Classical oncogenes and tumor suppressor genes: a comparative genomics perspective.

We have curated a reference set of cancer- related genes and reanalyzed their sequences in the light of molecular information and resources that have become available since they were first cloned. Homology studies were carried out for human oncogenes and tumor suppressors, compared with the complete proteome of the nematode, Caenorhabditis elegans, and partial proteomes of mouse and rat and the fruit fly, Drosophila melanogaster. Our results demonstrate that simple, semi-automated bioinformatics approaches to identifying putative functionally equivalent gene products in different organisms may often be misleading. An electronic supplement to this article provides an integrated view of our comparative genomics analysis as well as mapping data, physical cDNA resources and links to published literature and reviews, thus creating a "window" into the genomes of humans and other organisms for cancer biology.

Determination of crystalline silica in silica fume.

Silica fume is formed as a by-product in the manufacture of silicon from quartzite. This paper describes an analytical method for the determination of crystalline silica in silica fume. The crystalline silica was determined after removal of amorphous silica from the fume. A gravimetric method was developed for the determination of the total crystalline silica in the fume, while the cascade impactor technique was used to determine the crystalline content in the -10 microm fraction. X-Ray diffraction, scanning electron microscopy and particle size distributions were used to validate the steps in the analytical procedure. The total crystalline silica content was found to vary from 2.7 to 8.6% with an RSD of +/-2%, while the crystalline silica content of the -10 microm fraction was 0.23 to 0.55% with an RSD of +/-10%. A knowledge of the crystalline silica content of silica fume is of great importance in the area of Occupational Health and Safety. The samples surveyed were shown to have levels of crystalline silica in the respirable fraction well within the draft guidelines for silica fume. It is proposed that this method be accepted as a standard method for the determination of crystalline silica in silica fume.

Gravimetric determination of free carbon and silicon carbide in silica fume.

Silica fume is formed as a by-product in the manufacture of silicon from quartzite. This paper describes an analytical method for the determination of free carbon and silicon carbide in silica fume. The silicon carbide was determined after removal of free carbon, amorphous silica, crystalline silica, graphite and silicon from the fume. The free carbon content was found to vary from 2 to 8% while the silicon carbide content ranged from 1 to 5%. X-ray diffraction, thermal analysis, scanning electron microscopy and Fourier Transform infrared spectroscopy were used to validate the steps used in the analytical procedure. The purpose of determining the free carbon and silicon carbide content of the fume is to help understand the efficiency of the reduction process and mechanism of the reaction.

Bronchial reactivity to histamine and bradykinin is unchanged after rhinovirus infection in normal subjects.

We investigated the effects of rhinovirus (RV) infection on airways reactivity. Twenty seven normal volunteers (11 atopic) were inoculated with RV 2 or RV EL. The provocative concentrations of histamine and bradykinin required to produce a 15% fall in the forced expiratory volume in one second (FEV1) (PC15FEV1) were measured before, 7 and 21 days after inoculation. Infection was determined by a fourfold rise in anti-viral antibody titre and by viral culture from nasal washings. Peak expiratory flow rate (PEF) was recorded three days before and for 21 days after inoculation. All subjects underwent the first two bronchial challenges, and 22 the third challenge. For the whole group and for atopic subjects, there were significant correlations between the PC15 values for bradykinin and histamine (r = 0.82 and r = 0.85, respectively). Twenty subjects were infected; six had clinical colds. For the 16 infected subjects who had all three challenges, the median (range) PC15FEV1 for the histamine challenges was 36 (0.89-64), 62 (1.5-64) and 34 (0.94-64) mg.ml-1, respectively, and 32 mg.ml-1 for each bradykinin challenge (range: 0.015-32, 0.088-32 and 0.033-32). There were no significant differences between study days for PC15FEV1 histamine or bradykinin for the whole group, the infected subjects, those with clinical colds or for those infected with either RV subtype. There was no significant change in mean daily PEF after viral infection. We conclude that airways reactivity to histamine and bradykinin is unchanged after experimental RV infection in normal volunteers.

Effects of zinc gluconate and nedocromil sodium on performance deficits produced by the common cold.

Two studies are reported on the effects of drugs on the performance impairments induced by experimentally- produced colds. The first study examined the effects of zinc gluconate on choice reaction time, and showed that the zinc removed the cold-induced performance impairment. The second experiment used nedocromil sodium and, again, the drug was effective in reducing the drop in performance observed in volunteers with colds. While the precise mode of action of these compounds is unclear it is speculated that one mechanism involves changes in trigeminal stimulation, and this could be responsible for both the clinical efficacy and CNS effects of these drugs.

Local hyperthermia benefits natural and experimental common colds.

OBJECTIVE: To determine whether inhaling fully humidified air at 43 degrees C gave more benefit to cold sufferers than inhaling air at 30 degrees C. DESIGN: Randomised double blind trial. Setting--General practice and the common cold research unit. SUBJECTS: 87 Unselected patients with typical acute nasal and upper respiratory symptoms (general practice study), and 84 volunteers aged 18-50 without a history of chronic or allergic diseases. INTERVENTIONS: Subjects breathed from apparatus delivering 40 litres of room air heated to 43 degrees C or 30 degrees C and fully humidified (relative humidity 100%) per minute. End point--Reduction in severity of disease. MEASUREMENTS and main results--Patients recorded their symptoms (general practice study) and observers recorded symptoms and signs, weight of nasal secretions, isolation of virus, and antibody responses in volunteers. Patients treated for 20 minutes at 43 degrees C had in the succeeding days roughly half the score for symptoms of those treated at 30 degrees C. Volunteers treated for 30 minutes on three occasions when they were starting a cold showed an 18% [corrected] reduction in symptoms. Treatment of volunteers for 20 minutes at the onset of the cold and for 10 minutes on succeeding days showed no difference between 43 degrees C and 30 degrees C. CONCLUSIONS: Nasal hyperthermia can improve the course of a common cold and also give immediate relief of symptoms.

Changes in human nasal mucosa during experimental coronavirus common colds.

Twenty-four adult volunteers were inoculated with nasal drops containing a coronavirus of 229E serotype to determine the differences in the clinical and physiological reactions which occur between clinically infected, sub-clinically infected and non-infected individuals. Thirteen volunteers were clinically infected, 8 had sub-clinical infections and 3 were uninfected. Nasal airway resistance and the temperature of the nasal mucosa increased in all infected subjects both with and without symptoms: the core temperature increased also but to a lesser extent. Mucosal blood flow and nasal secretion increased only in those with symptoms. The albumin content of the nasal secretion increased in the clinically infected, suggesting that it was derived, partially at least, from the circulation. The nasal cycle of variation in airway resistance between the two sides of the nose was observed in all three groups but increased only in those clinically infected.

Intranasal chalcone, Ro 09-0410, as prophylaxis against rhinovirus infection in human volunteers.

The antirhinovirus agent chalcone Ro 09-0410 was tested in double-blind place-controlled volunteer trials for its protective efficacy against experimental rhinovirus infection. Fifty volunteers received either drug (26 volunteers) or placebo (24 volunteers) both before and after challenge with 20-40 tissue culture infecting dose (TCID50) of human rhinovirus 2 (RV2). There was no evidence that medication significantly reduced the incidence of infection or illness, indeed there was some increase in the nasal secretion produced.

Prophylaxis and treatment of rhinovirus colds with zinc gluconate lozenges.

Following a tolerance study, double-blind placebo controlled trials were conducted to determine the prophylactic effect of zinc gluconate lozenges on rhinovirus challenge and, in a third study, their therapeutic efficacy when given at the start of colds caused by virus inoculation was tested. In the prophylaxis study a total of 57 volunteers received lozenges of either zinc gluconate (23 mg) (29 volunteers) or matched placebo (28 volunteers) every 2 h while awake during a period of four and a half days. They were challenged with 10(2) tissue culture infecting dose (TCID50) of human rhinovirus 2 (HRV-2) on the second day of medication, and were monitored daily for symptoms and signs of colds and laboratory evidence of infection. Zinc reduced the total mean clinical score from 8.2 in the placebo group to 5.7 and the reduction of the mean clinical score was statistically significant on the second day after virus challenge. In the therapeutic study 69 volunteers were inoculated with 10(2) TCID50 of HRV-2 and those who developed cold symptoms were randomly allocated to receive either zinc gluconate lozenges (six volunteers) or matched placebo lozenges (six volunteers) every two hours they were awake for six days. Treatment of colds with zinc reduced the mean daily clinical score and this was statistically significant on the fourth and fifth day of medication. Similarly, medication also reduced the mean daily nasal secretion weight and total tissue count and these reductions were statistically significant on days two and six for nasal secretion weights and days four to six of medication for tissue counts when compared with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in circulating somatomedin-C levels in bromocriptine-treated acromegaly.

To determine whether the improvement in clinical status of patients with active acromegaly correlates with a reduction of circulating somatomedin-C, serum immunoreactive somatomedin-C was measured in twenty-seven patients before and during bromocriptine therapy. The patients were assessed using a clinical and metabolic score which included both subjective criteria of improved sweating and facial features, and objective criteria of a reduction in ring circumference and the area under the glucose tolerance curve. Using this, together with the change in GH levels before and during bromocriptine therapy, the patients could be divided into three groups. In one group, there was no clinical improvement, a less than 30% decline in somatomedin-C, and in four of six patients no significant decline in GH. In both the other groups there was clinical improvement and a greater than 30% decrease in somatomedin-C. In one of these two groups, however GH did not decline, while in the other it was reduced significantly. The results suggest that during bromocriptine treatment of acromegaly, serum somatomedin-C concentrations correlate better with clinical status that does serum GH. Since some patients have no significant fall in GH but show both clinical improvement and a reduction in somatomedin-C, it seems likely that in some patients bromocriptine may improve acromegaly by a mechanism other than a simple decrease in total immunoreactive GH secretion.