.8 +/- 3.4 population doublings: P less than 0.05). Aldose reductase activity was present in the cultured fibroblasts (3.9 +/- 0.5 nmol/min per mg protein), and inhibitors of aldose reductase, including sorbinil (10(-4) M--10(-6) M) and tolrestat (10(-6) M--10(-8) M), completely prevented glucose-mediated inhibition of fibroblast proliferation, restored the response to PDGF, and allowed a normal replicative life span. Myo-inositol (11 microM--5.5 mM) also reversed the adverse effects of glucose. These in vitro data demonstrate that elevated concentrations of glucose inhibit cell growth and promote premature senescence, effects which can be prevented with inhibitors of aldose reductase or supplemental myo-inositol. These aldose reductase-related effects may explain the impaired growth and premature senescence of cultured connective tissue from diabetic patients.

Aldehyde Reductase↗

PubMed1986

Does the precommissural fornix excite neurons in the cat dorsal septum which project to the medial preoptic region?

The possibility that effects of fornix stimulation on units in the medial preoptic region (MPO) may be via an interposed neuron in the dorsal septum was investigated using electrophysiological techniques. We found a reciprocal monosynaptic linkage between the MPO and the dorsal, medial and fimbrial septal nuclei. When recording in the MPO, stimulation of the dorsal septum affected 59% of spontaneously active units. Of all MPO units synaptically excited by stimulation of the dorsal septum 33% also had an input from the fornix. When recording in the dorsal septum during stimulation of the MPO and fornix, units synaptically driven by, or antidromically invaded following MPO stimulation, were found in caudal regions of the DS and units excited by stimulation of the fornix were located in more rostral regions. Units excited by stimulation of the fornix were never antidromically invaded following stimulation in the MPO, so there was no direct pathway for fornix excitation in the dorsal septum to reach the MPO.

Action Potentials↗

PubMed1985

Distribution of osmosensitive cells in the preoptic and adjacent regions of cat brains.

The response of neurons in the preoptic and adjacent regions of the brain to intracarotid injection of hyperosmotic solutions was studied in 22 anesthetized cats. NaCl (0.5 M) caused a brisk acceleration of frequency lasting over 100 s in 120 of 207 units (58%). Glucose (2 M) and sucrose (2 M) had similar but smaller effects, and urea (2 M) was ineffective. Responding units were found in all parts of the preoptic region, the diagonal band of Broca (vertical limb), the lateral septal nucleus, nucleus accumbens and anterior hypothalamus.

Animals↗