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M Berelowitz

Publications and source records attributed to M Berelowitz.

At least 19 recordsLinked to original sources
PubMed2003

Sexually abused girls: patterns of psychopathology and exploration of risk factors.

This paper studies the patterns of psychopathology in sexually abused girls. It also explores some environmental risk factors for psychopathology including abuse characteristics and environmental experiences. The data are derived from the baseline assessment of 81 sexually abused girls referred to the London Child Sexual Abuse Psychotherapy Outcome Study (collaborative Tavistock and Maudsley project). Data about abuse were collected from the parent or foster parent using a standardised, semi-structured interview format. The girls' psychopathology was assessed using the Kiddie-SADS schedule. Widespread and serious psychopathology in sexually abused girls attending a psychotherapy clinic previously reported in a small-scale study was confirmed; so, too, was the extent of comorbidity and impairment of psychosocial functioning. Further, a significant association was found between children looked after away from home and high rates of Separation Anxiety Disorder. No such significant associations were found for Major Depressive Disorder nor impairment of functioning. Multivariate prediction analysis revealed that significant predictors of Major Depressive Disorder consisted of seriousness of abuse, the abuser not being a parent figure, and the abuse not being recent; the only significant predictor of Separation Anxiety Disorder was that the abuser was not a parent figure; finally, impairment of general functioning was strongly predicted by the greater seriousness of abuse and also by the abuser/s not being a parent figure. Theoretical explanations advanced for the reported associations have a sense of face validity: that girls abused by strangers will be at risk of developing Separation Anxiety Disorders; that serious sexual abuse is followed by the development of a Major Depressive Disorder and a high level of impairment of social functioning.

Adolescent↗
PubMed2002

Psychotherapy for sexually abused girls: psychopathological outcome findings and patterns of change.

BACKGROUND: Controversy exists about the efficacy of psychotherapy for the mental health problems of sexually abused children. AIMS: To compare the relative efficacy of focused individual or group therapy in symptomatic sexually abused girls, and to monitor psychiatric symptoms for persistence or change. METHOD: A multi-centre psychotherapy outcome study recruited 71 sexually abused girls aged 6-14 years who were randomly assigned to focused individual psychotherapy (up to 30 sessions) or psychoeducational group therapy (up to 18 sessions). Changes over the course of the study were monitored. RESULTS: Both treatment groups showed a substantial reduction in psychopathological symptoms and an improvement in functioning, but with no evident difference between individual and group therapy. However, individual therapy led to a greater improvement in manifestations of post-traumatic stress disorder (PTSD). CONCLUSIONS: The beneficial effects on PTSD support the use of individual therapy. However, the small sample size and lack of a control group limit conclusions about changes attributable to treatment.

Adolescent↗
PubMed2001

Colonic CD8 and gamma delta T-cell infiltration with epithelial damage in children with autism.

OBJECTIVES: We have reported colitis with ileal lymphoid nodular hyperplasia (LNH) in children with regressive autism. The aims of this study were to characterize this lesion and determine whether LNH is specific for autism. METHODS: Ileo-colonoscopy was performed in 21 consecutively evaluated children with autistic spectrum disorders and bowel symptoms. Blinded comparison was made with 8 children with histologically normal ileum and colon, 10 developmentally normal children with ileal LNH, 15 with Crohn's disease, and 14 with ulcerative colitis. Immunohistochemistry was performed for cell lineage and functional markers, and histochemistry was performed for glycosaminoglycans and basement membrane thickness. RESULTS: Histology demonstrated lymphocytic colitis in the autistic children, less severe than classical inflammatory bowel disease. However, basement membrane thickness and mucosal gamma delta cell density were significantly increased above those of all other groups including patients with inflammatory bowel disease. CD8(+) density and intraepithelial lymphocyte numbers were higher than those in the Crohn's disease, LNH, and normal control groups; and CD3 and plasma cell density and crypt proliferation were higher than those in normal and LNH control groups. Epithelial, but not lamina propria, glycosaminoglycans were disrupted. However, the epithelium was HLA-DR(-), suggesting a predominantly T(H)2 response. INTERPRETATION: Immunohistochemistry confirms a distinct lymphocytic colitis in autistic spectrum disorders in which the epithelium appears particularly affected. This is consistent with increasing evidence for gut epithelial dysfunction in autism.

Adolescent↗
PubMed2000

Enterocolitis in children with developmental disorders.

OBJECTIVE: Intestinal pathology, i.e., ileocolonic lymphoid nodular hyperplasia (LNH) and mucosal inflammation, has been described in children with developmental disorders. This study describes some of the endoscopic and pathological characteristics in a group of children with developmental disorders (affected children) that are associated with behavioral regression and bowel symptoms, and compares them with pediatric controls. METHODS: Ileocolonoscopy and biopsy were performed on 60 affected children (median age 6 yr, range 3-16; 53 male). Developmental diagnoses were autism (50 patients), Asperger's syndrome (five), disintegrative disorder (two), attention deficit hyperactivity disorder (ADHD) (one), schizophrenia (one), and dyslexia (one). Severity of ileal LNH was graded (0-3) in both affected children and 37 developmentally normal controls (median age 11 yr, range 2-13 yr) who were investigated for possible inflammatory bowel disease (IBD). Tissue sections were reviewed by three pathologists and scored on a standard proforma. Data were compared with ileocolonic biopsies from 22 histologically normal children (controls) and 20 children with ulcerative colitis (UC), scored in an identical manner. Gut pathogens were sought routinely. RESULTS: Ileal LNH was present in 54 of 58 (93%) affected children and in five of 35 (14.3%) controls (p < 0.001). Colonic LNH was present in 18 of 60 (30%) affected children and in two of 37 (5.4%) controls (p < 0.01). Histologically, reactive follicular hyperplasia was present in 46 of 52 (88.5%) ileal biopsies from affected children and in four of 14 (29%) with UC, but not in non-IBD controls (p < 0.01). Active ileitis was present in four of 51 (8%) affected children but not in controls. Chronic colitis was identified in 53 of 60 (88%) affected children compared with one of 22 (4.5%) controls and in 20 of 20 (100%) with UC. Scores of frequency and severity of inflammation were significantly greater in both affected children and those with UC, compared with controls (p < 0.001). CONCLUSIONS: A new variant of inflammatory bowel disease is present in this group of children with developmental disorders.

Adolescent↗
PubMed1999

Behavioural psychopathology of child sexual abuse in schoolgirls referred to a tertiary centre: a North London study.

The sexually abused girls in this study were a sub-sample of a group of girls referred to a Regional Centre for Psychotherapy for the whole of London, North Thames. An inclusion criterion was that they were psychologically symptomatic and so it is likely that they were more problematic cases causing concern in their locality. The control clinical group consisted of referrals to local Child and Family consultation services, were an opt-in matched sample and not a total clinic referral sample. In addition, the reasons for referral covered both child disorder and family problems. It is, therefore, important to bear in mind the differences between these two groups. Certain clear cut findings have emerged from this study. No disorders specific to child sexual abuse in girls were identified but the extent and severity of the disturbance in the sexually abused sample was most striking. In these girls an event (CSA), together with referral because of emotional symptoms, was associated with enhanced severity of disorder and comorbidity particularly with reference to a cluster of disorders comprising post-traumatic stress disorder, depressive disorder, anxiety disorders (general and separation), social phobias and reactive attachment disorder. In the community clinic sample the identified disorders were mainly those of separation anxiety disorders and adjustment. Wide comorbidity was common in the sexual abuse sample and also severity of impairment was notable when compared to the clinic sample. However, because of the selected nature of the abuse group the findings are not generalisable beyond the population from which they emerged. The view is advanced that there are strong grounds for exploring the utility of psychodynamic psychotherapy in similar samples of sexually abused girls. These findings are discussed in the light of the current literature.

Adolescent↗
PubMed1998

Characterization of the promoter region of the human somatostatin receptor subtype 2 gene and localization of sequences required for estrogen-responsiveness.

Somatostatin receptor (sst) subtype 2 mRNA is potently regulated by 17beta-estradiol (E2) in a time and dose-dependent manner in the estrogen receptor (+) human breast cancer cell line T47D. To explore the mechanism involved in E2 regulated expression of sst2, we isolated and characterized a genomic clone containing over 5.3 kilobase pairs (kb) of the 5' flanking region of the human sst2 gene. The 5'-flanking region lacks both TATA and CCAAT boxes. Primer extension and RNAase protection analysis revealed the existence of two transcriptional start sites, located within an initiator-like sequence, 85 and 82 bp upstream of the translational initiation methionine. The 5.3-kb 5'-flanking region was an active promoter in T47D cells but was inactive in MDA MB 435s cells, a human breast cancer cell line that does not express sst2. Deletion analysis identified both positive and negative regulatory elements within the 5.3-kb fragment. Furthermore, transcriptional regulation by E2 was mediated by a distal 1.5-kb fragment located 3.8 kb from the transcriptional start sites. Determining the precise ERE will provide important insights into the complex regulation of sst2 expression in normal and neoplastic tissue.

Base Sequence↗
PubMed1998

Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children.

BACKGROUND: We investigated a consecutive series of children with chronic enterocolitis and regressive developmental disorder. METHODS: 12 children (mean age 6 years [range 3-10], 11 boys) were referred to a paediatric gastroenterology unit with a history of normal development followed by loss of acquired skills, including language, together with diarrhoea and abdominal pain. Children underwent gastroenterological, neurological, and developmental assessment and review of developmental records. Ileocolonoscopy and biopsy sampling, magnetic-resonance imaging (MRI), electroencephalography (EEG), and lumbar puncture were done under sedation. Barium follow-through radiography was done where possible. Biochemical, haematological, and immunological profiles were examined. FINDINGS: Onset of behavioural symptoms was associated, by the parents, with measles, mumps, and rubella vaccination in eight of the 12 children, with measles infection in one child, and otitis media in another. All 12 children had intestinal abnormalities, ranging from lymphoid nodular hyperplasia to aphthoid ulceration. Histology showed patchy chronic inflammation in the colon in 11 children and reactive ileal lymphoid hyperplasia in seven, but no granulomas. Behavioural disorders included autism (nine), disintegrative psychosis (one), and possible postviral or vaccinal encephalitis (two). There were no focal neurological abnormalities and MRI and EEG tests were normal. Abnormal laboratory results were significantly raised urinary methylmalonic acid compared with age-matched controls (p=0.003), low haemoglobin in four children, and a low serum IgA in four children. INTERPRETATION: We identified associated gastrointestinal disease and developmental regression in a group of previously normal children, which was generally associated in time with possible environmental triggers.

Child↗
PubMed1996

Borderline personality disorder: study in adolescence.

The study of the presentation, symptomatology and family characteristics of an exclusively adolescent sample of patients with borderline personality disorder (BPD) was undertaken. Twenty-four cases of borderline personality disorder, 20 females, 4 males, identified using chart review and meeting the criteria of the Diagnostic Interview for Borderlines (DIB) and DSM III-R, were matched with psychiatric controls. Adolescents with borderline personality disorder were found to have high rates of affective symptomatology with Axis I diagnosis of major depressive disorder MDD (DSM-III-R), and high rates of interpersonal psychopathology, i.e., manipulation, devaluation, and a pervasive sense of boredom. The latter seem to be characteristic as for adults with borderline personality disorder. The families were particularly angry and volatile.

Adolescent↗
PubMed1996

Estrogen regulates somatostatin receptor subtype 2 messenger ribonucleic acid expression in human breast cancer cells.

Somatostatin (SRIF) and its analogs exhibit antiproliferative effects that are mediated by SRIF receptors (sst) present in responsive normal and neoplastic tissue including breast cancer. However, information regarding regulation of sst gene expression in cancer cells and modulation of SRIF binding is limited. In the present study we have determined the pattern of sst subtype messenger RNA (mRNA) expression in human breast cancer cells. Furthermore, we investigated the effect of 17beta-Estradiol (E2) treatment on steady state levels of sst mRNA by solution hybridization/nuclease protection analysis and on SRIF binding to membranes of treated cells by receptor binding assay. sst2 mRNA was highly expressed in T47D, ZR75-1, and MDA MB231 cells. Transcripts for sst1 were also detected at very low levels in ZR75-1 cells, whereas sst5 mRNA was expressed at low levels in MCF-7 cells. No sst subtype was detected in MDA MB 435s cells. When the estrogen receptor (ER)(+) cell lines T47D and ZR75-1 were cultured in phenol red-free media plus CS-FCS, sst2 mRNA levels decreased by 60-80% compared with complete serum controls. Adding E2 restored sst2 mRNA levels to control in both cell lines. Moreover, the effect of E2 on sst2 gene expression in T47D and ZR75-1 cells was dose- and time-dependent. In contrast, neither culturing in phenol red-free media plus CS-FCS nor E2 influenced sst2 expression in the ER(-) cell line MDA MB231. E2-induced regulation of SRIF binding and sst2 mRNA expression occurred in a parallel manner in T47D cells but were dissociated in ZR75-1 cells. The pure antiestrogen ICI 182 780 inhibited E2-induced sst2 expression in both cell lines. The antiestrogen 4OH tamoxifen showed strong estrogen-like effects on sst2 mRNA expression in T47D cells, while acting as a potent antiestrogen in ZR75-1 cells. Thus, these data suggest that E2 regulates sst2 expression in human breast cancer cell lines through the ER. The human breast cancer cell lines provide a useful model to examine the molecular mechanisms involved in E2 regulation of sst2 expression.

Breast Neoplasms↗
PubMed1996

Growth hormone-releasing factor expression is discordantly regulated in the hypothalamus and testis of streptozotocin-diabetic rats.

Growth hormone-releasing factor (GRF) mRNA expression in male rats occurs predominantly in the hypothalamus (mainly in the arcuate nucleus), and among extraneural sites primarily in the testis. Hypothalamic GRF is the physiological tropic stimulus to growth hormone secretion. However, the role of GRF in the testis is unknown. We have shown previously that hypothalamic GRF mRNA expression is significantly reduced in streptozotocin (STZ)-diabetic rats. This reduction is confined to the arcuate nucleus and probably accounts for the suppression of growth hormone pulsatility. The present studies were performed to evaluate GRF expression in the testis of streptozotocin (STZ)-diabetic rats. Diabetes was induced by injection of STZ (100 mg/kg i.p.). Seventeen to twenty days later diabetic rats were hyperglycemic compared with vehicle-injected controls and demonstrated growth failure. Insulin treatment reduced the glycemia and increased body weight towards normal. Total RNA was extracted from the hypothalamus and testis, and GRF mRNA levels estimated by solution hybridization/nuclease protection assay. Levels of hypothalamic somatostatin mRNA were measured to serve as control values. GRF mRNA was significantly (P < 0.001) decreased in the hypothalamus of STZ-diabetic rats (0.2 +/- 0.07 mean relative densitometric units, n = 8) compared with controls (1.0 +/- 0.19, n = 8) with no change in somatostatin mRNA expression. In contrast, testicular GRF mRNA was increased 70% (P < 0.05) in STZ-diabetic rats. Insulin treatment resulted in normalization of hypothalamic GRF mRNA levels (1.1 +/- 0.17, n = 5) with no effect on testicular GRF mRNA expression. In conclusion GRF gene expression is discordantly regulated in tissues of male STZ-diabetic rats. While reduced GRF expression may account for the low growth hormone state in this model, increased testicular GRF mRNA (with the previously reported reduction of insulin-like growth factor-I mRNA) resembles the response seen in growth hormone-sensitive tissue (especially the hypothalamus) to this growth hormone-deficient state.

Animals↗
PubMed1995

Characterization of the proximal promoter region of the rat somatostatin receptor gene, SSTR4.

In the present study, the putative promoter region of rSSTR4 gene has been cloned and characterized. Primer extension and RNAase protection analysis reveals the existence of multiple transcriptional initiation sites, the five major ones mapping between -126 and -18 relative to the ATG initiation codon. Sequence analysis reveals that the region lacks TATA and CCAAT promoter elements, possesses a high GC content and contains a number of potential SP1 binding sites. In addition, potential AP-2, GCF, and PuF binding sites and an octimer motif were also identified. Thus, the promoter of rSSTR4 shows similar features to promoters of highly regulated growth factor receptors and oncogenes. The potential role these transcriptional binding sites play in regulating rSSTR4 expression is currently being investigated.

Animals↗
PubMed1995

Regulation of somatostatin receptor mRNA expression.

The five somatostatin receptor mRNAs are expressed with distinct though overlapping patterns of distribution in the CNS and peripheral tissues. All receptor types are expressed in the anterior pituitary and hypothalamus and could therefore be modulated in states of growth hormone (GH) dysregulation. Metabolic perturbations such as food deprivation and diabetes mellitus lead to suppression of GH levels in the rat, in part due to increased somatostatin tone. In rats deprived of food, pituitary sstr1, 2 and 3 mRNAs were reduced by 80% compared to fed controls; sstr4 and sstr5 mRNAs were unchanged. Hypothalamic sstr mRNA expression was unaltered. In diabetic rats pituitary sstr1, 2 and 3 mRNAs were reduced by 50-80% with sstr1 mRNA restored in part by insulin therapy. Pituitary sstr4 mRNA and hypothalamic expression of these four types was unaffected. sstr5 mRNA is reduced by 70% in the pituitary and by 30% in the hypothalamus with restoration of both by insulin treatment. Altered pituitary sstr expression in food deprivation and diabetes could result from chronic exposure to increased plasma somatostatin. In rat GH3 pituitary tumour cells exposed to 1 microM somatostatin for up to 48 h, sstr1, 3, 4 and 5 mRNA increased dramatically while sstr2 mRNA exhibited a biphasic response. We observed a net increase in receptor binding associated with increased sstr mRNA. Somatostatin receptor expression is regulated in a tissue- and type-specific manner, adding further complexity to the action of the multifaceted peptide somatostatin.

Animals↗
PubMed1995

Classification and nomenclature of somatostatin receptors.

There is considerable controversy about the classification and nomenclature of somatostatin receptors. To date, five distinct receptor genes have been cloned and named chronologically according to their respective publication dates, but two were unfortunately given the same appellation (SSTR4). Consensually, a nomenclature for the recombinant receptors has been agreed according to IUPHAR guidelines (sst1, sst2, sst3, sst4, and sst5). However, a more informative classification is to be preferred for the future, employing all classification criteria in an integrated scheme. It is already apparent that the five recombinant receptors fall into two classes or groups, on the basis of not only structure but also pharmacological characteristics. One class (already referred to by some as SRIF1) appears to comprise sst2, sst3 and sst5 receptor subtypes. The other class (SRIF2) appears to comprise the other two recombinant receptor subtypes (sst1 and sst4). This promising approach is discussed but it is acknowledged that much more data from endogenous receptors in whole tissues are needed before further recommendations on somatostatin receptor nomenclature can be made.

Amino Acid Sequence↗
PubMed1995

Dexamethasone regulates somatostatin receptor subtype messenger ribonucleic acid expression in rat pituitary GH4C1 cells.

Ligand binding studies have shown that glucocorticoids down-regulate somatostatin receptor (sst) concentration in several endocrine target cells and cell lines including GH4C1 cells. However, it has not been determined whether this decrease in sst number occurred via transcriptional and/or posttranscriptional events. In the present study, we have investigated the effect of dexamethasone (Dex) treatment (1 microM) of GH4C1 cells for up to 48 h on the steady state level of messenger RNA (mRNA) for sst1, sst2, and sst3, the predominant isoforms expressed in this cell line, by solution hybridization-nuclease protection analysis. Exposure of GH4C1 cells to Dex for 2 h increased sst1 mRNA levels 2.5-fold and sst2 1.5-fold compared with controls (Con). Prolonged exposure, however, resulted in a decrease in mRNA levels of sst1 to 50% and sst2 to 30% of Con by 24-48 h. In contrast, sst3 mRNA levels were unchanged at 2 h, decreased to 30% of Con by 6 h, and remained decreased for up to 24 h. Longer exposure resulted in a dramatic increase in expression, reaching 350% of Con by 48 h. The Dex effect on expression of all subtypes was dose dependent, maximal at 10 nM. Steroid hormone regulation of sst mRNA expression in GH4C1 cells proved to be complex. Exposure to Dex for 24 h, as expected, decreased expression of all subtypes. Progesterone, however, increased sst1 mRNA levels, decreased sst3 levels, but was without effect on sst2; treatment with estrogen and testosterone increased expression of all three subtypes. Nuclear run-on assays indicated that the Dex-induced changes in sst1 and sst2 mRNA levels were associated with congruent changes in the transcription rate of sst genes. Thus, glucocorticoids regulate sst expression in GH4C1 cells, at least in part, by controlling the rate of transcription of sst genes.

Animals↗
PubMed1994

Somatostatin regulates somatostatin receptor subtype mRNA expression in GH3 cells.

Homologous up-regulation of somatostatin receptors (SSTR) was investigated in the GH3 clonal pituitary cell line. We report that chronic exposure to SRIF which has high affinity for all SSTR subtypes leads to a net increase in receptor binding and SSTR subtype mRNA. Treatment of cells with 1 microM SRIF increased specific [125I-Tyr11]SRIF binding to 280% of control values by 24 hr and to 350% by 48hr. Associated with the increase in SSTR binding was a net increase in SSTR subtype mRNA expression. Levels of SSTR1 increased to over 400% of control values by 6 hr and remained elevated for up to 48 hr. SSTR3, SSTR4, and SSTR5 mRNA was also dramatically increased at 24 and 48 hr. SSTR2 mRNA, in contrast, showed a biphasic response, initially increasing to 150% of control at 2 hr then decreasing to 50% at 6 hr with normalization by 48 hr. Our data suggests that multiple mechanisms contribute to the highly regulated expression of SSTR subtypes. The identification of specific molecular and cellular mechanisms mediating homologous SSTR up-regulation in GH3 cells and the involvement this process has in mediating the diverse biological effects of somatostatin are topics of current research.

Animals↗
PubMed1994

Pituitary and hypothalamic somatostatin receptor subtype messenger ribonucleic acid expression in the food-deprived and diabetic rat.

Prolonged food deprivation (FD) and streptozocin-induced diabetes (STZ diabetes) in the rat result in abolition of GH secretory episodes. We have previously shown that hypothalamic prepro-GRF messenger RNA (mRNA) expression is markedly reduced in the hypothalamus of FD and STZ diabetic rats, with no change in prepro-somatostatin (SRIF) mRNA and suggested that reduced GRF and increased SRIF tone explained the loss of GH secretion in FD and STZ diabetes. Altered SRIF peptide expression has been implicated in many physiological and pathological states; however, information on the regulation of SRIF receptor (SSTR) expression is lacking. Therefore, we examined the expression of mRNA for the five recently cloned SSTR subtypes in the pituitary and hypothalamus of FD and STZ diabetic rats. In addition, we measured SRIF binding to pituitary membranes of FD rats. SSTR1, SSTR2, and SSTR3 mRNA expression was reduced 80% in the pituitary of FD rats vs. fed controls, whereas pituitary levels of SSTR4 and SSTR5 mRNA were unaffected. The pituitary plasma membrane SSTR concentration was reduced over 50% in FD vs. fed animals. However, hypothalamic levels of the five isoforms were unchanged. In STZ diabetes, pituitary SSTR1, SSTR2, and SSTR3 mRNA expression was reduced 50-80%, with levels of SSTR1 partially restored by insulin, whereas SSTR4 mRNA was unchanged. In contrast to the effect of FD, SSTR5 mRNA levels were reduced 70% in the pituitary and 30% in the hypothalamus of STZ diabetic rats, with complete restoration by insulin. Thus, SSTR subtype mRNA expression is differentially regulated in two models of GH deficiency in the rat, FD and STZ diabetes. As chronic exposure to SRIF results in desensitization of transfected SSTR2 and SSTR3, and SSTR binding is decreased in FD and STZ diabetic rats, the possibility exists that the pituitary changes result from continued exposure to SRIF. In the hypothalamus, however, regulation appears more complex. These data support a role of increased SRIF with decreased GRF in mediating the loss of GH secretion in FD and diabetes.

Animals↗