PubMed Health⌕ Search

Biomedical subjects

M Morris

Publications and source records attributed to M Morris.

At least 37 records · Page 2Linked to original sources
PubMed2000

Crystal structures of two functionally different thioredoxins in spinach chloroplasts.

Thioredoxins are small ubiquitous proteins which act as general protein disulfide reductases in living cells. Chloroplasts contain two distinct thioredoxins ( f and m) with different phylogenetic origin. Both act as enzyme regulatory proteins but have different specificities towards target enzymes. Thioredoxin f (Trx f), which shares only low sequence identity with thioredoxin m (Trx m) and with all other known thioredoxins, activates enzymes of the Calvin cycle and other photosynthetic processes. Trx m shows high sequence similarity with bacterial thioredoxins and activates other chloroplast enzymes. The here described structural studies of the two chloroplast thioredoxins were carried out in order to gain insight into the structure/function relationships of these proteins. Crystal structures were determined for oxidized, recombinant thioredoxin f (Trx f-L) and at the N terminus truncated form of it (Trx f-S), as well as for oxidized and reduced thioredoxin m (at 2.1 and 2.3 A resolution, respectively). Whereas thioredoxin f crystallized as a monomer, both truncated thioredoxin f and thioredoxin m crystallized as non-covalent dimers. The structures of thioredoxins f and m exhibit the typical thioredoxin fold consisting of a central twisted five-stranded beta-sheet surrounded by four alpha-helices. Thioredoxin f contains an additional alpha-helix at the N terminus and an exposed third cysteine close to the active site. The overall three-dimensional structures of the two chloroplast thioredoxins are quite similar. However, the two proteins have a significantly different surface topology and charge distribution around the active site. An interesting feature which might significantly contribute to the specificity of thioredoxin f is an inherent flexibility of its active site, which has expressed itself crystallographically in two different crystal forms.

Amino Acid Sequence↗
PubMed2000

Condom acceptance is higher among travelers in Uganda.

OBJECTIVE: To examine the role played by mobile residents in the spread of HIV through rural Uganda. DESIGN: Travel history and sexual network data were collected from a random sample of 1627 residents aged 15-49 years in Rakai District, Uganda during 1994. METHODS: Travelers and non-travelers are compared with respect to socio-demographic attributes, risk exposure, knowledge, attitudes and use of condoms using descriptive statistics and multivariate logistic regression. A demographic profile of travelers' partners is developed using information from a local network survey module. RESULTS: The population is highly mobile, with over 70% reporting travel to a potentially higher risk destination in the past year. Travelers are somewhat more likely to have higher levels of sexual risk behavior, but the risk appears to be offset by significantly greater knowledge, acceptance, and use of condoms. In multivariate analysis, the sexual risk differential for travelers is explained by occupational exposure and higher socio-economic status. The differential in condom acceptance, by contrast, appears to be associated with travel itself. Condom use with non-spousal partners is three times higher among travelers than non-travelers (P< 0.001), and travel remains a significant predictor after controlling for age, education, residence, occupation and multiple partners. Travelers are more likely to use condoms with both their local and non-local partners. Partners of male travelers are likely to be younger and better educated than those of male non-travelers. CONCLUSIONS: The mobile population in this rural region appears willing to adopt risk reduction measures appropriate to their exposure. This suggests that targeting condom promotion programs to travelers and their partners is likely to be effective in reducing the spatial diffusion of HIV, and may be an efficient method for spreading behavioral change into rural areas.

Adolescent↗
PubMed2000

2 Micron Spectroscopy within 0&farcs;3 of Sagittarius A*

We present moderate- (R approximately 2700) and high-resolution (R approximately 22,400) 2.0-2.4 µm spectroscopy of the central 0.1 arcsec2 of the Galaxy obtained with the facility near-infrared spectrometer (NIRSPEC) for the Keck II telescope. The composite spectra do not have any features attributable to the brightest stars in the central cluster; i.e., after background subtraction, W12CO&parl0;2-0&parr0;<2 Å. This stringent limit leads us to conclude that the majority, if not all, of the stars are hotter than typical red giants. Coupled with previously reported photometry, we conclude that the sources are likely OB main-sequence stars. In addition, the continuum slope in the composite spectrum is bluer than that of a red giant and is similar to that of the nearby hot star IRS 16NW. It is unlikely that they are late-type giants stripped of their outer envelopes because such sources would be much fainter than those observed. Given their inferred youth (tauage<20 Myr), we suggest the possibility that the stars have formed within 0.1 pc of the supermassive black hole. We find a newly identified broad-line component (VFWHM approximately 1000 km s-1) toward the 2.2178 µm [Fe iii] line located within a few arcseconds of Sagittarius A*. A similar component is not seen in the Brgamma emission.

Journal Article↗
PubMed2000

Posttherapy surveillance of women with cervical cancer: an outcomes analysis.

OBJECTIVE: The aim of this study was to develop a surveillance program that optimizes clinical outcome following primary treatment of women with cervical cancer. METHODS: The records of 1096 patients with FIGO stage IB cervical cancer treated from 1983 to 1993 were retrospectively reviewed. Recurrence was analyzed by site, presence or absence of symptoms, method of detection, and survival. Univariate and multivariate analyses using a Cox proportional hazards model were performed. RESULTS: One hundred thirty-three patients (13%) developed recurrent disease. Of these, 114 were symptomatic and 19 were asymptomatic at the time of recurrence. Thirty-seven patients recurred in the central pelvis, 21 each in the lung or pelvic wall, 22 in nodes, and 35 in other sites. The median disease-free interval was 17 months for symptomatic patients and 16 months for asymptomatic patients. The median survival from initial diagnosis was 31 months for symptomatic and 83 months for asymptomatic patients (P = 0.001). The median survival from recurrence was 11 months for symptomatic and 42 months for asymptomatic patients (P < 0.001). Multivariate analysis revealed that symptom status at time of recurrence was a significant predictor of survival, even when known prognostic factors were considered (P < 0.001). All asymptomatic pelvic recurrences were diagnosed by pelvic exam; all asymptomatic pulmonary recurrences were detected by chest radiographs. Pap smears did not detect a single asymptomatic recurrence. CONCLUSIONS: Posttherapy surveillance programs are directed toward asymptomatic patients in whom early detection of recurrence may impact survival. These data indicate that a subset of women may benefit from surveillance. A model for surveillance is proposed.

Adult↗
PubMed2000

Goal-directed secondary motor tasks: their effects on gait in subjects with Parkinson disease.

OBJECTIVE: To investigate the effects of secondary motor tasks of three levels of difficulty on the spatial and temporal parameters of gait in subjects with Parkinson disease (PD) compared with control subjects. DESIGN: A two-group repeated measures design using a sample of convenience. Subjects performed 10-meter gait trials walking (1) freely, (2) carrying a tray, and (3) carrying a tray with four plastic glasses. SETTING: Subjects were tested in the gait laboratory at Kingston Centre, Victoria, Australia. SUBJECTS: Twelve subjects with PD and 12 control subjects matched for age, height, and sex were recruited from the Movement Disorders Clinic at Kingston Centre. OUTCOME MEASURES: Gait speed, stride length, cadence, and the proportion of the walking cycle spent in double limb support were measured in moderately disabled subjects with PD and control subjects. RESULTS: For all of the walking conditions, subjects with PD walked more slowly (F(1,22) = 16.54, p = .001, partial nu2 = .429) and with shorter steps (F(1,22) = 15.07, p = .001, partial nu2 = .406) than control subjects. In addition there were significant group by condition interaction effects for gait speed (F(2, 44) = 4.42, p = .018, partial nu2 = .167) and stride length (F(2, 44) = 4.95, p = .012, partial nu2 = .184). There was little deterioration in gait when subjects in either group carried a tray while walking compared with free walking; however, when required to carry four plastic glasses on the tray while walking, subjects in the PD group showed marked deterioration in gait speed (t(11) = 3.19, p = .009, alpha = .025) and stride length (t(11) = 3.82, p = .003, alpha = .025). Performance in the control subjects changed only marginally across the conditions. CONCLUSION: Subjects with moderate disability in PD experience considerable difficulty when they are required to walk while attending to a complex visuomotor task involving the upper limbs.

Adult↗
PubMed2000

Genetic variation within the ticks Ixodes holocyclus and Ixodes cornuatus from south-eastern Australia.

Ticks from mainland Australia (Victoria, New South Wales and Queensland) and Tasmania, identified morphologically as either Ixodes holocyclus or Ixodes cornuatus, were compared genetically using 24 enzyme loci. The results showed that ticks from three localities in Victoria were genetically similar to I. cornuatus in Tasmania, but both groups had fixed genetic differences at >45% of loci compared with other ticks on the mainland. In addition, there were fixed genetic differences at 0-60% of loci among I. holocyclus from different localities on the mainland. Ixodes holocyclus samples could be divided into four distinct clusters (with fixed genetic differences >15%), three of which were represented by one or two specimens. Nonetheless, these electrophoretic data suggest that I. holocyclus represents a species complex. The results also showed that the morphological criteria used to identify specimens were not always accurate because several specimens had been mis-identified morphologically. Despite limitations with the morphological identification, this study has demonstrated that I. cornuatus can be distinguished from the I. holocyclus species complex using six enzyme loci, providing the foundation for a re-examination of morphological characteristics. The present study has shown that I. cornuatus and the I. holocyclus complexes have a greater distribution than previously reported, with both occurring in sympatry at Cape Patterson, on the southern coastline of Victoria.

Alleles↗
PubMed2000

Outcome and reproductive function after conservative surgery for borderline ovarian tumors.

OBJECTIVE: To study reproductive function and disease outcome in women with borderline ovarian tumors who were treated with conservative surgery. METHODS: Patients with borderline ovarian tumors were identified from institutional databases. Patients were eligible if they had pathologically confirmed borderline ovarian tumors, no prior sterilization, no history of radiation therapy, retained their uterus and ovarian tissue, and were younger than age 45. Information was acquired by retrospective medical record review and patient interview. RESULTS: Forty-three patients met the eligibility criteria. The median age was 25 years, with a range of 15-39 years. Twenty-six patients had serous tumors, and 17 had mucinous tumors. Fifteen had stage I disease, three had stage III, and 25 were unstaged. Follow-up was available for all patients (median, 5.7 years). Twenty-nine remained disease-free, and 14 developed a new primary lesion/recurrence, with a median time to recurrence of 39.3 months. Recurrence was more frequent in patients treated with ovarian cystectomy than in those treated with oophorectomy alone (58% compared with 23%) (P <.04). After treatment, 29 of 36 patients (81%) retained normal menstrual cycles, and 12 of 24 patients attempting pregnancy conceived 25 pregnancies. Most patients were highly satisfied with conservative surgery. CONCLUSION: Conservative surgery remains a therapeutic option in selected patients with borderline ovarian tumors. Although the rate of new lesion/recurrence is relatively high, especially in those treated with ovarian cystectomy, mortality from cancer remains low. Many patients who desire pregnancy are able to conceive and deliver healthy offspring after conservative surgery.

Adolescent↗
PubMed2000

Postural instability in Parkinson's disease: a comparison with and without a concurrent task.

The purpose of this investigation was to determine the effects of dual task performance on postural instability in subjects with idiopathic Parkinson's disease (PD) compared with healthy elderly people. In particular, we aimed to divert attention to a secondary task so the full extent of balance disturbance could be revealed without compensation by attentional mechanisms. Forty-five subjects were tested: 15 PD subjects with a past history of falls; 15 PD subjects with no history of falls; and 15 unimpaired individuals. Groups were matched for age and sex and subjects with PD were tested at peak dose in the levodopa medication cycle. Each subject was tested on their ability to maintain stability in three conditions: (1) steady standing (feet apart, feet together, step stance, tandem stance, single leg stance); (2) in response to perturbations generated by self-initiated movements (arm raise test, step test); and (3) in response to an unexpected external perturbation in upright stance, the shoulder tug test. The concurrent task was verbal-cognitive and required subjects to recite the days of the week backwards. The concurrent task produced a significant deterioration in performance for the arm raise test in all groups, the step test for the PD fallers and controls and for tandem stance in the PD fallers. Ceiling effects were evident for timed tests with feet apart and feet together resulting in poor discriminative validity for these tests. The external perturbation test showed differences between the three groups for both unitask and concurrent task conditions, yet similar rates of change from unitask to dual task conditions. Because PD fallers had a more severe initial deficit than controls, deterioration placed them in that part of the balance continuum at high risk of losing equilibrium.

Accidental Falls↗
PubMed2000

Three-dimensional cellular development is essential for ex vivo formation of human bone.

Tissue engineering of human bone is a complex process, as the functional development of bone cells requires that regulatory signals be temporally and spatially ordered. The role of three-dimensional cellular interactions is well understood in embryonic osteogenesis, but in vitro correlates are lacking. Here we report that in vitro serum-free transforming growth factor (TGF)-beta1 stimulation of osteogenic cells immediately after passage results in the formation of three-dimensional cellular condensations (bone cell spheroids) within 24 to 48 hours. In turn, bone cell spheroid formation results in the up-regulation of several bone-related proteins (e.g., alkaline phosphatase, type I collagen, osteonectin) during days 3-7, and the concomitant formation of micro-crystalline bone. This system of ex vivo bone formation should provide important information on the physiological, biological and molecular basis of osteogenesis.

Alkaline Phosphatase↗
PubMed2000

A role for tyrosine phosphorylation in the regulation and sensitization of adenylate cyclase by melatonin.

Mimicking short photoperiod melatonin signals (16 h exposure) on primary cell cultures of melatonin target cells of the ovine pars tuberalis (PT) results in an enhanced cAMP response to forskolin stimulation relative to untreated cells, a phenomenon termed sensitization. The sensitized response of PT cells may be an important aspect of the interpretation of the melatonin signal to initiate appropriate seasonal physiological responses. The aim of this study is to add to our understanding of the molecular mechanisms involved in the sensitization of PT cells by melatonin. We demonstrate that sensitization of PT cells by melatonin is mediated via a G(i)-coupled melatonin receptor. The sensitized cAMP response is not only obtained with the pharmacological tool forskolin, but also with cholera toxin, an activator of G(salpha). Changes in the level of G(salpha) or G(ialpha) G-protein subunits are ruled out as part of the sensitization mechanism. However, changes in tyrosine phosphorylation may be involved as tyrosine kinase inhibitors sensitize ovine PT cells and tyrosine phosphatase inhibitors significantly blunt adenylate cyclase activity, including the sensitized response to melatonin. The adenylate cyclase isoforms mediating the sensitized response may be broad as 7 of the 9 isoforms of adenylate cyclase are expressed in the PT.

Adenylate Cyclase Toxin↗
PubMed2000

Evidence for a telomere-independent "clock" limiting RAS oncogene-driven proliferation of human thyroid epithelial cells.

An initiating role for RAS oncogene mutation in several epithelial cancers is supported by its high incidence in early-stage tumors and its ability to induce proliferation in the corresponding normal cells in vitro. Using retroviral transduction of thyroid epithelial cells as a model we ask here: (i) how mutant RAS can induce long-term proliferation in an epithelial cell in contrast to the premature senescence observed in fibroblasts; and (ii) what is the "clock" which eventually triggers spontaneous growth arrest even in epithelial clones generated by mutant RAS. The early response to RAS activation in thyroid epithelial cells showed two features not seen in fibroblasts: (i) a marked decrease in expression of the cyclin-dependent kinase inhibitor (CDKI) p27(kip1) and (ii) the absence of any induction of p21(waf1). When proliferation eventually ceased (after up to 20 population doublings) this occurred despite undiminished expression of mutant RAS and was tightly correlated with a return to the initial high level of p27(kip1) expression, together with the de novo appearance of p16(ink4a). Importantly, neither the CDKI changes nor the proliferative life span of RAS-induced epithelial clones was altered by induction of telomerase activity through forced expression of the catalytic subunit, hTERT, at levels sufficient to immortalize human fibroblasts. These data provide a basis for cell-type differences in sensitivity to RAS-induced proliferation which may explain the corresponding tumor-type specificity of RAS mutation. They also show for the first time in a primary human cell model that a telomere-independent mechanism can limit not only physiological but also oncogene-driven proliferation, pointing therefore to a tumour suppressor mechanism additional, or alternative, to the telomere clock.

Catalytic Domain↗
PubMed2000

Central oxytocin modulates exercise-induced tachycardia.

We have shown that vasopressinergic projections to dorsal brain stem are activated during exercise and facilitate exercise tachycardia in both trained (T) and sedentary (S) rats (Dufloth DL, Morris M, and Michelini LC. Am J Physiol Regulatory Integrative Comp Physiol 273: R1271-R1282, 1997). In the present study, we investigated whether oxytocinergic projections to the nucleus of the solitary tract (NTS)-dorsal motor nucleus of the vagus (DMV) complex (NTS/DMV) are involved in the differential heart rate (HR) response to exercise in T and S rats. Arterial pressure (AP) and HR responses to dynamic exercise (0.4-1.4 km/h) were compared in S and T pretreated with vehicle (saline), oxytocin (OT; 20 pmol/200 nl) or OT-receptor antagonist (OT(ant); 20 pmol/200 nl) into the NTS/DMV. OT content in specific brain regions and plasma were measured in separate S and T groups at rest and immediately after exercise. Exercise increased OT content in dorsal (4.5-fold) and ventral brain stem (2.7-fold) and spinal cord (3.4-fold) only in T rats. No significant changes were observed in neurosecretory regions or medial eminence and posterior pituitary, but plasma levels of T rats were reduced immediately after exercise. Blockade of NTS/DMV OT receptors did not change basal mean AP (MAP) and HR or the MAP response to exercise. However, OT(ant) potentiated exercise-induced tachycardia (average increase of 26%) only in the T group. Pretreatment with exogenous OT in the NTS/DMV blunted the tachycardic response both in S and T rats without changing the MAP response. Administration of OT-receptor antagonist or OT into the fourth cerebral ventricle had no effect on the cardiovascular response to dynamic exercise. Taken together, the results suggest that oxytocinergic projections to the NTS/DMV are stimulated when T rats exercise and that OT released at this level acts on OT receptors to restrain exercise-induced tachycardia.

Animals↗
PubMed2000

Abnormal water metabolism in mice lacking the type 1A receptor for ANG II.

Mice lacking AT(1A) receptors for ANG II have a defect in urinary concentration manifested by an inability to increase urinary osmolality to levels seen in controls after thirsting. This defect results in extreme serum hypertonicity during water deprivation. In the basal state, plasma vasopressin levels are similar in wild-type controls and Agtr1a -/- mice. Plasma vasopressin levels increase normally in the AT(1A) receptor-deficient mice after 24 h of water deprivation, suggesting that the defect in urine concentration is intrinsic to the kidney. Using magnetic resonance microscopy, we find that the absence of AT(1A) receptors is associated with a modest reduction in the distance from the kidney surface to the tip of the papilla. However, this structural abnormality seems to play little role in the urinary concentrating defect in Agtr1a -/- mice since the impairment is largely reproduced in wild-type mice by treatment with an AT(1)-receptor antagonist. These studies demonstrate a critical role for the AT(1A) receptor in maintaining inner medullary structures in the kidney and in regulating renal water excretion.

Angiotensin Receptor Antagonists↗
PubMed2000

You got a problem with that? Exploring evaluators' disagreements about ethics.

A random sample of American Evaluation Association (AEA) members were surveyed for their reactions to three case scenarios--informed consent, impartial reporting, and stakeholder involvement--in which an evaluator acts in a way that could be deemed ethically problematic. Significant disagreement among respondents was found for each of the scenarios, in terms of respondents' views of whether the evaluator had behaved unethically. Respondents' explanations of their judgments support the notion that general guidelines for professional behavior (such as AEA's Guiding Principles for Evaluators) can encompass sharply conflicting interpretations of how evaluators should behave in specific situations. Respondents employed in private business/consulting were less likely than those in other settings to believe that the scenarios portrayed unethical behavior by the evaluator, a finding that underscores the importance of taking contextual variables into account when analyzing evaluators' ethical perceptions. The need for increased dialogue among evaluators who represent varied perspectives on ethical issues is addressed.

Data Collection↗