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Biomedical subjects

K Anderson

Publications and source records attributed to K Anderson.

At least 271 records · Page 15Linked to original sources
PubMed1991

Calcitonin gene-related peptide and substance P decrease in the rabbit colon during colitis. A time study.

The sensory neuropeptides, substance P and calcitonin gene-related peptide, have been implicated in inflammatory reactions in several tissues. An immune-complex model of colitis was used in rabbits to determine the colonic content (nmol/g protein) of immunoreactive substance P and calcitonin gene-related peptide at various times after induction of inflammation to assess changes in these neuropeptides during the inflammatory response. Calcitonin gene-related peptide content was decreased by 66% 4 hours after induction of inflammation and reached a maximum of 80% at 48 hours. The substance P content was decreased at 8 hours, with a maximum decrease of 64% at 48 hours. Substance P decrease was detected in the muscle layer. The amounts of substance P in the mucosal/submucosal layer extracts were too low to allow accurate measurements. Calcitonin gene-related peptide decreased both in the muscle and the mucosal-submucosal layers. Immunohistochemical analysis showed that calcitonin gene-related peptide and substance P innervation patterns were comparable in normal and inflamed colon, even though there appeared to be a decrease in density and intensity of the staining, particularly for calcitonin gene-related peptide at 48 hours. The early decrease of calcitonin gene-related peptide and substance P during the time course of colitis might be due to release from nerve terminals of the gut during the inflammatory response. The profound changes in colonic calcitonin gene-related peptide and substance P content during colitis may have important implications during inflammation and subsequent tissue repair and may also lead to disturbances in gut motility.

Animals↗
PubMed1991

Hypospadias repair in an outpatient setting without proximal urinary diversion: experience with 113 urethroplasties.

A total of 113 consecutive patients underwent surgical repair of hypospadias. None had previously undergone a repair procedure. The median age of the patients at the time of surgery was 24 months (range, 5 months to 13 years). A meatal-based flap modified Mathieu technique was used in 48 children and a single- or double-faced transverse preputial island flap was used in 58 children. Urinary diversion was not performed. A 7F silicone rubber urethral stent with multiple perforations that drained freely was used in all cases. The stent was left indwelling for 7 days after meatal-based flap repairs and for 12 days preputial island flap repairs. Seventy-nine patients (70%) were discharged from the hospital the day of the operation. The results were cosmetically satisfactory in all cases. A total of 23 patients developed complications. Sixteen (14%) developed a urethrocutaneous fistula, 2 developed a stricture (1.7%), and 5 developed a urethral diverticulum (4.5%). There were no fistulas and only one stricture in the meatal based flap repairs. For 20 patients who suffered complications, a single outpatient surgical procedure corrected the problem. The remaining 3 patients required more than two surgical procedures. All complications were resolved within 12 months of the hypospadias repair.

Adolescent↗
PubMed1991

Nucleotide sequence analysis of the bovine respiratory syncytial virus fusion protein mRNA and expression from a recombinant vaccinia virus.

Bovine respiratory syncytial (BRS) virus is an important cause of serious respiratory illness in calves. The disease caused in calves is similar to that caused by human respiratory syncytial (HRS) virus in children. The two viruses, however, have distinct host ranges and the attachment glycoproteins, G, have no antigenic cross-reactivity. The fusion glycoproteins, F, of the HRS and BRS viruses, however, have some antigenic cross-reactivity. To further compare the BRS virus and HRS virus fusion proteins, we determined the nucleotide sequence of cDNA clones to the BRS virus F protein mRNA, deduced the amino acid sequence, and compared these sequences with the HRS virus F protein sequences. The BRS virus F mRNA was 1899 nucleotides in length and had a single major open reading frame which could code for a polypeptide of 574 amino acids with an estimated molecular weight of 63.8 kDa. Structural features predicted from the amino acid sequence included an NH2-terminal signal sequence (residues 1-26), a site for proteolytic cleavage (residues 131-136) to generate the disulfide-linked F1 and F2 subunits, and a hydrophobic transmembrane anchor sequence (residues 522-549). The nucleic acid identity between the BRS virus and the HRS virus F mRNA sequences was 71.5%. The predicted BRS virus F protein shared 80.5% overall amino acid identity with the HRS virus F protein with 89% identity in the F1 polypeptide but only 68% identity in the F2 polypeptide. The position and number of the cysteine residues in the F1 and F2 polypeptides were conserved among all F proteins. However, BRS virus F protein had only three potential N-linked carbohydrate acceptor sites in comparison to four or five for the HRS viruses. A difference in the extent of glycosylation between the BRS and HRS virus F2 polypeptides was shown to be responsible for differences observed in the electrophoretic mobility of these proteins. A cDNA containing the complete open reading frame of the BRS virus F mRNA was inserted into the thymidine kinase gene of vaccinia virus and following homologous recombination, a recombinant virus containing the BRS virus F gene was isolated. The BRS virus F protein was expressed in recombinant virus infected cells as demonstrated by immunoprecipitation and was transported to and expressed on the surface of infected cells as shown by indirect immunofluorescence.

Amino Acid Sequence↗
PubMed1991

Modulation by tumor necrosis factor-alpha of human astroglial cell production of granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF).

Phagocyte survival and function are enhanced by GM-CSF and G-CSF. The production of both CSFs can be induced in mesenchymal cells by tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1). We have recently demonstrated that IL-1 alpha and beta induced the production of GM-CSF and G-CSF by two human astroglial cell lines. In the present study, we examined the effects of TNF-alpha on the production of GM-CSF and G-CSF by U87MG, a human astroglial cell line that constitutively expresses GM-CSF and G-CSF, and U373MG, a second human astroglial cell line that does not produce CSF. We demonstrate that U87MG can be induced to increase its production of GM-CSF and G-CSF by exposure to TNF-alpha while U373MG is induced to produce GM-CSF but not G-CSF. These responses, measured by accumulation of elevated levels of CSF protein and mRNA, are rapid and sensitive. The implications of these findings to the immunopathogenesis of central nervous system infections are discussed.

Astrocytes↗
PubMed1991

Independent cellular and ontogenetic expression of mRNAs encoding three alpha polypeptides of the rat GABAA receptor.

Previous studies have shown that several distinct but related polypeptides can serve as alpha subunits of functional GABAA receptors. Furthermore, the diversity of these polypeptides at least partially accounts for the functional heterogeneity of GABAA receptors. In this paper, we report the results of in situ hybridization studies using probes derived from our recently reported cDNAs for alpha 1, alpha 2, and alpha 4 GABAA receptor polypeptides. We show that the mRNAs that encode these isoforms have distinct regional and cellular distributions and are present at widely varying levels within the rat brain. In addition, our Northern blot analyses indicate that each of these three alpha mRNAs has a distinct pattern of ontogenetic regulation. Differential regulation of alpha polypeptide isoforms may lead to changes in GABAA receptor function during ontogeny as well as to distinct cellular responses to GABA and GABA-related drugs.

Animals↗
PubMed1991

Effect of controlled-release salbutamol in predominantly non-reversible chronic airflow obstruction.

We conducted a multicentre, randomized, double-blind, placebo-controlled, parallel group study to determine the efficacy of controlled release salbutamol (SCR) tablets in clinically stable patients with predominantly non-reversible chronic airflow obstruction (CAO). Patients received either 8 mg SCR or matching placebo tablets twice daily for 6 weeks. Fifty-eight patients (30 on SCR and 28 on placebo) completed the study. Outcome measurements included FEV1, FVC, 6-min walking distance, and patient assessment of efficacy recorded at the clinic visits and twice daily PEFR measurements plus daytime symptom score recorded in diary cards. The absolute change between baseline and 6-week measurements with SCR was compared to that with placebo. Favourable trends were observed with SCR for all variables tested except FVC. The only significant difference between SCR and placebo was in FEV1 where there was a small net change of 95 ml in favour of SCR. We conclude, therefore, that the effects of lung function of long-term bronchodilator therapy with SCR in patients with stable non-reversible CAO are slight, and are likely to be of limited clinical benefit.

Albuterol↗
PubMed1991

Risk of coronary heart disease in middle-aged male bus and tram drivers compared to men in other occupations: a prospective study.

In the Gothenburg Primary Prevention Study the incidence of coronary heart disease (CHD) in 103 bus and tram drivers was compared with that of 6596 men in other occupation groups. The follow-up extended through a mean of 11.8 years. Bus and tram drivers had an incidence of CHD of 18.4% compared with 6.4% among the other men in the study; odds ratio (OR) 3.3 (95% confidence interval (CI) 2.0-5.5). The only other group with an increase in risk of similar magnitude were taxi drivers; OR 3.1 (1.6-6.2). No significant differences were noted as to smoking habits, serum cholesterol or blood pressure between bus and tram drivers and the other men. The bus and tram drivers tended to be more physically active during leisure time, but had a significantly higher body mass index than other men. In a multivariate logistic regression analysis with CHD as the dependent variable and age, serum cholesterol, blood pressure, smoking, body mass index, diabetes, marital state, family history of CHD, alcohol abuse, socioeconomic status, leisure time physical activity, physical activity at work, psychological stress and bus and tram driving as independent variables the OR for bus and tram driving was only slightly reduced to 3.0 (1.8-5.2). In this population, being a bus or tram driver was an independent predictor of CHD of considerable magnitude. The increased risk of taxi drivers was not significant in multivariate analysis.

Coronary Disease↗
PubMed1991

Quantifying serum antibody class and subclass responses by enzyme immunoassay in humidifier-related disease.

Antibody activity in the major classes and IgG subclasses against antigens in factory humidifier water was quantified by enzyme immunoassay (EIA) in 88 subjects who were exposed at work to the output from these contaminated humidifiers. Those with work-related symptoms had significantly higher mean titres than those who were symptom free, although values overlapped. The individuals with the highest IgG antibody titres also had the highest titres of IgM and IgA antibody, and these parameters did not discriminate between those with and without symptoms any better than the IgG titre. This was also true for the IgG subclasses where activity was predominantly measured in IgG1. Quantifying the IgG antibody allowed us to demonstrate a significant correlation with years of work exposure (P less than 0.001). There was no significant association between antibody and cigarette smoking, as assessed by smoking history and confirmed objectively by serum cotinine levels. There was a significant correlation with total IgG level (P less than 0.001) suggesting that a non-specific immune enhancement may accompany the specific response. The antibody titres were followed up to 3 years after modification of the humidification systems, and during this time symptoms resolved and the antibody levels progressively fell to undetectable levels. The EIA was adapted to measure antigen at nanogram levels thus providing a rapid test for screening of humidifer water as well as a technique that may help identify the nature of the antigens involved.

Air Conditioning↗
PubMed1991

The effects of a 16-N-homopiperidino analogue of vecuronium on neuromuscular transmission in anaesthetized cats, pigs, dogs and monkeys, and in isolated preparations.

Org 9991, a 16-N-homopiperidinium substituted vecuronium analogue, has been tested for neuromuscular blocking activity in anaesthetized cats, pigs, dogs and monkeys, and in isolated nerve-muscle preparations. Org 9991 exhibited non-depolarizing neuromuscular blocking activity of the competitive type, being reversible by neostigmine and showing no endplate channel blocking action in isolated preparations. In cats, 50% vagal block was observed at doses of Org 9991 approximately 10 times those producing 50% neuromuscular block; no ganglion block was seen at these doses. Effects on blood pressure or heart rate at 90% twitch blocking doses were either minor or absent. The potency and time course of action of Org 9991 remained similar in all four species: i.e. 90% block at ca 200-300 micrograms kg-1; onset time ca 1.2-1.9 min; duration 90% ca 4.5-8.9 min. This study suggests that 16-N-homopiperidinium analogues of vecuronium may provide leads in the quest for a potent non-depolarizing replacement for suxamethonium.

Androstanols↗
PubMed1991

Effect of acute ethanol on esophageal motility in cat.

In man, acute ethanol administration decreases lower esophageal sphincter pressure (LESP), prolongs the duration, and lowers the amplitude of esophageal contractions. These changes may contribute to gastroesophageal reflux and esophagitis. To evaluate the underlying mechanisms of these changes an animal model is needed. Hence, we studied the effect of various doses of ethanol on esophageal motility in cats, an animal with an esophagus similar to man's. Similar to man, intravenous administration of ethanol significantly decreased LESP and amplitude of lower (smooth muscle portion) esophageal contractions. It also prolonged the duration of lower esophageal contractions, even through it had no effect on contraction velocity. The effect of ethanol on upper (striated muscle portion) esophagus was different. Ethanol had no effect on the amplitude of contractions, whereas it prolonged their duration and decreased their velocity. The effect of acute ethanol on LESP in four withdrawing alcoholic cats was similar to controls. However, the acute effect of ethanol on the esophageal contractions was less marked in alcoholics. Bilateral cervical vagotomy and intravenous injection of the neurotoxin tetrodotoxin before the administration of ethanol did not prevent the effect of ethanol on LESP. This data suggests that cat esophagus is a good model for studying the underlying mechanisms of the effects of acute ethanol because its response is similar to the esophagus of man, and the acute effect of ethanol on LESP is not neurally mediated but is the result of its direct effect on muscle.

Alcohol Drinking↗
PubMed1991

A historical prospective study of European stainless steel, mild steel, and shipyard welders.

A multicentre cohort of 11,092 male welders from 135 companies located in nine European countries has been assembled with the aim of investigating the relation of potential cancer risk, lung cancer in particular, with occupational exposure. The observation period and the criteria for inclusion of welders varied from country to country. Follow up was successful for 96.9% of the cohort and observed numbers of deaths (and for some countries incident cancer cases) were compared with expected numbers calculated from national reference rates. Mortality and cancer incidence ratios were analysed by cause category, time since first exposure, duration of employment, and estimated cumulative dose to total fumes, chromium (Cr), Cr VI, and nickel (Ni). Overall a statistically significant excess was reported for mortality from lung cancer (116 observed v 86.81 expected deaths, SMR = 134). When analysed by type of welding an increasing pattern with time since first exposure was present for both mild steel and stainless steel welders, which was more noticeable for the subcohort of predominantly stainless steel welders. No clear relation was apparent between mortality from lung cancer and duration of exposure to or estimated cumulative dose of Ni or Cr. Whereas the patterns of lung cancer mortality in these results suggest that the risk of lung cancer is higher for stainless steel than mild steel welders the different level of risk for these two categories of welding exposure cannot be quantified with precision. The report of five deaths from pleural mesothelioma unrelated to the type of welding draws attention to the risk of exposure to asbestos in welding activities.

Europe↗
PubMed1991

Oncologists' reluctance to accrue patients onto clinical trials: an Illinois Cancer Center study.

Clinical trials are recognized as the standard of care for the cancer patient, and the randomized, controlled trial represents the most definitive method to determine the effectiveness or ineffectiveness of a cancer treatment. However, less than 3% of all eligible patients enter a clinical trial. Of the 437 physician members of the Illinois Cancer Center (ICC), 244 responded to a survey designed to determine factors that present a significant barrier to entering patients on clinical trials. Rigid protocol design was the primary deterrent to accrual, especially for medical oncologists. Surgeons, radiation oncologists, and medical oncologists differed with respect to several factors, including willingness to seek a clinical trial, tendency to treat patients off study, quality-of-life issues, and the belief that trials were too excessive in time commitment (P less than .05). Compared with hospital-based physicians, community oncologists had fewer patients on trial, were more likely to enter patients on the basis of age, and were more concerned about aspects of informed consent and the financial burden of a trial (P less than .01). One third of the physicians never pursued a clinical trial because of conflict with the priorities of individual care and excessive follow-up time. Fourteen percent indicated that they discouraged patients from participating in a clinical trial due to the risk of a patient receiving a placebo and patient follow-up requirements (P less than .05). Subgroups of physicians differ in their reluctance to accrue patients, and there are clusters of beliefs expressed by physicians concerning their clinical trial activity. Current conduct of clinical trials needs to be reassessed, and intervention studies are required to determine the best methodology to alter physician reluctance to pursue clinical trials.

Attitude of Health Personnel↗
PubMed1991

In vitro and in vivo pharmacologic activities of antisense oligonucleotides.

The use of antisense oligonucleotide as pharmacologic agents is a derivative of the central dogma of molecular biology and knowledge of the physical and chemical properties that govern the structure of nucleic acids. Oligonucleotides have been reported to inhibit the growth of a large number of viruses in cell culture, as well as the expression of numerous oncogenes, a variety of normal genes and transfected reporter genes controlled by several regulatory elements. The therapeutic activity of antisense compounds in animal disease models have also been reported. This review provides some general conclusions and trends regarding the pharmacologic action of antisense oligonucleotides, that can be formulated from studies previously reported in the literature. In addition, data is highlighted for two specific examples in which antisense oligonucleotides have demonstrated activity against herpes viruses and intracellular adhesion molecule RNA targets.

Animals↗
PubMed1991

The Maluhia Project: Home Health Care for the Uninsured.

This is a report of preliminary findings of the Maluhia Project: Home Health Care for the Uninsured based on its first 12 months of experience in providing services to clients from September 1989 to August 1990. This Project is now in its third year. This report will initially discuss the rationale for Hawaii's participation in this 5-state national demonstration project. It will cover the basic components of the Hawaii Project and its relative impact followed by a brief description of the clients enrolled. A major component of this program is case management. Given the variety of previous programs that have been referred to as case-management services, a comparison has been provided to note significant differences in approaches and target groups between the Maluhia Project and other existing programs. Finally, this report discusses a number of implementation and public policy issues which have emerged and require further discussion. We hope that as a result of this preliminary report from our first 12 months of operation, it will be possible to inform the medical community of the needs faced by this public health problem that has been previously not addressed.

Adult↗