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Biomedical subjects

S Reinsch

Publications and source records attributed to S Reinsch.

18 recordsLinked to original sources
PubMed1999

Rab6 coordinates a novel Golgi to ER retrograde transport pathway in live cells.

We visualized a fluorescent-protein (FP) fusion to Rab6, a Golgi-associated GTPase, in conjunction with fluorescent secretory pathway markers. FP-Rab6 defined highly dynamic transport carriers (TCs) translocating from the Golgi to the cell periphery. FP-Rab6 TCs specifically accumulated a retrograde cargo, the wild-type Shiga toxin B-fragment (STB), during STB transport from the Golgi to the endoplasmic reticulum (ER). FP-Rab6 TCs associated intimately with the ER, and STB entered the ER via specialized peripheral regions that accumulated FP-Rab6. Microinjection of antibodies that block coatomer protein I (COPI) function inhibited trafficking of a KDEL-receptor FP-fusion, but not FP-Rab6. Additionally, markers of COPI-dependent recycling were excluded from FP-Rab6/STB TCs. Overexpression of Rab6:GDP (T27N mutant) using T7 vaccinia inhibited toxicity of Shiga holotoxin, but did not alter STB transport to the Golgi or Golgi morphology. Taken together, our results indicate Rab6 regulates a novel Golgi to ER transport pathway.

Animals↗
PubMed1998

Mechanisms of nuclear positioning.

The mechanisms underlying two types of microtubule-dependent nuclear positioning are discussed. 'MTOC-dependent nuclear positioning' occurs when a nucleus is tightly associated with a microtubule organizing center (MTOC). 'Nuclear tracking along microtubules' is analogous to the motor-driven motility of other organelles and occurs when the nucleus lacks an associated MTOC. These two basic types of microtubule-dependent nuclear positioning may cooperate in many proliferating animal cells to achieve proper nuclear positioning. Microtubule polymerization and dynamics, motor proteins, MAPs and specialized sites such as cortical anchors function to control nuclear movements within cells.

Animals↗
PubMed1997

Movement of nuclei along microtubules in Xenopus egg extracts.

Microtubules are implicated in the movement and positioning of nuclei in many cell types. Nuclei can be moved by forces acting on microtubules nucleated at the spindle pole body, as in fungi [1], or microtubules nucleated at the centrosome, as during migration of the male (sperm) pronucleus towards the centre of the zygote after fertilization [2] [3] [4]. The dramatic movements of the female pronucleus towards the male pronucleus potentially involve another mechanism: movement along the microtubules of the sperm aster towards their slower growing, attached or 'minus' ends [3] [5]. Here, we have reconstituted this last type of nuclear movement in vitro. Synthetic nuclei assembled in cytoplasmic extracts made from interphase Xenopus eggs move along microtubules towards their minus ends. We provide strong experimental evidence that cytoplasmic dynein is the motor for nuclear movement in this in vitro system, and discuss our results in terms of current knowledge of motility of the endoplasmic reticulum.

Animals↗
PubMed1996

Rab11 regulates recycling through the pericentriolar recycling endosome.

Small GTPases of the rab family are crucial elements of the machinery that controls membrane traffic. In the present study, we examined the distribution and function of rab11. Rab11 was shown by confocal immunofluorescence microscopy and EM to colocalize with internalized transferrin in the pericentriolar recycling compartment of CHO and BHK cells. Expression of rab11 mutants that are preferentially in the GTP- or GDP-bound state caused opposite effects on the distribution of transferrin-containing elements; rab11-GTP expression caused accumulation of labeled elements in the perinuclear area of the cell, whereas rab11-GDP caused a dispersion of the transferrin labeling. Functional studies showed that the early steps of uptake and recycling for transferrin were not affected by overexpression of rab11 proteins. However, recycling from the later recycling endosome was inhibited in cells overexpressing the rab11-GDP mutant. Rab5, which regulates early endocytic trafficking, acted before rab11 in the transferrin-recycling pathway as expression of rab5-GTP prevented transport to the rab11-positive recycling endosome. These results suggest a novel role for rab11 in controlling traffic through the recycling endosome.

Animals↗
PubMed1995

The core of the mammalian centriole contains gamma-tubulin.

BACKGROUND: The microtubule network, upon which transport occurs in higher cells, is formed by the polymerization of alpha and beta tubulin. The third major tubulin isoform, gamma tubulin, is believed to serve a role in organizing this network by nucleating microtubule growth on microtubule-organizing centers, such as the centrosome. Research in vitro has shown that gamma tubulin must be restored to stripped centrioles to regenerate the centrosomal functions of duplication and microtubule nucleation. RESULTS: We have re-examined the localization of gamma tubulin in isolated and in situ mammalian centrosomes using a novel immunocytochemical technique that preserves antigenicity and morphology while allowing increased accessibility. As expected, alpha tubulin was localized in cytoplasmic and centriolar barrel microtubules and in the associated pericentriolar material. Foci of gamma tubulin were observed at the periphery of the organized pericentriolar material, as reported previously, often near the termini of microtubules. A further and major location of gamma tubulin was a structure within the proximal end of the centriolar barrel. The distributions were complementary, in that alpha tubulin was excluded from the core of the centriole, and gamma tubulin was excluded from the microtubule barrel. CONCLUSIONS: We have shown that gamma tubulin is localized both in the pericentriolar material and in the core of the mammalian centriole. This result suggests that gamma tubulin has a role in the centriolar duplication process, perhaps as a template for growth of the centriolar microtubules, in addition to its established role in the nucleation of astral microtubules.

Amino Acid Sequence↗
PubMed1994

Orientation of spindle axis and distribution of plasma membrane proteins during cell division in polarized MDCKII cells.

MDCKII cells differentiate into a simple columnar epithelium when grown on a permeable support; the monolayer is polarized for transport and secretion. Individual cells within the monolayer continue to divide at a low rate without disturbing the function of the epithelium as a barrier to solutes. This presents an interesting model for the study of mitosis in a differentiated epithelium which we have investigated by confocal immunofluorescence microscopy. We monitored the distribution of microtubules, centrioles, nucleus, tight junctions, and plasma membrane proteins that are specifically targeted to the apical and basolateral domains. The stable interphase microtubule cytoskeleton was rapidly disassembled at prophase onset and reassembled at cytokinesis. As the interphase microtubules disassembled at prophase, the centrioles moved from their interphase position at the apical membrane to the nucleus and acquired the ability to organize microtubule asters. Orientation of the spindle parallel to the plane of the monolayer occurred between late prophase and metaphase and persisted through cytokinesis. The cleavage furrow formed asymmetrically perpendicular to the plane of the monolayer initiating at the basolateral side and proceeding to the apical domain. The interphase microtubule network reformed after the centrioles migrated from the spindle poles to resume their interphase apical position. Tight junctions (ZO-1), which separate the apical from the basolateral domains, remained assembled throughout all phases of mitosis. E-cadherin and a 58-kD antigen maintained their basolateral plasma membrane distributions, and a 114-kD antigen remained polarized to the apical domain. These proteins were useful for monitoring the changes in shape of the mitotic cells relative to neighboring cells, especially during telophase when the cell shape changes dramatically. We discuss the changes in centriole position during the cell cycle, mechanisms of spindle orientation, and how the maintenance of polarized plasma membrane domains through mitosis may facilitate the rapid reformation of the polarized interphase cytoplasm.

Animals↗
PubMed1992

Attempts to prevent falls and injury: a prospective community study.

At 16 senior centers, we studied the effectiveness of exercise and cognitive-behavioral programs, compared with a discussion control program, in reducing falls and injuries among 230 older adults. After 1 year of the programs, we observed no significant difference in time to first fall. Even though a relatively high percentage (38.6%) suffered at least one fall, only 7.8% of these community-residing elderly required medical attention. Secondary outcome measures such as strength, balance, fear of falling, and perceived health did not significantly change.

Accidental Falls↗
PubMed1991

Adjusting for recall bias with the proportional hazards model.

In studying falling frequency in the elderly, we observed that having subjects keep a diary led to a larger number of falls reported than had been noted in a previous study in the same population. The previous study asked subjects to report any falls in the previous three months. We considered two related explanations for the observation of lower incidence reports with a 3-month recall survey. First, there may have been under-reporting of falls due to recall bias. Second, the less severe falls (which did not result in injuries) may not be reported. We suggest that the proportional hazards model may be used to adjust studies in which recall is used to determine incidence and time to falls.

Accidental Falls↗
PubMed1990

Mapping of the two mouse engrailed-like genes: close linkage of En-1 to dominant hemimelia (Dh) on chromosome 1 and of En-2 to hemimelic extra-toes (Hx) on chromosome 5.

The mouse genome contains two genes, En-1 and En-2, with sequence similarity to the engrailed gene of Drosophila. Using conventional linkage crosses, we have shown that En-1 maps approximately 0.28 cM distal to the dominant hemimelia (Dh) gene on chromosome 1 and that En-2 maps approximately 1.1 cM proximal to the hemimelic extra-toes (Hx) gene on chromosome 5. We have also shown by Northern blot analysis that En-1 transcripts in Dh homozygotes and En-2 transcripts in Hx homozygotes are of normal size and abundance. These data, in conjunction with previously published studies of the patterns of En-1 and En-2 expression in developing mouse embryos, suggest that Dh and Hx are very unlikely to be mutant alleles of En-1 or En-2, respectively. Instead, we suggest that En-1-Dh and En-2-Hx represent paralogous linkage groups that evolved following duplication of a common ancestral chromosome segment.

Animals↗
PubMed1990

Falling among the sensorially impaired elderly.

Recent studies of the healthy elderly indicate that accidental falls account for many lengthy hospital stays and permanent disabilities. An ongoing investigation by our group is examining the contribution of neuromuscular feedback and the possible substitution of visual-perceptual feedback as a major contributor to falling in this population. This combination of decreased weighting of neuromuscular factors and increased weighting of the visual-perceptual factors led to the following hypothesis: Those persons who cannot see should show less change in frequency of falling as they age than sighted cohorts. The deaf, who rely more than others on visual perceptual stimuli, are less likely to fall as they age than the general elderly population, who first begin to rely more heavily on visual stimuli when they age. Thus, the deaf and blind constitute a population whose change in frequency of falls with increased age should differ markedly from change in the frequency of falls among the nonblind and nondeaf segments of the population. Our results support the hypothesis. The blind demonstrated a higher rate of falls than the deaf or nonimpaired population. However, the more elderly blind failed to show the increase in falling demonstrated by the deaf and nonimpaired. If these findings are confirmed in subsequent studies, the nonimpaired and deaf elderly could be trained to focus on visual feedback. The blind may be able to reduce the frequency of falls by enhancing musculoskeletal feedback and strength via exercise.

Accidental Falls↗
PubMed1985

Visual perception dominance of fallers among community-dwelling older adults.

The authors postulated that older adult fallers show a greater tendency than older adult nonfallers to rely more on visual information sources in maintaining upright posture than on kinesthetic and vestibular cues. This paper presents descriptive statistics on 199 older adults living independently in the community. Their visual perception of the vertical and horizontal was analyzed with respect to age, sex, health status, and severity of injury as a result of a fall. The finding of significant impairments for fallers in visual perceptual abilities confirmed a trend previously established by one of the authors (Tobis). When the visual field entailed only misleading or ambiguous cues in the form of a tilted frame, fallers again showed a larger error than nonfallers in establishing the vertical and horizontal. The authors feel that this relatively greater dependence on visual sources may develop in response to impairment of feedback on posture and gait from the kinesthetic and vestibular systems as a result of age and chronic health problems. Errors in visual perception of the vertical and horizontal intercorrelated with age, sex, and a large number of medical problems. However, visual variables were more important in predicting faller status than physical characteristics.

Accidents↗
PubMed1984

Specific efficacy expectations mediate exercise compliance in patients with COPD.

Social learning theory has generated two different approaches for the assessment of expectancies. Bandura argues that expectancies are specific and do not generalize. Therefore, he prefers measures of specific efficacy expectations. Others endorse the role of generalized expectancies measured by locus of control scales. The present study examines specific versus generalized expectancies as mediators of changes in exercise behavior among 60 older adult patients with Chronic Obstructive Pulmonary Disease. The patients were given a prescription to increase exercise and randomly assigned to experimental groups or control groups. All groups received attention but only experimental groups received training to increase their exercise. After 3 months, groups given specific training for compliance with walking significantly increased their activity in comparison to the control group receiving only attention. These changes were mediated by changes in perceived efficacy for walking, with efficacy expectations for other behaviors changing as a function of their similarity to walking. A generalized health locus of control expectancy measure was less clearly associated with behavior change. The results are interpreted as supporting Bandura's version of social theory.

Aged↗
PubMed1981

Midtrimester amniocentesis. Subjective maternal responses.

Studies, through questionnaire and interview, of couples who elect or decline midtrimester amniocentesis demonstrate that both groups cope well with new decisions surrounding this procedure. The pregnancy monitored by genetic amniocentesis does not appear to receive special status as viewed by the parents, nor is the developing fetus placed in a special category during the pregnancy.

Adult↗
PubMedDate not supplied

Parental response to mid-trimester therapeutic abortion following amniocentesis.

This article reports the results of a retrospective study designed to examine the responses of couples to genetic amniocentesis and subsequent therapeutic abortions due to birth defects. Fourteen women and 12 men were interviewed by experienced interviewers using a structured format designed by the authors, and each interview was audiotaped for later rating. The 5 raters (all women) were instructed to independently rate each interview using forms designed by the authors to elicit information about many aspects of the participant's individual responses as well as perceptions of spouse's responses to the process of pregnancy, amniocentesis, therapeutic abortion, and sequelae. Ratings of all 5 raters were conjoined and an homogeneous narrative was constructed for each interview. Results indicate, in general, that the respondent couples coped well with this experience. In fact 70 per cent of the respondent couples described their marital relationships as becoming closer as a result of their experience. Only a few participants reported long-term deleterious effects. Most couples coped by relying on relatives, friends, and occasionally, professional counsellors. In addition, most participants in this study suggested ways to improve the medical and psychological aspects of this experience.

Abortion, Therapeutic↗
PubMedDate not supplied

Intergenerational relations: pre-med students at senior centers.

Misconceptions about aging and a negative bias against caring for older adults entail unfortunate consequences for society. This study explored the potential of frequent personal contact in reducing misconceptions and improving personal attitude towards older adults. Thirty students, predominantly Asian, with English as their second language, attended senior centers three times per week for 11 months, on the average. They assisted in teaching health promotion classes for the prevention of falls, conducted health assessments by interview, and collected physiological data. At the senior centers, a sample of 70 older adult Americans participated in the health promotion classes and in this evaluation of intergenerational relations. Students completed anonymously two questionnaires; one was objective, testing misconceptions about aging; the other was subjective, rating their reactions to elders at senior centers. Older adults completed, also anonymously, a subjective questionnaire on their reactions to students at their centers. Results on students' misconceptions about aging were similar to those among students at Duke University who did not experience frequent personal contact with well elderly. According to the Facts on Aging Quiz, the overall attitude among students at senior centers was more biased in the negative direction than among Duke students, especially among students who had just joined the project. However, in the subjective questionnaires, students at senior centers expressed feeling at ease at the centers and they disagreed with statements of impatience and frustration. Older adults at the centers had a positive attitude toward the students and most thought that students were sympathetic.

Journal Article↗
PubMedDate not supplied

Accuracy of self-monitoring of blood glucose: impact on diabetes management decisions during pregnancy.

PURPOSE: This study tested the hypothesis that the accuracy of self-monitoring of blood glucose (SMBG) values of patients with diabetes during pregnancy deviates substantially from reference values. METHODS: The patients' glucose values were measured on 6 different SMBG meters; reference values were from the HemoCue B Glucose Analyzer. Over a 5-year period, 1973 comparisons between SMBG values and reference values were recorded during clinic visits and used for this study. Data were analyzed for percent of values that varied more than +/- 10.5% and +/- 15.5% from the reference value. Out-of-range data at each variance level were analyzed to determine the impact on medical management if decisions were based solely on SMBG values. RESULTS: One third of SMBG readings deviated significantly, which could adversely affect treatment for half of these patients if diabetes management was based on SMBG values. At the 10.5% deviation level, 34% of SMBG meter readings were out of range; 54% of these would have implied erroneous treatment. At the 15.5% deviation level, 18% were out of range; 63% of these would have implied erroneous management. CONCLUSIONS: The accuracy of home meters should be verified at regular intervals, and SMBG values should not be the sole criterion for diabetes management during pregnancy.

Blood Glucose Self-Monitoring↗