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C Jacobs

Publications and source records attributed to C Jacobs.

At least 19 recordsLinked to original sources

Neurons expressing serotonin-1B receptor in the basolateral nuclear group of the amygdala in normally behaving and aggressive dogs.

The present study aimed to quantify neurons expressing the serotonin-1B receptor and evaluate numerical differences in normally behaving and pathologically aggressive dogs in order to assess whether the serotonin-1B receptor is involved in pathological canine aggression. Because previous studies have reported structural alterations in the basolateral nuclear group (BNG) of the amygdaloid body of aggressive dogs, this structure was selected as region of interest in the present study. Indirect immunohistochemistry was applied to visualise the serotonin-1B-receptor-positive neurons. Immunoreactivity was located predominantly within the neuronal cell bodies and adjacent neuronal processes. In the aggressive dogs the BNGs contained a significantly higher number of serotonin-1B-receptor-positive neurons compared to the normally behaving dogs. This number was strongly correlated with the total number of neurons per BNG, which was also significantly increased in aggressive dogs compared to normal dogs. The percentage of neurons expressing the serotonin-1B receptor did not differ significantly between both groups. No significant asymmetries were observed for the number and percentage of serotonin-1B-receptor-positive neurons. Potential relationships between the present findings and the etiology of aggressive behaviour, the neuroprotective role of the serotonin-1B receptor and receptor dysfunction are discussed.

Aggression↗

Neurokinin-1 receptor in the basolateral nuclear group of the canine amygdala--comparative study in normal and aggressive dogs.

Substance P and its NK-1 receptor are involved in the modulation of aggressive behavior. Because of the role of the basolateral nuclear group (BNG) of the amygdala in canine aggression, neurokinin-1 receptor (NK-1) immunoreactivity in this brain region was assessed stereologically in 7 normally behaving and 6 pathologically aggressive dogs. The first aim of this study was to obtain information about the absolute number of neurons expressing the NK-1 receptor in the canine BNG because absolute numbers of neurons expressing the NK-1 receptor are not documented in literature. Additionally, an exploratory comparison was made between NK-1 expressing neurons in the BNGs of normally behaving and aggressive dogs. Results showed a very low amount (1-2%) of BNG neurons containing the NK-1 receptor in both groups. Aggressive dogs had significantly more NK-1-receptor-positive BNG neurons than normal dogs, but the numerical densities and fractions of receptor-positive neurons did not differ significantly between both groups. Combined with the fact that aggressive dogs have 27% more neurons in their BNGs than normal dogs, as reported in a previous study, these findings suggest a limited role for the NK-1-receptor-positive neurons within the BNG in the modulation of canine aggression. The present report of absolute numbers of neurons expressing the NK-1 receptor in the canine BNG could however be useful for further quantitative studies.

Aggression↗

Increased volume and neuronal number of the basolateral nuclear group of the amygdaloid body in aggressive dogs.

Involvement of the basolateral nuclear group (BNG) in pathological canine aggression was assessed by stereological determination of the volume of the BNG and quantification of the numerical density and total number of BNG neurons in normally behaving and aggressive dogs. A bilateral BNG enlargement of 40% was observed in the aggressive group. This enlargement appeared to be caused by a significantly increased number of BNG neurons. Other alterations such as an increased vessel density, oedema and scar tissue were not observed in any of the examined BNGs. The potential role of neurotrophins and stress hormones in the increased number of BNG neurons is discussed.

Aggression↗

Increased number of neurons expressing androgen receptor in the basolateral amygdala of pathologically aggressive dogs.

The present study aimed to determine the extent to which the androgen receptor (AR) is directly involved in the hormonal modulation of pathological canine aggressive behaviour in the basolateral nuclear group (BNG) of the amygdaloid body. A stereological quantification of AR-positive neurons was performed in the BNGs of normally behaving and aggressive male dogs. The BNG was selected because it is involved in sexual and behavioural activities that are influenced by androgens. In the aggressive dogs the BNG contained a significantly higher number of AR-positive neurons compared with normally behaving dogs suggesting differences in androgen activity within the BNGs of both the groups. However, additional mechanisms are likely to be involved because the AR-negative fraction of BNG neurons was also increased in the aggressive dogs. It was concluded that most of the AR was unliganded because a cytoplasmic staining pattern of AR positivity was observed in the canine BNG neurons. This indicates that genomic androgen actions, which are mediated through the AR are of minor importance in the testosterone modulation of canine aggression within the BNG. Other non-genomic mechanisms through which androgens may exert their action in the BNG are discussed. The aromatase pathway is suggested to be the main mechanism through which testosterone exerts its action within the BNG.

Aggression↗

Insulin-like growth factor ligands, receptors, and binding proteins in cancer.

This review aims to summarize experimental evidence supporting the role of the insulin-like growth factor (IGF) signalling system in the progression, maintenance, and treatment of cancer. These data implicate the IGF system as an important modifier of cancer cell proliferation, survival, growth, and treatment sensitivity. The role of the IGF system in cancer should be examined in the context of the extra-cellular and intra-cellular signalling networks, in particular: phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt/PKB), mammalian target of rapamycin (mTOR), and forkhead transcription factors (FOXO). This review highlights evidence derived from molecular structure and functional genetics with respect to how the extra-cellular components of the IGF system function normally, and their subsequent modifications in cancer. The therapeutic relevance of the research evidence described is also addressed, as the challenge is to apply this knowledge to human health.

Amino Acid Sequence↗

Quantification of neurons expressing androgen receptor and volume estimation of the basolateral nuclear group of the canine amygdaloid body.

A protocol was developed for the stereological quantification of neurons expressing androgen receptor (AR) in the basolateral nuclear group (BNG) of the canine amygdaloid body. The Cavalieri method was used to estimate the BNG volume and the physical disector technique was applied for assessing the numerical densities and total numbers of both ordinary and AR-positive BNG neurons. The overall number of BNG neurons and the BNG volume were assessed on Nissl-stained sections, while AR was visualised using indirect immunohistochemistry. The morphological differentiation between neurons, astrocytes, and oligodendrocytes in these immunohistochemical sections was hampered by the cytoplasmic localisation of AR in these cells. Therefore, an additional criterion was developed based on the nuclear diameters of these cells. With the cutoff value of 7.4 microm, a sensitivity of 97.7% and specificity of 97.6% were obtained. A negative correlation was found between the BNG volume and the numerical density of its neurons, implicating that a large BNG will not necessarily have a higher number of neurons. Therefore, the numerical density or BNG volume should always be assessed in addition to the total number of neurons, justifying the use of the physical disector instead of the fractionator technique in the present study. However, higher coefficients of error were obtained for the total number of neurons with the physical disector method because of the indirect measurement of cell numbers. Therefore, the precision of the estimates must be high enough when using the disector method to compensate the precision loss caused by this indirect calculation of the total cell number.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗

Volumetric analysis of the growth rate of incompletely resected intracranial meningiomas.

OBJECTIVE: Intracranial meningiomas are mostly considered to be slow growing tumors. However, only a few previous reports provide information on the growth rate of these tumors. The aim of this study was to determine the growth rates of intracranial meningiomas after subtotal resection, analysing their relation to radiological appearance and histological features. Results are compared with our previous analysis of growth rates in incidental meningiomas . METHODS: The hospital charts, follow up records and imaging studies were reviewed in 36 patients with subtotally resected intracranial meningiomas. The tumor growth rates were determined by calculating the absolute and relative growth rates and the tumor volume doubling times. RESULTS: In the group of 33 patients with histologically verified grade 1 meningiomas, the mean absolute growth rate was 1.51 cm (3)/year, the median relative growth rate and tumor doubling time was 14.18 %/year and 5.228 years. In young patients annual relative growth rates were significantly higher. The median annual relative growth rate of meningiomas with calcification was significantly lower than in tumors without calcification. Also tumors with hypo- or isointense T (2)-signals on MRI revealed a lower growth rate. There was no significant difference between males and females. Histological studies revealed 22 meningiomas of a meningotheliomatous subtype, 8 fibrous and 3 psammomatous meningiomas. The comparison of growth rates between these subtypes did not show any significant differences. In atypical meningiomas (WHO grade 2), absolute and relative growth rates were significantly higher and tumor doubling times shorter. CONCLUSION: The majority of intracranial meningiomas are slow growing tumors, although the growth rates may vary widely even among benign grade 1 meningiomas. In meningiomas after subtotal surgical resection, the age of the patients seems to present a predictive factor for tumor growth in analogy to our previous observation in incidental meningiomas. Significantly higher relative growth rates were detected in younger patients. Gender does not seem to play a major role as a predictive factor. Radiological features such as calcification or T (2)-signal intensity may provide additional information to predict the growth potential of meningiomas. Close clinical and radiological observation should be performed in young patients harboring tumors with absence of calcification or high T (2)-signal intensities due to the higher growth potential in this patient group.

Adult↗

The childhood experience of care and abuse questionnaire (CECA.Q): validation in a community series.

BACKGROUND: Childhood neglect and abuse, as measured by retrospective interview, is highly predictive of psychiatric disorder in adult life and has an important role in aetiological models. However, such measures are labour-intensive, costly, and thus restricted to relatively modest sample sizes. A compact self-report assessment of childhood experience is invaluable for research screening purposes and large-scale survey investigation. METHOD: A self-report questionnaire (CECA.Q) was developed to mirror an existing validated interview measure: the childhood experience of care and abuse (CECA). The questionnaire assessed lack of parental care (neglect and antipathy), parental physical abuse, and sexual abuse from any adult before age 17. A high-risk series of 179 London women were interviewed using the CECA together with the PSE psychiatric assessment, and completed the CECA.Q at later follow-up. Repeat CECA.Qs were returned for 111 women and 99 women additionally completed the parental bonding instrument (PBI; Parker, Tupling, & Brown, 1979). RESULTS: Satisfactory internal scale consistency was achieved on the CECA.Q for antipathy (alpha = .81) and neglect (alpha = .80) scales. There was satisfactory test-retest for both care and abuse scales. Significant associations were found between CECA.Q scales and the parallel interview scales with cut-offs determined for high sensitivity and specificity. CECA.Q neglect and antipathy scales were also significantly related to PBI parental care. CECA.Q scales were significantly related to lifetime history of depression. Optimal cut-off scores revealed significant odds ratios (average of 2) for individual scales and depression. When indices were compiled to reflect peak severity of each type of adversity across perpetrator, odds-ratios increased (average 3). A dose-response effect was evident with the number of types of neglect/abuse and rate of lifetime depression. CONCLUSION: The CECA.Q shows satisfactory reliability and validity as a self-report measure for adverse childhood experience. The merits of having parallel questionnaire and interview instruments for both research and clinical work are discussed.

Adolescent↗

Severe contracture of the proximal interphalangeal joint in Dupuytren's disease: does capsuloligamentous release improve outcome?

This prospective study assessed whether patients with severe proximal interphalangeal joint contracture (#10878;60 degrees ) due to Dupuytren's disease which persisted after fasciectomy alone benefited from an additional capsuloligamentous release. Forty-three patients with 43 severely contracted proximal interphalangeal joints underwent operative correction followed by a standardized postoperative rehabilitation programme. All were followed for 6 months. In 11 patients correction of the proximal interphalangeal joint to 20 degrees could not be achieved by fasciectomy alone, and an additional capsuloligamentous release was performed which effectively corrected all their residual flexion contractures. There were no statistically significant differences between the capsulotomy and the non-capsulotomy group with respect to the residual proximal interphalangeal joint contracture at the end of surgery, or at their last follow-up examination.

Adult↗

[Rehabilitation after flexor tendon surgery].

During the last 20 years there have been significant innovations in injury repair and aftercare for patients who sustain zone 2 flexor injuries. Based on improvements in our understanding of the mechanism of repair, new differentiated concepts could be developed. Active extension, passive flexion as introduced by Kleinert is still the standard in flexor tendon surgery. New stronger suture techniques allow immediate active flexion. The purpose of this article is to review the current concepts of flexor tendon and pulley repair as well as reconstruction of these structures and the rehabilitation programs for tenolysis.

Aftercare↗

The Vulnerable Attachment Style Questionnaire (VASQ): an interview-based measure of attachment styles that predict depressive disorder.

BACKGROUND: The Vulnerable Attachment Style Questionnaire (VASQ) was developed to provide a brief self-report tool to assess adult attachment style in relation to depression and validated against an existing investigator-based interview (Attachment Style Interview--ASI). This paper describes the development and scoring of the VASQ and its relationship to poor support and major depression. METHOD: Items for the VASQ reflected behaviours, emotions and attitudes relating to attachment relationship style, drawn directly from the ASI. The VASQ was validated against the ASI for 262 community-based subjects. Test-retest was determined on 38 subjects. RESULTS: Factor analysis derived two factors, labelled 'insecurity' and 'proximity-seeking'. The VASQ insecurity dimension had highest mean scores for those with interview-based Angry-dismissive and Fearful styles and was significantly correlated with degree of interview-based insecurity. The proximity-seeking VASQ scores had highest mean for those with Enmeshed interview attachment style and was uncorrelated with ASI insecurity. VASQ scores were highly correlated with a well-known self-report measure of insecure attachment (Relationship Questionnaire) and text-retest reliability of the VASQ was satisfactory. The total VASQ score and the insecurity subscale proved highly related to poor support and to depressive disorder. This was not the case for the proximity-seeking subscale. CONCLUSION: The VASQ is a brief self-report measure that distinguishes individuals with attachment styles vulnerable for depressive disorder. The use of the measure for screening in research and clinical contexts is discussed.

Aged↗

Assessing the pathological extent of aggressive behaviour in dogs. A review of the literature.

In this review the variety of parameters used for evaluating the pathological extent of aggressive behaviour is summarised and the practical usefulness of each parameter is discussed. The selected parameters are: the objective analytic description of the aggressive behaviour, the function of the aggression, the presence of the three phases of a normal aggression sequence, the number of bites per attack, the duration of the attack and the frequency of the aggressive behaviour. Other criteria such as the appropriateness of the aggression in relation to the context, the predictability of the aggression and the severity of the caused injury are biased because of the variation caused by numerous external factors. The relevance of the most suitable parameters will be assessed in a further study in which the distribution of aggression modulating neurotransmitter receptors will be determined.

Aggression↗

Skewed balance in basal expression and regulation of activating v inhibitory Fcgamma receptors in macrophages of collagen induced arthritis sensitive mice.

BACKGROUND: Recently, it has been found that collagen type II arthritis susceptible mouse strains are hyperreactive to immune complexes (ICs), locally deposited into their knee joints. OBJECTIVE: To investigate whether this strain specific knee joint hyperreactivity is related to a disturbed regulation of activatory and inhibitory FcgammaR on their macrophages before and after stimulation with ICs. METHODS: Macrophages from collagen induced arthritis susceptible strains (DBA/1 and B10.RIII) and non-susceptible strains (C57BL/6 and BALB/c) were compared. FcgammaR levels on macrophages were detected at protein level by flow cytometric analysis and at mRNA level by reverse transcriptase-polymerase chain reaction. Macrophages were stimulated with ICs, and production of cytokines and enzymes was measured at different times. RESULTS: On synovial and peritoneal macrophages of DBA/1 mice a higher basal FcgammaRII and III expression was found, which was skewed towards the activating FcgammaRIII. In B10.RIII macrophages, however, FcgammaRIII levels were much lower. Regulation of FcgammaR mRNA levels in macrophages was tested after stimulation with ICs for one and three days. DBA/1 and B10.RIII macrophages showed a prolonged up regulation of activating FcgammaRI and III, whereas the inhibiting FcgammaRII was significantly down regulated compared with non-susceptible strains. In line with this, DBA/1 and B10.RIII macrophages showed a higher interleukin 1 (IL1) and matrix metalloproteinase (MMP) production after IC exposure, whereas IL6 production was significantly reduced. CONCLUSIONS: This study indicates that macrophages derived from collagen type II arthritis susceptible mice show a disregulated FcgammaR expression before, and even more clearly, after activation by ICs involved in inflammation and cartilage degradation, resulting in prolonged expression of activatory FcgammaRI and III, down regulation of inhibitory FcgammaRII and increased release of IL1 and MMP.

Animals↗

Buparvaquone mucoadhesive nanosuspension: preparation, optimisation and long-term stability.

The poorly soluble drug buparvaquone is used in experimental clinics against the gastrointestinal persisting parasite Cryptosporidium parvum. It was produced as nanosuspension by high pressure homogenisation. Main advantages of nanosuspensions (amongst others) are their increase of saturation solubility and dissolution velocity, improving the bioavailability of drugs. The buparvaquone nanosuspension had a bulk population of about 600 nm (analysed by photon correlation spectroscopy (PCS)). The additional analysis performed with laser diffraction showed that only a very small content of microparticles occurred, which is, for the special features of nanosuspensions, negligible because they were still below 3 microm. Another feature of nanosuspensions is the adhesion properties to surfaces, e.g. mucosa. To further increase the adhesion time of the buparvaquone nanosuspension to C. parvum, the nanosuspension was formulated with hydrogels made from mucoadhesive polymers, e.g. different types of Carbopol and chitosan. Only a small increase of the particle size of the bulk population occurred directly after the incorporation of buparvaquone nanosuspension into the hydrogels. The nanosuspension/hydrogel systems were physically long-term stable over a period of 6 months as indicated by the unchanged particle sizes.

Adhesives↗

Changes in psychological distress after cancer genetic counselling: a comparison of affected and unaffected women.

This study sought to examine changes in psychological distress following cancer genetic counselling. Women attending a family cancer clinic completed questionnaires before their appointment and at 2 weeks, 6 months and 12 months after their appointment. Twenty-six women were at low risk of developing breast or ovarian cancer, 76 were at moderate risk, 46 were at high risk and 46 women had previously had breast or ovarian cancer. All groups were compared with regard to measures of anxiety, depression, general psychological distress, worry about developing breast and ovarian cancer, and perceived risk of developing breast/ovarian cancer and perceived likelihood of carrying a genetic mutation. General psychological distress did not change over the course of the study and the groups did not differ on these measures. Worry about developing breast cancer and perceptions of the likelihood of carrying a genetic mutation significantly reduced following genetic counselling. On the whole women who had already had breast/ovarian cancer showed more concerns about ovarian cancer and raised perceptions of risk in comparison with the other groups, indicating the need for sensitive counselling of such women.

Anxiety↗

A contact model with ingrowth control for bone remodelling around cementless stems.

This work presents a computational model for bone remodelling around cementless stems. The problem is formulated as a material optimisation problem considering the bone and stem surfaces to be in contact. To emphasise the behaviour of the bone/stem interface, the computer model detects the existence of bone ingrowth during the remodelling; consequently, the contact conditions are changed for a better interface simulation. The trabecular bone is modelled as a strictly orthotropic material with equivalent properties computed by homogenisation. The distribution of bone relative density is obtained by the minimisation of a function that considers both the bone structural stiffness and the biological cost associated with metabolic maintenance of bone tissue. The situation of multiple load conditions is considered. The remodelling law, obtained from the necessary conditions for an optimum, is derived analytically from the optimisation problem and solved numerically using a suitable finite element mesh. The formulation is applied to an implanted femur. Results of bone density and ingrowth distribution are obtained for different coating conditions. Bone ingrowth does not occur over the entire coated surfaces. Indeed, we observed regions where separation or high relative displacement occurs that preclude bone ingrowth attachment. This prediction of the model is consistent with clinical observations of bone ingrowth. Thus, this model, which detect bone ingrowth and allow modification of the interface conditions, are useful for analysis of existing stems as well as design optimisation of coating extent and location on such stems.

Animals↗