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Biomedical subjects

B Cooper

Publications and source records attributed to B Cooper.

At least 55 records · Page 3Linked to original sources

Current perspectives on pain upon injection of drugs.

A limitation in the administration of parenteral products is the pain caused upon injection. Injection site pain has been predominately associated with intravenous, intramuscular, and subcutaneous administration. It becomes important for the formulation scientist to have a basic understanding of the physiology underlying the pain process, as well as the pharmaceutical factors associated with injection site pain. Initially, this review will provide the reader with a primer on the mediation of pain in the periphery and a compilation of those drugs that have been associated with pain on injection. In addition, this review will present important considerations and general formulation approaches or methods that have been used to overcome pain on injection. Finally, a brief overview of the various experimental systems used to investigate injection site pain is discussed.

Humans↗

Domains of the TMV movement protein involved in subcellular localization.

To identify and map functionally important regions of the tobacco mosaic virus movement protein, deletions of three amino acids were introduced at intervals of 10 amino acids throughout the protein. Mutations located between amino acids 1 and 160 abolished the capacity of the protein to transport virus from cell to cell, while some of the mutations in the C-terminal third of the protein permitted function. Despite extensive tests, no examples were found of intermolecular complementation between mutants, suggesting that function requires each movement protein molecule to be fully competent. Many of the mutants were fused to green fluorescent protein, and their subcellular localizations were determined by fluorescence microscopy in infected plants and protoplasts. Most mutants lost the ability to accumulate in one or more of the multiple subcellular sites targeted by wild-type movement protein, suggesting that specific functional domains were disrupted. The order in which accumulation at subcellular sites occurs during infection does not represent a targeting pathway. Association of the movement protein with microtubules or with plasmodesmata can occur in the absence of other associations. The region of the protein around amino acids 9-11 may be involved in targeting the protein to cortical bodies (probably associated with the endoplasmic reticulum) and to plasmodesmata. The region around residues 49-51 may be involved in co-alignment of the protein with microtubules. The region around residues 88-101 appears to play a role in targeting to both the cortical bodies and microtubules. Thus, the movement protein contains independently functional domains.

Amino Acid Sequence↗

Previous psychiatric history as a risk factor for late-life dementia: a population-based case-control study.

OBJECTIVE: To test the hypothesis that risk for dementia in late life is increased by a history of earlier psychiatric illness, and to examine the specificity of any such association. METHODS: Frequency of earlier treated psychiatric illness was established by record searches and informant histories for all persons aged over 60 who were entered on the Camberwell dementia case register over a 2-year period and for an individually matched control group of the local elderly population, drawn from the files of the area Family Health Services Authority. RESULTS: Of 559 persons with a clinical diagnosis of dementia, 70 (12.5%) had a history of psychiatric illness long preceding, and apparently unrelated to, the onset of dementia. When these patients were compared with a matched comparison group of dementia register patients who had no recorded psychiatric history, the two groups appeared broadly similar in type of dementia, severity and clinical features. Sixty-three of the earlier psychiatric histories could be identified from the available medical records alone. Applying the same procedure to the matched control group of Camberwell residents yielded from the 559 only 19 (3.4%) with a history of treated psychiatric illness before the age of 70. The difference in case frequency between the two groups was highly significant and corresponded to an estimated odds ratio of 3.6. The increase in risk, which was not restricted to dementia of Alzheimer type, appeared to be characteristic of major psychiatric illness, rather than specific for depression. CONCLUSION: There is a positive association between previous psychiatric history and late-life dementia which is of predictive significance. The underlying causal links merit further research.

Aged↗

An algorithm for early aggressive treatment of frostbite with limb salvage directed by triple-phase scanning.

Frostbite injuries have traditionally been treated with expectant observation. With the exception of early blister aspiration tissues are allowed to demarcate before definitive debridement is accomplished. Triple-phase bone scanning has been used to define the extent of fatally damaged tissues in an attempt to allow for early debridement and wound closure. We suggest extending this technology to assess injury and direct debridement in patients for whom early aggressive salvage attempts are indicated. We present two cases in which triple-phase scanning was used to direct early debridement for aggressive limb salvage with flap reconstruction. Bone, ligament, tendon, and nerve were preserved and covered with vascularized tissue before the onset of frank necrosis. Postoperative scans reveal revascularization of these tissues. An algorithm incorporating triple-phase scanning for the evaluation and treatment of frostbite is presented.

Adult↗

A look at the facts.

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Attitude of Health Personnel↗

The development of strains, forces and nociceptor activity in retrodiscal tissues of the temporomandibular joint of male and female goats.

Chronic pain in the temporomandibular (TM) joint is predominantly manifested in women. We examined biomechanical and neural factors that could contribute to this differential representation. Relationships between jaw rotation, soft tissue strains and soft tissue forces were examined in the goat TM joint. Strains were minimal until the jaw was rotated beyond the normal range of motion (7.25 deg). There were no significant differences in rotation-strain patterns in males and females. Stress developed as strains were introduced by jaw rotation. Gender differences were observed. Males manifested higher failure loads (15.94 +/- 1.98 and 11.37 +/- 2.02 N, for males and females respectively) and higher elastic stiffness than females (5.62 +/- 1.19 N/mm and 1.64 +/- 0.31 N/mm, for males and females respectively). Recordings were made from cell bodies in the trigeminal ganglion whose distal processes innervated the retrodiscal tissue of the temporomandibular joint of the goat (n = 48). Nociceptor reactivity was characterized with respect to the capacity to transduce mandibular rotation (rotation-interval functions; n = 29). On the basis of established relationships between rotation, strain and tissue forces, rotation-interval functions were transformed into strain-interval and force-interval functions. Comparisons were made between nociceptor properties grouped by gender. No differences in properties were observed when nociceptors were characterized with respect to jaw rotation; however, gender differences were obtained when nociceptor reactivity was characterized with respect to retrodiscal strains or forces. Consistent with smaller failure loads, nociceptors of retrodiscal tissues of females manifested a smaller range (1.12 vs 4.33 N), force to average (1.51 vs 4.64 N), force to minimum (0.95 vs 2.48 N) and force to asymptotic discharge (2.07 vs 6.81 N). Consistent with lower elastic stiffness, nociceptors of female tissues manifested higher average strain (54.4% vs 41.9%) and peak strain (74.0% vs 58.1%) to asymptotic discharge relative to those sampled from male tissues. The implications of these findings for TM joint injury and chronic pain are considered.

Animals↗

The comorbidity of anxiety and depression.

OBJECTIVE: This study explored the effect of comorbid anxiety disorders in patients admitted to an inpatient specialist Mood Disorders Unit for the treatment of a primary major depressive episode. METHOD: Subjects were assessed on admission and discharge. DSM-III-R diagnoses for major depression and anxiety disorders were established using CIDI-Auto; comorbid anxiety disorders were coexistent in time with the major depression, with both conditions meeting diagnostic criteria at the time of assessment. Severity of illness was assessed using the Hamilton Depression/Melancholia Scale, the revised Hamilton Anxiety Scale and the revised Beck Depression Inventory. RESULTS: For the analysis, the study cohort was divided into three groups: depression alone (n = 33), one comorbid anxiety disorder (n = 15), and two or more comorbid anxiety disorders (n = 24). No particular anxiety disorder predominated. Interestingly, the presence or absence of comorbid anxiety with severe major depression made no significant difference to treatment choice or outcome results. Specifically, there was no significant difference between the three groups in the utilisation of electroconvulsive therapy and pharmacotherapy (including antidepressants, benzodiazepines and neuroleptics); all subjects improved significantly on both depression and anxiety ratings, and length of inpatient stay did not vary significantly between the three groups. CONCLUSIONS: The existence of comorbid anxiety disorders in those patients who presented for treatment of a primary major depressive episode did not significantly effect choice of treatment or treatment outcome, suggesting that there is a close interrelationship between the two conditions.

Adult↗

Autoradiographic studies indicate regional variations in the characteristics of L-glutamate transporters in the rat brain.

Quantitative autoradiography of [3H]L-aspartate binding in thaw-mounted sections of rat brain has shown that L-trans-pyrrolidine-2,4-dicarboxylate and D-threo-3-hydroxyaspartate but not DL-2 aminoadipate strongly interacted with the binding sites while dihydrokainate, kainate and beta-aminoadipate produced only weak effects. The potency of inhibitors did not vary from one region to another in the telencephalon (neocortex, hippocampus and neostriatum) but, D-threo-3-hydroxyaspartate, L-trans-pyrrolidine-2,4-dicarboxylate, kainate and dihydrokainate inhibited [3H]L-aspartate binding in the cerebellar cortex less potently than that in the forebrain. Characteristics of the known excitatory amino acid transporters can, in part, explain the present results but contributions from additional transporter molecules to the heterogeneity of [3H]L-aspartate binding sites cannot be ruled out.

ATP-Binding Cassette Transporters↗

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↗

Multicentric epithelioid angiosarcoma of the bone. Pitfalls in clinical and morphological diagnosis.

Epithelioid angiosarcoma of the bone represents a challenging diagnosis by bone marrow biopsy. We present a case of a multicentric high grade angiosarcoma of the bone with epithelioid features. On the basis of the clinical presentation, the radiological findings, and the appearance of loosely clustered tumor cells detected in the initial bone marrow biopsy, the main differential diagnoses considered were a poorly differentiated non-secretory multiple myeloma and metastatic carcinoma. Subsequent morphologic, immunohistochemical and electron microscopic examination of tissue samples clarified the nature of the tumor as epithelioid angiosarcoma. We discuss potential pitfalls in clinical and morphological diagnosis. The strong reactivity of the tumor cells with the nonspecific but ubiquitous mesenchymal marker vimentin in similar cases should direct early attention to the rare malignant bone tumor, epithelioid angiosarcoma, with subsequent confirmation of this diagnosis with specific immunohistochemical endothelial cell markers and/or electron microscopy.

Aged↗

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↗

Cross-national interrater reliability of dementia diagnosis in the elderly and factors associated with disagreement.

Thirteen researchers from five centers in Australia, Germany, the Netherlands, United Kingdom, and United States applied DSM-III-R and Clinical Dementia Rating (CDR) syndrome-level dementia criteria to written vignettes of 100 elderly people identified in clinics or community surveys. Subjects ranged in type from cognitively intact to severely demented and many were also frail, partially sighted, or deaf. This paper concerns reliability within and between centers, and the relationship between reliability and factors such as diagnostic criteria, dementia severity, and respondents' clinical characteristics. Within-center interrater reliability was high, more so for "yes-no" DSM-III-R diagnoses than the multi-level CDR. Between-center rates were lower but still moderate to good. Concordance was lower for intermediate dementia levels than for no dementia and severe dementia. Physical disability made an additional contribution to uncertainty but deafness, poor vision, anxiety, and depression had no discernible effects. Reliability levels are likely to be lower in representative aged populations than in carefully selected clinical groups.

Aged↗

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↗