Prostanoid stimulation of anion secretion in guinea-pig gastric and ileal mucosa is mediated by different receptors.

1. The receptors that mediate stimulation of anion secretion by prostanoids in isolated preparations of guinea-pig gastric and ileal mucosa have been compared by use of selective prostanoid agonists and antagonists. 2. In gastric mucosa, the relative potency of agonists suggested that the control of anion secretion in this tissue was complex and may be mediated by EP2, EP3, and TP receptors. A role for TP receptors was confirmed with the TP-selective antagonist AH23848 which inhibited short circuit current responses to the TP receptor agonist U-46619 with a pA2 value of 8.44 but was without effect on responses to prostaglandin E2 (PGE2) or the EP selective agonist, sulprostone. 3. In ileal mucosa, the relative potency of agonists differed from that observed in gastric mucosa and was consistent with the view that anion secretion in this region of intestine was controlled by DP and EP2 receptors. 4. These studies suggest that anion secretion in gastric and ileal mucosa is controlled by different prostanoid receptor subtypes and so provide important information for the design of prostanoids which may protect gastric mucosa and that are free from side effects such as diarrhoea.     

How do clinicians learn to request permission for autopsies?

A postal survey of 434 clinicians at four local hospitals was undertaken in order to identify the methods by which clinicians learn how to request permission for hospital autopsies and to assess the preferred techniques and timing of relevant communication skills training. The majority of 128 responding clinicians had learnt through personal experience with some assistance from senior colleagues and peers. Few clinicians appeared to have learnt through formal training. The preferred methods for the provision of communication skills training were training in small groups (such as seminars or tutorials) and observation of clinicians at work. The most desirable time for the provision of this training was considered to be between the beginning of the final undergraduate year and the end of the pre-registration house officer year. The communication skills training provided within medical education is in need of improvement. More emphasis should be given to clinical-task- or situation-specific applications such as requesting permission for autopsies.     

Presence of 3-fucosyl-N-acetyllactosamine shown by monoclonal antibody AGF 4.48 in Reed-Sternberg cells.

A series of 50 specimens of Hodgkin's disease and 10 of reactive follicular hyperplasia were examined by means of indirect immunoperoxidase staining with a monoclonal antibody AGF 4.48: this is known to bind to 3-fucosyl-N-acetyllactosamine, which, in particular, is expressed by granulocyte series cells. Most Reed-Sternberg and many Hodgkin's cells were labelled by the antibody after pretreatment with neuraminidase. Routinely processed paraffin wax embedded sections proved suitable for staining. The findings were comparable with those reported by others with monoclonal antibodies to various other granulocyte markers. This technique is of potential diagnostic value.     

Interaction of Angiotensin with Disseminated Intravascular Coagulation: A Possible Mechanism in the Genesis of Acute Renal Failure

Because of the importance of the renin-angiotensin system in renal homeostatic mechanisms, the effect of angiotensin administration upon disseminated intravascular coagulation has been studied in rabbits. An infusion of angiotensin II (0.1 μg/kg/min for 2 hours) produced neither histologic abnormalities in the kidneys nor an elevation of creatinine. After an infusion of thrombin (2.0 units/kg/min for 2 hours) only 3 of 10 rabbits, when sacrified 24 hours later, showed histologic lesions comprised of occasional fibrin thrombi and foci of tubular necrosis. Creatinine levels did not rise. In contrast, the combination of angiotensin and thrombin resulted in renal lesions in 12 of 14 animals. Four had frank cortical necrosis, while combinations of tubular necrosis, glomerular thrombosis and segmental glomerular infarction occurred in the others, together with elevated creatinine levels. Blockade of α-adrenoreceptors with phenoxybenzamine in 12 animals did not prevent either these histologic changes or creatinine elevation, showing that the effect of angiotensin was independent of α-adrenoreceptor stimulation. The synergistic interaction between angiotensin and disseminated intravascular coagulation was not explained by differences in the consumption of plasma fibrinogen but apparently was due to localization of fibrin thrombi within glomerular capillaries by the vasomotor actions of angiotensin, as has previously been shown to occur with α-adrenoreceptor simulation. Such a mechanism might contribute to renal glomerular deposition of fibrin in acute ischemic renal failure.     

Studies of human myeloid antigens using monoclonal antibodies and variant lines from the promyeloid cell line HL60.

Monoclonal antibodies were produced using mice immunized with the human promyeloid cell line HL60. Two antibodies are described which identify antigens selectively expressed by myeloid cells. Studies using normal bone marrow and myeloid leukaemia cells demonstrated that one of these antibodies (AGF4.48) identifies an antigen expressed throughout the promyeloid to neutrophil stages of maturation. In contrast, the second antibody (AGF4.36) identifies an antigen expressed at the promyeloid to metamyeloid stages and is absent from most blood neutrophils. The HL60 line can be induced to differentiate into neutrophils by 1 . 25% dimethylsulphoxide (DMSO) (Collins et al., 1978). Variant lines from HL60, unresponsive to 1 . 25% DMSO, lack the 'transient' myeloid antigen (AGF4.36) and show a reduced expression of the myeloid antigen (AGF4.48). The variant lines can be induced to mature using higher DMSO concentrations (1 . 5-1 . 75%) and do not express the 'transient' antigen (AGF4.36) during their maturation. The use of these lines in studies of myelopoiesis is discussed.     

CD1 genotyping of patients with Mycobacterium malmoense pulmonary disease

Mycobacterium malmoense is an opportunistic mycobacterium that occasionally causes disease in non-immunosuppressed individuals. As only a few individuals exposed to these organisms actually develop clinical disease, it is possible there is a genetic component to susceptibility. CD1 molecules are capable of presenting antigens from more virulent mycobacteria to T cells; therefore, we were interested in discovering whether recently described polymorphisms in CD1 molecules modulated susceptibility to M. malmoense pulmonary disease. The CD1 system comprises five genes (CD1A, -B, -C, -D, and -E) located on chromosome 1 (1q22-23). CD1 molecules are structurally and functionally related to major histocompatibility complex (MHC) class I molecules and are expressed on dedicated antigen-presenting cells. The primary function of CD1 molecules is to present lipid and glycolipid antigens to T cells. We have developed an allele-specific polymerase chain reaction-sequence-specific primer (PCR-SSP) method of CD1 genotyping. Using this method, we compared the allele and haplotype frequencies of CD1 in 49 HIV-negative patients with M. malmoense pulmonary disease with those in 342 normal controls. The CD1A and CD1E alleles were nominally identified as CD1A*01, CD1A*02, CD1E*01 and CD1E*02, and the control gene frequencies were found to be 5%, 95%, 67% and 33%, respectively. No significant difference was observed between the patient and control cohorts. Positive linkage disequilibrium values of 0.73 were observed between CD1A*02 and CD1E*01 (P<0.0001; chi2 test), and 0.94 between CD1A*01 and CD1E*02 (P<0.0001; chi2 test). Typing was also performed for two previously described CD1D alleles (CD1D*01 and CD1D*02), although only CD1D*01 was detected.     

The novel HLA-Cw*1802 allele is associated with B*5703 in the Bubi population from Equatorial Guinea

The HLA-Cw*1801 specificity, a Cw7/Cw4 hybrid allele, has recently been described in association with B*8101 (formerly B"DT"). In this study, the new Cw*1802 variant, differing from Cw*1801 at exon 5. is found associated with B*5703 in Bubi individuals from Equatorial Guinea. Confirmatory complete coding regions of B*5703 and B*3910 are also reported.     

The Mechanism of Renal Glomerular Capillary Retention of Carbon in Disseminated Intravascular Coagulation

In rabbits, when renal glomerular capillary thrombosis was induced by an infusion of thrombin, injected colloidal carbon particles localized within glomeruli. When administered after the thrombin had been infused, carbon was attached to the surface of fibrin deposits. Carbon also attached to platelets within capillaries containing fibrin, but not to leukocytes or endothelial cells. If administered simultaneously with thrombin, the carbon was incorporated into the developing mass of fibrin. These observations demonstrate that disseminated intravascular coagulation leads to the deposition of colloidal materials from the circulating blood in regions remote from reticuloendothelial organs, and illustrate a nonimmunologic mechanism whereby foreign particles and abnormal proteins might be trapped within the renal microcirculation.     

Factors differentiating personality-disordered individuals with and without a history of unipolar mood disorder

The relationship between mood disorders and personality disorders has been of longstanding interest to clinicians. Despite theoretical reasons to do so, virtually no studies have examined factors that discriminate personality-disordered subjects with a history of mood disorder (PD/HMD) from personality-disordered subjects without a history of mood disorder (PD). This study examined demographic variables, patterns of comorbidity, measures of life functioning, personality traits, and early life experiences differentiating PD/HMD (n = 83) from PD (n = 214). Diagnoses were assigned using structured clinical interviews and a best-estimate procedure. The results suggest that subjects with borderline personality disorder are more likely to have a life history of mood disorder than are subjects with other personality disorders. In addition, PD/HMDs are more likely to receive a diagnosis of anxiety disorder or alcoholism, to have lower Global Assessment of Functioning (GAF) scores, and to have sought treatment than PDs. On self-report measures of personality, PD/HMDs endorse higher levels of trait anxiety and affective lability (e.g., Harm Avoidance, Neuroticism) than do PDs. PD/HMDs are also more likely to report childhood physical and emotional abuse than are PDs, and to describe their parents as using affectionless control. No differences were found between Axis II clusters as a function of mood disorder history. The discussion suggests a potential model in which early environmental stress interacts with constitutional vulnerabilities to put individuals at an increased risk for both mood and anxiety disorders as well as personality disorders.