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PubMed2001

Functional domains of the LIM homeodomain protein Xlim-1 involved in negative regulation, transactivation, and axis formation in Xenopus embryos.

The Xenopus LIM homeodomain protein Xlim-1 is specifically expressed in the Spemann organizer region and assumed to play a role in the establishment of the body axis as a transcriptional activator. To further elucidate the mechanism underlying the regulation of its transcriptional activity, we focused on the region C-terminal to the homeodomain of Xlim-1 (CT239-403) and divided it into five regions, CCR1-5 (C-terminal conserved regions), based on similarity between Xlim-1 and its paralog, Xlim-5. The role of Xlim-1 CT239-403 in the Spemann organizer was analyzed by assaying the axis-forming ability of a series of CCR-mutated constructs in Xenopus embryos. We show that high doses of Xlim-1 constructs deleted of CCR1 or CCR2 initiate secondary axis formation in the absence of its coactivator Ldb1 (LIM-domain-binding protein 1), suggesting that CCR1 and CCR2 are involved in negative regulation of Xlim-1. In contrast, while Xlim-1 is capable of initiating secondary axis formation at low doses in the presence of Ldb1, deletion of CCR2 (aa 275-295) or substitution of five conserved tyrosines in CCR2 with alanines (CCR2-5YA) abolished the activity. In addition, UAS-GAL4 one-hybrid reporter assays in Xenopus showed that CCR2, but not CCR2-5YA, with its flanking regions (aa 261-315) functions as a transactivation domain when fused to the GAL4 DNA-binding domain. Finally, we show that none of the known transcriptional coactivators tested (CBP, SRC-1, and TIF2) interacts with the Xlim-1 transactivation domain (aa 261-315). Thus, Xlim-1 not only contains a unique tyrosine-rich activation domain but also contains a negative regulatory domain in CT239-403, suggesting a complex regulatory mechanism underlying the transcriptional activity of Xlim-1 in the organizer.

Amino Acid Sequence↗
PubMed2001

Axis induction by wnt signaling: Target promoter responsiveness regulates competence.

The modulation of inductive competence is a major theme in embryonic development, but, in most cases, the underlying mechanisms are not well understood. In principle, the capacity of extracellular signals to elicit particular responses could be regulated by changes in cell surface receptors, in intracellular signaling pathways, or in the responsiveness of individual target gene promoters. As an example of regulated competence, we have examined dorsal axis induction in Xenopus embryos by Wnt signaling. Competence of Wnt proteins such as Xwnt-8 to induce an ectopic axis or the dorsal early response genes siamois and Xnr3 is lost by the onset of gastrulation, when these same ligands now produce a distinct set of "late" effects, including anterior truncation and induction of the midbrain/hindbrain marker engrailed-2. Although other Wnts apparently make use of alternative signaling mechanisms, we demonstrate that late-expressed Xwnt-8 continues to employ the canonical Wnt signaling pathway used earlier in dorsal axis induction, stabilizing cytosolic beta-catenin, and activating gene expression through Tcf/Lef transcription factors. Moreover, an activated, hormone-inducible version of XTcf-3 (TVGR) that can reproduce both early and late Wnt responses when activated at appropriate stages becomes unable to induce siamois and secondary axes at the same time as Wnt ligands themselves. Finally, we show that TVGR also loses the ability to induce expression of a reporter construct containing a small fragment of the siamois promoter, implying that this fragment contains sequences governing the loss of Wnt responsiveness before gastrulation. Together, these results argue that the competence of Wnts to induce a dorsal axis is lost in the nucleus, as a result of changes in the responsiveness of target promoters.

Animals↗
PubMed2001

Boundaries and functional domains in the animal/vegetal axis of Xenopus gastrula mesoderm.

Patterning of the Xenopus gastrula marginal zone in the axis running equatorially from the Spemann organizer-the so--called "dorsal/ventral axis"--has been extensively studied. It is now evident that patterning in the animal/vegetal axis also needs to be taken into consideration. We have shown that an animal/vegetal pattern is apparent in the marginal zone by midgastrulation in the polarized expression domains of Xenopus brachyury (Xbra) and Xenopus nodal-related factor 2 (Xnr2). In this report, we have followed cells expressing Xbra in the presumptive trunk and tail at the gastrula stage, and find that they fate to presumptive somite, but not to ventrolateral mesoderm of the tailbud embryo. From this, we speculate that the boundary between the Xbra- and Xnr2-expressing cells at gastrula corresponds to a future tissue boundary. In further experiments, we show that the level of mitogen-activated protein kinase (MAPK) activation is polarized along the animal/vegetal axis, with the Xnr2-expressing cells in the vegetal marginal zone having no detectable activated MAPK. We show that inhibition of MAPK activation in Xenopus animal caps results in the conversion of Xnr2 from a dorsal mesoderm inducer to a ventral mesoderm inducer, supporting a role for Xnr2 in induction of ventral mesoderm.

Actins↗
PubMed2001

Expression cloning of Xenopus Os4, an evolutionarily conserved gene, which induces mesoderm and dorsal axis.

Multiple factors, including members of the FGF, TGF beta, and Wnt family of proteins, are important mediators in the regulation of dorsal-ventral pattern formation during vertebrate development. By using an expression cloning approach to identify novel factors that could regulate dorsal-ventral patterning in the Xenopus embryo, we isolated the Xenopus homologue of the human Os4 gene by virtue of its ability to induce a secondary dorsal axis. While Os4 homologues have been identified in a variety of species, and human Os4 is overexpressed in human tumors, the biological function of Os4 is unknown. To explore the mechanism by which Xenopus Os4 (XOs4) induces a secondary dorsal axis, we used Xenopus explant and whole-embryo assays. The secondary axis induced by XOs4 is distinct from that induced by activation of Wnt or FGF pathways but similar to that induced by inhibition of BMP signaling or activation of an Activin pathway. However, XOs4 did not inhibit BMP signaling in dissociated animal cap explants, indicating that XOs4 does not inhibit BMP signaling. Similar to activation of an Activin-like pathway, expression of XOs4 induces molecular markers for mesoderm in animal cap explants, although expression of gastrula-stage mesodermal markers was very weak and substantially delayed. Yet, XOs4 does not require activity of the Activin signal-transduction pathway for mesoderm induction as dominant-negative components of the Activin/Nodal/Vg1 pathway did not prevent XOs4-mediated induction of mesodermal derivatives. Finally, like Activin/Nodal/Vg1 pathways, XOs4 requires FGF signaling for expression of mesoderm markers. Results presented in this study demonstrate that XOs4 can induce mesoderm and dorsalize ventral mesoderm resulting in ectopic dorsal axis formation, suggesting a role for this large evolutionarily conserved gene family in early development.

Activins↗
PubMed1994

Gonadal steroid hormone receptors and sex differences in the hypothalamo-pituitary-adrenal axis.

The rapid activation of stress-responsive neuroendocrine systems is a basic reaction of animals to perturbations in their environment. One well-established response is that of the hypothalamo-pituitary-adrenal (HPA) axis. In rats, corticosterone is the major adrenal steroid secreted and is released in direct response to adrenocorticotropin (ACTH) secreted from the anterior pituitary gland. ACTH in turn is regulated by the hypothalamic factor, corticotropin-releasing hormone. A sex difference exists in the response of the HPA axis to stress, with females reacting more robustly than males. It has been demonstrated that in both sexes, products of the HPA axis inhibit reproductive function. Conversely, the sex differences in HPA function are in part due to differences in the circulating gonadal steroid hormone milieu. It appears that testosterone can act to inhibit HPA function, whereas estrogen can enhance HPA function. One mechanism by which androgens and estrogens modulate stress responses is through the binding to their cognate receptors in the central nervous system. The distribution and regulation of androgen and estrogen receptors within the CNS suggest possible sites and mechanisms by which gonadal steroid hormones can influence stress responses. In the case of androgens, data suggest that the control of the hypothalamic paraventricular nucleus is mediated trans-synaptically. For estrogen, modulation of the HPA axis may be due to changes in glucocorticoid receptor-mediated negative feedback mechanisms. The results of a variety of studies suggest that gonadal steroid hormones, particularly testosterone, modulate HPA activity in an attempt to prevent the deleterious effects of HPA activation on reproductive function.

Adrenocorticotropic Hormone↗
PubMed1997

The role of the hypothalamic-pituitary-adrenocortical axis in memory-related effects of anxiolytics.

Two major classes of antianxiety drugs, benzodiazepines and partial agonists of 5-HT1A receptors, have dissimilar effects on learning. Benzodiazepines induce amnesic effects in humans and animals. In contrast, partial agonists of 5-HT1A receptors do not suppress memory in humans and have variable effects in animal learning models. The two groups of drugs shift activity of the hypothalamic-pituitary-adrenocortical (HPA) axis in opposite ways. Benzodiazepines, given at antianxiety doses, suppress HPA axis excitability. Partial agonists of 5-HT1A receptors facilitate HPA excitability and, at higher doses, directly stimulate ACTH secretion. Assuming that certain components of the HPA axis are involved in memory acquisition, it is hypothesized that antianxiety drugs may affect learning through the regulation of HPA axis excitability.

Adrenocorticotropic Hormone↗
PubMed1996

Modulation of vergence by off-vertical yaw axis rotation in the monkey: normal characteristics and effects of space flight.

Horizontal movements of both eyes were recorded simultaneously using scleral search coils in 2 rhesus monkeys before and after the COSMOS 2229 space-flight of 1992-1993. Another 9 monkeys were tested at comparable time intervals and served as controls. Ocular vergence, defined as the difference in horizontal position between the left and right eyes, was measured during off-vertical yaw axis rotation (OVAR) in darkness. Vergence was modulated sinusoidally as a function of head position with regard to gravity during OVAR. The amplitude of peak-to-peak modulation increased with increments in tilt of the angle of the rotational axis (OVAR tilt angle) that ranged from 15 degrees to 90 degrees. Of the 11 monkeys tested, 1 had no measurable modulation in vergence. In the other 10, the mean amplitude of the peak to peak modulation was 5.5 degrees +/- 1.3 degrees at 90 degrees tilt. Each of these monkeys had maximal vergence when its nose was pointed close to upward (gravity back; mean phase: -0.9 degree +/- 26 degrees). After space flight, the modulation in vergence was reduced by over 50% for the two flight monkeys, but the phase of vergence modulation was not altered. The reduction in vergence modulation was sustained for the 11-day postflight testing period. We conclude that changes in vergence are induced in monkeys by the sinusoidal component of gravity acting along the naso-occipital axis during yaw axis OVAR, and that the modulation of the vergence reflex is significantly less sensitive to linear acceleration after space flight.

Animals↗
PubMed1991

Orientation bias of cat dorsal lateral geniculate cells: directional analysis of the major axis of the receptive field centre.

The receptive field centre of cells in the dorsal lateral geniculate nucleus were mapped as iso-sensitivity contours. 94% of the cells were found to have elliptical centres, and analysis of the major axis orientation showed that 29% and 59% of units had their major axis oriented within +/- 20 degrees of the radial and horizontal directions, respectively. The data for Y-cells showed a greater dispersion in their orientation biases (R = 0.57) compared with X-cells (R = 0.79). Nevertheless, a horizontal orientation bias was found in both classes of cells: 47% of Y-cells and 73% of X-cells. In addition, an examination of the major axis orientations was undertaken for cells with receptive field centres located along the radial direction of 35 degrees below the horizontal meridian. In this 35 degree Radial Group a horizontal bias was also confirmed. Analysis of the dispersion of major axis orientations with eccentricity from the area centralis showed a statistically significant decrease in scatter and, hence, indicated an increase in the horizontal bias with eccentricity.

Animals↗
PubMed1987

Vestibular and optokinetic eye movements evoked in the cat by rotation about a tilted axis.

Horizontal and vertical eye movements were recorded from cats in response to either off-vertical axis rotation (OVAR) at a range of velocities (5-72 deg/s) and a range of tilts (0-60 deg) or horizontal (with respect to the cat) optokinetic stimulation (10-80 deg/s), also around a range of tilted axes (0-60 deg). The responses to stopping either of these stimuli were also measured: post-rotatory nystagmus (PRN) following actual rotation, and optokinetic after nystagmus (OKAN) following optokinetic stimulation. The response found during OVAR was a nystagmus with a bias slow-phase velocity that was sinusoidally modulated. The bias was dependent on the tilt and reached 50% of its maximum velocity (maximum was 73 +/- 23% of the table velocity) at a tilt of 16 deg. The phase of modulation in horizontal eye velocity bore no consistent relation to the angular rotation. The amplitude of this modulation was roughly correlated with the bias with a slope of 0.13 (deg/s) modulation/(deg/s) bias velocity. There was also a low-velocity vertical bias with the slow-phases upwardly directed. The vertical bias was also modulated and the amplitude depended on the bias velocity (0.27 (deg/s) modulation/(deg/s) bias velocity). When separated from the canal dependent response, the build up of the OVAR response had a time constant of 5.0 +/- 0.8 s. Following OVAR there was no decline in the time constant of PRN which remained at the value measured during earth-vertical axis rotation (EVAR) (6.3 +/- 2 s). The peak amplitude of PRN was reduced, dependent on the tilt, reaching only 20% of its EVAR value for a tilt of 20 deg. When a measurable PRN was found, it was accompanied by a slowly-emerging vertical component (time constant 5.4 +/- 2 s) the effect of which was to vector the PRN accurately onto the earth horizontal. OKN measured about a tilted axis showed no differences in magnitude or direction from EVAR OKN even for tilts as large as 60 deg. OKAN following optokinetic stimulation around a tilted axis appeared normal in the horizontal plane (with respect to the animal) but was accompanied by a slowly emerging (time constant 4.1 +/- 2 s) vertical component, the effect of which was to vector the overall OKAN response onto the earth horizontal for tilts less than 20 deg. These results are compared with data from monkey and man and discussed in terms of the involvement of the velocity storage mechanism.

Animals↗
PubMed1988

Nystagmus induced by off-vertical rotation axis in the cat.

1) In the alert cat, nystagmus induced by off-vertical axis rotation (OVAR) was recorded following steps in head velocity or ramps of velocity at constant acceleration below canal threshold. Dependence of nystagmus characteristics on tilt angle of rotation axis and head velocity was studied. Similar results were obtained with both types of stimulation. 2) Mean and modulation amplitude of horizontal eye velocity increased with tilt angle in the range 0-30 degrees. 3) Both variables increased also with head velocity, but with different trends, probably because they are set by different mechanisms. When head rotational velocity was increased above 80 degrees/s, mean eye velocity progressively decreased to zero. 4) In spite of variations from one animal to another, some regularity was observed in the phase of eye velocity modulation. In several cases, a reduction in phase lead of eye velocity with respect to conventional origin of phases (nose-down position) was observed when head velocity increased. 5) Time constant of post-OVAR nystagmus decreased with the tilt angle of the rotation axis from gravity, but not with the orientation of the head with respect to rotation axis. 6) The results could be accounted for by a general equation describing the vestibulo-ocular reflex, provided that estimates of kinematic variables of head movement (head rotational and translational velocities), and visual target distance could be computed by the Central Nervous System.

Animals↗
PubMed1995

Ontogenetic studies of tolerance development: effects of chronic morphine on the hypothalamic-pituitary-adrenal axis.

Endogenous opiates are important regulators of the hypothalamic-pituitary-adrenal (HPA) axis in rats. Tolerance clearly develops to morphine-induced stimulation of the HPA axis in adult rats (Ignar and Kuhn 1990). The goal of the present study was to determine whether tolerance to morphine-induced stimulation of the HPA axis developed in neonatal and weanling rats treated chronically with morphine. Rats were injected with morphine or saline between days 4-8 postnatal (pups) or days 21-25 (weanlings) and tolerance assessed by determining dose-response curves for ACTH and corticosterone secretion following an acute morphine challenge. Weanlings displayed marked tolerance to the stimulation of ACTH and corticosterone secretion by morphine. Tolerance was also observed in pups to morphine-stimulated ACTH and corticosterone release. These findings suggest that the relative adaptability of the HPA axis to chronic morphine in neonatal and weanling rats is similar.

Adrenocorticotropic Hormone↗
PubMed1996

Color axis evaluation of the Farnsworth Munsell 100-hue test in primary open-angle glaucoma and normal-pressure glaucoma.

BACKGROUND: It was the aim of the present study to analyze a separate color-axis evaluation of the Farnsworth Munsell 100-hue test (FM 100) in primary open-angle glaucoma (POAG) and normal pressure glaucoma (NPG). PATIENTS AND METHODS: One eye of each of 112 individuals (age 35-65 years, visual acuity > 20/28, myopia < -7.5 D) was included. The groups consisted of 62 normal subjects and 50 glaucoma patients (33 POAG and 17 NPG). We evaluated the FM 100 overall error score and the error scores of the protan, deutan and tritan axes. The results were compared with perimetric (Octopus G1 mean defect) and morphometric data of the optic disc. RESULTS: All error scores were significantly higher in the glaucoma group than in the normal group. In an age-related evaluation, differences were significant in age groups above 45 years. No significant differences were found between the POAG and NPG groups. The sensitivity of the overall score to identify glaucoma was 62% (specificity 80%). In the glaucoma group the overall score and the protan score increased significantly with the mean defect (r > 0.3, P < 0.01). Several scores increased slightly with decreasing neuroretinal rim area, but not on a significant level. Separate color-axis evaluations did not show any stronger correlations and did not reveal any differences between POAG eyes and NPG eyes. This was true even for the tritan axis error. CONCLUSIONS: Although FM 100 error scores are higher in glaucoma eyes and increase with glaucomatous damage, they do not separate well. In the sample of this study, separate color-axis evaluation did not improve the diagnostic value. With the FM100 a different pattern of color vision defects in POAG and NPG eyes could not be detected.

Adult↗
PubMed2003

Hypothalamo-pituitary-adrenal axis in acute myocardial infarction treated by percutaneous transluminal coronary angioplasty: effect of time of presentation.

Acute myocardial infarction (AMI) is associated with a stimulation of cortisol which lasts 24 hours in patients treated by thrombolysis. Percutaneous transluminal coronary angioplasty (PTCA) is an alternative treatment for AMI which reduces the length of myocardial ischemia. Our objective was the determination of the amplitude and duration of cortisol and other hormones of the hypothalamo-pituitary-adrenal (HPA) axis release in patients undergoing PTCA. These responses were also analyzed in relation with the time of onset of AMI. The effect of coronarography with or without angioplasty in patients without AMI was also studied. Plasma ACTH, cortisol, corticotropin-releasing hormone and arginine vasopressin levels were determined during the first 48 hours in 20 patients with first AMI, treated by PTCA and in 10 patients without AMI undergoing coronarography (and angioplasty in five of them). A strong stimulation of the HPA axis was observed in AMI patients, but the duration of cortisol secretion was significantly reduced (less than 8 hours) as compared with previous studies in patients treated with thrombolysis. A clear-cut ACTH-cortisol dissociation was also observed after the third hour. ACTH and cortisol stimulation was higher in patients admitted between 04:00 h and 16:00 h than in patients admitted between 16:00 h and 04:00 h In patients without AMI, coronarography induced a moderate, but significant short-lasting ACTH and cortisol stimulation. In conclusion, our data suggest that the degree of stimulation of the HPA axis may depend upon the type of treatment and the circadian rhythm of this axis.

Adrenocorticotropic Hormone↗
PubMed1996

Acute stimulation of the hypothalamic-pituitary-adrenal axis by IL-1 beta, TNF alpha and IL-6: a dose response study.

We investigated the effects of i.v. and intracerebroventricular (i.c.v) administration of increasing doses of recombinant human IL-1 beta, TNF alpha and IL-6 on plasma corticosterone (B) levels in rats. Rats were equipped with a jugular cannula for repeated blood sampling anda subgroup of rats also received an i.c.v implanted cannula. I.v. administration of IL-1 beta, TNF alpha or IL-6 and i.c.v administration of IL-1 beta and IL-6 induced a significant dose-dependent increase in plasma B levels, whereas i.c.v injection of TNF alpha in doses up to 1000 ng/rat was not effective. I.v. pretreatment of rats with anti-CRH antiserum had no significant overall effect on the plasma B response to i.v. administered IL-1 beta (500 and 3000 ng/rat), whereas the plasma B response to i.v. TNF alpha or IL-6 administration (3000 ng/rat) were significantly reduced. I.v. pretreatment of the animals with recombinant human IL-1 receptor antagonist (IL-1ra) significantly blocked the plasma B response to i.v. treatment with IL-1 beta, whereas the TNF alpha- and IL-6-induced increases in plasma B levels were not affected. Our data show that 1) i.v. administration of IL-beta, TNF alpha or IL-6 and i.c.v administration of IL-1 beta or IL-6 dose-dependently stimulate the HPA axis; 2) when given i.v. or i.c.v, IL-1 beta is more powerful than TNF alpha and IL-6 in activating the HPA axis; 3) endogenous CRH is involved in the activation of the HPA axis by acute i.v. administration of TNF alpha and IL-6. It is most likely that in case of i.v. treatment with IL-1 beta a CRH-independent mechanism is involved. This study provides no arguments for the involvement of endogenous IL-1 in TNF alpha- or IL-6-induced activation of the HPA axis.

Adrenal Glands↗
PubMed2004

Investigation of the hypothalamo-pituitary-adrenal axis (HPA) by 1 microg ACTH test and metyrapone test in patients with primary fibromyalgia syndrome.

Primary fibromyalgia syndrome (PFS) is characterized by widespread chronic pain that affects the musculoskeletal system, fatigue, anxiety, sleep disturbance, headache and postural hypotension. The pathophysiology of PFS is unknown. The hypothalamic-pituitary-adrenal (HPA) axis seems to play an important role in PFS. Both hyperactivity and hypoactivity of the HPA axis have been reported in patients with PFS. In this study we assessed the HPA axis by 1 microg ACTH stimulation test and metyrapone test in 22 patients with PFS and in 15 age-, sex-, and body mass index (BMI)- matched controls. Metyrapone (30 mg/kg) was administered orally at 23:00 h and blood was sampled at 08:30 h the following morning for 11-deoxycortisol. ACTH stimulation test was carried out by using 1 microg (iv) ACTH as a bolus injection after an overnight fast, and blood samples were drawn at 0, 30 and 60 min. Peak cortisol level (659.4 +/- 207.2 nmol/l) was lower in the patients with PFS than peak cortisol level (838.7 +/- 129.6 nmol/l) in the control subjects (p < 0.05). Ten patients (45%) with PFS had peak cortisol responses to 1 microg ACTH test lower than the lowest peak cortisol detected in healthy controls. After metyrapone test 11-deoxycortisol level was 123.7 +/- 26 nmol/l in patients with PFS and 184.2 +/- 17.3 nmol/l in the controls (p < 0.05). Ninety five percent of the patients with PFS had lower 11-deoxycortisol level after metyrapone than the lowest 11-deoxycortisol level after metyrapone detected in healthy controls. We also compared the adrenal size of the patients with that of the healthy subjects and we found that the adrenal size between the groups was similar. This study clearly shows that HPA axis is underactivated in PFS, rather than overactivated.

Adrenal Glands↗
PubMed2004

The endocrinology of adrenal tuberculosis: the effects of tuberculosis on the hypothalamo-pituitary-adrenal axis and adrenocortical function.

Tuberculosis may affect many of the endocrine glands including the hypothalamus, pituitary, thyroid and adrenals. The most commonly involved endocrine organ in tuberculosis is the adrenal gland. Adrenal glands may be directly or indirectly affected by tuberculosis. Tuberculous Addison's disease is still an important cause of primary adrenocortical insufficiency particularly in the developing countries. Recent improvements in imaging techniques and modern endocrinological tests for the investigation of adrenal function have given us greater insight into the endocrinology of adrenal tuberculosis. Hypothalamo-pituitary-adrenal (HPA) axis is also involved in tuberculosis and recent findings revealed that HPA axis is activated rather than underactivated in active pulmonary tuberculosis. Activated HPA axis in tuberculosis causes increased cortisol secretion which results in a shift in the Th1/Th2 balance towards Th2. T cell dysfunction due to high cortisol and low DHEAS levels may be responsible for immunologically-mediated tissue damage in tuberculosis. In this review, recent findings concerning the adrenocortical function, radiological changes in adrenal glands and HPA axis involvement in tuberculosis are discussed.

Addison Disease↗
PubMed2003

The helical axis of the mandible during the opening and closing movement of the mouth.

BACKGROUND: The movement of a rigid body through space may be comprehensively described by constructing a "finite helical axis" (FHA). The rigid body carries out a rotation around this axis for discrete periods of time while at the same time moving along this axis. MATERIAL AND METHODS: The free opening and closing movement of the mouth was registered in eight asymptomatic test persons, using the CADIAX electronic axiography system (GAMMA-DENTAL, Klosterneuburg, Austria). Subsequently, the position of the FHA in space, the angle of rotation around this axis, and the amount of translation along the FHA were determined for each subject, using the coordinates of the measuring styluses. RESULTS: During the initial phase of the mouth-opening movement, the FHAs were near the condyle. Over the course of the opening movement, they moved toward downward backward, downward and downward forward, and finally to forward upward toward the condyle upon reaching maximum mouth opening. During the closing movement, the FHAs shifted back in the reverse direction. During both the opening and the closing movement, there was a slight translational movement along the FHAs, which provided an indication of mandibular deviation.

Diagnosis, Computer-Assisted↗
PubMed2005

The associations between substance use disorders, schizophrenia-spectrum disorders, and Axis IV psychosocial problems.

BACKGROUND: Substance abuse among individuals with schizophrenia-spectrum disorders (SSDs) is associated with a range of adverse psychosocial outcomes in the areas of occupational functioning, housing stability, economic independence, access to health care, and involvement with the legal system. The aim of this study was to estimate the effects of substance use disorders (SUDs), SSDS, and dual diagnosis with both disorders on the risk for six important Axis IV psychosocial problems. This was accomplished using a large dataset of patients who are representative of individuals in routine US psychiatric practice. METHOD: Weighted data from the 1999 Study of Psychiatric Patients and Treatments from a practice-based research network of the American Psychiatric Institute for Research and Education were analyzed. Some 615 US psychiatrists provided detailed clinical, psychosocial, and health services information on 1,843 patients, including 285 patients with one or more SUDs without an SSD, 180 patients with a diagnosis of an SSD without substance abuse comorbidity, and 68 dually diagnosed patients. Logistic regression models were used to determine effect estimates (adjusted odds ratios), and corresponding 95% confidence intervals were calculated. RESULTS: After adjusting for sociodemographic variables and for SSD diagnosis, SUD diagnosis was independently associated with increased risk for five of the Axis IV psychosocial problems of interest (occupational problems, housing problems, economic problems, problems with access to health care services, and problems related to interaction with the legal system/crime) when compared to all other psychiatric patients (n=1,310). After adjusting for the sociodemographic variables and for SUD diagnosis, SSD diagnosis (compared to all other psychiatric diagnoses) was associated with Axis IV economic problems, but not with the other five psychosocial problems of interest. The presence of both an SUD and an SSD diagnosis (dual diagnosis) was associated with a greater risk for four of the six Axis IV psychosocial problems studied, compared to the risks associated with either diagnosis alone. Limiting the substance of abuse to alcohol resulted in similar findings. CONCLUSIONS: Although SUDs are associated with increased risk for poor social adjustment, the comorbidity of SUDs and SSDs is associated with greatly compounded psychosocial burdens. These findings, from a large sample of representative US psychiatric patients, demonstrate the ongoing need for improved services and policies for those specially burdened patients with the dual diagnosis of both an SSD and substance abuse or dependence.

Adult↗