STUDIES ON BLOOD COAGULATION FACTORS IN A CASE OF LIVER CIRRHOSIS. REMISSION OF THE HEMORRHAGIC TENDENCY ON TREATMENT WITH HEPARIN.
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An adverse reaction to the intravenous anaesthetic agent propanidid is described in which the main features were hypotension, facial erythema, and abdominal pain. Changes in serum complement levels and differential white cell counts indicate that this was an immune reaction mediated by the classical complement pathway. The immune reaction apparently involved antibodies other than those of the IgE (reagin) class, and circumstantial evidence suggests that it was specific to propanidid rather than to the entire formulation or to Cremophor EL.
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Interstitial cystitis is a chronic inflammatory disorder of the urinary bladder that predominantly afflicts middle-age women. The end stage of the disease is ulceration of the urothelium, the so-called Hunner's ulcer. The aetiology of interstitial cystitis remains obscure. We have studied bladder biopsies from 22 cases of interstitial cystitis and control groups consisting of six cases of bacterial cystitis and eight healthy women. Indirect immunofluorescence was performed on the biopsies using murine MoAbs to human HLA class I molecules, and class II molecules, HLA-DP, HLA-DQ and HLA-DR. In interstitial cystitis, bacterial cystitis and normal controls most cells expressed HLA class I products. In six cases of interstitial cystitis and one case of bacterial cystitis there was evidence of HLA class I hyperexpression. In normal bladder and bacterial cystitis HLA class II expression was restricted to submucosal dendritic cells, Langerhans cells macrophages, vascular endothelial cells and activated lymphocytes. All but two cases of interstitial cystitis showed surface expression of HLA-DR (but not HLA-DP or DQ). In all cases of interstitial cystitis there was an increase in the numbers of macrophages, activated lymphocytes and vascular endothelial cells expressing HLA class II molecules within the submucosa. These findings provide further evidence for the importance of inappropriate HLA molecule expression in a disease suspected of having an autoimmune pathogenesis and where cellular autoimmune mechanisms play a decisive role in the destruction of the target cells--the bladder urothelium.
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The cell surface complement regulatory (CReg) proteins CD46, CD55 and CD59 are widely expressed on human lymphoid and non-lymphoid cells. This study aimed to compare systematically levels of CReg expression by different leucocyte subsets and to determine whether levels were increased following activation in vitro. Levels of each CReg protein were similar on freshly isolated monocytes and all major lymphocyte subsets, except that CD4(+) cells expressed significantly less CD46 than CD8(+) cells (P < 0.05) while the reverse was observed for CD55 (P < 0.02). CD56(+) cells, predominantly natural killer cells, expressed significantly lower levels of CD59 than T cells (P < 0.02). CD45RO(+) cells had higher levels of surface CD46 and CD59, but lower levels of CD55, than CD45RO(-) cells (P < 0.02); CD25(+) cells also expressed significantly less CD55 than CD25(-) cells (P < 0.002). Neutrophils expressed higher levels of CD59, but lower levels of CD55, than monocytes. Following activation with phytohaemagglutinin, CD46 was up-regulated on all leucocyte subsets with the exception of CD56(+) cells. Both CD55 and CD59 were also markedly up-regulated on monocytes, and CD55 expression was greater on CD8(+) than CD4(+) cells following activation (P < 0.02). Lipopolysaccharide treatment did not significantly alter B-cell expression of CReg proteins whereas CD55 and CD59, but not CD46, were significantly up-regulated on monocytes (P < 0.02). These observations that CReg proteins are up-regulated on certain activated leucocyte subsets indicate that levels would be increased following immune responses in vivo. This could enhance both protection against local complement activation at inflammatory sites and also the immunoregulatory properties of these leucocytes.
Human palatine tonsil sections were examined to investigate the distribution of cells bearing the cell surface markers of peripheral blood natural killer (PB-NK) cells. Leu-7+ (HNK-1+) cells were localized predominantly in lymphoid follicles, whereas OKM1-, Mac-1-, and Mo2-labelled cells were found in the epithelial and subepithelial regions and epithelial crypts. OKT10+ cells showed a variable distribution, being found in follicles and interfollicular or subepithelial regions. No. B73.1+ cells could be identified in tonsil sections. Leu-7+ cells appeared not to be responsible for tonsillar natural cytotoxicity, since Leu-7 (HNK-1) antibody- and complement-mediated lysis under conditions that markedly reduced PB-NK activity failed to abolish cytotoxicity, and positive selection by means of the FACS IV gave no enrichment of activity. Similarly, cells labelled with the antibodies B73.1, Leu-11b, OKT8, OKT10, and TDR 31.1 (anti-major histocompatibility complex class II framework determinant) were not enriched with regard to NK activity either. However, positive selection with OKM1, Mac-1, or Mo2 showed that cells bearing these markers were responsible for essentially all tonsillar NK activity. No large granular lymphocytes were identified in such populations enriched for NK activity. The observation that PB-NK cells labelled faintly with Mo2 weakens the argument that a non-adherent mononuclear phagocyte population was responsible for the activity. These data therefore support the existence of heterogeneity within naturally cytotoxic cell populations.
Clones were derived from highly purified human CD4-8- lymphocytes from three different donors and maintained in the presence of interleukin 2 and phytohaemagglutinin. Considerable variation was noted between donors in the phenotype and T-cell receptor (TCR) gamma gene rearrangements of CD4-8- -derived clones. In one donor, most clones remained CD4-8- and all were CD3+WT31- and therefore expressed gamma/delta heterodimers. TCR gamma gene rearrangements almost all involved C gamma 1. In contrast, most clones from a second donor were CD3+WT31+, and therefore expressed alpha/beta heterodimers, and many were positive for CD4 or CD8. Most clones from a third donor were CD3+WT31- with a high proportion of TCR gamma gene rearrangements involving C gamma 2. The V gamma 9JP rearrangement was exclusively confined to CD3+WT31- clones and was present in the majority of clones. Almost all CD3+WT31- clones showed TCR beta as well as gamma gene rearrangements. Most CD3+WT31- clones with at least one chromosome rearranged to C gamma 1 exhibited high non-major histocompatibility complex (MHC)-restricted cytotoxic activity, while most of those with two C gamma 2 rearrangements, and therefore expressing a non-disulphide-linked gamma/delta heterodimer, had low activity. Preincubation of effector cells with anti-CD3 strongly inhibited the cytotoxicity of CD3+WT31- clones while that of CD3+WT31+ clones was enhanced. This implicates the CD3-gamma/delta complex in target cell recognition by cytotoxic gamma/delta-bearing T-cell clones. The results show that there is heterogeneity between donors in the relative proportions of CD4-8- -derived clones expressing alpha/beta heterodimers and the different forms of the gamma/delta heterodimer.
T-cell receptor gamma and delta gene expression was determined using V-region-specific monoclonal antibodies in conjunction with Southern blot analysis in panels of gamma delta T-cell clones from human peripheral blood (n = 77) and reproductive tissue (n = 9). Whereas 53 out of 77 (69%) clones from peripheral blood expressed V gamma 9 and V delta 2J1, only 2 out of 9 (22%) from reproductive tissues expressed V delta 2J1. Two out of eight decidual clones expressed both V gamma 9 and V delta 1J1, while this configuration was rare in clones from peripheral blood. The majority of clones from the peripheral blood of one donor expressed V gamma 8 and V delta 3J1. Clones were identified which expressed V delta 1J1 in the disulphide-linked C gamma 1 form of the receptor and which expressed a gene other than V delta 1 in the non-disulphide-linked C gamma 2 form, indicating incomplete concordance between expression of V delta 1 and C gamma 2. V delta 3 could be expressed in the disulphide-linked or non-disulphide-linked form of the receptor. At least 5 out of 77 peripheral clones were expressing V delta genes other than V delta 1, V delta 2, or V delta 3 in conjunction with C gamma 1 or C gamma 2. There was a strong but incomplete correlation between high non-NHC-restricted cytotoxic function and C gamma 1 expression. Clones from the same donor expressing both V gamma 9JPC gamma 1 and V delta 2J1 showed either high or negligible cytotoxicity, and cytotoxic clones expressing C gamma 2 were found. Thus no complete correlation between cytotoxic function and expression of a particular form of the gamma delta heterodimer was identified. The results also suggest that gamma delta T cells from reproductive tissues are less likely to express V delta 2J1 than those from peripheral blood.
Expression of the human mucosal lymphocyte antigen, HML-1 (CD103), recently identified as a novel alpha E beta 7 integrin, was studied on peripheral blood lymphocytes activated with mitogen or specific antigen. HML-1 was up-regulated on PHA activated T-lymphoblasts cultured in 100IU/ml interleukin-2 (IL-2), reaching a peak of > 50% positive cells at day 7, and expression was maintained at this level throughout the 28-day culture period. Following a transient decrease in the percentage of L-selectin cells, expression of this molecule was maintained on most PHA T-lymphoblasts. Cells activated by purified protein derivative of M. tuberculosis (PPD) or in mixed lymphocyte culture also up-regulated and maintained HML-1 expression for 14 days. In contrast, in all cases the percentage of CD25+ cells rose initially but subsequently declined over the same time periods. When freshly isolated cells from tonsil, spleen, mesenteric lymph node and lung were analysed, only lung contained significant numbers (39 +/- 6%) of HML-1+ cells. In both freshly isolated and activated cell populations the great majority of HML-1+ cells co-expressed CD8 although some HML-1+ CD8- cells were also present. Production of TGF-beta 1 peaked early during T-lymphoblast and MLR cultures and was not related to induction of HML-1 expression. Immunoprecipitation studies showed that the HML-1 molecule expressed on 10-day PHA T-lymphoblasts was indistinguishable from that found on intestinal intraepithelial lymphocytes and that no alpha 4 beta 7 integrin was expressed by these cells. Although HML-1 expression is essentially restricted to mucosal leucocytes in vivo, these experiments show that it is readily induced and maintained along with co-expression of L-selectin following CD8+ T-lymphocyte activation in vitro.
UNLABELLED: Recent studies have suggested that there is a familial association of sleep apnoea syndrome and that this is not entirely explained by inheritance of known risk factors. Maori (M) and Pacific Islanders (PI) have many of the body habitus features associated with sleep apnoea and therefore might be expected to exhibit more severe disease than Europeans (E). OBJECTIVE: To compare the clinical and physiological characteristics of the different ethnic groups and to determine if race was an independent predictor of severity of sleep apnoea. METHODOLOGY: A prospective evaluation of patients attending the Sleep Disordered Breathing Clinic which serves the whole of Auckland (population 1.1 million), New Zealand was conducted for the period July 1994 to August 1995. The evaluation included history including a 26 question questionnaire, Epworth sleepiness score, examination, and where indicated, full polysomnography. RESULTS: A total of 233 patients (154 E, 48 M and 33 PI), underwent full polysomnography. Forty-one (85%) of the M and 31 (94%) of PI had obstructive or mixed sleep apnoea compared with only 74 (49%) of the E (P < 0.0001; chi 2). There were few racial differences in the responses to the sleep questionnaire. M and PI were shown to have much greater neck and waist circumference and body mass indices. Severity parameters (apnoea-hypopnoea index, wake and minimum oxygen saturation, and apnoea duration) were greater for both M and PI compared with E (P < 0.001; Mann-Whitney U-test). Stepwise regression identified neck size, body mass index and age as independent predictors of severity. CONCLUSION: When other factors were controlled for, race was not an important independent predictor of severity of sleep apnoea.
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The instillation of diluted Bonney's blue into the bladder during gynaecological operations has been quite common practice over the last 50 years. Bonney's blue is composed of a 1:1 mixture of brilliant green and crystal violet dissolved in ethanol (90%) or industrial methylated spirit. Before insertion into the bladder this solution must be diluted with water to a 0.5% solution. Failure to do this will result in a severe inflammatory reaction within the bladder. The degree of resultant damage depends upon the duration of exposure. Persistent pain is a feature of this condition, although the other symptoms (frequency and urgency) may settle in time. Two cases of chemical cystitis resulting from the use of undiluted Bonney's blue are described to illustrate the possible consequences. Both patients were awarded 6-figure sums as compensation.
The accuracy, reliability and cost effectiveness of 5 currently marketed flow meters have been assessed. The mechanics of each meter is briefly described in relation to its accuracy and robustness. The merits and faults of the meters are discussed and the important features of flow measurements that need to be taken into account when making diagnostic interpretations are emphasised.
The main prevalence of vesicoureteric reflux (VUR) is in the adult female population. Although recognised as a clinical entity in adult males, little detailed information is available on this subject. A retrospective analysis was carried out on the results of 1519 consecutive videocystometrograms performed on male patients. VUR had an overall incidence of 8.6% within this population, with a range of 5.1% in patients with normal urodynamics to 15.6% in those with detrusor-sphincter dyssynergia. The common denominator between VUR and urodynamic measurement appears to be the generation of high intravesical pressures. These findings suggest that VUR is not uncommon in the male population, is usually asymptomatic and should respond to the treatment of any underlying bladder abnormality.