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Biomedical subjects

L Miller

Publications and source records attributed to L Miller.

At least 361 records · Page 20Linked to original sources

Light chain dependent effects of actin binding on the S-1/S-2 swivel in myosin.

The S-1/S-2 swivel in myosin provides a flexible link between the head and tail portions of the molecule. We have investigated the properties of the swivel by employing limited proteolysis methods. Our results indicate that the binding of actin to heavy meromyosin inhibits both the chymotryptic and papain cleavage of the S-1/S-2 swivel, and that this effect is dependent on the presence of intact LC-2 light chains. Actin did not slow digestions carried out using heavy meromyosin previously treated with proteases to nick the LC-2 chains to 17,000 or 14,000 Mr fragments. Although the integrity of the LC-2 light chain appears to be required to transmit the effects of actin binding from the myosin head to the S-1/S-2 swivel, the binding of Ca2+ to the 17,000 Mr LC-2 fragment can still affect the chemical reactivity of SH1 thiol groups. Both chymotryptic and papain digestions of heavy meromyosin containing intact or fragmented LC-2 light chain show substantial temperature sensitivity between 5 degrees C and 35 degrees C. Calculated apparent activation energies for this process indicate that the S-1/S-2 swivel in myosin can undergo temperature-dependent structural changes independently of the state of the LC-2 light chain. Thus, both actin binding and temperature variations can induce structural transitions in the S-1/S-2 swivel.

Actins↗

Developmental changes in keratin patterns during epidermal maturation.

The biochemical maturation of the epidermis of Xenopus laevis was examined through an identification of the keratins expressed at selected stages of development. The keratin patterns obtained were compared to those observed in the adult epidermis and two Xenopus non-epidermal, epithelial cell lines. The keratins expressed during development can be grouped into three classes: (1) keratins which are restricted to the embryonic epidermis (58 and 59 kDa); (2) keratins which are prominent during development, but become minor components of the adult epidermis (47, 48, and 60 kDa); and (3) keratins which accumulate during development to become the major keratins of the adult epidermis (49, 53, 56, and 63 kDa). The embryo-specific keratins are present at all developmental stages prior to metamorphosis which we have investigated, but disappear when the epidermis keratinizes during metamorphosis. Both class 1 and 2 keratins, while undetectable or minor components of the adult skin, are present in the two non-epidermal cell lines. In contrast, the class 3 keratins show little overlap with the keratins of these cell lines. All of the class 3 keratins appear after hatching with the exception of the 53-kDa keratin which is present at the earliest developmental stage which we have examined. All of the major keratins of the adult epidermis accumulate as metamorphosis proceeds, while the embryo-restricted keratins are gradually lost.

Animals↗

Cognitive risk-taking after frontal or temporal lobectomy--I. The synthesis of fragmented visual information.

Patients with unilateral cerebral excisions and control subjects performed two visual tasks in which target items had to be guessed on the basis of partial information. In one task, no points were at stake, but in the second, each cumulatively provided clue was assigned successively lower point-value, these points being risked whenever the subject responded. The right fronto-temporal group chose to guess more often after seeing only one clue than any other group. The right temporal-lobe group and both frontal-lobe groups were impaired at synthesizing the fragmented line-drawings, with patients in the frontal-lobe groups making the most perceptual errors.

Adolescent↗

Cognitive risk-taking after frontal or temporal lobectomy--II. The synthesis of phonemic and semantic information.

Patients with unilateral cerebral excisions and control subjects performed two tasks in which target words had to be guessed on the basis of either phonemic or semantic partial-information clues. Each cumulatively provided clue was assigned successively lower point-value, these points being risked whenever the subject responded. Patients with frontal-lobe excisions chose to make a guess after seeing only one clue more often than did a combined group of subjects without frontal-lobe damage, but this guessing-score was also related to extent of right temporal-lobe removal. Patients with left temporal-lobe or left frontal-lobe lesions had difficulty solving the verbal clues, occasionally failing to recognize that a response generated in the context of one clue satisfied all the clues.

Adolescent↗

Characterisation of the delta-opioid receptor on the hamster vas deferens.

It has recently been reported that the hamster vas deferens contains only delta-opioid receptors. We have demonstrated that three delta-receptor agonists [D-Ala2, D-Leu5]enkephalin (DADLE), [D-Pen2, D-Pen5]enkephalin (DPDPE) and [D-Thr2, Leu5, Thr6] enkephalin (DTLET) appear to mediate their effects via the delta-receptor since they are readily reversed by the selective delta-receptor antagonist ICI 174864. In addition, a number of classical mu and k receptor compounds were devoid of activity in this preparation. However it was observed that some compounds such as etorphine and MR 2034 reported to possess delta-receptor affinity in other assay systems were weak or inactive on the hamster vas deferens.

Animals↗

Neuropsychological assessment of substance abusers: review and recommendations.

Neuropsychological assessment of substance abusers frequently proves useful for the evaluation of those aspects of cognitive functioning that may be relevant for optimal therapeutic management and treatment planning. Research has demonstrated the presence of neuropsychological impairment in chronic abusers of CNS depressants, including alcohol, as well as opiates and possibly cocaine, especially when such substances are combined in a polydrug pattern of abuse. Clinical neuropsychological evaluation of individual substance abusers should take into account the various personal, demographic and neuromedical background variables that can affect cognitive functioning. Efforts should be made to distinguish between acute drug effects and more longterm stable deficits that may not become apparent for some time. Neuropsychological referrals should be made, and measures selected to answer particular questions about neurocognitive functioning that are relevant to treatment and eventual overall adjustment. A neuropsychological review of systems is likely to show a pattern of impairment in substance abusers that involves the integration of different cognitive functions for effective problem solving. Strongly focal or lateralized deficit patterns are less likely to be the result of drug abuse alone, and should prompt the appropriate neuromedical follow-up.

Adolescent↗

Breast reduction utilizing the maximally vascularized central breast pedicle.

Experience using a maximally vascularized central breast pedicle to nourish the nipple-areola is presented. The pedicle is designed to incorporate vascular contributions from the lateral thoracic artery, intercostal perforators, internal mammary perforators, and thoracoacromial artery by means of the pectoralis major muscle. The basic technique is as follows: First, the areola is incised and 2-cm-thick skin and subcutaneous flaps are dissected medially, laterally, and superiorly, freeing the entire central breast mound. Second, the breast is reduced in a "Christmas tree" manner, being careful not to narrow the base of the pedicle. Third, excess skin and subcutaneous tissue is excised inferomedially and laterally and the nipple is inset into proper locations. The advantages of this technique are (1) large and small reductions can be done, (2) pedicle length does not appear to be a problem, and (3) the central mound gives the forward projection needed for good contour and good aesthetic results. Sixty-five patients with follow-up to 4 years are presented.

Adult↗

Bupropion in the long-term treatment of cyclic mood disorders: mood stabilizing effects.

The effects of bupropion HCl in treating 11 patients with bipolar or schizoaffective disorder were examined in an open trial. Most patients had been intolerant of or showed minimal to moderate improvement on lithium, neuroleptics, antidepressants, or a combination of these drugs. All patients were maintained on bupropion alone or bupropion in combination with low-dose neuroleptics or anxiolytics for 1 year or more, with little or no relapse and few side effects.

Adult↗

Sherlock Holmes' methods of deductive reasoning applied to medical diagnostics.

Having patterned the character of Sherlock Holmes after one of his professors, Sir Arthur Conan Doyle, himself a physician, incorporated many of the didactic qualities of the 19th century medical diagnostician into the character of Holmes. In this paper I explore Holmes's techniques of deductive reasoning and their basis in 19th and 20th century medical diagnostics.

Diagnosis↗

Production of monoclonal antibodies in culture.

Factors that affected the production of monoclonal antibodies by a mouse-mouse hybridoma cell line, propagated in vitro in stirred vessels, were investigated. The purpose of the research was to estimate the efficiency of this system for large scale production of monoclonal antibodies. The antibody produced by these hybridoma cells was an IgG2a, specific for a surface antigen on Rhizobium japonicum NR-7 cells. Antibody content in the culture supernatant was determined by a radial-immunodiffusion assay using rabbit anti-mouse IgG antibodies in the immobile phase and mouse IgG (the monoclonal antibody) as the antigen in the mobile phase. This method was found to be more reproducible and reliable compared with an ELISA method. Cells were adapted to grow in an inexpensive, low protein content medium based on Dulbecco's Modified Eagle Medium (DMEM) supplemented with 0.25% Primatone RL, 0.01% Pluronic polyol F-68 and fetal bovine serum as low as 1%. Doubling time for the cells averaged 24 hrs, and final yields reached 2 X 10(6) cells per ml. The hybridoma cells were grown in the newly developed medium in 3 liter fermentors. Monoclonal antibody was produced during the early growth phase (3 days), however, most of the antibody was produced during a later growth phase (3-10 days) when 30 to 90% of the cells were dead. Final antibody yields were estimated to be 100-200 micrograms/ml. A low level of dissolved oxygen (25% air saturation) in the culture was found to increase the amount of antibody produced as compared with cells propagated at 60% air saturation (the optimal level for cell propagation) since the cells were kept alive for longer periods at the lower dissolved oxygen concentration. Using a fed-batch propagation method we were able to keep cells alive for long periods (up to 1 month) at a concentration of about 1 X 10(6) cells per ml, and thus to increase further monoclonal antibody production. Yields of 300-400 micrograms/ml were obtained.

Animals↗

Acute tubular necrosis after inhalation exposure to methylene chloride. Report of a case.

Nephrotoxic reaction occurred after inhalation exposure to methylene chloride. This exposure is associated with acute renal failure, myoglobinuria, hypocomplementemia, and liver enzyme elevations. Pathologic specimens, both light and electron microscopic, demonstrate renal tubular damage. We conclude that methylene chloride may have potential as both a hepatotoxic and nephrotoxic agent when inhaled at high concentrations over an extended period of time.

Acute Kidney Injury↗

Ingestion of egg raises plasma low density lipoproteins in free-living subjects.

In addition to their usual diet, 17 lactovegetarian college students consumed 400 kcal of test foods per day containing one extra-large egg for three weeks and similar isocaloric eggless foods for an additional three weeks in a randomised double-blind crossover trial. Ingestion of the egg increased dietary cholesterol from 97 to 418 mg per day. Mean plasma low density lipoprotein (LDL) cholesterol was 12% higher (p = 0.005) and mean plasma apolipoprotein B was 9% higher (p = 0.007) when eggs were being consumed than during the eggless period. Mean plasma high density lipoprotein cholesterol, apolipoproteins A-I and A-II, very low density lipoprotein cholesterol, and total triglycerides did not change significantly. Thus, ingestion of egg seems selectively to raise cholesterol and protein in LDL particles in the plasma of free-living normal people. Plasma LDL may be more sensitive to cholesterol at low intakes than at moderate to high intakes.

Adolescent↗

The molecular structures and interactions of bovine and human gamma-crystallins.

Knowledge of the three-dimensional structure of bovine gamma II-crystallin has provided the basis for building molecular models using computer graphics of two human gamma-crystallins, the sequences of which have recently been determined. The tertiary structures of these gamma-crystallins are predicted to be highly conserved. They have extensive networks of interacting charges on their surfaces, which may contribute to their thermodynamic stability and partially define the degree of water retention in the lens. The human crystallins appear to be more hydrophobic than the bovine molecule. All have arrangements of cysteine thiols which may be important as electron sinks and reserve redox potential in the normal lens but which may contribute to protein aggregation in cataract.

Amino Acid Sequence↗