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Biomedical subjects

R Joseph

Publications and source records attributed to R Joseph.

At least 91 records · Page 5Linked to original sources

Platelet secretory products have a damaging effect on neurons.

We studied the direct effect of platelet secretory products on rat spinal cord explants. Morphological changes in the ventral horn neurons were assessed after staining for acetylcholinesterase (AChE). Compared to control, exposure to platelet secretory products was associated with a significant decrease in the number of AChE-positive neurons per ventral horn. Aspirin appeared to partially prevent this neurotoxicity. These results suggest that platelet secretory products may contribute to neuronal injury.

Acetylcholinesterase↗

Platelet activity and stroke severity.

Although platelets constitute the major component of a thrombus, its role in determining the clinical severity of thrombotic stroke is unknown. Therefore, we investigated the relationship between platelet ionized calcium ([Ca2+i]), a measure of platelet activity and presumably proneness to thrombosis, and clinical stroke severity in 45 consecutively studied acute ischemic stroke patients. Even though there was no correlation between the clinical neurological scores and the levels of baseline and activated platelet [Ca2+i], stroke was less severe in patients who had been taking aspirin at the time of stroke onset. These results raise several important questions: (a) is the extent of platelet activation a reflection of thrombus volume, (b) does the clinical severity of neurological deficit reflect the causative thrombus volume, and (c) whether the beneficial effect of aspirin in stroke prophylaxis is through its inhibition of platelets alone.

Aged↗

Septic arthritis following arthroscopy: clinical syndromes and analysis of risk factors.

During a 4-year study of 4,256 knee arthroscopies, eighteen patients became infected (infection rate 0.42%). Occurrence of infection was strongly associated with use of long-acting intraarticular intraoperative corticosteroids. Infection was more common among patients with longer surgery operating times, increased numbers of procedures during surgery, prior procedures, and performance of chondroplasty or soft tissue debridement. Subsequent to the study, the infection rate fell to 0.1%. Twenty-four infections were studied (our eighteen plus six other concurrent community cases); twelve were due to Staphylococcus aureus, eleven to coagulase-negative staphylococci, and one to Enterobacter cloacae. Seventy percent of the patients had onset of symptoms within 3 days of surgery. Most patients with coagulase-negative staphylococcal infections had fevers less than 38.3 degrees C (101 degrees F), negative Gram stains on synovial fluid, normal peripheral leukocyte counts, and somewhat indolent, mild clinical syndromes, while most patients with S. aureus infections had higher fevers, positive synovial Gram stains, peripheral leukocytosis, and more acute and severe clinical syndromes. Knee pain, swelling, and warmth always occurred, but erythema was noted in only 30% of patients. Treatment with 2 weeks of intravenous antibiotics was successful in all but one patient. Long-term results were excellent in sixteen of twenty-two patients.

Adolescent↗

Defining and accomplishing clinically related objectives in an eight-hour oncology course for first-year medical students.

Designing a clinically relevant cancer curriculum for freshmen attending medical schools with a traditional curriculum poses the following challenges: (1) there is limited curriculum time; (2) the subject matter is complex. The authors defined some of the responsibilities of the general physician in regard to cancer and six related objectives that first-year students could accomplish in an eight-hour multidisciplinary oncology course. A case-based, modified essay examination required students to demonstrate that they could begin to integrate principles of prevention, screening, diagnosis and staging, and treatment modalities. Ninety percent of the students accomplished the objectives. However, in working up the cancer case, 70% of the students did not mention the physical examination and 53% forgot multidisciplinary consultation. In a curriculum with limited objectives, first-year students can begin to deal efficiently with the complexities of cancer. Evaluation data revealed those objectives and related physician responsibilities requiring reinforcement in subsequent training.

Curriculum↗

Study of platelet-mediated neurotoxicity in rat brain.

BACKGROUND AND PURPOSE: The mechanism of ischemic neuronal injury is not fully resolved. The present view is that vascular occlusion per se does not fully account for the extent of neurological dysfunction. We previously hypothesized that platelet secretory products might contribute to neuronal injury in the central nervous system. Our preliminary studies using organotypic rat spinal cord cultures exposed to human platelet and its secretory products revealed that platelet products had neurotoxic properties. METHODS: Further studies, using the same methods, were conducted, with the addition of several refinements such as use of gel-filtered platelets (as opposed to washed platelets) and adding additional relevant controls including platelet membranes, red blood cells, and washed rat platelets. RESULTS: Exposure of spinal cord explant cultures to platelet secretory products resulted in reduced number of neurons per ventral horn compared with control. CONCLUSIONS: Our findings suggest that platelet secretory products have neurotoxic properties. This effect was seen with platelet secretion obtained from physiological platelet concentrations. It appears possible that more abundant release of platelet products at the site of thrombus formation could have pathological significance in vivo.

Animals↗

Molecular characterization and in-vitro hormonal requirements for expression of two casein genes from a marsupial.

Two marsupial casein genes have been isolated from a tammar wallaby (Macropus eugenii) mammary gland cDNA library. Comparisons of the tammar alpha- and beta-casein genes with their eutherian homologous reveal extensive divergence at the levels of nucleotide and amino acid sequences. Regions of similarity between the tammar and eutherian Ca(2+)-sensitive caseins are restricted to the major phosphorylation sites and the signal peptides. Quantification of casein mRNA levels in hormone-stimulated mammary gland explants from tammars in late pregnancy suggests that maximal induction of the beta-casein gene is dependent upon prolactin and insulin, while maximal induction of the alpha-casein gene is dependent upon prolactin, insulin and cortisol. These results are in contrast to earlier studies which show that the maximal induction of a putative 19 kDa casein, alpha-lactalbumin and beta-lactoglobulin in the tammar mammary gland is dependent upon prolactin alone. The expression of the latter three genes is not modulated by other hormones known to play a role in the in-vitro initiation of lactation in eutherians.

Amino Acid Sequence↗

Neurologic evaluation and its relation to acupuncture. Acupuncture for neurologic disorders.

Acupuncture provides companion animal veterinarians a valid therapeutic alternative to medicine and surgery in a variety of neurologic disorders. The veterinarian must arrive at a lesion localization in the nervous system and determine a presumptive diagnosis before instituting acutherapy. Signalment, type of neurologic disorder, efficacy of conventional treatments versus acupuncture, financial constraints, and ethical issues are useful patient selection criteria. In general, animals experiencing pain respond faster and more completely to acupuncture than those demonstrating neurologic deficits consistent with loss of function. Acupuncture offers clients a noninvasive alternative when medications are contraindicated or surgery is not an option. This chapter serves as an introduction to acupuncture for neurologic disorders in pets. It is hoped that the information here will inspire clinical investigations to evaluate more completely patient selection, patient response, and long-term outcome.

Acupuncture Therapy↗

Diagnosis of acute diffuse pulmonary infiltrates in immunosuppressed patients by open biopsy of the lung.

Herein is a review of the results of open biopsies of the lung performed upon immunosuppressed patients between the years 1982 and 1988. The goal was to assess the safety and value of the procedure on a group of patients who are many times in extremis because of multiorgan failure. Obtaining the correct diagnosis and establishing treatment poses a challenge. The study includes 74 patients. Fifty-four had malignant tumors; 20 had various diseases associated with immunosuppression. The biopsy was obtained from the left side in 65 instances. An adequate thoracotomy was done to permit exploration of the thoracic cavity and obtain a representative sample of tissue. The mortality rate related to the operation was 1.4 percent and the complication rate was 11.0 percent. Forty-six percent of the infiltrates were the result of infection. In 42 percent, a change in treatment was made. Thirty-two percent survived and were discharged from the hospital. Patients with adverse drug reaction, with nonspecific pneumonitis and with bacterial infection had a favorable prognosis and benefited most from open biopsy of the lung.

Acute Disease↗

Cancer control and the older person. Psychosocial issues.

Three major areas related to psychosocial issues pertinent to the provision of cancer control services to older people have been delineated. These are values and medical decision making, psychosocial barriers to screening and access to care and services, and quality of life, including rehabilitation. These areas are explored, salient issues are defined, and specific questions and areas for consideration in future research are identified at the macro and micro levels.

Age Factors↗

Endothelin-1 and human platelet activity.

Endothelin-1, a peptide produced by endothelium, causes vascular smooth muscle contraction possibly by mobilizing intracellular calcium. Shifts in ionized calcium may also play a role in platelet activation. Accordingly, the effects of endothelin on platelet ionized calcium and aggregation were studied. The measurements were made in aequorin-loaded gel-filtered human platelets derived from healthy donors. Endothelin even in a final concentration of 10(-6) M did not cause a measurable change in platelet ionized calcium or aggregation. When tested in combination with collagen, thrombin and platelet activating factor, endothelin showed no synergistic effect. These observations raise the possibility that endothelin may not interact with platelets in a physiologically significant way.

Adult↗

Hormone-responsive survival of mammary gland explants from the pregnant tammar wallaby (Macropus eugenii) in the absence of exogenous hormones and growth factors.

1. The level of beta-lactoglobulin mRNA increased maximally in mammary explants from late pregnant tammars cultured for 3 days in media containing either prolactin or insulin, cortisol and prolactin. 2. The same level of accumulation occurred when explants were first cultured for 4 days in a chemically defined medium with no exogenous hormones, serum or growth factors, suggesting that the tissue remains viable and hormone-responsive during the initial incubation. 3. Mammary explants cultured for 4 days in medium with no hormones demonstrated a progressive increase in the rate of RNA and DNA synthesis suggesting that the tissue is under a positive autocrine/paracrine stimulus.

Animals↗

Platelet glycine, glutamate and aspartate in primary headache.

Platelet levels of glutamic and aspartic acid and glycine were measured in patients with migraine with aura, migraine without aura, tension headache and cluster headache. High levels of these amino acids were found in patients with migraine with aura compared to normal subjects and other headache groups. During headache, glutamate levels further increased in migraine with aura patients. These findings may have relevance to the neurological symptoms of migraine with aura.

Aspartic Acid↗

Platelet secretory products may contribute to neuronal injury.

BACKGROUND: We do not fully understand the mechanisms for neuronal damage following cerebral arterial occlusion by a thrombus that consists mainly of platelets. The view that certain endogenous substances, such as glutamate, may also contribute to neuronal injury is now reasonably well established. Blood platelets are known to contain and secrete a number of substances that have been associated with neuronal dysfunction. Therefore, we hypothesize that a high concentration (approximately several thousand-fold higher than in plasma, in our estimation) of locally released platelet secretory products derived from the causative thrombus may contribute to neuronal injury and promote reactive gliosis. SUMMARY OF COMMENT: We have recently been able to report some direct support for this concept. When organotypic spinal cord cultures were exposed to platelet and platelet products, a significant reduction in the number and the size of the surviving neurons occurred in comparison with those in controls. We further observed that serotonin, a major platelet product, has neurotoxic properties. There may be other platelet components with similar effect. CONCLUSIONS: The hypothesis of platelet-mediated neurotoxicity gains some support from these recent in vitro findings. The concept could provide a new area of research in stroke, both at the clinical and basic levels.

Animals↗

A marsupial beta-lactoglobulin gene: characterization and prolactin-dependent expression.

Analysis of the tammar wallaby beta-lactoglobulin cDNA and inferred amino acid sequences reveal extensive sequence divergence from the eutherian beta-lactoglobulins. Conserved residues include the cysteines and a number of individual amino acids involved in structure and ligand-binding. The only region of extended similarity is a heptapeptide sequence which may impart specificity to its interaction with a receptor protein. Northern analysis of total mammary RNA revealed two transcripts which result from differential utilization of polyadenylation signals. The concentration of beta-lactoglobulin mRNA increased in late lactation and correlates with increases in milk production and levels of milk fat. Quantification of beta-lactoglobulin mRNA levels in hormone-stimulated mammary gland explants from tammars in late pregnancy suggests that maximal induction of the gene is dependent on prolactin alone and that expression is not modulated by other hormones known to play a role in the initiation of lactation in eutherians.

Amino Acid Sequence↗

De novo biosynthesis and localization of inhibin in marmoset (Callithrix jacchus) and rat epididymis.

Using specific polyclonal antibodies generated against a 13 Kd human testicular inhibin, immunocytochemical localization was carried out in epididymis of intact and castrated marmoset monkey and rat epididymis. Inhibin was found to be present in the cytoplasm of epithelial cells of caput, corpus and cauda epididymis. The intensity of staining and pattern of distribution did not change following castration. Further, the in vitro biosynthesis of inhibin studied by incorporating 3H-leucine and precipitating it with specific antibody indicated maximum biosynthesis in the corpus epididymis in case of marmosets and cauda in case of rats. Following castration in rats, the epididymal tissue still retained the capacity to biosynthesize inhibin. These studies indicate that marmoset and rat epididymis are capable of biosynthesizing/absorbing inhibin and whose synthesis does not depend on androgens.

Animals↗