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Biomedical subjects

J Dean

Publications and source records attributed to J Dean.

At least 91 records · Page 5Linked to original sources

Obstetrical and gynecological complications in fragile X carriers: a multicenter study.

We have conducted a multicenter obstetrical and gynecological survey of women in fragile X families. Included in the study were 131 gene carriers (39 with a full mutation and 92 with a premutation) and 109 noncarriers. Analysis indicated that higher numbers of fragile X gene carriers reported having irregular menses and other gynecological complications. As a group they also experienced cessation of menses prior to age 40 years at a significantly higher rate. The data appear to indicate that the FMR1 gene may play a role in the development and proliferation of oogonia.

Abortion, Spontaneous↗

Control of human arm movements in two dimensions: paths and joint control in avoiding simple linear obstacles.

In order to examine path planning and the control of redundant degrees of freedom in the human arm, the movements of the shoulder, elbow and wrist were recorded as subjects moved a pointer to a target and avoided a simple obstacle. With respect to joint control, the results show that the extra degree of freedom provided by the wrist is incorporated into target movements in a systematic manner for both large and small obstacles; it is not used only when there is no geometrical alternative. For the wrist, two strategies are apparent, depending upon the length of the obstacle. Wrist extension predominates for shorter obstacles, while flexion or extension and flexion predominate for longer obstacles. These wrist movements shorten the effective length of the distal segments (lower arm plus hand and pointer) and thus reduce the excursion required at the proximal joints. In part, they correspond to assuming the most comfortable arm configuration at each point in the new path necessitated by the obstacle and can be described by static cost functions. However, wrist extension is also used to move the hand and pointer away from the obstacle as shoulder and elbow movements carry the wrist itself towards the obstacle. Wrist flexion is also used to move the pointer tip rapidly past the obstacle. These components, which cannot be explained by static cost functions alone, confirm for the human arm the hypothesized use of redundant degrees of freedom in obstacle avoidance. With respect to path planning, the results show that the minimum distance between pointer and obstacle remains fairly constant over a large range of obstacle lengths; this relative invariance is interpreted to support the hypothesis that workspace coordinates are important for movement planning. However, minimum distance and several other path parameters do depend significantly on the orientation and location of the movement in the workspace. This inhomogeneity implies that movement planning does not occur exclusively in workspace coordinates; it suggests an influence of joint space criteria. In frontal movements, for example, the systematic decline in the minimum distance with increasing obstacle length is interpreted as a compromise reducing the amount of extra joint movement and the discomfort of arm configurations.

Adult↗

Biology and structure of the zona pellucida: a target for immunocontraception.

Although reversible interference of sperm-egg interactions with pharmacological agents has not yet been achieved, animal models have provided increasing evidence that immunological reagents directed against mammalian gametes can effectively inhibit fertilization. One potential target of immunocontraception is the zona pellucida, an extracellular matrix that surrounds the growing oocyte and ovulated egg. Recent advances in our knowledge of the biosynthesis and molecular biology of the zona pellucida have provided much information useful in the rational design of immunocontraceptive vaccines. There remain, however, major obstacles to using immunological reagents to prevent fertilization, including potential toxic side effects, the lack of adequate delivery systems and the possibility of incomplete reversibility. This review summarizes current understanding of the production of the zona pellucida during folliculogenesis, the structure of the conserved proteins and genes in the zona pellucida, and the progress made in the development of immunocontraceptive strategies that focus on this oocyte-specific structure.

Animals↗

Effects of electrical stimulation on lymphatic flow and limb volume in the rat.

BACKGROUND AND PURPOSE: The mechanism by which electrical stimulation affects edema has not been elucidated. The purpose of this study was to determine whether subcontraction high-voltage stimulation (SC-HVS) (ie, electrical stimulation that did not elicit a visible contraction) applied to the right hind limbs of rats would (1) alter the rate of lymphatic uptake of injected albumin labeled with Evans blue dye (AL-EBD) and (2) affect experimentally induced edema. SUBJECTS AND METHODS: The paws of 28 anesthetized Sprague-Dawley rats (mean weight = 263 g, SD = 48 g) were injected with AL-EBD. The experimental group (n = 13) received 1 hour of SC-HVS, and the control group (n = 15) received sham treatment consisting of the same treatment administered to the experimental group but without the SC-HVS. Blood samples and volume measurements were obtained at intervals over a 7-hour period. RESULTS: Analysis of variance and post hoc testing indicated that higher amounts of AL-EBD were taken up by the lymph of the experimental group animals as compared with the control group animals at each time period following the treatment. The experimental group's AL-EBD reached significance immediately after treatment, whereas the control group required an additional 4 hours. There was no significant reduction in limb volume in either group. CONCLUSION AND DISCUSSION: The SC-HVS significantly increased the uptake of AL-EBD by lymphatic vessels, but it did not cause a significant decrease in the induced edema. The results of this study indicate that SC-HVS has the potential to reduce edema by increasing lymphatic uptake of proteins.

Albumins↗

Ascertainment and severity of Marfan syndrome in a Scottish population.

This study in north east Scotland has shown that Marfan syndrome has a minimal birth incidence of 1:9802 live births, a minimal prevalence of 1:14217, and that 8/30 (26.7%) of cases in our series are new mutations. The calculated mutation rate is 15 +/- 6.7 x 10(-6) and there is evidence of reduced reproductive fitness.

Adolescent↗

Intersegmental and local interneurons in the metathorax of the stick insect Carausius morosus that monitor middle leg position.

1. In the stick insect, proprioceptive information from the middle leg is used to define the target for the swing movement of the adjacent rear leg ("targeting behavior"). To investigate the underlying neural circuits, intracellular recordings were made in the ganglion controlling the rear leg, the metathoracic ganglion, while systematically moving the tarsus of the middle leg. 2. Several intersegmental interneurons and one local interneuron were identified as possible contributors to the targeting behavior. The intersegmental interneurons code the position of the middle leg tarsus in a highly simplified manner: test movements of the middle leg in the dorsal, lateral, and caudal directions from the standard starting position at right angles to the thorax elicit phasic-tonic responses in three different intersegmental neurons. The response in each interneuron actually reflects the movement and position at only one joint of the middle leg: for the neurons responding primarily to movement in the caudal, dorsal, and lateral test directions, the adequate stimulus is movement at the subcoxal joint, the coxa-trochanter joint, and the femur-tibia joint, respectively. 3. The metathoracic local interneuron integrates information from ipsilateral middle and rear legs in such a way as to provide an approximate measure of the distance between the two tarsi in the longitudinal direction. It is depolarized in a phasic-tonic manner both by caudal movements of the ipsilateral middle leg and by rostral movements of the ipsilateral rear leg. The adequate stimulus in each case is the change in the angle at the subcoxal joint of the leg moved. Depolarization of this neuron activates retractor motoneurons, which is consistent with a role in terminating the swing movement. 4. Altogether the results indicate first, that the targeting behavior could be controlled by very few intersegmental channels and, second, that the nervous system encodes the position of the middle leg tarsus in terms of joint angles rather than in abstract, body-centered coordinates.

Animals↗

Conservation of mammalian secondary sperm receptor genes enables the promoter of the human gene to function in mouse oocytes.

The human zona pellucida is an extracellular sheath composed of three major proteins (ZP1, ZP2, and ZP3) which surround the ovulated egg and mediate the initial interactions with sperm. Although fertilization is relatively species-specific and human sperm will not bind to mouse zona, there is a high degree of conservation between the coding regions of human ZP3 and mouse Zp-3 (the primary sperm receptor) genes. We now report the characterization of the human ZP2 gene and demonstrate that the sequences of its coding regions are 70% identical with those of the mouse Zp-2 (the secondary sperm receptor) gene. In addition, the first 300 bp of the 5' flanking regions of human ZP2 and mouse Zp-2 are highly conserved. This region of 5' flanking DNA contains a previously described 12-bp DNA sequence (element IV) that forms an oocyte-specific DNA-protein complex important for mouse Zp-2 and Zp-3 promoter activity. Human element IV forms a DNA-protein complex in gel mobility shift assays when incubated with human or mouse ovarian extracts. The formation of this complex is inhibited with molar excess of either human or mouse element IV sequences and is not present in extracts of testes, uterus, spleen, lung, or kidney. The human promoter region (0.3 kbp), coupled to a luciferase reporter gene and microinjected into the nuclei of 50-microns-diameter mouse oocytes, results in reporter gene activity at a level comparable to that of the homologous mouse promoter. Clustered point mutations in element IV in either the mouse or the human sequence dramatically decrease reporter gene activity. These results indicate that the similarity between mouse Zp-2 and human ZP2 genes enables the human promoter to utilize the heterologous transcription machinery in mouse oocytes. The observed transcription may involve the recognition of promoter sequences in element IV by conserved transcription factor(s).

Adolescent↗

ZAP-1 DNA binding activity is first detected at the onset of zona pellucida gene expression in embryonic mouse oocytes.

ZAP-1 (zona pellucida gene activating protein-1) is a putative transcription factor controlling the oocyte-specific expression of mouse and human zona pellucida genes. The DNA binding activity of ZAP-1 first appears in oocytes from 19-day-old mouse embryos and reaches a maximum level at 10 days after birth. This developmental profile closely parallels that of mouse zona pellucida gene transcription, which is detected in oocytes at 19 days of fetal life using a sensitive RT-PCR method and is maximal in 10-day-old animals. DNA binding activity similar to that of ZAP-1 is present in ovarian extracts from rat, human, and opossum, suggesting that the ZAP-1 protein may be conserved among mammals.

Animals↗

Reduction of animal use with improved procedure for acute tolerance assessment.

A retrospective evaluation of previously conducted acute tolerance tests in rats and mice, following oral and intravenous routes of administration, and a review of the literature indicated that a minimum of three animals per group was adequate to characterize acute tolerance. Limited exploratory testing, using six compounds for which classical LD50 tests had been performed previously, indicated that fewer numbers of rats gave comparable results. A method is proposed by which the acute tolerance of a compound may be adequately characterized in both sexes using approximately 30 animals instead of the 70 to 100 used in the classical LD50 test. The objective of the testing procedure is identification of the maximum nonlethal dose or the minimum lethal dose, rather than determination of the LD50.

Administration, Oral↗

Rigid fixation of mandibular condyle fractures.

This article reviews the anatomy and surgical approaches for treating fractures of the mandibular condyle with plate and screw fixation. Advantages and disadvantages of the preauricular, submandibular, intraoral, retromandibular, and rhytidectomy approaches are presented.

Bone Plates↗

Affect and age: cross-sectional comparisons of Structure and prevalence.

The self-reports of 207 young-adult (ages 18-30), 231 middle-aged (ages 31-59), and 828 older-adult (age 60 and over) Ss were used to study the structure of affect. Affects were represented by terms included in various circumplex arrays of emotions as presented by previous investigators. A set of 46 affects was subjected to exploratory analysis, and a final set of 38 affects was subjected to confirmatory factor analysis. The goodness of fit of each group's factor loadings to the hypothesized factors of positive affect, depression, anxiety-guilt, contentment, hostility, and shyness was not up to the desired .90 level, and some significant differences in factor structure were observed for each age-group comparison. There were few age differences in levels of positive affect. Depression was most frequent among younger Ss and least frequent among older Ss. Younger Ss were most often anxious and shy. Older Ss were most often content and least often hostile.

Adult↗

Preimplantation diagnosis or chorionic villus biopsy? Women's attitudes and preferences.

The objective of this work was to assess women's attitudes and preferences to two methods of prenatal diagnosis for genetic disease: embryo and chorionic villus biopsy (CVS). The design involved a structured postal questionnaire sent to women in the Grampian region with different reproductive experiences. The population sample included 46 women who had had genetic counselling because of a family history of a single gene disorder, 18 women who had had CVS for a single gene disorder, 158 women who had had CVS for other reasons, 200 women who had recently delivered a normal baby and 50 women who had experience of in-vitro fertilization (IVF). The main outcome measures were attitudes to family limitation, prenatal diagnosis, termination for fetal abnormality, embryo biopsy and CVS. Of the women surveyed, 38% preferred embryo diagnosis, whereas 42% favoured CVS and termination. Women with previous experience of CVS preferred this option whereas those with experience of IVF as infertility treatment were more likely to favour embryo diagnosis, as were women who had had genetic counselling for a single gene disorder. It was concluded that a substantial number of women find embryo diagnosis more acceptable than CVS when the pregnancy is at high risk. This is especially true amongst those with experience of IVF or who are at risk themselves. A demand for embryo diagnosis has been demonstrated.

Adolescent↗

Antenatal cystic fibrosis carrier screening--whether, when and how?

Population screening for carriers of cystic fibrosis (CF) is now possible. Such screening may have both advantages and disadvantages and hence must be evaluated before it becomes routine practice. As the potential benefits of screening are wide and the drawbacks may include psychological effects, a combination of approaches is needed to assess screening thoroughly instead of only counting numbers of terminations or carrier tests. We describe the issues concerned and our methodology for a rigorous evaluation of population antenatal carrier screening for cystic fibrosis.

Anxiety↗

Recombinant mouse ZP3 inhibits sperm binding and induces the acrosome reaction.

Mammalian fertilization involves interactions of sperm surface receptors with ligands of the zona pellucida, an extracellular matrix surrounding the ovulated egg. In mouse, the zona is composed of three glycoproteins. One of them, ZP3, participates in primary sperm binding and in the subsequent triggering of the sperm's acrosome reaction. Considerable evidence suggests that carbohydrate determinants of ZP3 are responsible for binding to sperm and may be important for acrosomal exocytosis. A full-length cDNA encoding mouse ZP3 was assembled and cloned into expression vectors that contained either a cytomegalovirus (CMV) or a vaccinia (P11) promoter. Mouse L-929 cells were stably transformed with the pZP3-CMV constructs, and green monkey CV-1 cells were infected with a recombinant vaccinia virus containing ZP3. rZP3 was affinity purified from culture media and detected on Western blots as a single 60- to 70-kDa band, which differed in molecular weight from native ZP3 (mean, 83 kDa). Nevertheless, rZP3 is biologically active. rZP3 decreases sperm-zona binding with a potency equivalent to that of native zona pellucida and, like native ZP3, rZP3 triggers acrosomal exocytosis in capacitated mouse sperm. Thus, rZP3 isolated from both rodent and primate cells appears to contain those carbohydrate and protein structures necessary for ZP3's dual role in fertilization.

Animals↗

Dimensions of affective experience in three age groups.

The dimensions by which adults of differing ages experience emotion were studied by self-administering questionnaires administered to older adults (n = 828) recruited from Elderhostel programs, middle-aged (ages 30-59) children of Elderhostel attenders (n = 231), and young adult (ages 18-29) subjects recruited from college classes or through Elderhostel participants (n = 207). Elders were higher in emotional control, mood stability, and emotional maturity through moderation and leveling of positive affect and lower in surgency, psychophysiological responsiveness, and sensation seeking. These findings are consistent with the hypothesized increase in self-regulatory capacity with age. These cross-sectional differences cannot, however, be distinguished from cohort-related explanations; they require considerable replication across different types of subjects and further characterization of the dimensions in terms of their functions for self-regulation.

Adult↗