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Biomedical subjects

B Cooper

Publications and source records attributed to B Cooper.

At least 19 recordsLinked to original sources

Cell-to-cell transport of movement-defective cucumber mosaic and tobacco mosaic viruses in transgenic plants expressing heterologous movement protein genes.

To determine if the movement proteins (MPs) of cucumber mosaic cucumovirus (CMV) and tobacco mosaic tobamovirus (TMV) are complementary in function, transgenic plants expressing genes encoding TMV or CMV MP were inoculated with movement-defective mutants of TMV and CMV. Transgenic plants expressing the MP gene of CMV strain S (subgroup II) complemented the cell-to-cell and systemic spread of a movement-defective mutant of CMV strain Fny (subgroup I) but not the local or systemic spread of a movement-defective mutant of TMV. Plants that contained the MP gene from CMV-S were not resistant to wild-type TMV infection. When inoculated with a movement-defective mutant of TMV that produced beta-glucuronidase, transgenic plants with the CMV MP gene supported only subliminal infection. Conversely, immunodetection and in situ localization techniques revealed that transgenic plants accumulating the TMV MP supported cell-to-cell spread, but not systemic transport, of a movement-defective CMV. These studies suggest that the transgenic TMV MP shares some of the functions with the CMV MP required to transport CMV, whereas the transgenic CMV MP is deficient in functions that are needed to mobilize the spread of TMV infection.

Amino Acid Sequence

Hormone-binding and solubility properties of fusion proteins containing the ligand-binding domain of the human androgen receptor.

The ligand-binding properties of the human androgen receptor (AR) reside in the carboxy terminus of the receptor and are retained in fusion proteins encoding this domain. Despite a wealth of information pertaining to the importance of specific amino acid residues in the binding of ligands, the precise amino terminal boundary of this domain has not been determined for the androgen receptor. The current studies focused on the expression of a series of AR fusion proteins in bacteria. These experiments demonstrate that specific androgen binding is detected in a fusion protein encoding amino acid residues 675-917, although this binding is of lower affinity than that observed for the native AR. Inclusion of an additional segment (residues 622-675) restores the capacity of the hormone-binding domain to bind mibolerone with high affinity. Detailed studies of the ligand-binding properties and solubility of one AR fusion protein (625-917) indicate that although the levels of ligand binding and soluble receptor fusion protein usually vary in parallel, this is not true at all time points and the proportion of soluble AR fusion that is able to bind hormone is highest when the levels of soluble AR fusion protein are lowest. This observation, coupled with the changes in the quantity of soluble and insoluble fusion protein occurring at different times following induction at 12 degrees C, 22 degrees C, and 37 degrees C, suggests that the saturation of one or more steps is required for folding of the AR hormone-binding domain to a conformation that is both soluble and competent to bind hormone under conditions of high-level expression. Analysis of the solubility of six different fusion proteins containing different portions of the AR hormone-binding domain suggests that a discrete segment of this domain is not responsible for its synthesis as predominantly insoluble aggregates in bacteria when expressed at high levels.

Base Sequence

Early development and progression of dementing illness in the elderly: a general-practice based study.

In a study carried out in 21 general practices in Mannheim, Germany, a stratified random sample (N = 507) of patients over the age of 65 years was drawn from the total of nearly 4000 who were medically documented. Eighty per cent of the sample were examined, using the Hierarchic Dementia Scale to test cognitive functioning and the CAMDEX criteria to assess global clinical severity. Repeat assessment after a mean interval of 27 months showed that all new cases of clinical dementia had arisen in persons with mild deficits initially and represented one-fifth of this group. The first-assessment ratings of cognitive function proved to be strongly predictive of risks for age-corrected mortality, admission to long-term care and dependency at follow-up, as well as of further progressive cognitive decline.

Activities of Daily Living

A defective movement protein of TMV in transgenic plants confers resistance to multiple viruses whereas the functional analog increases susceptibility.

Transgenic tobacco plants that express a gene encoding a defective mutant of the tobacco mosaic virus (TMV) movement protein which are known to be resistant to several tobamoviruses were inoculated with viruses from different taxonomic groups to determine the breadth of resistance. There were significant delays in the time of appearance of disease symptoms and/or there was reduced systemic accumulation of virus in upper leaves of plants inoculated with tobacco rattle tobravirus, tobacco ringspot nepovirus, alfalfa mosaic alfamovirus, peanut chlorotic streak caulimovirus, and cucumber mosaic cucumovirus. Conversely, tobacco plants that express a gene encoding the functional tobacco mosaic virus wild-type movement protein accelerated symptom development, enhanced the severity of symptom formation, and/or increased the accumulation of these viruses and, additionally, TMV. Our results indicate that there are similar functions among the movement proteins of a number of plant viruses despite the apparent lack of sequence similarity between them.

Mosaic Viruses

In vitro antimicrobial susceptibility of glycopeptide-resistant enterococci.

The results of susceptibility testing of 48 phenotyped strains of glycopeptide antibiotic-resistant enterococci are reported. Minimum inhibitory and bactericidal concentrations (MICs and MBCs) were determined for 27 vanA, 17 vanB, and 4 vanC strains. Antibiotics exhibiting the greatest activity included novobiocin (MIC90 = 8 micrograms/ml and MBC90 = 32 micrograms/ml), ramoplanin (MIC90 = 2 micrograms/ml and MBC90 = 4 micrograms/ml), and the streptogramin RP59500 (MIC90 = 4 micrograms/ml and MBC90 = 32 micrograms/ml). These antibiotics warrant further investigation as potentially useful agents, either alone or in combination, for treating enterococcal infections.

Anti-Bacterial Agents

Factors determining reopening of the ductus arteriosus after successful clinical closure with indomethacin.

OBJECTIVE: To examine the role of ductus arteriosus (DA) constriction and loss of luminal blood flow in producing permanent closure of the DA in human infants. METHODS: We studied 77 newborn infants (gestational age, 23 to 33 weeks) with asymptomatic patent ductus arteriosus (PDA), who had "complete clinical closure" (defined as the disappearance of all PDA signs) after treatment with indomethacin (three doses within 36 hours). All infants had an echocardiogram 24 to 36 hours after the last dose of indomethacin. They were then followed for the development of ductus reopening. RESULTS: Despite the absence of clinical signs, 18 (23%) of 77 infants still had some residual luminal blood flow according to their echocardiograms. The failure to obliterate luminal blood flow completely was directly related to the infant's postnatal age when treatment was begun and to the amount of fluid administered before treatment. Subsequently the DA reopened in 16 (21%) of 77 infants. As predicted, infants with residual luminal blood flow after indomethacin treatment had a higher rate of subsequent clinical reopening than did those with no luminal flow. In addition, immature infants had a significantly higher reopening rate than did more mature infants. The increased risk of reopening in immature infants was seen even when indomethacin caused complete obliteration of ductus luminal blood flow. CONCLUSION: The DA of immature infants is resistant to the constriction-induced ischemic damage that is necessary for subsequent permanent closure of the vessel.

Ductus Arteriosus

Pharmacological properties of 403U76, a new chemical class of 5-hydroxytryptamine- and noradrenaline-reuptake inhibitor.

403U76 (5-chloro-[[2-[(dimethylamino)methyl]phenyl]thio]benzene- methanol hydrochloride) is a potent, competitive, inhibitor of 5-hydroxytryptamine (5-HT) and noradenaline reuptake into rat brain synaptosomes. Inhibition of 5-HT uptake in-vivo by 403U76 was demonstrated by potentiation of the behavioural effects of 5-hydroxytryptophan in rats and mice and blockade of p-induced depletion of 5-HT in rats. The firing of 5-HT-ergic dorsal raphe neurons in rats was decreased after intravenous administration of low doses of 403U76 as would be predicted for a 5-HT uptake inhibitor. 403U76 antagonized tetrabenazine-induced sedation, an effect associated with inhibitors of noradrenaline uptake, but not with inhibitors of 5-HT uptake. Thus 403U76 affects noradrenergic as well as 5-HT-ergic neurotransmission in-vivo. Potential anxiolytic activity was indicated by reductions in isolation-induced vocalizations in neonates after 403U76 treatment. Low intravenous doses of 403U76 were well tolerated and had no sustained cardiovascular effects. There were no deleterious behavioural side-effects at active doses. Effects observed on isolated tissues or transmitter receptors occurred only at very high concentrations and were pharmacologically unimportant. Thus 403U76 can be considered a potential antidepressant/anxiolytic agent that is a potent, selective inhibitor of 5-HT and noradrenaline reuptake.

5-Hydroxytryptophan

[Utilization of social departments before and after effectiveness of the 'need for disability care' health service reform in Mannheim].

Constituting a part of the new health reform in Germany ("Bundesgesundheitsreformgesetz"), a new arrangement to support home care for the very frail and severely disabled took effect in 1991. Since then the costs of basic nursing care and home-making services are partly covered by health insurance. To examine the impact of the new arrangement on the use of the community nursing services (the so-called "Sozialstationen") we compared two cross-sections of elderly patients under care in the city of Mannheim. The cross-sections encompassed all over 65-year old patients visited during January 1990 (first cross-section) and during May 1993 (second cross-section) by the "Sozialstationen" in Mannheim. The characteristics of the patients (degree of disability in everyday life, level of cognitive functioning etc.), together with the forms of care provided, were recorded by the nurses. The results show that the number of patients cared for by the "Sozialstationen" was smaller in May 1993 (n = 1649) than in January 1990 (n = 1842); especially the number of the severely disabled and demented patients was reduced. Although these findings can be viewed only as preliminary, one can conclude that--contrary to all expectations--there was no run on the "Sozialstationen" in the course of the implementation of the new social code.

Activities of Daily Living

The value of HIDA scans in the initial evaluation of patients for cholecystitis.

One hundred twenty-two consecutive patients who had hepato-iminodiacetic acid (HIDA) scans over a 5-month period were reviewed. These scans were found to have 94% sensitivity, but only 36% specificity for correctly diagnosing pathological variants of cholecystitis. Frequently, HIDA scans were misinterpreted to show common bile duct obstruction (CBDO); only 20% of cases of CBDO suggested on HIDA could be confirmed surgically. Sonography gave 88% to 90% sensitivity and 91% specificity in correctly diagnosing pathological variants of cholecystitis and correctly demonstrated CBDO in 80% of the cases. As first-line studies to evaluate biliary tract disease, HIDA scans are costly and should be eliminated.

Acute Disease

Rational vancomycin use recommendations.

The increasing occurrence of VRE will dramatically affect the management of infections in hospitalized patients, as well as increase morbidity and mortality. Vancomycin is the therapy of choice for certain gram-positive infections in patients with significant allergic histories to beta-lactam antibiotics and for infections with gram-positive microorganisms that are resistant to beta-lactam antibiotics. Conservative use of vancomycin in the future may help to avoid the further development of resistant organisms.

Centers for Disease Control and Prevention, U.S.

Activation of mechanonociceptors by pro-inflammatory peptides melittin and PLAP peptide.

Studies were conducted to characterize the chemical reactivity of A and C fiber mechanical and mechanoheat nociceptors that innervate the goat palatal mucosa. In mechanical nociceptors, no significant chemical reactivity to either serotonin, bradykinin, prostaglandin E1, or prostaglandin E2 was observed, regardless of whether substances were injected singly or in spaced sequential combinations. Weak reactivity was observed in mechanoheat nociceptors. In contrast, both mechanical and mechanoheat nociceptors were activated by novel proinflammatory peptides. Nineteen of 30 mechanonociceptors and 12 of 13 mechanoheat nociceptors were activated by the insect venom peptide, melittin or its endogenous mammalian homologue PLAP (phospholipase A2 activating protein) peptide. Low threshold mechanoreceptors were never activated by melittin or PLAP peptide.

Animals

Incidence and relative risk of dementia in an urban elderly population: findings of a prospective field study.

To ascertain the frequency and distribution of new cases of dementing illness in the elderly population of Mannheim (population 308,000), a survey sample of community residents of > 65 years of age was re-examined after an interval of 7-8 years, and a sample of elderly persons in long-stay care after 5-6 years. The estimated annual incidence rate for all forms of dementia, after correction for ageing of the samples, was 15.4 per 1000 persons aged > 65, made up of dementia of Alzheimer type (8.9 per 1000), vascular dementia (4.4 per 1000) and other forms (2.1 per 1000). Apart from the expected association with age > 65 years, the most powerful predictors of onset of a dementing illness were residence in long-stay care and the presence of minor cognitive deficits at the initial examination, each of which was associated with a highly significant increase in risk. In addition, a number of socio-demographic characteristics (marital status, occupational history and quality of present living accommodation) was found to be predictive, though analysis of larger samples or pooled research data would be necessary to establish their importance in this respect. The findings suggest that identification of mild cognitive impairment on screening could prove helpful in assessing risk for dementia from two to three years before the condition becomes clinically apparent.

Aged

Sociology in the context of social psychiatry.

The author addresses various aspects of the interface between sociology and social psychiatry, among them the labelling process related to mental deviance, problems related to diagnosis and social ethology. The need for interdisciplinary work is emphasized, not least in the context of prevention. It is underlined that effective preventive measures can precede the full causal elucidation of a disease.

Community Psychiatry

Folnegović & Folnevogić-Smalc's "Schizophrenia in Croatia: inter-regional differences in prevalence and a comment on constant incidence".

"STUDY OBJECTIVE--The aim was to examine why differences exist in schizophrenia prevalence and risk in some areas of Croatia, when schizophrenia incidence rates do not appear to vary. DESIGN--Areas differing by schizophrenia admission rates in patients born in 1953 and admitted by the age of 31 years are compared using a number of indicators relating both to general population characteristics and to those of schizophrenic cases in these populations. SETTING--The study covers the whole of Croatia (4,601,469 inhabitants, 1981 census). SUBJECTS--By the age of 31 years, out of 80,445 individuals born in Croatia in 1953, 464 were admitted for and diagnosed as having schizophrenia. MAIN RESULTS--Admission risk rates are higher in those parts of Croatia where emigration rates are high and lower where immigration rates are high. There is also a positive correlation with schizophrenia prevalence and manic depressive psychosis rates. There is a negative correlation with age of onset of schizophrenia and with schizophrenic reproduction rates. In the study areas, hospital incidence rates are not significantly different. CONCLUSIONS--Economic migration and negative selection in the domestic population are likely to be the most significant factors leading to differences in schizophrenia prevalence. The approximately equal incidence rates in the population, with different prevalence and admission risks, are linked to differences in the disease onset among schizophrenics with a positive family history for this condition. In other words, these patients, when part of the population with a greater prevalence and a greater hereditary loading, experience the onset more often at an earlier age. Thus they have a lower reproduction rate than in a population with a lower prevalence and a lower hereditary loading. Thus incidence rates in populations with different prevalences and different hereditary loads are maintained roughly equal over generations."

Adolescent

Person-environment assessments in occupational therapy.

Occupational therapists have begun to recognize the importance of considering how the environment influences occupational performance. Models of person-environment fit provide a theoretical context within which occupational therapists can consider the influence of the environment on function. The challenge for occupational therapists is to select assessments that incorporate concepts of person-environment fit. However, limited awareness of appropriate environmental assessments that have undergone psychometric testing has limited their introduction into clinical practice. This paper reviews 41 environmental assessments and considers each in terms of its purpose, environmental attribute, environmental application, clinical utility, instrument development, and psychometric testing. A case example illustrates the applicability to the practice of occupational therapy.

Activities of Daily Living