Colonic mucosal T lymphocytes in ulcerative colitis: Expression of CD7 antigen in relation to MHC class II (HLA-D) antigens

T-cell subsets and their activation state were examined by double-label immunofluorescence of cryostat tissue sections of the colon from 21 patients with ulcerative colitis (UC) and 30 histologically normal controls. Expression of MHC class I (HLA-A, B, C) and class II (HLA-D) antigens was studied in parallel. In the normal colonic mucosa, the CD4CD8 ratio in the epithelial compartment approximated 11, and in the lamina propria, 2.551. Of the CD8⁺ (cytotoxic/suppressor) subset, approximately half did not express the CD5 pan-T marker in either compartment. Virtually no Leu 8⁺ cells were observed, implying that the CD4⁺ subset consisted of helper, rather than suppressor-inducer cells. Classical markers of T-cell activation (CD25, HLA-D) and proliferation were absent, and strong expression of the CD7 immunostimulation marker was approximately equal in both CD4 and CD8 subsets. The epithelium was uniformly negative for class II antigens, but positive for class I. In UC, there were no significant alterations in CD4CD8 ratios in either compartment, and there were no changes with respect to phenotype of the subsets. In 11 of 19 patients (mainly with total colitis), enterocytes were HLA-D⁺. In this HLA-D⁺ group, there was an increase in the percentage of CD4⁺ cells coexpressing CD7; this difference was significant (P<0.02) in the lamina propria. Increased expression of CD7 was also found by the CD6⁺ T cell subset (P<0.05). These results suggest that class II expression is mediated by immunostimulated T helper cells in UC, with consequences for antigen presentation and maintenance of the chronic inflammatory state.HLA-D is used as a generic term for class II major histocompatibility complex (MHC) gene products (HLA-DR, DP, DQ) unless specified otherwise.     

Effect of β-adrenergic stimulation on free fatty acid content in subepicardial and subendocardial layers of the dog heart in situ. Separation and assay by capillary gas chromatography

Summary The effects of -adrenergic stimulation produced by an infusion of isoproterenol (1 g·kg^–1 min^–1, 30 min) were studiedin situ in the anaesthetized dog placed under a total cardiopulmonary bypass. Samples of the subepicardial and the subendocardial layers were homogenized separately prior to the extraction and methylation of free fatty acids (FFA). Gas chromatography on Carbowax 20 M capillary columns was used for the quantitation of myristic (C 140), palmitic (C 160), palmitoleic (C 161), stearic (C 180), oleic (C 181), linoleic (C 182), and arachidonic (C 204) acids.Within 5 min, isoproterenol decreased the tissue content of FFA significantly. The decrease was more pronounced in the endocardial layer where the FFA concentration reached its minimum at the 5th or the 15th min. In the epicardial layer, all the FFA reached their minimal concentration at the 30th min of the isoproterenol infusion. In both layers, lactate content remained unchanged at 5 and 15 min and rose at the 30th min only and content in phosphorylated compounds (ATP, creatine-phosphate—CP) did not show any significant variation during the -stimulation period. A significant correlation was found between the chronotropic effect of isoproterenol and the reduction of FFA concentration.With the technical assistance of Agnès Bacconin.     

The effect of dbcAMP on the lysolecithin induced hemolysis of calf and adult cattle erythrocytes

Summary The calf erythrocytes have an increased sensitivity against lysolecithin as compared to their adult counterparts. 10^–3M dbcAMP increases the hemolysis induced by 5g of lysolecithin in 0.15 M NaCl containing 10 mM phosphate buffer (pH 7.4). By increasing the level of phosphate buffer (75 mM) in the incubation mixture, 10^–3M dbcAMP decreases the hemolysis induced by 5g of lysolecithin. These data suggest a dual effect exerted by dbcAMP: the relatively labilizing or stabilizing effect prevails as a function of exogenous inorganic phosphate level.10-⁶M dbcAMP also has a relative protective effect against lysolecithin.The combined addition of cAMP (10^–3) and theophyllin (10^–4M) does not stabilize the membrane.By increasing the level of lysolecithin to 20g/ml the stabilizing effect of dbcAMP disappears.DbcAMP (10^–3) as well as cAMP (10^–3M) and theophyllin (10^–4M) have a minimum increasing effect on hemolysis in the absence of lysolecithin, too.

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Abbreviations dbcAMP N⁶-20-dibutyryladenosine 35-monophosphate - cAMP cyclic 35-adenosine monophosphate     

Isolierung von freien Nucleotiden aus verschiedenen Geweben

Zusammenfassung Es wurden die freien Nucleotide aus dem säurelöslichen Extrakt des Sarkom 37 (Ascitesform) durch Anionenaustauschchromatographie isoliert. Die Befunde werden mit den Ergebnissen an normalen und anderen Tumorgeweben verglichen.In der Arbeit werden folgende Abkürzungen verwendet Ad Adenosin - A2MP Adenosin-2-monophosphat - A3MP Adenosin-3-monophosphat - AMP Adenosin-5-monophosphat - ADP Adenosin-5-monophosphat - ATP Adenosin-5-triphosphat - G2MP Guasonin-2-monophosphat - G3MP Guanosin-3-monophosphat - GMP Guanosin-5-monophosphat - GDP Guanosin-5-diphosphat - GTP Guanosin-5-triphosphat - C2MP Cytidin-2-monophosphat - C3MP Cytidin-3-monophosphat - CMP Cytidin-5-monophosphat - CDP Cytidin-5-diphosphat - CTP Cytidin-5-triphosphat - U2MP Uridin-2-monophosphat - U3MP Uridin-3-monophosphat - UMP Uridin-5-monophosphat - UDP Uridin-5-diphosphat - UTP Uridin-5-triphosphat - UDPA Uridin-5-diphosphat-N-acetylglucosamin - UDPG Uridin-5-diphosphat-glucose - UDPGa Uridin-5-diphosphatgalaktose - UDPGl Uridin-5-diphosphatglucuronsäure - TPN Triphosphopyridinnucleotid - DPN Diphosphopyridinnucleotid - FAD Flavin-adenin-dinucleotid - HS Harnsäure - RNS Ribonucleinsäure - IMP Inosin-5-monophosphat Mit 6 Textabbildungen.Den soliden Tumor verdanken wir Herrn Dr. Dr.Ch. Hackmann, Farbenfabriken Bayer, Wuppertal-Elberfeld. Dieser Tumor wurde von Herrn Dr.H. Wrba im hiesigen Institut in die Ascitesform übergeführt.     

Risk of human immunodeficiency virus (HIV) transmission by anti-HIV-negative blood components in Germany and Austria

In order to estimate the residual risk of transfusion-transmitted HIV infection we have analyzed the data from two transfusion centers in Austria (Vienna) and Germany (Göttingen) from 1985 to 1994. In Vienna, an incidence of 142000 positive anti-HIV tests in repeat donors and a prevalence of 17000 in first-time donors were found in 1993. In Göttingen, the indicence was 167000 and the prevalence 17900 from 1985 to 1993. Based on a mathematical model which takes (a) the window period and (b) the false-negative rate of anti-HIV tests, as well as (c) human and operational errors into consideration, we have calculated the residual risk of HIV infection. The residual risk (third generation anti-HIV test) was found to be 1520000 (95% confidence interval 11340000-1210000), and 1900000 (95% confidence interval 12340000-1380000) for Vienna and Göttingen, respectively, in 1993. Look-back studies from 1985 till 1994 revealed transfusion-transmitted HIV infections in three recipients (for 1.9 million donations in Vienna) and one recipient (for 160000 donations in Göttingen) of blood components. Based on our model, as well as on prevalence and incidence rates of HIV infection, it is also possible to predict the efficacy of additional measures introduced to further decrease the risk of transfusion-transmitted HIV infection through blood components.     

Comparison of mRNA contents of interleukin-1Β and nitric oxide synthase in pancreatic islets isolated from female and male nonobese diabetic mice

Summary Interleukin-1 (IL-1) has been suggested to mediate beta-cell destruction in insulin-dependent diabetes mellitus (IDDM) by inducing nitric oxide production. In this study, we assessed the levels of IL-1 and the inducible form of nitric oxide synthase (iNOS), using a semi-quantitative polymerase chain reaction assay, and performed determinations of nitrite accumulation and IL-1 bioactivity, on pancreatic islets isolated from 5- and 16-week-old female and male nonobese diabetic (NOD) mice and from nondiabetes prone NMRI mice. NOD mouse islets contained notable amounts of IL-1 mRNA. At 5 weeks of age, but not at 16 weeks, the values were higher in islets isolated from NOD females compared to males. The IL-1 bioactivity showed differences roughly reflecting the mRNA levels in the NOD mouse islets. In the NMRI mouse islets the IL-1 bioactivity was very low. The expression of iNOS mRNA increased in both male and female islets between 5 and 16 weeks of age. Immunocytochemistry of pancreatic sections indicated the presence of macrophages especially in the peri-insular area of the NOD mice which suggests that IL-1 was produced by macrophages. The levels of IL-1 activity and mRNA in freshly isolated islets from NOD 5-week-old females did not correlate to the iNOS mRNA content or to the nitrite production. However, after incubation with IL-1 in vitro, both NOD and NMRI islets responded with a marked increase in nitric oxide production. It is concluded that the presence of IL-1 in isolated NOD mouse islets, via an induction of iNOS expression and nitric oxide production, cannot explain the gender difference in diabetes incidence in NOD mice.Abbreviations BB BioBreeding - GAPDH glyceraldehyde-3-phosphate dehydrogenase - IDDM insulin-dependent diabetes mellitus - iNOS inducible form of nitric oxide synthase - IL-1 interleukin-1 - IL-1ra interleukin-1 receptor antagonist protein - IL-6 interleukin-6 - NMRI Naval Marine Research Institute - NO nitric oxide - NOD nonobese diabetic - PAP peroxidase-antiperoxidase - PCR polymerase chain reaction - SDS sodium dodecyl sulphate - TNF tumour necrosis factor - OD optical density     

Clinical usefulness of free light chain concentration as a tumor marker in multiple myeloma

Monoclonal immunoglobulin, as a marker for monoclonal gammopathy, is evaluated by protein electrophoresis (PEP) and immunofixation electrophoresis (IFE). However, PEP and IFE are not satisfactory in sensitivity, objectivity, and facility. Recently, a highly sensitive, automated immunoassay for measurement of free light chain (FLC) concentrations in serum and urine has been developed for the identification and monitoring of patients with monoclonal gammopathy. To explore the clinical usefulness of measurement of FLC concentrations, we measured the and FLC concentrations and calculated the / FLC ratios for three groups [multiple myeloma (MM), other diseases, and control] and compared the results of the FLC assay with the results of PEP or IFE. The concentrations of serum and FLCs and the / FLC ratios for the MM group and non-MM groups were distinct. In the MM group, some sera and urine samples had no evidence of M protein on PEP and IFE, but FLC assay showed abnormal concentrations of FLCs and abnormal / FLC ratios in most cases. As compared with the PEP, the / FLC ratio revealed higher sensitivity in all diagnostic ranges with different cutoff values. Particularly, when the cutoff value 2.0 for / FLC ratio was used, specificity and positive predictive value were largely improved than when the cutoff values 1.2 and 1.5 were used. These findings indicated that FLC assay enables to detect myeloma patients with very low M protein due to early stage or after therapy and to distinguish patients with monoclonal increase of FLC from patients with polyclonal increase of FLC due to other conditions, particularly using / FLC ratio 0.3–2.0 as a diagnostic range. Despite some technical limitations of the assay, the incorporation of / FLC ratios with FLC concentrations is useful in the detection of M protein, particularly with negative serum or urine IFE results, and differentiation of monoclonal gammopathies from patients with polyclonal increase in FLC due to other conditions.     

Effects of short-term high dose intake of evening primrose oil on plasma and cellular fatty acid compositions, α-tocopherol levels,and erythropoiesis in normal and Type 1 (insulin-dependent) diabetic men

Summary In addition to their usual diet, nine Type 1 (insulin-dependent) diabetic men and ten male control subjects took 20 g d,ga-tocopheryl acetate enriched evening primrose oil (14.45 g 182c,6, 1.73g 183c,6, 400 mg d,-tocopheryl acetate) daily for one week. At start, diabetic patients had more 140, 150 and 18 2c,6, and less 160, 161c,7, 181c,7, 183c,6, 203c,9, 203c,6, 204c,6 and 226c,3 in plasma, erythrocytes and/or platelets. Furthermore, they had lower 161c,7/160, 181c,7/160, and 204c,6/203c,6 ratios and a higher 203c,6/183c,6 ratio. In diabetic patients, -tocopherol levels in erythrocytes were lower, whereas those in plasma were normal. In both groups, oil intake changed fatty acid profiles. Most markedly, 203c,6 increased, whereas the ratios 203c,6/ 183c,6 and 204c,6/203c,6 decreased. 204c,6 increased in control subjects, but not in diabetic patients. Erythrocytes and platelets responded differently in their fatty acid profiles, -tocopherol rose in plasma and, although less for diabetic patients, in erythrocytes. In diabetic patients as well as in control subjects, erythrocyte count, haemoglobin level, mean corpuscular haemoglobin content and concentration increased and glycosylated haemoglobin percentage decreased without an apparent decline in blood glucose levels. Plasma -thromboglobulin and platelet factor 4 decreased, especially in diabetic patients. In conclusion, diabetic patients had abnormal fatty acid patterns, suggesting an impaired 9, 6 and 5 desaturation and an enhanced chainelongation, and had lower erythrocyte a-tocopherol levels; and short-term high dose intake of evening primrose oil increased 203c,6 in both groups, but 204c,6 only in control subjects, gave fatty acid responses which were different for erythrocytes and platelets, enhanced erythropoiesis, and lowered indices of in vivo platelet activation.     

Hypomagnesaemia in Type 2 (non-insulin-dependent) diabetes mellitus is not corrected by improvement of long-term metabolic control

Summary Low levels of magnesium have frequently been reported in diabetes mellitus especially in poorly controlled Type 1 (insulin-dependent) diabetic patients. Furthermore hypomagnesaemia might contribute to insulin resistance in Type 2 (non-insulin-dependent) diabetes. As the influence of improved metabolic control on plasma magnesium levels is unknown in Type 2 diabetic patients we studied magnesium plasma levels in 50 patients 1) before, 2) one and 3) three months after the initiation of insulin therapy or intensified treatment with oral hypoglycaemic agents. Magnesium plasma levels were measured by a colorimetric method and were significantly reduced in diabetic patients compared to healthy control subjects (0.79±0.01 mmol/l vs 0.88±0.01 mmol/l; p<0.0001). Metabolic control was significantly improved as documented by reduced HbA_1C levels in both insulin-treated patients or the patients on oral hypoglycaemic agents (p<0.003). However, plasma magnesium levels remained unchanged during the follow-up in the insulin-treated group (10.79±0.02 mmol/l; 20.81±0.02 mmol/l; 30.79±0.01 mmol/l) as well as in the patients on oral hypoglycaemic agents (10.79±0.03 mmol/l; 20.78±0.02 mmol/ l; 30.84±0.04 mmol/l). This study shows that even marked improvement of glycaemic control does not correct hypomagnesaemia in Type 2 diabetes. We conclude that hypomagnesaemia might be related to the insulin-resistant state and that possible beneficial effect of chronic magnesium administration should be evaluated in these patients.     

Involvement of α2-Adrenoceptors in mechanism of intragastric nicotine protection against ethanol injury in rat stomach

To elucidate the role of - and -adrenoceptors in the mechanism of intragastric nicotine protection against ethanol-induced gastric mucosal injury, the following studies were performed. At 0.5-hr prior to the injury study, rats were pretreated with: subcutaneous control, prazosin (0.5 mg/kg) or yohimbine (5 mg/kg) to block ₁- or ₂-adrenoceptors; or intraperitoneal control, metoprolol (2 mg/kg) or butoxamine (4 mg/kg) to block ₁- or ₂-adrenoceptors, respectively. At 1-hr intervals, rats received intragastric vehicle or nicotine (4 mg/kg) and 40% ethanol (10 ml/kg). Total lengths of the linear gastric corpus mucosal lesions were measured by an unbiased observer using a caliper. In a separate study, 0.5-hr after subcutaneous control or yohimbine (5 mg/kg), rats were treated with intragastric vehicle or nicotine (4 mg/kg). One hour later, gastric mucus volume, gastric juice volume and pH, and titratable acid in the gastric juice were measured. In the rat stomach, the intragastric nicotine protection against 40% ethanol-induced mucosal injury was not blocked by selective ₁-(prazosin), ₁-(metoprolol), or ₂-(butoxamine) adrenoceptor antagonists. The protection was significantly reduced although not completely abolished by selective ₂-(yohimbine) adrenoceptor antagonist. Yohimbine also significantly reduced basal and nicotine-stimulated increase in gastric mucus volume. These data suggest that ₂-adrenoceptors are involved in the protective effect of intragastric nicotine against 40% ethanol-induced gastric mucosal injury possibly by a mucus-dependent mechanism.Supported by Veternas Administration Medical Research Funds, and in part by research grants (0162-01, 02, and 291-01) from the Smokeless Tobacco Research Council, Inc., and by funds (1RT 80) provided by the Cigarette and Tobacco Surtax Fund of the State of California through the Tobacco-Related Disease Research Program of the University of California to F.W.L. Dr. Endoh is a recipient of the University of California Tobacco-Related Disease Research Program Research Fellowship Award (FT 37).     

Enzymatic determination of serum 3α-sulfated bile acids concentration with bile acid 3α-sulfate sulfohydrolase

A newly developed enzymatic method for determining urinary 3-sulfated bile acids was used to measure serum 3-sulfated bile acid levels in 114 patients with hepatobiliary diseases and 56 healthy subjects. The lowest measurable amount of the 3-sulfated bile acids was 0.5 µmol/liter. The standard curves for glycolithocholic acid 3-sulfate, glycoursodeoxycholic acid 3-sulfate, and lithocholic acid 3-sulfate were linear from 0.5 to 250 µmol/liter. Specificity of the assay was satisfactory and intra- and interassay variations ranged from 0.8 to 4.4% and from 1.2 to 7.9%, respectively. Analytical recovery was more than 91%. The values obtained by this assay were well correlated with those by gas-liquid chromatography measurement (r=0.91,P<0.01). The fasting serum 3-sulfated bile acids level in healthy subjects ranged from undetectable to 1.9 µmol/liter (mean±se; 0.9±0.1 µmol/liter). The percentage of 3-sulfated bile acids in total bile acids (sum of 3-sulfated and 3-hydroxy bile acids) in serum was 16.8±1.5%. In subjects with hepatobiliary diseases, serum 3-sulfated bile acids levels were elevated; however, the percentage of 3-sulfated bile acids in total bile acids was decreased and correlated with the severity of hepatocellular insufficiency. This enzymatic assay is simple, rapid, and accurate for the determination of serum 3-sulfated bile acids.     

γ/δ Receptor-expressing T-cell clones from a cutaneous T-cell lymphoma suppress hematopoiesis

Summary Recently we described a cutaneous T-cell lymphoma expressing the / T-cell receptor [5]. The patient suffering from this lymphoma showed low numbers of myeloid and T cells in peripheral blood, while B and NK cells were relatively increased. In vitro culture of the patient's bone marrow (BM) cells revealed a significant suppression of myeloid/monocyte colony formation (GM-CFU) compared with normal controls. This was not due to infiltration of the BM with lymphoma cells. We speculated that a soluble factor either secreted or induced by the lymphoma cells might be responsible for the marked suppression of hematopoiesis in this patient. From a skin biopsy with infiltrating / T-lymphoma cells we established T-cell clones bearing the / T-cell receptor and resembling the phenotype of the lymphoma cells. The supernatant (SN) of these / T-cell clones reduced the number of colonies in a CFU-GM assay (using normal control BM) in comparison to SN of / T-cell clones established from the same biopsy. This suppression was seen mainly on day 7 of culture and was not neutralized by the addition of placenta-CM. The main mediator of this suppression seems to be IFN-,since it was detectable in high amounts in the SN of these / T-cell tumor clones as well as in the serum of the patient. In addition, anti-IFN- antibodies can reverse the T-cell SN-mediated suppression of CFU-GM. We conclude that high serum levels of interferon-, which is secreted in high amounts from / T-cells grown from a biopsy of a cutaneous lymphoma, can suppress hematopoiesis.Abbreviations TCR T-cell receptor - IFN- interferon- - SN supernatant - placenta CM placenta conditioned medium - BM bone marrow - CFU-GM myeloid/monocyte colony formation - NK cells natural killer cells - Ab antibody M. Wilhelm was supported by theDeutsche Forschungsgemeinschaft (DFG Wi 728-2)     

Plasma acidic glycohydrolases in insulin-dependent diabetes mellitus

Summary We assayed plasma activities of -galactosidase, -hexosaminidase, -mannosidase, -fucosidase and -galactosidase involved in degradation of the glycoprotein molecule in 110 insulin-dependent diabetics aged 3-1/2 to 19 years and compared them to a group of normal youngsters. We correlated the plasma enzyme activities with the duration, control and sequelae of insulin-dependent diabetes. Insulin-dependent diabetics had a significantly higher plasma activity of -hexosaminidase and -mannosidase (p<0.01) and a significantly lower plasma activity of -fucosidase and -galactosidase (p<0.01). Of the 5 enzymes studied, only plasma -hexosaminidase correlated with fasting and postprandial blood sugar (p<0.01), cholesterol and triglycerides (p<0.05). Additionally, poor control of diabetes was also associated with a significantly higher plasma -hexosaminidase activity (p<0.01). Proteinuria or an abnormal Addis count suggestive of renal involvement was associated with various changes in plasma acidic hydrolases. These changes may be related to insulin deficiency rather than hyperglycemia and may be genetically determined.Deceased on August 2, 1981.     

Rapid detection of −α 4.2 deletion of α-thalassemia-2 by polymerase chain reaction

Summary We sequenced part of the X boxes of-thalassemia-1 of Southeast Asia type (- -SEA) with– ^4.2,– ^3.7,– ^G-Taichung, and ^CS. We found the X box of– ^3.7 belonged to the X box of 2 globin gene and the X box of ^cs contained X boxes of both al and2 globin gene, whereas the X box of– ^4.2 and– ^G-Taichung was a hybrid of X boxes of 2 and 1 globin gene. We also found there are two types of– ^4.2 deletion; type 1 is a common type of– ^4.2 deletion and type 2 is linkage to– ^G-Taichung. We used a combination of two methods, the amplification refractory mutation system (ARMS) and the amplified created restriction sites (ACRS), to amplify the hybrids of X boxes specifically. The upstream primer for X box of2 globin gene was designed following the standard ARMS procedure to amplify the X segment of the-globin gene. The downstream primer was designed according to the ACRS method to check the specificity of PCR products. Using this approach, we can diagnose the different types of– ^4.2 deletion. This kind of approach can also be used to amplify the specific region from the cluster of highly homologous genes.     

Isolierung von freien Nucleotiden aus verschiedenen Geweben

Zusammenfassung In Erweiterung früherer Mitteilungen wird über den Gehalt des Flexner-Jobling-Carcinoms der Ratte an freien Nucleosidmono- und-polyphosphorsäureestern berichtet.Die vorliegenden Untersuchungen wurden zum Teil dankenswerter-weise durch denAnna-Fuller-Fund und dieDeutsche Forschungsgemeinschaft unterstützt.In der Arbeit werden folgenden Abkürzungen verwendet Ad Adenosin - AMP Adenosin-5-monophosphat - ADP Adenosin-5-diphosphat - ATP Adenosin-5-triphosphat - GMP Guanosin-5-monophosphat - GDP Guanosin-5-diphosphat - GTP Guanosin-5-triphosphat - CMP Cytidin-5-monophosphat - CDP Cytidin-5-diphosphat - CTP Cytidin-5-triphosphat - UMP Uridin-5-monophosphat - UDP Uridin-5-diphosphat - UTP Uridin-5-triphosphat - UDPA Uridin-5-diphosphat-N-acetylglucosamin - UDPG Uridin-5-diphosphat-glucose - UDPGa Uridin-5-diphosphat-galaktose - UDPGl Uridin-5-diphosphat-glucuronsäure - IMP Inosin-5-monophosphat - DPN Diphosphopyridinnucleotid - HS Harnsäure - RNS Ribonucleinsäure - DNS Desoxyribonucleinsäure - TPN Triphosphopyridinnucleotid Mit 19 TextabbildungenDer überwiegende Teil der dieser Arbeit zugrunde liegenden Versuche wurde 1952/53 im McArdle Memorial Laboratory, University of Wisconsin durchgeführt.     

CD4+ and CD8+ subsets: Naive and memory cells in the peripheral blood of patients with systemic sclerosis

Summary Systemic Sclerosis (SSc; scleroderma) is associated with several immunological abnormalities, including altered proportion between lymphocyte subsets. Peripheral blood lymphocyte subsets from 25 patients with SSc were studied by two-colour flow cytometry using monoclonal antibodies against CD45RA and CD29 markers, which allow a dissection of CD4+ and CD8+ populations into naive and memory subsets. A decrease of the percentage of CD8+ (p<0.05) and of CD8+ CD29+ (p<0.001) cells was observed compared to that in 20 age and sex-matched controls. These abnormalities were not significantly associated with the extension of cutaneous disease or other clinical features of SSc nor with treatment, pattern of autoantibodies or HLA phenotype.     

Large-bowel cancer in the young: A national survival study

Large-bowel cancer in young patients is reported to be a more aggressive and advanced disease at presentation and is believed to be associated with a relatively poor prognosis. Of 2420 patients registered in New Zealand (1968 to 1970), 131 were under 40 years of age and 2289 were over 40 years of age. The annual average incidence of treatable colorectal cancer in patients under 40 years of age was 2.36 per 100,000 and 82.93 in patients over 40 year of age. There were predominantly more females in both age groups with colonic tumors, 5044 (femalemale), and 759652 (femalemale). The rectal tumor male-to-female ratio of 10.68 in those over 40 years of age was reversed in those under 40 years of age (12.08). There was no significant difference in the subsite distribution of colorectal cancers between the two groups. There was a higher proportion of Stage 1 tumors in those under 40 years of age and a correspondingly higher proportion of Stage 2 tumors in those over 40 years of age. The overall crude and relative five-year survival rates for patients under 40 years of age were both 60 percent, whereas the crude rate for older patients was 42 percent, with a corresponding relative rate of 53 percent. Ten-year survival rates were generally higher in younger patients. From this study, there was no evidence to suggest that younger patients (less than 40 years old) with colorectal cancer had worse prognoses and did not survive as long as older patients (40 years and over).Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, Anaheim, California, June 12 to 17, 1988.     

Expression and prognostic roles of integrins and interleukin-1 receptor type I in patients with ductal adenocarcinoma of the pancreas

To Investigate the prognostic indicator, we examined the expression of ₆- and ₅- integrin and interleukin-1 receptor type I (IL-1RI) immunohistochemically, and analyzed the correlation between immunohistochemical findings and clinicopathological factors in pancreatic cancer. In patients with a strongly expressing ₆- integrin subunit or weakly expressing ₅₁-integrin in pancreatic cancer tissues there was a significant association with advanced TNM stage (P = 0.027 and 0.014, respectively), presence of liver metastases (P = 0.032 and 0.002, respectively), and poor prognosis (P = 0.0155 and 0.0056, respectively). In patients with a weakly expressing ₆ integrin subunit or weakly expressing ₅₁-integrin in noncancerous pancreatic tissues there was a significant association with poor prognosis (P = 0.0324 and 0.0396, respectively). Multivariate analysis demonstrated that strong expression of ₆- and weak expression of ₅₁-integrin were found to be independent prognosticators in pancreatic cancer patients. Our present results indicate that ₆₁- and ₅₁-integrin expression can be a significant prognostic indicator in pancreatic cancer.     

α2-Adrenergic stimulation counteracts glucose-induced rise of sodium in pancreatic islets exposed to ouabain

The effects of ₂-adrenergenic activation by clonidine on sodium handling were analysed in beta-cell-rich pancreatic mouse islets. In the steady-state situation, clonidine (1 M) amplified lowering of sodium induced by 20 mM glucose, while the content remained unchanged in 3 mM glucose. The loss of sodium in Na⁺-deficient medium was stimulated by glucose but was not affected by clonidine. This agonist also did not influence the ouabain-induced uptake of sodium at 3 mM glucose but partially counteracted additional uptake in response to 20 mM glucose. Although lacking effects of its own, 5 M yohimbine completely counteracted the action of clonidine. The glucose amplification of the ouabain-induced uptake of sodium was suppressed also by 10 M of the Ca²⁺-channel blockers methoxyverapamil and diltiazem. Both tolbutamide (100 M) and dibutyryl cyclic AMP (1 mM) mimicked the action of glucose by promoting clonidine-sensitive uptake of sodium in the presence of ouabain. It is concluded that activation of ₂-adrenoceptors has profound effects on the sodium handling of pancreatic beta-cells exposed to glucose and other stimulators of insulin release.     

Expression of interferon-γ and tumor necrosis factor-α in bone marrow T cells and their levels in bone marrow plasma in patients with aplastic anemia

Immune-mediated stem cell damage has been postulated to be responsible for disease initiation and progression in aplastic anemia (AA). It is hypothesized that T lymphocytes play a major role in destroying the bone marrow (BM) stem cells of AA patients by infiltrating the BM and secreting excessive levels of anti-hematopoietic cytokines, interferon-gamma (IFN-), and tumor necrosis factor-alpha (TNF-). We undertook this study to assess the pathogenic significance of anti-hematopoietic cytokines such as IFN- and TNF- in BM T cells and plasma of AA patients. Significantly elevated levels of IFN- and TNF- were found in the BM plasma of AA patients compared to controls (p=0.05 and 0.006, respectively). Intracellular IFN- and not TNF- in BM CD3⁺ T cells of AA patients was significantly higher compared to controls (p=0.04 and p=0.2, respectively). A follow-up analysis of expression of these cytokines in BM T cells and their levels in BM plasma in five AA patients before and 180 days (6 months) after antithymocyte globulin (ATG) and cyclosporin A (CsA) therapy showed a decline 180 days after therapy compared to pre-therapy. We thus conclude that increased production of both IFN- and TNF- in the BM may contribute to disease pathogenesis in AA and ATG therapy may induce hematological remission by suppressing the elevated levels of IFN- and TNF- in AA BM.