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Biomedical subjects

P B Jones

Publications and source records attributed to P B Jones.

At least 19 recordsLinked to original sources

Autoimmune diseases in the pedigrees of schizophrenic and control subjects.

Autoimmune diseases aggregate in individuals and within pedigrees, and it has been postulated that autoimmune mechanisms may account for a proportion of schizophrenia. Structured questionnaires were used to interview the mothers of 121 DSM-III-R schizophrenic patients and the mothers of 116 controls in order to determine the prevalence of schizophrenia and of autoimmune diseases in their pedigrees. Patients with a schizophrenic first degree relative were significantly more likely to also have a parent or sibling with an autoimmune disease (60% vs. 20%, OR = 6.1, 95% CI = 2.3-6.5, p = 0.0003). A significant excess of insulin dependent diabetes mellitus (IDDM) was present in the parents and siblings of schizophrenic patients (OR = 9.65, 95% CI = 1.3-429.2, p = 0.009). These findings suggest that autoimmune mechanisms may play a role in the aetiology of schizophrenia, particularly familial schizophrenia. Associations have been established between autoimmune diseases and the HLA encoding genes of the major histocompatibility complex on chromosome six, and it may be that some of the genetic liability to schizophrenia involves these genes.

Adult

Do obstetric complications cause the earlier age at onset in male than female schizophrenics?

We compared the age at onset of 184 patients with functional psychoses with and without a history of obstetric complications (OCs) as defined by the scale of Lewis et al. (1989). OCs had no significant influence on the age at onset in those patients who had affective psychoses or were non-white. There were 73 white patients with a DSM-III-R diagnosis of schizophrenia. The mean age at onset of those 25 who had a history of at least one definite OC was 2.6 years earlier than that of the 48 patients with no history of OCs. This effect was entirely due to the male patients with histories of OCs who had, on average, a 3.5 years earlier age at onset. There were no gender differences in age at onset among schizophrenics without a history of OCs. We suggest that a subgroup of male patients with a history of OCs is responsible for the earlier age at onset in male compared to female schizophrenics.

Black or African American

A factor analytic study of symptoms in acute schizophrenia.

The three-syndrome model of schizophrenic phenomenology has been well established in chronic illness. We report an attempt to replicate this concept in a sample of acutely unwell schizophrenic patients. Factor analysis was performed using PSE data collected within a week of admission from 114 patients who met DSMIII(R) diagnostic criteria for schizophrenia. Four main factors accounted for 58% of the variance. The first two factors closely resembled Liddle's disorganisation and psychomotor poverty syndromes. Hallucinations and delusions loaded separately under the third and fourth factors. To examine the validity of these four syndromes, the relationships between factor scores and other clinical data were examined. The disorganisation syndrome was associated with a history of multiple past admissions and a longer lifetime duration of in-patient treatment.

Acute Disease

Mixed-handedness in patients with functional psychosis.

BACKGROUND: An excess of non-right-handedness has been shown among patients with schizophrenia. However it is not clear whether this finding can be accounted for by an increase in left-handedness, mixed-handedness or both. It is not known whether atypical patterns of hand preferences occur in other functional psychotic illnesses. METHOD: The Annett hand preference questionnaire was administered to patients with schizophrenia (n = 120); affective psychosis (n = 55); schizoaffective psychosis (n = 41), and control subjects (n = 86). Handedness was classified into three categories: right, mixed and left-handedness. RESULTS: The hand preference patterns of patients with functional psychotic illnesses were not significantly different from controls. Patients with schizophrenia showed a non-significant excess of mixed-handedness compared with controls. Patients with schizophrenia and affective psychosis showed a non-significant decrease in left-handedness compared with controls. CONCLUSIONS: Although our results showed a trend in the hypothesised direction, we failed to demonstrate that patients with psychotic illness differed from controls on self-reported hand preference patterns.

Adult

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Computer Communication Networks

Minor physical anomalies in psychoses: associations with clinical and putative aetiological variables.

This study of patients with functional psychoses set out to examine associations between minor physical anomalies (MPAs) and demographic, clinical, CT scan measures, and putative aetiological variables. 157 psychotic patients had minor physical anomalies assessed using a modified Waldrop scale. RDC diagnoses for these patients were: schizophrenia (n = 79), schizoaffective disorder (n = 31), mania (n = 24), major depression (n = 13), unspecified functional psychosis (n = 8), other organic psychosis (n = 2). 63 healthy white controls were also assessed with the modified Waldrop scale. Minor physical anomalies were not associated with any particular diagnosis. For white subjects, patients had significantly more MPAs than well controls. Anomalies of the palate were the most frequent item reported in patients and controls. For males, there was a weak association between the presence of MPAs and positive family history of a major psychiatric disorder. Those with MPAs required more frequent and longer psychiatric admissions, and showed impaired ability on a test sensitive to left parietal system function. Within the patient group, there were no associations between MPAs and gender, age at onset, negative symptoms, premorbid level of functioning, estimated premorbid intelligence, pregnancy and birth complications, and selected CT variables. Minor physical anomalies are found in a range of functional psychoses. There may be overlap between the various genes that predispose to psychiatric illness (especially in males) and those genes that predispose to developmental instability.

Adult

Cerebral ventricle dimensions as risk factors for schizophrenia and affective psychosis: an epidemiological approach to analysis.

A case-control study was undertaken of volumetric computerized tomographic scan measures in 216 consecutive admissions for functional psychosis and 67 healthy community controls. Odds ratio analysis demonstrated significant linear trends in the association between increasing lateral and third ventricle volumes, and both RDC schizophrenia (N = 121) and schizo-affective disorder (N = 41); cases were consistently associated with larger volumes than controls. There was an association between larger third, but not lateral, ventricle size in affective psychoses (N = 54). These associations were statistically independent of intracranial volume, sex, social class and ethnicity, factors which were significantly associated with ventricular measures in the controls. There was no evidence of a threshold corresponding to the notion of normal versus enlarged ventricles. Within the schizophrenia group, there were no large or significant associations between ventricle dimensions and age at onset, duration of illness or pre-morbid social functioning. Neither obstetric complications nor a family history of schizophrenia or other psychiatric illness was associated with large ventricles in these cases.

Adolescent

Endothelial cell stimulating angiogenesis factor--a new biological marker for disease activity in ankylosing spondylitis?

Endothelial cell stimulating angiogenesis factor (ESAF) is raised in conditions of neovascularization, such as may occur at the endochondral surface of the bone growth plate or in association with syndesmophyte formation. Syndesmophytes are formed in response to chronic enthesitis. Twenty unselected patients with AS were studied and enthesitis was measured clinically using a previously validated enthesitis index. Biochemical and haematological markers of disease activity were measured along with ESAF. Radiographs were scored for the degree of sacroiliitis and syndesmophyte formation and all these measurements were correlated to the enthesitis index. ESAF was raised in AS compared with normal controls. ESAF correlated positively with the enthesitis index but not with any of the biochemical or haematological indices. Higher levels of ESAF were found in those with more advanced sacroiliitis. High ESAF activity may be reflecting the angiogenic process involved in new bone formation associated with sacroiliitis and syndesmophyte formation. ESAF may be a biochemical marker for disease activity in AS.

Adult

A case-control study of family history and cerebral cortical abnormalities in schizophrenia.

The relationship between family history of psychosis and cortical sulcal widening on CT scans was investigated. Forty-two schizophrenic subjects with a positive family history were individually matched to 42 schizophrenics with no documented family history and 42 healthy controls. Abnormally wide sulci, as defined on the basis of the normal control data, were significantly more common in the family history negative group (9/42) than in the family history positive group (1/42) or the controls (2/36). No significant correlation was found between cerebral cortical ratings and ventricular size.

Case-Control Studies

Premorbid social underachievement in schizophrenia. Results from the Camberwell Collaborative Psychosis Study.

In an investigation of the timing and precursors of social decline in schizophrenia and affective psychosis, 195 subjects from the Camberwell Collaborative Psychosis Study were currently of lower social class than were their fathers. A comparison between father's occupation and proband's best premorbid occupational level indicated underachievement confined to DSM-III schizophrenia, there being no such effect in affective psychosis. Decline in social status following onset of psychosis, analysed by comparing best premorbid occupation with current occupation, was marked in both schizophrenia and affective psychosis, indicating a non-specific effect. Schizophrenic patients who failed to achieve their fathers' social status had poorer educational qualifications than those who equalled or bettered their paternal social class, despite similar premorbid IQ (NART) scores and age at onset of psychosis. These results indicate that schizophrenia may be manifest before the onset of psychosis, and lend weight to the notion of a developmental origin to this disorder.

Adolescent

Computed tomography in sternocostoclavicular hyperostosis.

Sternocostoclavicular hyperostosis is a rare but recognized entity characterized by new bone formation and ligamentous ossification which limits mobility of the sternoclavicular joints. Aetiology is obscure and debated. There may be considerable delay in establishing the diagnosis, even by specialists. In confirming the diagnosis plain radiography is of limited value but radionuclide bone scan and computed tomography (CT) may be helpful. Four cases are described to emphasize these points and illustrate the clinical and radiological features of the condition. High resolution CT with thin sections (5 mm or less) is the examination of choice for demonstrating the characteristic features and is essential if the condition is to be confirmed in its early stages when treatment might be more successful in delaying progression.

Adult

Left temporal lobe damage in Asperger's syndrome.

In the search for neurobiological factors in the aetiology of autism, interest has focused on the temporal lobes. We present a case of Asperger's syndrome in an otherwise healthy adult with direct evidence of left temporal lobe damage on computerised tomography.

Adult

Alpha 2-macroglobulin and tissue inhibitor of metalloproteinases: collagenase inhibitors in human preovulatory ovaries.

Extensive remodeling of the follicular extracellular matrix occurs during the process of ovulation. This remodeling involves the breakdown of collagen, which is regulated, in part, by the action of the metalloproteinase collagenase and its associated inhibitors. In the present study, follicular metalloproteinase inhibitors were characterized to determine whether they were serum-borne or of ovarian origin, possibly a tissue-derived inhibitor known as tissue inhibitor of metalloproteinase (TIMP). Human follicular fluid and granulosa cells were obtained from preovulatory follicles of patients in an in vitro fertilization program. Chromatographic separation of follicular fluid on Sepharose 6B resulted in two peaks of inhibitory activity. The large molecular radius (Mr) inhibitor was similar in size to the serum-borne metalloproteinase inhibitor alpha 2-macroglobulin (i.e. Mr 700,000) whereas the small Mr inhibitor approximated the size of TIMP (i.e. Mr 29,000). Incubation of aliquots from either of the two peaks of inhibitor activity or an alpha 2-macroglobulin standard with an antibody to alpha 2-macroglobulin decreased the inhibitory activity in both the large Mr peak and the alpha 2-macroglobulin standard by 86.6 +/- 1.7% and 71.5 +/- 7.7% (n = 4, P less than 0.005), respectively, implying cross-reactivity with the alpha 2-macroglobulin antibody. The inhibitory activity in the small Mr peak, however, was unchanged. Northern analysis of total granulosa cell RNA demonstrated TIMP messenger RNA (mRNA) in all eight granulosa cell samples examined whereas alpha 2-macroglobulin mRNA was virtually undetectable. A positive correlation (r = 0.85, P less than 0.01) was observed between the levels of TIMP mRNA and the ratio of the follicular estradiol-progesterone concentration. However, inhibitor activity in the follicular fluid was not correlated with the levels of TIMP mRNA (r = 0.05). These findings confirm the presence of alpha 2-macroglobulin in follicular fluid and demonstrate that human preovulatory granulosa cells contain mRNA for TIMP, an inhibitor that regulates metalloproteinases such as collagenase, gelatinase, and proteoglycanase. Additionally, the expression of TIMP mRNA is steroid related and may be hormonally regulated. It is proposed that TIMP produced in the granulosa cell compartment in conjunction with alpha 2-macroglobulin from the serum may act to control the site and extent of ovarian connective tissue remodeling.

Antibodies

The role of ovarian proteases and their inhibitors in ovulation.

To assess the role of inhibitors of proteolytic enzymes, such as plasminogen activator (PA) and collagenase in the ovulatory process, inhibitor activity and mRNA levels were examined in periovulatory rat and human ovaries. In the rat, immature animals received 20 IU of pregnant mare serum gonadotropin (PMSG) followed 52 h later by 10 IU of hCG. Ovaries were removed at intervals from 0 to 20 h after human chorionic gonadotropin (hCG) administration. Inhibitor activity for metalloproteinases, such as collagenase, increased from 60.5 +/- 4.1 inhibitor units/ovary at 0 h (i.e., time of hCG treatment) to a maximum of 218.2 +/- 11.4 units/ovary at 8 h after hCG before decreasing at 12 h (time of ovulation) and 20 h (122.2 +/- 7.9 and 71.6 +/- 8.1 units/ovary, respectively). Human follicular fluid and granulosa cells were obtained from preovulatory follicles of patients in our in vitro fertilization program. Metalloproteinase inhibitor activity was evaluated in follicular fluid as well as the levels of PA and PA inhibitor (PAI) mRNA by Northern analysis. Increasing metalloproteinase inhibitor activity was positively correlated with follicular levels of estradiol (p less than 0.001) and progesterone (p less than 0.02, N = 26). Chromatographic separation of follicular fluid resulted in two peaks of metalloproteinase inhibitor activity. The large molecular weight (MW) inhibitor had an approximate size of 700 kilodaltons (kDa) and may represent alpha 2-macroglobulin, a serum-derived inhibitor. The small MW inhibitor shared many of the characteristics of tissue-derived inhibitors of metalloproteinases. Partial purification of the small MW inhibitor by Concanavalin A-Sepharose and Heparin-Sepharose chromatography demonstrated the inhibitor to be a glycoprotein with an approximate MW = 28-29 K. Northern analysis of human granulosa cell total RNA from preovulatory follicles showed little or no detectable tissue-type PA or urokinase-type PA mRNA. In contrast, two species of PA inhibitor type-1 mRNA were detected in relative abundance. The present findings demonstrate the presence of proteolytic inhibitors in periovulatory ovaries of the rat and human. These ovarian inhibitors may play a role in regulating connective tissue remodeling during follicular rupture.

Animals

Plasminogen activator and plasminogen activator inhibitor in human preovulatory follicular fluid.

To evaluate the roles of plasminogen activator (PA) and PA inhibitor (PAI) in human ovulation, we obtained follicular fluid and granulosa cells from individual preovulatory follicles of patients undergoing gamete intrafallopian tube transfer. The follicular fluid samples (n = 25) were analyzed for total tissue-type PA antigen, PA enzyme activity by fibrin autography, PAI activity, PAI type 1 (PAI-1) antigen, and PAI-1 mRNA. The follicular fluid of preovulatory follicles contained low levels of total tissue-type PA antigen (less than 1 ng/mL). Fibrin autography experiments indicated little or no detectable PA activity associated with free or unbound PA. The results of the PAI activity assay and PAI-1 antigen determination support the concept of a relative abundance of PAI compared with PA. Hybridization analysis was used to measure the relative amounts of granulosa cell PAI-1 mRNA. The levels of PAI-1 mRNA correlate with follicular fluid PAI concentrations in individual follicles. Taken together, these results support the idea that there is very little free, or active, PA in follicular fluid of human preovulatory follicles, but there is an abundance of PAI. Furthermore, PAI-1 produced by the granulosa cells may represent a major form of PAI in follicular fluid.

Antigens