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Biomedical subjects

S Miller

Publications and source records attributed to S Miller.

At least 487 records · Page 27Linked to original sources

Cyclic AMP modulation of ion transport across frog retinal pigment epithelium. Measurements in the short-circuit state.

In the frog retinal pigment epithelium (RPE), the cellular levels of cyclic AMP (cAMP) were measured in control conditions and after treatment with substances that are known to inhibit phosphodiesterase (PDE) activity (isobutyl-1-methylxanthine, SQ65442) or stimulate adenylate cyclase activity (forskolin). The cAMP levels were elevated by a factor of 5-7 compared with the controls in PDE-treated tissues and by a factor of 18 in forskolin-treated tissues. The exogenous application of cAMP (1 mM), PDE inhibitors (0.5 mM), or forskolin (0.1 mM) all produced similar changes in epithelial electrical parameters, such as transepithelial potential (TEP) and resistance (Rt), as well as changes in active ion transport. Adding 1 mM cAMP to the solution bathing the apical membrane transiently increased the short-circuit current (SCC) and the TEP (apical side positive) and decreased Rt. Microelectrode experiments showed that the elevation in TEP is due mainly to a depolarization of the basal membrane followed by, and perhaps also accompanied by, a smaller hyperpolarization of the apical membrane. The ratio of the apical to the basolateral membrane resistance increased in the presence of cAMP, and this increase, coupled with the decrease in Rt and the basolateral membrane depolarization, is consistent with a conductance increase at the basolateral membrane. Radioactive tracer experiments showed that cAMP increased the active secretion of Na (choroid to retina) and the active absorption of K (retina to choroid). Cyclic AMP also abolished the active absorption of Cl across the RPE. In sum, elevated cellular levels of cAMP affect active and passive transport mechanisms at the apical and basolateral membranes of the bullfrog RPE.

Animals↗

Prenatal computed tomography: are there indications?

In carefully selected diagnostic problem cases prenatal CT of the fetus was performed. In three of five cases anatomic or physiologic information was obtained that proved useful in the management of the pregnancy.

Adult↗

High-speed eight-channel thermocouple amplifier.

An eight-channel thermocouple amplifier system was constructed to measure rapid changes in temperature of only 1 or 2 degrees C simultaneously from many sites within the heart. The system has a response time of less than 5 ms, a resolution of less than 0.025 degrees C, and a voltage gain of approximately 2,500.

Animals↗

Bacterial peritonitis. Protecting the high-risk patient.

Cefamandole in combination with tobramycin was evaluated in the treatment of peritonitis as an adjunct to laparotomy and performance of the indicated surgical procedure in 88 patients. The clinical response was judged satisfactory in 91 per cent. Of four deaths, only one could be attributed to infection. Side effects noted were decreased creatinine clearance in 16 patients, increased liver enzymes in ten patients, and eosinophilia in nine patients. Microbiologic studies revealed aerobic peritonitis in 44 cultures and anaerobic in 32. Eighty-five per cent of the gram-negative and 69 per cent of the gram-positive strains were susceptible to cefamandole. Cefamandole alone or in combination with tobramycin appears to be an effective and safe antibiotic when used in appropriate doses for the treatment of bacterial peritonitis.

Adolescent↗

Infections due to Actinobacillus actinomycetemcomitans. A report of 3 cases.

Three cases are described which show the typical range of infections which may be caused by Actinobacillus actinomycetemcomitans, namely an actinomycosis-like infection, a prosthetic cardiac valve endocarditis and a post-traumatic soft-tissue infection. Cultural studies are detailed, and a short review of the disease-producing potential of this organism and its treatment is presented.

Abscess↗

Corynebacterium parvum versus BCG adjuvant immunotherapy in human malignant melanoma.

One-hundred and sixteen patients with Stage I and Stage II malignant melanoma were randomized to treatment with either Bacillus Calmette-Guerin (BCG) (Tice) or subcutaneous Corynebacterium parvum (Burroughs-Wellcome). Life table analysis failed to reveal a difference between these two forms of treatment in 68 Stage I patients. The relapse rate was significantly reduced in Stage II patients treated with C. parvum.

BCG Vaccine↗

Effects of lateral suprasylvian visual cortex lesions on visual localization, discrimination, and attention in cats.

Experiments were carried out to begin to define the behavioral functions of the lateral suprasylvian (LS) visual area of the cat's cortex. Behavioral tasks were chosen for analysis on the basis of previous suggestions in the literature concerning possible functions of LS cortex and its afferent pathways. These tasks included the ability of cats to orient the head and eyes to a stimulus presented in particular locations in the visual field, the ability to learn successive reversals of a two-choice visual pattern discrimination, and the ability to maintain or shift attention between relevant or irrelevant visual form and brightness cues. Eight cats were trained on each of these tasks. Four of the cats then received bilateral lesions of LS cortex, including the AMLS and PMLS regions, and the remaining 4 cats were used to assess normal retention. The LS cortex lesions had no significant effect upon performance of any of the behaviors tested. Thus, this region of cortex appears to play no essential role in simple brightness, form, and pattern discrimination performance, visual reversal learning, maintaining and shifting visual attention, or orienting the head and eyes to stimuli in the visual field. These results are discussed in relation to previous lesion studies involving large regions of the cat's extrastriate cortex and studies in other species. Possible functions of LS cortex, based upon recent electrophysiological studies, are suggested.

Animals↗

Improvement in neuropsychological performance in patients with refractory seizures after intensive diagnostic and therapeutic intervention.

Tests of cognitive, perceptual, motor, and memory function were administered to patients with refractory seizures before and after intensive treatment on a specialized epilepsy unit. Improved test performance related to withdrawal of barbiturates and an overall reduction in the number of antiepileptic drugs but not with reduction of seizure frequency.

Adolescent↗

Urinary 5-S-cysteinyldopa in Parkinsonism after DOPA and carbidopa.

The effect of anti-Parkinson therapy on the urinary excretion of 5-S-cysteinyldopa (5SCD), a catechol metabolite of dihydroxyphenylalanine (DOPA) and marker for the melanocyte, was studied by means of high performance liquid chromatography. 5SCD was normal in Parkinson patients treated with anticholinergics. DOPA administration increased 5SCD excretion. Carbidopa and DOPA together elevated 5SCD markedly in a dose-dependent manner to values higher than seen in some patients with metastatic malignant melanoma. The effect of anti-Parkinson therapy should be considered when using 5SCD as a tumor marker or when a Parkinson patient has a melanoma.

Adult↗

Transient appearance of the lupus anticoagulant in three family members sharing the A11B35DR4 haplotype.

A prolonged partial thromboplastin time in a patient was investigated, as well as those of his family members. One sibling, the mother, and the patient all shared a lupus-like anticoagulant and low Factor XII levels in association with the A 11, Bw 35, DR 4 haplotype previously found in familial lupus erythematosis. The rest of the family had normal coagulation profiles and the entire family had normal findings when tested for ANA, complement and immune complexes. After being confirmed in a second coagulation laboratory, the lupus-like anticoagulants in the three affected members of the family disappeared upon retesting 3-8 weeks later.

Adolescent↗

Thermography in breast diagnosis.

The role of two types of thermography in the diagnosis of breast disease was studied in 502 women seen over a two-year period. Thirteen cancers were diagnosed in eleven women. The most significant finding was the large number of equivocal or abnormal thermograms in women with normal breasts of benign disease, while in patients with proven cancer, the thermogram was abnormal in less than half. Clinical diagnosis of breast cancer was not enhanced by either or both types of thermogram. Despite specific criteria, thermographic interpretation was inconsistent except in the thermograms reported as "normal." On the basis of the findings, the authors could not recommend that an abnormal thermogram be used as an indication for mammography, since this would result in an inordinate number of these studies, particularly in young women. The findings suggest that thermography is not a sufficiently precise modality for use in routine breast diagnosis.

Adult↗

Fecal steroid metabolites and breast cancer risk.

Women with breast cancer (n = 78) had a higher excretion of total fecal steroids in mg/gm of dry weight (56 + 37) compared to controls (45 + 29; n = 71) (P = 0.03). Increases in both total neutral steroids and total bile acids in cases contributed to this significant difference. Lean women (Quetelet's index less than 3.5) with breast cancer seemed to have inappropriately high excretion of total fecal steroids (56 +/- 35), which was significantly higher than that of controls (41 +/- 27) (P = 0.03). Obesity resulted in higher excretion of fecal steroids only in controls. The differences persisted, even after pairing control cases for race-ethnicity and menopausal status. In 59 such pairs, cases had higher values (56 +/- 33), compared to controls (41 +/- 26) (P = 0.008). Significant differences (P = 0.005) were also present in 24 postmenopausal pairs, while in 35 premenopausal pairs a similar trend, but no significant differences were noted. Women with benign breast disease had higher total fecal steroids (51 +/- 34) compared to other controls (38 +/- 21) (P = 0.05). This observation suggests a common etiology between benign breast disease and breast cancer. There were no significant differences in dietary intake of total calories, total fat or dietary cholesterol between controls and cases suggesting that the observed differences in fecal steroids could be attributed to higher endogenous synthesis of cholesterol in cases.

Bile Acids and Salts↗

Ligand interactions with the solubilized porcine atrial muscarinic receptor.

Ligand interactions with porcine atrial muscarinic receptor solubilized in a mixed-detergent system (0.4% w/v digitonin and 0.08% w/v cholate) are described. The solubilized receptor interacts with ligands in a stereospecific manner, showing about the same affinity for local anesthetics and antagonists as was found for the membrane-bound protein [Schimerlik, M. I., & Searles, R. P. (1980) Biochemistry 19, 3407-3413]. Agonists appear to interact with a single class of noninteracting sites that correspond to the low-affinity agonist sites in the membrane-bound preparation. Kinetic studies of L-[3H]quinuclidinyl benzilate binding to the receptor indicated a two-step mechanism. The first step, in rapid preequilibrium (K = 5.7 x 10(-9) M), was followed by a slow conformational change (k1 = 4 x 10(-3) s-1; k-1 = 1.7 x 10(-4) s-1) in the receptor-ligand complex. The overall dissociation constant calculated from the association kinetics (2.3 x 10(-10) M) agreed well with the thermodynamic value for Kov (2.5 x 10(-10) M); however, direct determination of K-1 gave a value about 4-fold lower (4.0 x 10(-5) s-1) than predicted. Possible reasons for this discrepancy are discussed.

Animals↗

Comparison of five assays for immune complexes in the rheumatic diseases. An assessment of their validity for rheumatoid arthritis.

Clinical assessment (disease activity, severity, and extraarticular manifestations) of 101 rheumatoid arthritis patients was correlated with several laboratory tests, including 5 immune complex assays: the bovine conglutinin, 125I-Clq binding, monoclonal rheumatoid factor inhibition, Raji cell, and staphylococci binding assays. Elevated disease activity indices were most closely associated with the presence of immune complexes detected by the 125I-Clq and staphylococci binding assays. There were significant but weak correlations between the level of disease activity and the level of immune complexes as measured by the bovine conglutinin, 125I-Clq binding, Raji cell, and staphylococci binding assays. Articular disease severity, as measured by anatomic stage, was discriminated by the bovine conglutinin, monoclonal rheumatoid factor inhibition, and staphylococci binding assays. Extraarticular manifestations were best discriminated by the Raji cell and staphylococci binding assays. We concluded that the sensitivity, specificity, predictive value, and overlap of the associations were not sufficient to warrant their wide use for the diagnosis and management of rheumatoid arthritis in individual patients. Conversely, the 125I-Clq and staphylococci binding assays were as good as the erythrocyte sedimentation rate and the IgG rheumatoid factor test (the 2 best of many examined) in assessing disease activity. Further prospective studies with these assays will determine their usefulness in following rheumatoid arthritis for a prolonged period.

Antigen-Antibody Complex↗

Variance in rotavirus infection rates in different urban population groups in South Africa.

Rotavirus infection in black infants contrasts markedly with that of white infants in being much less common and showing no seasonal variation. In this multicentre study in Johannesburg, the aetiology of winter infantile gastroenteritis in black, coloured, and white infants was investigated. Stools were examined by electron microscopy and also by enzyme-immunoassay to detect subparticular antigen which may be missed by electron microscopy in patients presenting late in the course of the illness. Stools were also examined bacteriologically by conventional techniques. Rotavirus was the most common pathogen in all three population groups with bacteria playing a relatively minor role. Striking differences were observed in the rotavirus rates between the three groups. Infection in the whites was five times more common than in the blacks (60% versus 12%) with the coloureds intermediate at 40%. The hypothesis was put forward that the relative protection of the black population may be due to a greater degree of colonization of neonates, thus inducing protection against symptomatic infection at the target age of 6 to 24 months. This may well have important implications in immunoprophylaxis. The reason for the lack of seasonal variation in the black population is still unclear.

Animals↗