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Biomedical subjects

L M Miller

Publications and source records attributed to L M Miller.

At least 73 records · Page 4Linked to original sources

Synthesis of a "free" form of hyaluronic acid by articular chondrocytes in monolayer culture.

Primary and first passage rabbit chondrocyte cultures synthesized a "free" form of hyaluronic acid (HA-f) previously characterized in rabbit cartilage. HA-f was isolated from the [3H] glcN/35SO4-labelled cell-associated-fraction (CAF) and from the culture medium by successive equilibrium centrifugations in Cs2SO4/CsCl/Cs2SO4 under low salt conditions. The culture medium HA-f appeared in the void volume of Sepharose CL-2B eluted with low salt, (0.5M sodium acetate), and was susceptible to digestion with Streptomyces hyaluronidase. HA-f aggregated purified rabbit cartilage proteoglycan monomer. These results indicated that HA-f probably subserves hyaluronic acid already complexed with proteoglycan monomer. Newly synthesized HA-f may be required for the continual formation of proteoglycan aggregates.

Animals↗

Relief of upper airway obstruction by adenotonsillectomy.

Adenotonsillectomy is often performed to relieve upper airway obstruction, even in children who do not present with severe apnea. Although adenotonsillectomy provides dramatic relief from obstructive sleep apnea, little evidence is available as to the efficacy of surgery in the far more prevalent cases of partial airway obstruction. We report the results of a prospective study of 100 children with adenotonsillar obstruction (without severe apnea) and 50 age-matched control children. The majority of patients exhibited appreciable sleep disturbances preoperatively, as compared to controls, and had substantial postoperative improvement, as demonstrated by parental questionnaire and sleep sonography--the computer-aided analysis of respiratory sounds. Mouth breathing and behavior problems were also prevalent preoperatively and were affected positively by adenotonsillectomy. It appears that surgery in such cases can have far-ranging benefits, even for the child whose obstruction does not demonstrate severe apnea.

Adenoidectomy↗

Human alveolar macrophages: HLA-DR-positive macrophages that are poor stimulators of a primary mixed leukocyte reaction.

Previous studies demonstrated that alveolar macrophages (AM) from most normal human volunteers failed to stimulate the antigen-induced proliferation of peripheral blood T lymphocytes although greater than 90% of AM expressed HLA-DR antigens. The current studies establish that AM also fail to induce allogeneic peripheral blood mononuclear cells to proliferate in a mixed leukocyte reaction (MLR). Suppressive activity by AM was not an explanation for their failure to induce an MLR. Indirect immunofluorescence established the presence of both HLA-DR and DQ antigens on the majority of AM and the persistence of these antigens on cells in culture for up to 6 days, the period of time required to observe a maximal MLR. Metabolic labeling experiments also demonstrated that HLA-DR antigens were synthesized by AM. It was recently reported that AM secrete relatively small amounts of IL 1, an important ancillary signal provided by accessory cells to enhance the stimulation of lymphocyte proliferation. However, addition of optimal concentrations of IL 1 to cultures containing AM failed to enhance the MLR. Thus, there is at least one additional, but as yet undefined, requirement for an accessory cell to induce an optimal MLR besides the display of HLA-D region antigens and the secretion of IL 1. In contrast, AM were effective in specifically stimulating proliferation of alloreactive T cell lines, suggesting that at least some cell lines do not require this nonspecific undefined second signal. We speculate that although AM may not initiate primary immune responses in the lung, they may be important in maintaining immune-mediated inflammatory responses by specifically restimulating already activated T cells.

Adult↗

Ataxia and weakness associated with fourth ventricle vascular anomalies in two horses.

Two adult horses with progressive neurologic signs were examined clinically and at necropsy. Both horses had signs of progressive ataxia and weakness, clinically diagnosed as spinal cord in origin. Differential diagnoses for cervical spinal ataxia in horses included cervical vertebral malformation, equine degenerative myeloencephalopathy, equine herpes-virus-I myeloencephalopathy, and equine protozoal myeloencephalopathy. Necropsy findings in both horses were similar and consisted of a large hematoma in the fourth ventricle, with upward compression of the cerebellum and downward compression of the pons and rostral portion of the medulla.

Animals↗

Effects of polymethylmethacrylate on rabbit articular chondrocytes in monolayer culture.

The effects of polymethylmethacrylate (PMMA) on DNA, protein, and sulfated-proteoglycan synthesis by rabbit articular chondrocytes were observed in monolayer cultures. PMMA pellets in ratios of 1:1 and 1:2 (liquid monomer:powder) significantly reduced [3H]thymidine incorporation into DNA during the first 24 h of culture and less so after 48 and 72 h. The reduction in [3H]thymidine incorporation was restricted to the cohort of chondrocytes nearest the PMMA. Consequently, cellular proliferation was unaltered by PMMA. By contrast, PMMA failed to inhibit [3H]leucine or [3H]serine/35SO4 incorporation. Both control and PMMA (1:1)-treated chondrocyte CsCl density gradient medium fraction dA1 eluted as a retarded peak on Sepharose CL-2B under associative conditions. The average partition coefficient (Kav) of PMMA-treated fraction dA1 was 0.41, as compared with 0.27 for control cultures. The Kav of medium fraction dD1 (proteoglycan monomer) was unaltered. Both control and PMMA-treated dA1 fraction elution profiles on Sepharose CL-2B were altered by incubation with Streptomyces hyaluronidase, indicating the presence of proteoglycan aggregate. The PMMA-treated cultures synthesized smaller proteoglycan aggregates. Since PMMA has been a critical factor in the success of total joint arthroplasty, defining interactions of differentiated cells with the cement is imperative for an understanding of the effects of PMMA on the biology of cartilage and bone.

Animals↗

Congenital myasthenia gravis in 13 smooth fox terriers.

In 13 Smooth Fox Terriers with a congenital form of myasthenia gravis, clinical signs included intermittent, progressive muscle weakness that became more pronounced with exercise; muscle wasting; megaesophagus; and aspiration pneumonia. Neurologic abnormalities were apparent only during periods of weakness and included inability to retract the fore- and hindlimbs from painful stimuli. A decrement of the compound muscle action potential was evident during repetitive supramaximal nerve stimulation. Intravenous injection of a short-acting cholinesterase inhibitor evoked immediate improvement of clinical and electromyographic signs. Intracellular microelectrode studies of a biopsied external intercostal muscle revealed reduced amplitude of miniature end-plate potentials, as occurs in acquired myasthenia gravis. However, in contrast to acquired myasthenia gravis, antibodies directed against acetylcholine receptors were not demonstrable in serum and were not bound to acetylcholine receptors in muscle. Despite lack of complexing with immunoglobulin, the amount of acetylcholine receptor protein in biopsied external intercostal muscles from 9 affected pups was less than 25% of the amount in 5 unaffected littermates. The latter finding accounted for the reduction in amplitude of miniature end-plate potential and the failure of neuromuscular transmission. Treatment with a long-acting cholinesterase inhibitor in 6 cases resulted in temporary improvement in muscle strength.

Animals↗

Ischemic heart disease in systemic lupus erythematosus in the young patient: report of six cases.

To clarify the clinical spectrum of coronary arterial abnormalities in systemic lupus erythematosus, the data were reviewed on six patients who had a diagnosis of lupus at ages 15 to 29 years and who had ischemic heart disease before age 35. Two patients had coronary arteritis diagnosed on postmortem examination. In a third patient alterations in coronary arterial anatomy occurred with angiographic improvement temporally related to the initiation of steroid therapy. The other three patients had severe diffuse atherosclerotic coronary disease that was identified in two at postmortem examination. In the third patient the course of the disease strongly suggested coronary atherosclerosis, and eventually coronary bypass grafting was performed for relief of angina. In summary, clinically important extramural coronary arteritis and atherosclerosis both occur, although rarely, in young patients with lupus. Coronary artery disease may occur with or without coexisting active extracardiac lupus manifestations. Short-term steroid therapy and follow-up angiography for those with angina and in whom coronary arteritis is suspected warrant consideration. When stable coronary arterial anatomy is demonstrated on follow-up angiography, management is determined by the patient's symptoms irrespective of the prior history of lupus and, if indicated, cardiac surgery for symptomatic relief can be safely performed.

Adolescent↗

Teen advocate program.

The South Bay Free Clinic's Teen Advocate Program is comprised of three basic components: Clinic duties, outreach and CARE-line. The ten Teen Advocates (TA's) spend a total of ten hours per week divided among these activities. In the Clinic, they perform such duties as intake, blood pressure and hematocrit measurement, exam room assistance, birth control raps and answering the phones. Outreach consists mainly of speaking informally with their peers at school, home, parties or wherever young people congregate. Occasionally, TAs speak formally in high school classrooms or at youth-serving agency meetings (e.g. YWCA). They also distribute evaluation forms for each group presentation given. The CARE-line, a health information and referral helpline for teenagers, is staffed by Teen Advocates Monday-Thursday, 4-8 p.m. Adult volunteer supervisors provide necessary support and guidance for the teen listeners.

Adolescent↗

Synthesis of heteroaromatic potential beta-adrenergic antagonists by the glycidol route.

The synthesis of several 3-alkylamino-2-hydroxypropyl heteroaryl ethers (13-15, 17, and 18) is described. These compounds were prepared by the alkylamination of the corresponding glycidyl ethers (6-8, 10, and 11), which in turn were obtained from the requisite heteroaryl halides and the sodium salt of glycidol. The above basic ethers exhibited beta-blocking activity, but the potency of the tested compounds was considerably less than that of propanolol. Only 3-tert-butylamino-2-hydroxyl-1-(1,2,4-thiadiazol-5-yl) propyl ether (13) showed some selective myocardial beta-blocking activity.

Adrenergic beta-Antagonists↗