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Biomedical subjects

J Muller

Publications and source records attributed to J Muller.

At least 73 records · Page 4Linked to original sources

[Witches' ointments and love-potions: a contribution to the cultural history of nightshades].

The nightshades (solanaceae) were used as intoxicants since the ancient civilizations and are still in use today. Their alkaloids, atropine and scopolamine, were the major active substances of the ointments of witches, of medieval "anaesthetics", and of modern poisons for murder. In a medium dose-range the predominant symptoms are hallucinations and illusions. This explains the use of nightshades in fortune-telling and religious rituals. In higher doses the alkaloids produce coma and apnea. Scopolamine enjoyed a particular popularity as a poison for murder. In the 19th century the nightshade alkaloids were also in clinical use. This article focusses on the medical history of the psychosis due to intoxication with solanaceae.

Alkaloids↗

[Not Available].

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Aphrodisiacs↗

Assessment of the total artificial heart (TAH) pulsatility: the coalition between pulsatility and ejection time in TAH in vitro study.

There are many types of pulsatile pumps with various pulsatile flow waveforms. These authors perceived that pulsatility was an important characteristic for a pulsatile pump. The effect of a total artificial heart (TAH) was estimated using a pulse power index (PPI) in a mock loop. This method helps in the development of a standard criterion for measurement of a pulsatile waveform. The pulsatility of the TAH was found to be useful as a physiological control method. At first the relationship between ejection time and dp/dt was examined and then the relation between PPI, ejection time and preload. The dp/dt was unchanged by ejection time and PPI was unchanged by preload. However, PPI was changed by the ejection time. There was an inverse correlation between ejection time and PPI (r = 0.80). The PPI at ejection time 150 msec was significantly higher than the other ejection time's PPI. These results suggest that the TAH should be driven with an ejection time of 150 msec, because this ejection time has a high pulsatility and can obtain a higher flow. This happens without increasing the dp/dt and this ejection time can be preplanned, because a fixed ejection time improves the durability of the actuator.

Biomechanical Phenomena↗

Emotional memory and psychopathology.

A leading model for studying how the brain forms memories about unpleasant experiences is fear conditioning. A cumulative body of work has identified major components of the neural system mediating this form of learning. The pathways involve transmission of sensory information from processing areas in the thalamus and cortex to the amygdala. The amygdala's lateral nucleus receives and integrates the sensory inputs from the thalamic and cortical areas, and the central nucleus provides the interface with motor systems controlling specific fear responses in various modalities (behavioural, autonomic, endocrine). Internal connections within the amygdala allow the lateral and central nuclei to communicate. Recent studies have begun to identify some sites of plasticity in the circuitry and the cellular mechanisms involved in fear conditioning. Through studies of fear conditioning, our understanding of emotional memory is being taken to the level of cells and synapses in the brain. Advances in understanding emotional memory hold out the possibility that emotional disorders may be better defined and treatment improved.

Animals↗

Modulation of murine melanocyte function in vitro by agouti signal protein.

Molecular and biochemical mechanisms that switch melanocytes between the production of eumelanin or pheomelanin involve the opposing action of two intercellular signaling molecules, alpha-melanocyte-stimulating hormone (MSH) and agouti signal protein (ASP). In this study, we have characterized the physiological effects of ASP on eumelanogenic melanocytes in culture. Following exposure of black melan-a murine melanocytes to purified recombinant ASP in vitro, pigmentation was markedly inhibited and the production of eumelanosomes was decreased significantly. Melanosomes that were produced became pheomelanosome-like in structure, and chemical analysis showed that eumelanin production was significantly decreased. Melanocytes treated with ASP also exhibited time- and dose-dependent decreases in melanogenic gene expression, including those encoding tyrosinase and tyrosinase-related proteins 1 and 2. Conversely, melanocytes exposed to MSH exhibited an increase in tyrosinase gene expression and function. Simultaneous addition of ASP and MSH at approximately equimolar concentrations produced responses similar to those elicited by the hormone alone. These results demonstrate that eumelanogenic melanocytes can be induced in culture by ASP to exhibit features characteristic of pheomelanogenesis in vivo. Our data are consistent with the hypothesis that the effects of ASP on melanocytes are not mediated solely by inhibition of MSH binding to its receptor, and provide a cell culture model to identify novel factors whose presence is required for pheomelanogenesis.

Agouti Signaling Protein↗

Spheroid body myopathy revisited.

Having reported spheroid body myopathy from Indiana (IN) inherited in an autosomal-dominant fashion several years ago, we now describe additional findings from the Oregon branch--briefly recorded earlier--and confirm earlier studies in another clinically affected IN member of this kinship demonstrating identical spheroid bodies within the myopathic muscle specimens. The spheroid bodies also contained increased amounts of desmin, alpha-B crystallin, and ubiquitin within muscle fibers. Our studies now have established that spheroid body myopathy is a member of the growing family of desminopathic neuromuscular conditions.

Adult↗

Functional inactivation of the lateral and basal nuclei of the amygdala by muscimol infusion prevents fear conditioning to an explicit conditioned stimulus and to contextual stimuli.

The GABAa agonist, muscimol (0.5 microgram in 0.5 microliter saline), or vehicle was infused into the lateral and basal amygdala nuclei prior to fear conditioning or testing in rats. Rats given muscimol before conditioning and saline before testing showed much less freezing to the conditioned stimulus (CS) and the context than did controls given saline before training and testing. Rats given saline before training and muscimol prior to testing also showed low levels of freezing to the CS and the context. In follow-up procedures, rats with acquisition initially blocked by pretraining muscimol infusions froze in a manner similar to that of controls when retrained and retested with saline infusions. Rats trained with saline but tested with muscimol presumably became conditioned but could express the learning. When retested with saline, they froze in the same manner as controls. Thus, activity in the lateral and basal amygdala appears to play an essential role in the acquisition and expression of fear conditioning.

Amygdala↗

A specific cell surface antigen of Streptococcus gordonii is associated with bacterial hemagglutination and adhesion to alpha2-3-linked sialic acid-containing receptors.

A Ca2+-independent lectin activity for alpha2-3-linked sialic acid-containing receptors is associated with Streptococcus gordonii DL1 (Challis) but not with a spontaneous mutant, strain D102, that specifically lacks hemagglutinating activity. Comparison of crossed-immunoelectrophoresis patterns of parent and mutant sonicated cell extracts identified a unique antigen (Hs antigen) in the parent cell extract that was purified by DEAE Sephacel column chromatography and by a wheat germ agglutinin (WGA) lectin affinity column. The purified antigen formed a single arc in crossed immunoelectrophoresis with anti-DL1 serum and migrated as a diffuse band above the 200-kDa marker in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Immunoelectron microscopy with specific anti-Hs antibody revealed labeling of structures in the fibrillar layer of strain DL1 and no labeling of fibrillar structures on strain D102. Rabbit anti-DL1 serum and anti-Hs Fab inhibited the hemagglutinating activity of strain DL1, and the inhibition was specifically neutralized by purified Hs antigen. Anti-Hs Fab did not inhibit the hemagglutinating activities of several heterologous S. gordonii strains; however, these bacteria were agglutinated by anti-Hs immunoglobulin G and also by WGA. In contrast, two S. gordonii strains that lacked hemagglutinating activity did not react with anti-Hs antibody or with WGA. These findings associate the sialic acid-binding lectin activity of S. gordonii DL1 with a specific fibrillar antigen, which is composed of protein and WGA reactive carbohydrate, and indicate that cross-reactive antigens occur on other strains of this species that possess hemagglutinating activity.

Animals↗

[A rare breast tumor: mammary fibromatosis. Two case reports and a review of the literature].

Aggressive fibromatosis of the breast is an uncommon benign disease. The clinical and X-Ray findings can simulate breast cancer. The diagnosis relies on histology. The typical feature of this disease is a locally aggressive but non metastasizing lesion with high recurrence rate. Treatment consists in wide excision. The role of radiation and drug therapy including antiestrogens has not been clearly established. Colonoscopy is indicated to research for an association with Gardner syndrome.

Adult↗

Inhibition of melanoma-associated antigen expression and ecotropic retrovirus production in B16BL6 melanoma cells transfected with major histocompatibility complex class I genes.

We have previously reported that expression of the melanoma-associated antigen (MAA) recognized by MM2-9B6 monoclonal antibody in B16 melanoma was closely associated with C-type ecotropic retroviral particle production. Our present data show that this MAA is encoded by the env gene of an ecotropic retrovirus produced by B16 melanoma cells. Transfection of H-2Kb or H-2Kd genes into two individual clones isolated from B16BL6 melanoma, BL6-8 (H-2Kb-, H-2Db+) and BL6-2 (H-2Kb-, H-2Db-), resulted in a loss of MAA expression. Electron immunohistochemical analysis of melanoma cells and reverse transcriptase assay revealed that the loss of MAA expression in the H-2K gene-transfected cells paralleled the elimination of retroviral particles. In contrast, expression of the endogenous H-2Db gene or transfection with the H-2Dd or H-2Ld gene had no effect on MAA expression or retrovirus production. Northern blot analysis showed equivalent retroviral messages in retrovirus-producing and -nonproducing BL6 melanoma clones. Southern blot analysis revealed that H-2Kb-negative BL6 melanoma cells contain at least four different ecotropic retroviruses with different insertion sites that somatically emerged during malignant transformation or progression. Restriction enzyme analysis showed various changes in proviral DNAs from the H-2Kb- and H2Kd-transfected cells that failed to produce retroviral particles. The observed alterations in the patterns of PstI- and HindIII-digested proviral DNA were found to be due to the appearance of PstI and loss of HindIII restriction sites in the pol region as a result of several nucleotide substitutions. Thus, BL6 melanoma cells produce melanoma-specific ecotropic murine leukemia viruses that encode serologically detectable cell surface MAA. The transfection of BL6 melanoma cells with H-2Kb or H2Kd genes but not H-2Dd or H-2Ld genes resulted in a loss of MAA expression that was attributed to the changes in proviral DNA and loss of melanoma-specific ecotropic retrovirus particle production.

Animals↗

Identification of a heparin-binding hemagglutinin present in mycobacteria.

Adherence to mammalian host tissues is an important virulence trait in microbial pathogenesis, yet little is known about the adherence mechanisms of mycobacteria. Here, we show that binding of mycobacteria to epithelial cells but not to macrophages can be specifically inhibited by sulfated carbohydrates. Using heparin-Sepharose chromatography, a 28-kD heparin-binding protein was purified from culture supernatants and cell extracts of Mycobacterium bovis and Mycobacterium tuberculosis. This protein, designated heparin-binding hemagglutinin (HBHA), promotes the agglutination of rabbit erythrocytes, which is specifically inhibited by sulfated carbohydrates. HBHA also induce mycobacterial aggregation, suggesting that it can mediate bacteria-bacteria interactions as well. Hemagglutination, mycobacterial aggregation, as well as attachment to epithelial cells are specifically inhibited in the presence of anti-HBHA antibodies. Immunoelectron microscopy using anti-HBHA monoclonal antibodies revealed that the protein is surface exposed, consistent with a role in adherence. Immunoblot analyses using antigen-specific antibodies indicated that HBHA is different from the fibronectin-binding proteins of the antigen 85 complex and p55, and comparison of the NH2-terminal amino acid sequence of purified HBHA with the protein sequence data bases did not reveal any significant similarity with other known proteins. Sera from tuberculosis patients but not from healthy individuals were found to recognize HBHA, indicating its immunogenicity in humans during mycobacterial infections. Identification of putative mycobacterial adhesins, such as the one described in this report, may provide the basis for the development of new therapeutic and prophylactic strategies against mycobacterial diseases.

Animals↗

Target-induced death by apoptosis in human lymphokine-activated natural killer cells.

Activated human natural killer (NK) cells undergo rapid apoptotic cell death after ligand binding to the Fc receptor (CD16). We examined whether human NK cells die after engagement in cytolytic functions. Peripheral blood NK cells, with and without prior activation in vitro with interleukin-2 (IL-2), were tested for the occurrence of cell death after incubation with K562, the prototype NK-sensitive target cell. A proportion (15.2%) of NK cells that were stimulated for 3 days with IL-2 and then incubated for 4 hours with K562 cells showed rapid cell death, but NK cells not stimulated with IL-2 did not. This cell death was found to involve nuclear condensation and fragmentation and DNA cleavage, all of which are characteristic of apoptosis. These data indicate that a proportion of activated human NK cells undergo apoptosis as they engage in target cell lysis. Target-induced NK cell death may represent an important mechanism for regulation of inflammatory processes involving NK cells.

Apoptosis↗

Characterization of a melanosomal transport system in murine melanocytes mediating entry of the melanogenic substrate tyrosine.

In this study, we identify a transport system for tyrosine, the initial precursor of melanin synthesis, in the melanosomes of murine melanocytes. Melanosomes preloaded with tyrosine demonstrated countertransport of 10 microM [3H]tyrosine, indicating carrier-mediated transport. Melanosomal tyrosine transport was saturable, with an apparent Km for tyrosine transport of 54 microM and a maximal velocity of 15 pmol of tyrosine/unit of hexosaminidase/min. Transport was temperature-dependent (Ea = 7.5 kcal/mol) and showed stereospecificity for the l-isomer of tyrosine. Aromatic, neutral hydrophobic compounds (such as tryptophan and phenylalanine), as well as the small, bulky neutral amino acids (such as leucine, isoleucine, and methionine) competed for tyrosine transport. Tyrosine transport was inhibited by the classical system L analogue, 2-aminobicyclo[2.2.1]heptane-2-carboxylic acid and by monoiodotyrosine, but not by cystine, lysine, glutamic acid, or 2-(methylamino)-isobutyric acid. Tyrosine transport showed no dependence on Na+ or K+, and did not require an acidic environment or the availability of free thiols. These results demonstrate the existence of a neutral amino acid carrier in murine melanocyte melanosomes which resembles the rat thyroid FRTL-5 lysosomal system h. This transport system is critical to the function of the melanosome since tyrosine is the essential substrate required for the synthesis of the pigment melanin.

Amino Acids↗

Reproducibility of videokeratographic digital subtraction maps after excimer laser photorefractive keratectomy.

BACKGROUND: Digital subtraction photokeratography can best identify topographic changes after excimer laser photorefractive keratectomy (PRK). To evaluate the reproducibility of these topographic maps, the authors used a topographic modeling system to generate multiple subtraction maps from different combinations of technically acceptable preoperative and postoperative maps for eyes that underwent PRK. The assigned patterns for each patient then were evaluated for consistency. METHODS: Seven hundred twenty-two individual subtraction maps were generated for 64 eyes that underwent PRK. A mean of 11.3 maps were generated for each eye. The topography of each map was individually classified as normal, central island, peninsula, or asymmetric. All maps within a set (consisting of examinations for 1 patient at a single postoperative interval) then were examined as a unit to determine the overall topographic classification for that set of maps. Each set in which each constituent map had the same topographic assignment as the set was considered "nonvariant," whereas those sets in which one or more individual subtraction maps had different topographic assignments were considered "variant." RESULTS: Of the 64 sets, 33 (52%) were variant and 31 (48%) were nonvariant. CONCLUSIONS: Any one subtraction map produced by the topographic modeling system may not be a reliable indicator of the excimer effect.

Cornea↗

Phenotypic changes and loss of melanoma-specific endogenous C-type retroviruses in BL6 melanoma cells transfected with the H-2Kb gene.

The murine B16 melanoma and its sublines are low or totally deficient in expression of the H-2Kb class I major histocompatibility complex (MHC) gene. In clones derived from the B16F10BL6 subline, expression of the transfected or endogenous H-2Kb gene resulted in alterations of various phenotypic properties of these melanoma cells, among which was the loss of melanoma-associated antigen (MAA) expression. Because our previous immunoelectron microscopy studies showed that MAA was associated with a C-type ecotropic retrovirus specific for melanomas of C57BL/6 origin, we examined the effect of class I H-2Kb as well as class II H-2IAk gene expression on retrovirus production in subclones of BL6 melanoma cells. Here we have shown that expression of the transfected or endogenous H-2Kb gene resulted in the loss of production of budding, MAA-specific, C-type retrovirus particles. Northern blot analysis demonstrated expression of ecotropic retroviral mRNAs in both particle-producing and non-producing BL6 melanoma clones. Southern blot analysis of high-molecular-weight cellular DNAs using an ecotropic env-specific DNA probe indicated that the parental BL6-8 melanoma cells contained the C57BL/6 endogenous ecotropic MuLV (Emv-2) and at least three additional, novel ecotropic retroviral DNAs. Restriction enzyme analysis of the proviral DNA suggests that the loss of retrovirus production in the H-2Kb-expressing melanoma clones is the result of multiple rearrangements in the novel proviral DNAs. Thus, phenotypic changes observed in the H-2Kb gene-transfected BL6 melanoma cells were associated with loss of endogenous melanoma-specific ecotropic retrovirus production.

Animals↗

Loss of intracisternal A-type retroviral particles in BL6 melanoma cells transfected with MHC class I genes.

Electron microscopy of B16 melanoma and its sublines revealed that these cells produce numerous intracisternal A-type retroviral particles (IAPs). To identify and sequence the melanoma-associated IAPs of C57BL/6 mice, a cDNA library was constructed from IAP-producing BL6.8 cell RNA and screened using MIA14 IAP DNA as a probe. A 6-8 kb mRNA was identified that represents the full-length message for a new subfamily of IAP, termed MeIAP. The melanoma-derived IAP cDNA showed high similarity to MIA14 with major differences in the LTR. A nine base motif of the R region showed that this IAP differs from other previously sequenced IAPs. Analysis of the individual clones from BL6 melanoma revealed that IAPs were produced only in the clones that failed to express H-2Kb molecules. No IAPs were found in the melanoma clones that expressed endogenous H-2Kb. To analyse further the association between MHC class I genes and IAP production, the H-2Kb-negative clones of BL6 melanoma were transfected with various H-2 genes. Transfection of the H-2Kb or H-2Kd, but not H-2Dd or H-2Ld genes resulted in the elimination of IAPs. Northern blot analysis revealed that loss of IAPs in the H-2K gene-transfected BL6 melanoma cells was due to lack of IAP transcripts. Elimination of IAPs in the H-2Kb-positive BL6 melanoma cells was also accompanied by alterations in expression of various cellular genes and changes of their phenotypic properties.

Animals↗

Excimer laser phototherapeutic keratectomy.

The objective of this study was to evaluate the safety and efficacy of excimer laser phototherapeutic keratectomy in the treatment of anterior corneal pathology in a group of 45 patients. Forty-five patients were treated with the Visx Excimer Laser System for various types of anterior corneal pathology including postinflammatory and postsurgical scars, stromal dystrophies, surface degenerations, pterygia, and epithelial basement membrane dystrophies. Excimer laser phototherapeutic keratectomy (PTK) has been used to treat anteriorly located corneal pathology since 1990; however, most published studies thus far have been composed of small numbers of patients with limited duration of follow-up. The present study is one of the largest domestic PTK series with one of the longest mean follow-ups. Forty patients were followed for > or = 6 months with a mean follow-up of just less than 1 year (11.25 months). Statistically significant improvement was achieved in irritative symptoms and visual acuity. Best spectacle corrected visual acuity (BSCVA) improved a mean of two lines (range, -3 to +7) with 20/50 or better BSCVA present in 29% of patients preoperatively improving to 60% postoperatively. Refractive changes were unpredictable. Mean spherical equivalent underwent a hyperopic shift of 2.81 diopters (D). Fifty percent of patients developed > or = 1 D of refractive astigmatism. Complications occurred in six patients with loss of BSCVA, three patients with topical corticosteroid associated increased intraocular pressure, and three patients with recurrent herpes simplex stromal keratouveitis. Excimer laser phototherapeutic keratectomy can consistently achieve a modest to a more substantial improvement in irritative ocular symptoms and/or visual acuity with significant potential for adverse results that appear to be less severe than the complications associated with alternative treatment by keratoplasty.

Adolescent↗