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Biomedical subjects

R Jacobs

Publications and source records attributed to R Jacobs.

At least 73 records · Page 4Linked to original sources
PubMed1999

A multisensory integration model of human stance control.

A model is presented to study and quantify the contribution of all available sensory information to human standing based on optimal estimation theory. In the model, delayed sensory information is integrated in such a way that a best estimate of body orientation is obtained. The model approach agrees with the present theory of the goal of human balance control. The model is not based on purely inverted pendulum body dynamics, but rather on a three-link segment model of a standing human on a movable support base. In addition, the model is non-linear and explicitly addresses the problem of multisensory integration and neural time delays. A predictive element is included in the controller to compensate for time delays, necessary to maintain erect body orientation. Model results of sensory perturbations on total body sway closely resemble experimental results. Despite internal and external perturbations, the controller is able to stabilise the model of an inherently unstable standing human with neural time delays of 100 ms. It is concluded, that the model is capable of studying and quantifying multisensory integration in human stance control. We aim to apply the model in (1) the design and development of prostheses and orthoses and (2) the diagnosis of neurological balance disorders.

Afferent Pathways↗
PubMed1999

Absence of the alpha6(IV) chain of collagen type IV in Alport syndrome is related to a failure at the protein assembly level and does not result in diffuse leiomyomatosis.

X-linked Alport syndrome is a progressive nephropathy associated with mutations in the COL4A5 gene. The kidney usually lacks the alpha3-alpha6 chains of collagen type IV, although each is coded by a separate gene. The molecular basis for this loss remains unclear. In canine X-linked hereditary nephritis, a model for X-linked Alport syndrome, a COL4A5 mutation results in reduced mRNA levels for the alpha3, alpha4, and alpha5 chains in the kidney, implying a mechanism coordinating the production of these 3 chains. To examine whether production of alpha6 chain is under the same control, we studied smooth muscle cells from this animal model. We determined the canine COL4A5 and COL4A6 genes are separated by 435 bp, with two first exons for COL4A6 separated by 978 bp. These two regions are >/= 78% identical to the human sequences that have promoter activity. Despite this potential basis for coordinated transcription of the COL4A5 and COL4A6 genes, the alpha6 mRNA level remained normal in affected male dog smooth muscle while the alpha5 mRNA level was markedly reduced. However, both alpha5 and alpha6 chains were absent at the protein level. Our results suggest that production of the alpha6 chain is under a control mechanism separate from that coordinating the alpha3-alpha5 chains and that the lack of the alpha6 chain in Alport syndrome is related to a failure at the protein assembly level, raising the possibility that the alpha5 and alpha6 chains are present in the same network. The lack of the alpha6 chain does not obviously result in disease, in particular leiomyomatosis, as is seen in Alport patients with deletions involving the COL4A5 and COL4A6 genes.

Animals↗
PubMed1999

Long-term efficacy of treatment of chronic hepatitis C with alpha interferon or alpha interferon and ribavirin.

The major objective of treatment of chronic hepatitis C virus (HCV) infection is to prevent progression to cirrhosis, and thereby prevent complications of end-stage liver disease. The established treatment of chronic HCV is with alpha interferon. Recent results with ribavirin and alpha interferon together suggest that combination antiviral therapy will become the benchmark treatment. For both naive and relapsed patients, however, it has become important to assess the long-term outcome of treatment, in order to gauge whether treatment has indeed modified the natural history of chronic hepatitis C virus infection. It seems likely that most sustained responders (85-90%) treated with combination ribavirin and alpha interferon will continue to have a long-term biochemical and virological response, as has been demonstrated with alpha interferon alone, but further long-term follow-up of patients treated with combination therapy is required.

Antiviral Agents↗
PubMed1999

Effects of fentanyl on cellular immune functions in man.

In order to analyze the effects of the opioid agonist fentanyl on cells of the innate immune system, seven healthy individuals were treated intravenously with the opioid fentanyl and five subjects received a placebo. Respiratory burst of polymorphonuclear cells (PMNC) and phenotypes of peripheral blood lymphocytes (PBL) were analyzed from blood samples drawn before, 15 and 30 min after fentanyl or placebo application. In addition, in vitro effects of fentanyl on natural killer (NK) activity was assessed. Fentanyl administration affected neither superoxide production of PMNC nor circulating numbers of B-and T-lymphocytes. In contrast, NK cell (CD16+/CD56+) numbers significantly increased in response to fentanyl. However, no direct influence of fentanyl on NK cell function in vitro could be detected. These results suggest a transient effect of fentanyl on NK cell circulation which seemed to be centrally mediated rather than a direct effect of this opioid on NK cells.

Adult↗
PubMed1999

Predictability of reformatted computed tomography for pre-operative planning of endosseous implants.

OBJECTIVES: To determine the reliability of reformatted 2D-CT for pre-operative planning of implant placement. METHODS: One hundred consecutive partially or fully edentate patients underwent 2-D reformatted CT pre-operative planning and subsequent implant placement. The number, site and size of the implants, the available bone height and anatomical complications were recorded. The pre-operative planning and the outcome at surgery were compared statistically using a percentage agreement and Kendall's correlation coefficient. RESULTS: Agreement between the pre- and intra-operative data was good for the number of implants (60%) and the selected sites (70%). From a total of 416 implants planned, 21 implants could not be placed because of intra-operative findings. Agreement was relatively poor for implant size (44%) and anatomical complications (46%). Kendall's correlation coefficient was highest for the number of implants (0.80) and implant sites (0.81). It was much lower for implant sizes (0.51) and did not reach significance for anatomical complications (0.09). CONCLUSIONS: Reformatted 2D-CT is reliable for the pre-operative assessment of the number and sites of implants in the jaws. It is less predictable for the implant size needed and poor for anatomical complications.

Adolescent↗
PubMed1999

Predictability of a three-dimensional planning system for oral implant surgery.

OBJECTIVES: To compare 2D CT alone with 2D + 3D reconstruction for pre-operative planning of implant placement. METHODS: Spiral CT scans of 33 consecutive patients were used for both reformatted 2D and 3D computer-assisted planning. The number, site and size of implants and the occurrence of anatomical complications during planning and implant placement were statistically compared using the percentage agreement and the Kendall's correlation coefficients (tau). Although planning was performed in 33 patients, implants were only placed in 21 patients. In 11 patients surgery was based on 2D + 3D imaging and in ten patients on 2D planning. RESULTS: Agreement between planning and placement of implants was highly significant for the implant sites selected. For 2D based planning and placement, agreement reached 68% (tau = 0.94). For 2D + 3D based planning and placement, agreement attained 73% (tau = 0.89). For planning and placement of implant size based on 2D images, agreement was 31% and not significant (tau = 0.23). When based on 2D + 3D images, agreement for implant size was 44% (tau = 0.5). Agreement was not significant for anatomical complications: 69% for 2D planning and 71% for 2D + 3D planning (tau = 0.24 for 2D and tau = 0.21 for 2D + 3D). CONCLUSIONS: The 3D planning system is a reliable tool for pre-operative assessment of implant placement. Both 2D and 2D + 3D planning have a good predictability for the number and site of the implants but less so for anatomical complications. However, the 2D + 3D planning provides a better pre-operative assessment of implant size.

Adult↗
PubMed1999

Clinical presentation of tuberculosis in culture-positive children. Pediatric Tuberculosis Consortium.

BACKGROUND: Because tuberculosis (TB) in children implies recent infection, children serve as sentinels for disease transmission within a community. Despite the significance of diagnosing tuberculosis in children, most cases are diagnosed on clinical evidence rather than laboratory findings. METHODS: We analyzed the demographic and clinical presentation of 156 children with culture proven tuberculosis using Epi-Info Version 6. RESULTS: Although the clinical characteristics of this population were generally consistent with those seen in previous studies, several unexpected results were observed. Boys were overrepresented in the group of very young children (72% < 1 year). Many of the children had coexisting diseases not known to predispose to TB (37%). Cavitation, usually observed in older children, was seen in four children < or = 1 year of age. Few children were homeless or HIV-infected, but many (42%) lived in female-headed households. Of the adult contacts at risk for TB, many (49%) were recent immigrants to the US. Overall 34% of the population was either foreign born or the children of recent immigrants. CONCLUSIONS: This series of 156 culture-positive children provides an understanding of the risk factors and clinical presentation of pediatric tuberculosis. The data emphasize the impact of the child's environment on the risk for tuberculosis.

Adolescent↗
PubMed1999

Effects of fentanyl and low doses of alcohol on neuropsychological performance in healthy subjects.

The effects of the opioid fentanyl and low doses of alcohol on neuropsychological functions in healthy volunteers were measured. Twenty-four healthy male volunteers participated in this study. Two randomised placebo-controlled cross-over trials were conducted. In group 1, 6 subjects received fentanyl (0.2 microgram/kg body weight) in the order of fentanyl/placebo and 6 subjects in the order of placebo/fentanyl. Group 2 received alcohol in a similar procedure by continuous intravenous infusion, leading to a blood alcohol concentration (BAC) of 0.03%. Impairment was measured via different neuropsychological tests. The results indicate that fentanyl in concentrations commonly used in out-patient surgical procedures produces pronounced cognitive impairment (auditory reaction time, signal detection, sustained attention, recognition) in comparison to placebo. After application of low doses of alcohol (BAC 0.03%) only visual reaction time was impaired in comparison to placebo.

Adult↗
PubMed1999

Influence of inflammatory reactions vs. occlusal loading on peri-implant marginal bone level.

Plaque accumulation on abutments or implant surfaces induces an inflammatory reaction in the gingiva/alveolar mucosa just as around teeth. The longevity of oral implants can be jeopardized by either peri-implantitis and/or an occlusal overload. In the partially edentulous patient in whom pockets around teeth act as a reservoir for the colonization of the pockets around implants, the risk for inflammatory reactions of the peri-implant soft tissues seems especially more plausible than in the fully edentulous patient. This is especially true for implants with a very rough surface (e.g., plasma-sprayed), because of the positive relationship between surface roughness and supra- as well as subgingival plaque formation. Several medium-term (from 5 to 10 years) clinical studies support this hypothesis, through the observation of ongoing bone loss and subsequent decreasing success/survival percentages. Occlusal overload increases the risk for microfractures at the implant-bone interface in two-stage implants, which can result in significant marginal bone loss and even failure. There is ample evidence that occlusal factors are related to marginal angular defects around two-stage implants.

Alveolar Bone Loss↗
PubMed1999

[Preoperative planning for the placement of a single implant].

Radiography is of primary importance for the preoperative planning of oral implant placement. Depending on the indication, various techniques are available, each with its own merits and drawbacks. In general, it can be stated that the intra-oral radiography using the paralleling technique is the method of choice for a solitary tooth replacement. Panoramic radiography is indicated for implant placement in the symphyseal area of the lower jaw. Cross-sectional imaging is performed when information is needed in the bucco-lingual dimension. Conventional tomography is recommended for preoperative planning of limited edentulous areas. CT-scan imaging is required for rehabilitation of extended edentulous areas or in complex maxillofacial surgery combined with implant placement. Choosing the optimal technique can be performed by weighing the radiation dosage and the diagnostic information required.

Dental Implantation, Endosseous↗
PubMed1998

EAE TCR motifs and antigen recognition in myelin basic protein-induced anterior uveitis in Lewis rats.

T cells infiltrating the iris/ciliary body of Lewis rats with anterior uveitis (AU) that had been induced by myelin basic protein (MBP) immunization were previously found to share surface markers common to the T cells that cause experimental autoimmune encephalomyelitis (EAE). To determine whether these AU-associated T cells are in fact the same as those that infiltrate the central nervous system to cause EAE, we examined TCR V gene expression in T cells infiltrating the anterior chamber in rats with AU. As with EAE, we found a biased expression of Vbeta8.2 and Valpha2 in the iris/ciliary body and, although one would expect an influx of nonspecific inflammatory T cells, these biases were still evident at the peak of AU. An analysis of the TCR Vbeta8.2 and Valpha2 sequences derived from the iris/ciliary body demonstrated the presence of the same complementarity determining region 3 motifs found in MBP-specific T cells that are pathogenic for EAE and found in T cells derived from the central nervous system of rats with EAE. Finally, T cells isolated from the iris/ciliary body of rats with AU were found to proliferate in a specific fashion to MBP Ags. Thus, it appears that MBP-specific T cells are pathogenic for AU as well as EAE in the Lewis rat. In addition, the long-term presence of this highly restricted MBP response in the iris/ciliary body indicates that distinct immunoregulatory mechanisms exist in the environment of the eye. This provides an interesting model with which to address questions pertaining to the nature of T cells infiltrating the eye and their regulation during EAE and other systemic diseases.

Animals↗
PubMed1998

Neonatal exposure of TCR BV8S2 transgenic mice to recombinant TCR BV8S2 results in reduced T cell proliferation and elevated antibody response to BV8S2, and increased severity of EAE.

Transgenic (Tg) mouse models are unique tools for investigating regulatory mechanisms of the immune system. Mice bearing a T cell receptor (TCR) BV8S2 transgene derived from an encephalitogenic T cell clone are highly susceptible to experimental autoimmune encephalomyelitis (EAE), a T cell-mediated neurological disorder. Although the pathogenesis of EAE is not yet fully understood, TCR-specific regulatory T cells seem to play a role in its remission and/or recovery process. In previous studies, we showed that immunization of BV8S2 Tg mice with recombinant BV8S2 protein induced TCR-specific T cells and protection against EAE, clearly indicating the persistence of a functional TCR regulatory network in spite of the highly skewed T cell repertoire. To further investigate the natural regulatory role of TCR-specific T cells, we evaluated the effect on EAE of inducing neonatal tolerance to heterologous (rat) and homologous BV8S2 proteins in Tg mice. Neonatal exposure to rat BV8S2 protein induced "split" tolerance, characterized by decreased T cell proliferation but increased antibody responses to both rat and mouse BV8S2 proteins that are known to be cross-reactive. When challenged as adults with an encephalitogenic emulsion, Tg mice tolerized with rat but not mouse BV8S2 protein developed more severe EAE compared to control mice. These results demonstrate that immunity to BV8S2 determinants in BV8S2 Tg mice is naturally induced and functions to limit the severity of EAE.

Animals↗
PubMed1998

Endocrine mechanisms of stress-induced DHEA-secretion.

Acute psychological stress of a first time parachute jump stimulated DHEA and cortisol secretion in healthy volunteers. A significant shift from cortisol to DHEA occurred during this stress exposure. This effect was more pronounced in subjects receiving the beta-adrenoceptor antagonist propranolol prior to the jump. In contrast, infusion of epinephrine (0.10 microgram/kg/min) or norepinephrine (0.15 microgram/kg/min) for 20 min neither affected DHEA plasma levels nor the DHEA/cortisol ratio. However, pretreatment with propranolol resulted in a significant increase of the DHEA/cortisol ratio upon infusion of the beta-adrenoceptor agonist epinephrine. These data demonstrate that during acute psychological stress stimulation of adrenal steroid release is accompanied by a shift towards DHEA. Augmentation of this effect by beta-adrenoceptor blockade indicates a beta-adrenoceptor-dependent mechanism affecting DHEA release.

Acute Disease↗
PubMed1998

Effects of beta-adrenoceptor-blockade on stress-induced adrenocorticotrophin release in humans.

We investigated the mechanisms of stress-induced alterations in adrenocorticotrophin (ACTH) release. Tandem parachutists received either a placebo or the beta-adrenoceptor antagonist propranolol prior to a first time parachute jump. Blood samples were drawn 4 h before, immediately after, and 1 h after the jump. Cortisol and catecholamine concentrations displayed a significant stress-induced increase in both groups. The ACTH plasma concentrations significantly increased in the placebo and the propranolol group, with significantly more pronounced changes in the propranolol-treated subjects compared to the placebo group. These data demonstrated a stress-induced increase of ACTH plasma concentrations in humans that was enhanced by beta-blockade.

Adrenergic beta-Antagonists↗
PubMed1998

Oral stereognosis: a review of the literature.

Stereognosis is the ability to recognise and discriminate forms. Oral stereognostic ability has been studied in different reports. The experimental design of the test is of primary importance as both the method used and the material applied may influence the results dramatically. The form, size and surface characteristics of the test piece, the presentation order, subject-related factors and the method of scoring all have their effect on the results. With regard to subject-related factors, ageing has a negative influence on stereognostic ability; gender is considered of no importance. Another influencing factor is dental status. A healthy natural dentition offers a very good oral stereognostic ability. Edentulous subjects usually show a decreased oral stereognostic ability, depending on the rehabilitation form. A number of questions have been addressed, especially with regard to the perception itself. Receptors mainly involved in oral stereognostic ability are located in various oral structures and form perception results from an association of more than one group of receptors. The following review tries to deal with these questions and attempts to provide clear guidelines for further research on oral stereognosis.

Humans↗
PubMed1998

Stress-induced endocrine and immunological changes in psoriasis patients and healthy controls. A preliminary study.

BACKGROUND: Clinical observations suggest that psychological stress can induce exacerbation of psoriasis. It is hypothesized that these stress effects on the course and outcome of psoriasis are caused by neuroendocrine modulation of immune functions. Therefore we investigated the cardiovascular, endocrine and immunological response to a laboratory stressor in psoriasis patients and healthy controls. METHODS: Untreated (n = 7) and PUVA-treated (n = 4) psoriatics and healthy controls (n = 7) were exposed to a brief laboratory stressor (public speaking and mental arithmetic). Heart rate and blood pressure, catecholamine, cortisol, and DHEA plasma concentration, as well as distribution of T and NK lymphocytes were analyzed before, immediately after and 1 h after stress exposure. RESULTS: Heart rate and blood pressure increased in all three groups during stress exposure with the most pronounced changes in PUVA-treated patients. Psoriasis patients displayed higher adrenaline values but diminished cortisol and DHEA plasma concentrations compared to controls. NK cell numbers (CD16+, CD56+), but not T lymphocyte subsets, increased immediately after stress exposure in untreated patients and controls. This effect was significantly diminished in PUVA-treated patients. CONCLUSIONS: The data of this pilot study indicate an enhanced stress-induced autonomic response and diminished pituitary-adrenal activity in psoriasis patients. PUVA treatment seems to interfere with the cardiovascular and NK cell response to acute psychological stress. Future studies will analyze the stress-induced neuroimmunological mechanisms in psoriatics in more detail.

Adult↗
PubMed1997

Adrenergic control of natural killer cell circulation and adhesion.

Natural killer (NK) cell circulation is subject to adrenergic regulation. Exactly how NK cells are released into the circulation is unknown. In an attempt to identify some of the mechanisms, the present report focuses on aspects of adhesion regulation of NK cells. Results demonstrate that interactions between NK and endothelial cells (EC) in vitro can be reduced by beta 2-adrenoceptor stimulation for as long as the receptor stimulation occurs. The level of soluble adhesion molecules (sICAM-1, sE-selectin, sVCAM-1) in vivo remained unchanged during adrenaline infusion. In vitro analyses further reveal the requirement for Ca2+/Mg2+ in NK-EC adhesion. Blocking studies indicate the involvement of several members of the beta 1(CD29)- and beta 2(CD18)-integrin family, reducing NK cell adhesion by 28 to 39%. Stimulation of beta 2-adrenoceptors in the presence of these blocking antibodies further reduced NK adhesion by an average of 22%. Analysis of NK cell adhesion to various extracellular matrix components demonstrates significant NK cell adhesion to fibronectin but much less to laminin or collagens I and IV. NK cell adhesion to fibronectin was reduced by 50% upon beta 2-adrenoceptor stimulation, independent of the VLA-4/VLA-5 binding site on fibronectin. Together these results contribute to understanding the influences of beta-adrenoceptor stimulation on NK cell circulation and adhesion.

Cell Adhesion↗