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Biomedical subjects

C M Anderson

Publications and source records attributed to C M Anderson.

At least 55 records · Page 3Linked to original sources
PubMed1999

Glutamate induces rapid upregulation of astrocyte glutamate transport and cell-surface expression of GLAST.

Glutamate transporters clear glutamate from the extracellular space by high-affinity binding and uptake. Factors that regulate glutamate transporter expression and activity can thereby influence excitatory neurotransmission. Transporter function in GABAergic and other systems has been shown to be regulated by transporter substrates. Here, glutamate regulation of glutamate transport was studied using primary murine astrocyte cultures that express the GLAST (EAAT1) and GLT-1 (EAAT2) transporter subtypes. Glutamate was found to stimulate glutamate transport capacity (V(max)) in a dose- and time-dependent manner. The maximal increase was 100%, with an ED(50) of 40 microM glutamate and with onset beginning approximately 15 min after onset of glutamate exposure. The uptake stimulation was reproduced by D-aspartate, which is also a transporter substrate, but not by nontransported glutamate receptor agonists. Moreover, glutamate incubation did not stimulate transport when performed in a sodium-free medium, suggesting that the stimulatory effect of glutamate is triggered by increased transporter activity rather than receptor activation. Treatment with the actin-disrupting agents cytochalasin B or cytochalasin D prevented the glutamate-induced increase in glutamate uptake. Biotinylation labeling of membrane surface proteins showed that glutamate incubation produced an increase in GLAST expression at the astrocyte cell surface. These results suggest that cell-surface expression of GLAST can be rapidly regulated by glutamate through a process triggered by GLAST activity and involving the actin cytoskeleton. This feedback loop provides a mechanism by which changes in extracellular glutamate concentrations could rapidly modulate astrocyte glutamate transport capacity.

ATP-Binding Cassette Transporters↗
PubMed1999

Molecular analysis of the pheromone and pheromone receptor genes of Ustilago hordei.

Cell-cell signaling is an integral part of the sexual and disease cycles of the smut fungi, which must mate to be pathogenic. This study reports the cloning and characterization of the pheromone genes Uhmfa1 and Uhmfa2 from MAT-1 and MAT-2 mating types of U. hordei, respectively, and the pheromone receptor gene Uhpra2 from MAT-2 cells. Similar to other fungal pheromone genes, Uhmfa1 and Uhmfa2 encode precursor peptides. Uhpra2 encodes a protein with sequence similarity to the 7-transmembrane class of G-protein coupled receptors. Deletion of Uhmfa1 and Uhpra1, and their subsequent replacement, confirmed the role of these genes in initiation of the sexual cycle. Uhmfa1 and Uhmfa2 were differentially expressed in various cell types and when opposite mating-type cells were grown together. The predicted mature pheromones of each mating type were synthesized, and each specifically induced conjugation tube formation in cells of the opposite mating type.

Amino Acid Sequence↗
PubMed1999

Identification of residues in the CH2/CH3 domain interface of IgA essential for interaction with the human fcalpha receptor (FcalphaR) CD89.

Cellular receptors for IgA (FcalphaR) mediate important protective functions. An extensive panel of site-directed mutant IgAs was used to identify IgA residues critical for FcalphaR (CD89) binding and triggering. Although a tailpiece-deleted IgA1 was able to bind and trigger CD89, antibodies featuring CH3 domain exchanges between human IgA1 and IgG1 could not, indicating that both domains but not the tailpiece are required for FcalphaR recognition. To further investigate the role of the interdomain region, numerous IgA1s, each with a point substitution in either of two interdomain loops (Leu-257-Gly-259 in Calpha2; Pro-440-Phe-443 in Calpha3), were generated. With only one exception (G259R), substitutions produced either ablation (L257R, P440A, A442R, F443R) or marked reduction (P440R) in CD89 binding and triggering. Further support for involvement of these interdomain loops was provided by interspecies comparisons of IgA. Thus a human IgA1 mutant, LA441-442MN, which mimicked the mouse IgA loop sequence through substitution of two adjacent residues in the Calpha3 loop, was found, like mouse IgA, not to bind CD89. In contrast, bovine IgA1, identical to human IgA1 within these interdomain loops despite numerous differences elsewhere in the Fc region, did bind CD89. We have thus identified motifs in the interdomain region of IgA Fc critical for FcalphaR binding and triggering, significantly enhancing present understanding of the molecular basis of the IgA-FcalphaR interaction.

Amino Acid Sequence↗
PubMed1999

Distribution of mRNA encoding a nitrobenzylthioinosine-insensitive nucleoside transporter (ENT2) in rat brain.

Nucleoside transporters may play a role in regulating levels of extracellular adenosine and adenosine receptor activity. Two members of the equilibrative nucleoside transporter family have recently been cloned. ENT1 is potently inhibited by nitrobenzylthioinosine (NBMPR) (K(i) approximately 1 nM) and was previously found to have a wide distribution in rat and human brain. ENT2 is insensitive to inhibition by NBMPR at low nanomolar concentrations and there is limited information describing its distribution in rat brain. The present study used RT-PCR, northern blot and in situ hybridization and detected rENT2 transcript in several brain regions including hippocampus, cortex, striatum and cerebellum. Our results indicate a wide cellular and regional distribution for ENT2 in rat brain, similar to ENT1, indicating that control of adenosine levels in brain is achieved by multiple transport processes.

Animals↗
PubMed1999

Infant temporal contrast sensitivity functions (tCSFs) mature earlier for luminance than for chromatic stimuli: evidence for precocious magnocellular development?

In order to investigate the development of luminance and chromatic temporal contrast sensitivity functions (tCSFs), we obtained chromatic and luminance contrast thresholds from individual 3- and 4-month old infants, and compared them to previously obtained functions in adults. Stimuli were moving sinusoidal gratings of 0.27 cyc/deg, presented at one of five temporal frequencies: 1.0, 2.1, 4.2, 9.4 or 19 Hz (corresponding speeds: 3.8, 7.7, 15, 34, 69 deg/s). Previous studies, including our own, have shown that adult tCSFs are bandpass for luminance stimuli (peaking at 5-10 Hz), yet lowpass for chromatic stimuli (sensitivity falling at > 2 Hz), and that the two functions cross one another near 4-5 Hz when plotted in terms of cone contrast. In the present study, we find that the shapes and peaks of the luminance tCSF in both 3- and 4-months-olds appear quite similar to those of adults. By contrast, chromatic tCSFs in infants are markedly different from those of adults. In agreement with our earlier report (Dobkins, K. R., Lia, B., & Teller, D. Y. (1997). Vision Research, 37(19), 2699-2716), the chromatic function in 3-month-olds is rather flat, lacking the sharp high temporal frequency fall-off characteristic of the adult function. In addition, the luminance tCSF in 3-month-olds is elevated above the chromatic tCSF, and the two functions do not exhibit an adult-like cross-over within the range of temporal frequencies tested. By 4 months of age, substantial development of chromatic contrast sensitivity takes place at the lowest temporal frequencies. Although still immature, the 4-month-old chromatic tCSF has begun to adopt a more adult-like shape. In addition, similar to adults, luminance and chromatic tCSFs in 4-month-olds cross one another near 5 Hz. In adults, magnocellular (M) and parvocellular (P) pathways are thought to underlie the bandpass luminance and lowpass chromatic tCSF, respectively (e.g. Lee, B. B., Pokorny, J., Smith, V. C., Martin, P. R., & Valberg, A. (1990). Journal of the Optical Society of America (a), 7(12), 2223-2236). Based on this correspondence between psychophysical and neural responses in adults, our results suggest that the relatively slow development of the chromatic tCSF in infants may reflect immature chromatic responses in the P pathway and/or reliance on chromatic responses originating in the M pathway.

Adult↗
PubMed1999

Distribution of equilibrative, nitrobenzylthioinosine-sensitive nucleoside transporters (ENT1) in brain.

Nucleoside transport processes may play a role in regulating endogenous levels of the inhibitory neuromodulator adenosine in brain. The cDNAs encoding species homologues of one member of the equilibrative nucleoside transporter (ENT) gene family have recently been isolated from rat (rENT1) and human (hENT1) tissues. The current study used RT-PCR, northern blot, in situ hybridization, and [3H]nitrobenzylthioinosine autoradiography to determine the distribution of mRNA and protein for ENT1 in rat and human brain. Northern blot analysis indicated that hENT1 mRNA is widely distributed in adult human brain. 35S-labeled sense and antisense riboprobes, transcribed from a 153-bp segment of rENT1, were hybridized to fresh frozen coronal sections from adult rat brain and revealed widespread rENT1 mRNA in pyramidal neurons of the hippocampus, granule neurons of the dentate gyrus, Purkinje and granule neurons of the cerebellum, and cortical and striatal neurons. Regional localization in rat brain was confirmed by RT-PCR. Thus, ENT1 mRNA has a wide cellular and regional distribution in brain, indicating that this nucleoside transporter subtype may be important in regulating intra- and extracellular levels of adenosine in brain.

Adenosine↗
PubMed1999

Perceived understanding and self-disclosure in the stepparent-stepchild relationship.

The relationship between self-disclosure and perceived understanding in the stepparent-stepchild relationship was investigated. Stepchildren (N = 165) completed a questionnaire about their communication with their stepparents. Participants reported on their self-disclosure (intentionality, amount, positiveness, depth, and honesty) and their feelings of being understood by their stepparents. The results showed that self-disclosure was positively related to perceived understanding. This was especially true for the relationship between honesty of self-disclosure and perceived understanding. Analyses involving gender of the individuals in the stepchild-stepparent dyad showed several differences. The relationship between self-disclosure and perceived understanding was more significant for stepdaughters than for stepsons.

Adoption↗
PubMed1999

Initial treatment engagement in a rural community mental health center.

The charts of patients who received an initial assessment at a rural mental health center were reviewed to identify patient, system, and clinical characteristics that predicted return to the center for at least one treatment visit in the following three months. Among 112 patients, the overall rate of return was 46 percent. Patients who were seen for assessment within one week of their initial request for services were significantly more likely to return, as were those who had lower scores on the Global Assessment of Functioning scale. Patients referred for assessment by agencies of social control were the least likely to return for treatment.

Appointments and Schedules↗
PubMed1999

Primary myeloid leukemia presenting concomitantly with primary multiple myeloma: two cases and an update of the literature.

We report one case of primary acute myelogenous leukemia (AML) and one case of refractory anemia with excess blasts in transformation (RAEB-T) each presenting concomitantly with multiple myeloma, an unusual finding. The twin diagnoses in each patient were confirmed by cytochemical and immunohistochemical studies, and in one of our cases, by ultrastructural, flow cytometric, and molecular studies. The last three methods have not been previously used to document this phenomenon.

Aged↗
PubMed1998

The development of nuchal atonia associated with active (REM) sleep in fetal sheep: presence of recurrent fractal organization.

The behavioral state of active or rapid eye movement sleep (REMS) is dominant during fetal life and may play an important role in brain development. One marker of this state in fetal sheep is neck nuchal muscle atonia (NA). We observed burst within burst NA patterns suggestive of recurrent fractal organization in continuous 13 day in utero recordings of NA during the third trimester. Consistent with fractal renewal processes, the cumulative mean and standard deviation (SD) diverged over this time and the tail of NA distributions fit a stable Lévy law with exponents that remained invariant over the periods of development examined. The Hurst exponent, a measure of self-affine fractals, indicated that long-range correlations among NA intervals were present throughout development. A conserved complex fractal structure is apparent in NA which may help elucidate ambiguities in defining fetal states as well as some unique properties of fetal REMS.

Animals↗
PubMed1998

Breast feeding on campus: personal experiences, beliefs, and attitudes of the university community.

Breast feeding a new baby is a special challenge for college students and university employees. Although success is usually associated with availability of support from the community, little is known about the social context for breast feeding on campus. Personal breast feeding experiences, beliefs about outcomes of breast-feeding and bottle feeding, attitudes toward breast feeding and bottle feeding, and regard for appropriateness of various settings for breast feeding in the campus community were investigated. One hundred seven students, faculty, staff, and administrators at a North Central state university participated in the study. Almost all reported at least one personal breast-feeding experience. Benefits of breast feeding over bottle feeding were acknowledged; however, the university community regarded both feeding methods favorably and saw practical advantages to bottle feeding. Personal spaces, such as infant home or family car, were regarded as more appropriate for breast feeding than public settings. Implications for promotion, support, and protection of breast feeding on campus are discussed.

Adult↗
PubMed1998

Nitric oxide and neopterin levels and clinical response in stage III melanoma patients receiving concurrent biochemotherapy.

The combination of cisplatin-based chemotherapy with interleukin-2 (IL-2) and interferon-alpha (IFN-alpha), referred to as biochemotherapy, has produced overall response rates of greater than 50% in advanced melanoma patients, with durable complete responses in the range of 5-10%. The mechanism of action of biochemotherapy is unknown. Preclinical work suggests synergistic interactions between the cytotoxic agents, especially cisplatin, and the biological agents in killing melanoma cells. Immune effector cells activated by the components of the biochemotherapy may also be involved, as direct cytotoxic effectors and/or as sources of secondary cytokines, which can induce nitric oxide (NO) production in a wide variety of cell types. In addition, high levels of neopterin, a marker of monocyte/macrophage activation, have been found in patients undergoing immunotherapy or biochemotherapy for melanoma. Based on these data, we hypothesized that the degree of elevation of serum NO metabolic products and neopterin during treatment would correlate with the response to biochemotherapy in melanoma patients. Blood samples were obtained before and during preoperative biochemotherapy with cisplatin, vinblastine, dacarbazine, IL-2 and IFN-alpha in 45 melanoma patients with locoregionally advanced disease. NO was measured as nitrite after enzymatic reduction, using the colorimetric assay of Griess, and neopterin was measured by radioimmunoassay. Our results demonstrate a higher day 5 nitrite level (of borderline statistical significance, P = 0.057) in major responders to the therapy than in those who did not achieve a major response, while there was no difference in the elevation in neopterin level during therapy between major and non-major responders. These results suggest that induction of NO during biochemotherapy may be playing a role in the mechanism of action of this therapy, while the role of monocyte/macrophage activation is still in question.

Adult↗