Antiviral properties of 3-quinolinecarboxamides: a series of novel non-nucleoside antiherpetic agents

Despite the long history in medicine, the pathophysiological mechanism(s) of seasonal affective disorder (SAD) remain largely unknown. By employing a meta-analytic methodology, the authors of this study attempted to verify the validity of different pathophysiological mechanism(s) proposed for SAD. The findings showed that for phototherapy of medium light intensity, a combination of morning-evening therapy regime yielded the best therapeutic effect, and the antidepressant effect of the morning-evening light regime was superior to a single pulse of light administered at other times of day. Furthermore, the data showed that the antidepressant effect of a single pulse of light was similar for morning, midday, and evening light. These findings supported the photon-count hypothesis and refuted the proposed photoperiod, melatonin, and phase-shifting models of SAD.     

cDNA sequence analysis of the human brain insulin receptor

Brain tissue mRNA was amplified using polymerase chain reaction (PCR) with eight overlapping sets of primers that span the cDNA coding sequence for the human placental insulin receptor. Only the A isoform (lacking exon 11) of the receptor was detected. No difference was found in the predicted amino acid sequence of brain derived insulin receptor cDNA compared with the receptor from human placenta. A silent polymorphism was detected at nucleotide position 1698 (amino acid 523), confirming that mRNA corresponding to both alleles of the human brain receptor was sequenced. Our findings indicate that the unique glycosylation properties of brain insulin receptors do not stem from differences in primary structure, but rather are due to tissue-specific differences in post-translational processing.     

Staphylococcal food poisoning caused by imported canned mushrooms

From February through April 1989, four outbreaks of staphylococcal food poisoning in the United States were associated with eating mushrooms canned in the People's Republic of China (PRC). In the four outbreaks, 99 persons who ate at a suspect facility developed gastrointestinal symptoms within 24 h, including 18 who were hospitalized. Illness was associated with eating mushrooms at a university cafeteria (relative risk [RR] = 53.0), a hospital cafeteria (RR = 13.8), a pizzeria (odds ratio [OR] = infinity), and a restaurant (OR = infinity) (all P < .0001). Staphylococcal enterotoxin A was found by ELISA in mushrooms at the sites of two outbreaks and in unopened cans from the three plants thought to have produced mushrooms implicated in outbreaks. These investigations led to multistate recalls and a US Food and Drug Administration order to restrict entry into the United States of all mushrooms produced in the PRC; until this action, the United States imported approximately 50 million pounds yearly.     

Secondary structures comparison of aquaporin-1 and bacteriorhodopsin: a Fourier transform infrared spectroscopy study of two-dimensional membrane crystals

Aquaporins are integral membrane proteins found in diverse animal and plant tissues that mediate the permeability of plasma membranes to water molecules. Projection maps of two-dimensional crystals of aquaporin-1 (AQP1) reconstituted in lipid membranes suggested the presence of six to eight transmembrane helices in the protein. However, data from other sequence and spectroscopic analyses indicate that this protein may adopt a porin-like beta-barrel fold. In this paper, we use Fourier transform infrared spectroscopy to characterize the secondary structure of highly purified native and proteolyzed AQP1 reconstituted in membrane crystalline arrays and compare it to bacteriorhodopsin. For this analysis the fractional secondary structure contents have been determined by using several different algorithms. In addition, a neural network-based evaluation of the Fourier transform infrared spectra in terms of numbers of secondary structure segments and their interconnections [sij] has been performed. The following conclusions were reached: 1) AQP1 is a highly helical protein (42-48% alpha-helix) with little or no beta-sheet content. 2) The alpha-helices have a transmembrane orientation, but are more tilted (21 degrees or 27 degrees, depending on the considered refractive index) than the bacteriorhodopsin helices. 3) The helices in AQP1 undergo limited hydrogen/deuterium exchange and thus are not readily accessible to solvent. Our data support the AQP1 structural model derived from sequence prediction and epitope insertion experiments: AQP1 is a protein with at least six closely associated alpha-helices that span the lipid membrane.     

Night-to-night variability in CPAP use over the first three months of treatment

Caries of the pits and fissures of permanent teeth continues to be a problem for children, newly erupted permanent molars being particularly at risk. Oral hygiene measures have been shown to be able to reduce the incidence of caries. The aim of this study was to compare the caries-preventive effects on newly erupted first permanent molars of a professional tooth cleaning and oral health education program (test) with a standard preventive program (control), comprising selective fissure sealing and application of topical fluorides. School Dental Service clinics of the Health Department of Western Australia, in Perth, were assigned to four test or four control clinics. Schoolchildren, mean age 6.3 +/- 0.3 (s) years with sound, newly erupted first permanent molars were included in the study (207 test, 197 control). After 12 months, 186 test and 163 control children were examined by an examiner who was 'blind' to the test or control status of the children. Caries of the first permanent molars developed in 34 test and 35 control children; the estimated risk ratio was 0.86 (95% CI 0.56, 1.30). Children in the test group had an average DFT score of 0.26 +/- 0.62 compared with 0.29 +/- 0.64 DFT in the control group (t-test, P = 0.67). The 12-month results suggest that there was no statistically significant difference between the caries-preventive effects of a professional tooth cleaning and oral health education program and a program based on selective fissure sealing and application of topical fluorides.     

Expression of cyclins D1 and E in human colon adenocarcinomas

Cyclins D1 and E play critical roles in the progression of cells through the G1 phase of the cell cycle. Amplification and/or overexpression of the cyclin D1 gene and aberrant expression of cyclin E have been described in several forms of human cancer. In the present study, we examined the expression of these two genes by Western, Northern and Southern blot analyses in a series of primary human colon carcinomas of various stages and degrees of differentiation and in paired adjacent normal mucosa samples, and also in a series of human colon carcinoma cell lines. About 50% of the colon carcinomas displayed a two to five fold increase in the expression of cyclin D1 mRNA and protein, when compared with the paired normal mucosa samples. Six out of eight carcinomas examined showed a four to nine fold increase in cyclin E mRNA and about 50% of the carcinomas displayed a two to three fold increase in cyclin E protein. Low molecular weight cyclin E-related proteins were observed in four out of ten carcinomas. These changes in cyclins D1 and E occurred in both early and late stage tumors. Three of the six cell lines examined displayed a high expression of cyclin D1 mRNA and protein. A very high level of cyclin E mRNA expression was seen in HCT116 cells and this was associated with the presence of low molecular weight cyclin E-related proteins. None of the primary colon carcinomas nor the six cell lines examined displayed amplification of either the cyclin D1 or cyclin E genes. Thus, an aberrant expression of both cyclins D1 and E occurs in a significant fraction of human colon carcinomas.     

Molecular epidemiology of rabies epizootics in Texas

Glucocorticoids are potent osteopenic agents, producing negative calcium and bone balance via actions at many sites. The most significant adverse effects of glucocorticoid drugs on the skeleton are probably a direct inhibition of matrix synthesis by the osteoblast, reductions in calcium absorption in both the gut and the renal tubule, and the production of hypogonadism, particularly in men. Reductions in bone density of 10-40% result, the loss being more marked in trabecular bone and in patients receiving a high cumulative dose of the steroid. Fractures occur in about 30% of individuals who take these drugs for an average of 5 years. Bone loss is reversible when glucocorticoid treatment is withdrawn. Bone density can also be increased by sex hormone replacement in those with demonstrable deficiency, by bisphosphonates, and possibly by vitamin D metabolites. All patients treated with glucocorticoids for more than 6 months should be considered for bone densitometry and be offered appropriate drug treatment if values are towards the lower end of the young normal range or if there is already evidence of fractures occurring after minimal trauma. With this approach, the significant morbidity associated with steroid osteoporosis might be substantially avoided.     

Exacerbation of inflammation-associated colonic injury in rat through inhibition of cyclooxygenase-2

Cyclooxygenase type 1 is constitutively expressed and accounts for synthesis of prostaglandins in the normal gastrointestinal tract. Cyclooxygenase-2 is expressed at sites of inflammation. Selective inhibitors of cyclooxygenase-2 have been suggested to spare gastrointestinal prostaglandin synthesis, and therefore lack the ulcerogenic effects associated with standard nonsteroidal antiinflammatory drugs. However, the effects of cyclooxygenase-2 inhibitors on inflamed gastrointestinal mucosa have not been examined. We examined cyclooxygenase-2 mRNA and protein expression before and after induction of colitis in the rat, the contribution of cyclooxygenase-2 to colonic prostaglandin synthesis during colitis and the effects of selective inhibitors of cyclooxygenase-2 on colonic injury in this model. Cyclooxygenase-2 mRNA expression increased three to sixfold during the period 24 h to 1 wk after induction of colitis, with marked increases in cyclooxygenase-2 protein expression in the lamina propria and muscularis of the colon during colitis. Cyclooxygenase-1 expression (mRNA and protein) was not affected by the induction of colitis. The prostaglandins produced during colitis were largely derived from cyclooxygenase-2. Treatment with selective cyclooxygenase-2 inhibitors resulted in exacerbation of colitis, with perforation occurring when the compounds were administered for a week. These studies demonstrate that suppression of cyclooxygenase-2 can result in exacerbation of inflammation-associated colonic injury.     

Transient loss of dopamine autoreceptor control in the presence of highly potent dopamine agonists

The concentrations of endogenous ligands generally remain in a bounded range around a basal level, a manifestation of control. The dopaminergic system is an excellent example of a control system in which a negative feedback signal is associated with receptor occupancy of a D2-like dopamine autoreceptor. A consequence of the control theory is that autoreceptor occupancy by an agonist results in dopamine levels below the basal, whereas similar stimulation by a dopamine competitive antagonist results in an increase of dopamine to levels above the basal. These consequences of control theory were tested and verified in the rat striatum by infusing graded doses of either the agonist, quinpirole, or the antagonist, sulpiride, into the rat striatum via a microdialysis probe and sampling dopamine and metabolite levels at various times after the start of infusion. Control was maintained even at the very highest doses of these compounds, i.e., striatal dopamine concentration rose in response to the antagonist and fell in response to the agonist. In contrast, administration of each of two high affinity dopamine agonists, 7-OH-DPAT and PPHT showed dose-dependent control only up to certain doses. Above these doses the dopamine concentration actually increased to levels well above basal, an indication of loss of control. These findings suggest that the control of this endogenous ligand does not extend to the very highest levels of autoreceptor occupancy.