Differential immune response of congenic mice to ultraviolet-treated major histocompatibility complex class II-incompatible skin grafts

The influence of ultraviolet (UVB) irradiation on the survival of H-2 class II-disparate skin grafts was studied in congenic mouse strains. Isolated skin was UVB irradiated in vitro at a dose of 40 mJ/cm2 from both sides to remove Ia immunogenicity. Immediately after irradiation the skin was transplanted onto the flank of allogeneic mice. When B10.AQR grafts were transplanted onto B10.T(6R) recipients, a significant prolongation of the survival time was observed, while 50% of the UVB-treated grafts were not rejected at all. However, in the opposite direction--i.e., B10.T(6R) grafts onto B10.AQR recipients, no significant prolongation of the survival was observed. To test whether this effect was due to a difference in susceptibility of the donor skin to UVB irradiation or to a different immune response in the recipients, (B10.T(6R) x B10.AQR) grafts were transplanted onto the parent strains. Similar results were obtained, in that UVB-treated grafts did not show a prolonged survival in B10.AQR recipients, whereas a significant prolongation (50% of the grafts survived more than 100 days) was observed in B10.T(6R) recipients. UVB-treated (B10.T(6R) x B10.AQR)F1 grafts were also transplanted onto (B10.T(6R) x C57B1/10)F1, (B10.AQR x C57B1/10)F1, (B10.T(6R) x Balb/c)F1 and (B10.AQR x Balb/c)F1 recipients--but in none of these combinations was a prolonged survival time observed. These data suggest that, in contrast to all in vitro experiments, the abrogation of the immune response by UVB treatment of the stimulator cells is, in vivo, not a general phenomenon. The genetic constitution of the responder mice seems to play an important role in determining whether or not an immune response takes place.     

Increased plasma fibronectin concentration in diabetic patients with microalbuminuria

Raised levels of plasma fibronectin (PF), an alpha 2-glycoprotein produced by vascular endothelia, have been previously described in diabetic patients with retinopathy and overt nephropathy. The aim of this study was to investigate whether the presence of microalbuminuria is associated with increased PF concentrations. Twenty Albustix-negative diabetic outpatients with microalbuminuria [median albumin excretion rate (AER): 30.2 micrograms/min; range 12.1-194 micrograms/min] were compared with 58 sex- and age-matched patients without microalbuminuria (median AER 3.1 micrograms/min; range 0.8-12 micrograms/min) and 34 control subjects (median AER 2.8 micrograms/min; range 0.8-12.1 micrograms/min). Mean PF was significantly higher in the group with microalbuminuria (406.7 +/- 85.5 micrograms/ml) than in the group without it (325.3 +/- 76.5 micrograms/ml or in control subjects (334.5 +/- 76 micrograms/ml; P less than .05). PF increase associated with microalbuminuria was independent of the presence of retinopathy. Furthermore, in the whole group of diabetic patients, PF was significantly correlated with AER (r = .33; P = .003). Such correlation also remained significant (P = .0002) after covariance analysis by a stepwise discriminant procedure taking into account age, duration of disease, sex, blood pressure, body weight, therapy, and HbA1. In conclusion, PF increase is associated with microalbuminuria independent of the other considered variables; its role as a possible marker for early diabetic nephropathy remains to be fully clarified.     

Malignant glioma-derived soluble factors regulate proliferation of normal adult human astrocytes.

Malignant gliomas are characteristically surrounded by marked gliosis. To assess whether glioma-derived products contribute to the proliferation of astrocytes, a feature of the gliosis response, we evaluated the influence of culture supernatants from malignant human glioma lines and tumor cyst fluids collected from two patients with glioblastoma multiforme on the proliferation of non-transformed adult human astrocytes. Both the culture supernatants and cyst fluids significantly increased DNA synthesis in astrocytes as assessed by a double immunofluorescence glial fibrillary acidic protein-bromodeoxyuridine technique. The net proliferative effect mediated by glioma cell line supernatants was tumor growth phase-dependent, being preferentially expressed during the logarithmic phase of glioma cell growth. Specific growth factor molecules and cytokines known to be secreted by gliomas (epidermal growth factor, fibroblast growth factor, platelet-derived growth factor, transforming growth factor-beta, interleukin-6, and tumor necrosis factor-alpha) could not reproduce the mitogenic effects of the glioma-derived soluble factors. Cytokines which can induce DNA synthesis by adult human astrocytes in vitro, gamma-interferon and interleukin-1, were not detected in the culture supernatant of glioma lines used in this study. In conjunction with the documented effects of glioma products on endothelial and lymphoid cells, the current study suggests that soluble glioma products can contribute to the production of surrounding gliosis observed in vivo.     

Influence of the mother-child relationship on the development of the Type A Behavior Pattern

Investigation of the Type A Behavior Pattern (TABP) of pre-school children was conducted to determine the influence of the mother-child relationship on the development of TABP. The incidence of TABP was 44.2% (51.7% in boys and 38.7% in girls). The TABP tendency of the boys decreased as the manifest dissension or conflict in the family grew, in marked contrast with the tendency seen in girls, suggesting that conflict in the family can either weaken or reinforce TABP.     

Ligand-mediated internalization of glucagon receptors in intact rat liver.

The ligand-induced internalization of the hepatic glucagon receptor has been studied in rats in vivo using cell fractionation. Injection of glucagon (11 nmol/100 g BW) led to a 2- to 3-fold increase in glucagon-binding activity in Golgi-endosomal (GE) fractions along with a 10-20% decrease in binding activity in plasma membrane (PM) fractions. These changes were time and dose dependent, reaching a maximum by 12-24 min and undergoing reversal in 2 h. Glucagon injection also caused a 20% decrease in glucagon binding to the total particulate fraction, which did not occur when binding was measured in the presence of the detergent octylglucoside. The change in glucagon-binding activity in PM and GE fractions resulted mainly from a change in receptor number; affinity remained unaffected (apparent Kd, 0.5 and 5 nM, respectively). A 5- to 10-fold increase in the glucagon content of GE fractions was observed in glucagon-treated rats. Neither the distribution of PM and Golgi marker enzymes nor that of the asialoglycoprotein receptor was affected by glucagon treatment. Regardless of glucagon treatment, glucagon receptors in GE fractions were less sensitive to GTP than receptors in PM fractions with respect to both inhibition of steady state binding and dissociation of prebound ligand. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis, glucagon-receptor complexes formed in PM and GE fractions and subsequently cross-linked showed the same apparent mol wt (57 kilodaltons). In addition, they were identically sensitive to N-glycanase treatment, with two major species of lower mol wt generated. However, only cross-linked complexes associated with PM fractions showed detectable GTP sensitivity. GE fractions displayed a GTP-sensitive adenylate cyclase activity that was about 12 times lower than that of PM fractions. In both fractions, activity was stimulated by the addition of forskolin (8-fold) and, to a lesser extent, glucagon (3-fold). In vivo glucagon treatment led to an increase in activity in GE, but not PM, fractions. These results are consistent with the view that upon acute occupancy, hepatic glucagon receptors are rapidly and specifically internalized along with their ligand. During this process, receptor retained structural integrity and uncouple, albeit partially, from other components of the adenylate cyclase system.     

Chronic peritoneal dialysis in paediatrics: Experience of a national registry

The results of the first 3 year' collaboration of the Italian Registry of Paediatric Chronic Peritoneal Dialysis (CPD) (1986–1988) are presented. This Registry acquired data on the majority of the paediatric patients treated with CPD in Italy, thus providing a national picture in a field where few nationwide surveys are available. Patients of less than 15 years of age at the start of dialysis were enrolled and clinical data collected until the age of 19 years. The number of nephrological paediatric centres participating in the Registry increased from 7 in 1986 to 11 in 1988. The total number of patients on CPD was 70 and the percentage of dialysed children treated with CPD ranged from 40.2% to 43.6%. Data on 89 peritoneal catheters were collected: during 1417 dialysis-months 70 catheter-related complications were observed (1:20.8 dialysis-months); actuarial catheter survival was 92.7% at 6 months, 84.8% at 1 year and 68.8% at 2 years. The incidence of peritonitis changed from 1 episode every 10.9 patient-months in 1986 to 1 every 19.8 in 1988. Abdominal hernias were the other main clinical complication observed. The survival of patients was 92.5% at 3 years, while the technique survival at the same time was 84%.     

The course of severe foot infection in patients with diabetes.

Infection of the foot is a limb threatening condition for patients with diabetes mellitus. Identification of patients with diabetes and severe infection of the foot most likely to benefit from early revascularization or major amputation would improve the results of a treatment policy to prevent limb loss and avoid futile delays in amputation. During a nine year period, 79 diabetic patients underwent emergency procedures for severe infection of the foot during the initial hospitalization period. None of the patients underwent arterial reconstruction. Eventually, 21 of the patients required a major amputation, eight during the initial hospitalization and 13 on a subsequent admission. Stepwise discriminant analysis of clinical independent variables revealed that the patients most likely to require a major amputation during the initial hospitalization were those with an absent dorsalis pedis pulse and a polymicrobial infection (p = 0.018). The overall amputation rate (immediate or subsequent amputation) was higher for patients of either sex with nonpalpable pedal pulses when compared with those with at least one palpable pulse (p less than 0.05). Males who were not dependent on insulin had the highest risk of overall limb loss (p = 0.01). Patients undergoing delayed amputation required a significantly higher number (p = 0.01) of readmissions to the hospital for recurrent infection of the foot than those who did not undergo amputation. Data in the current study suggest that early major amputation in a subset of patients would prevent delay in the rehabilitation process of the amputee, decrease long term morbidity and reduce health care cost. An aggressive policy of early revascularization in patients with a pulse deficit may reduce the amputation rate in those with diabetes with severe infection of the foot.     

Retrosternal coloplasties: contribution of postoperative mesenteric arteriography

Postoperative mesenteric angiograms were obtained after substernal coloplasty (SC) in fifteen patients, 8 male and 7 female, aged from 18 to 61 yrs old (mean = 34 yrs old). The aim of this study was to determine whether: 1) vascularization as assessed by angiography was correlated with the occurrence of cervical complications (fistulae and/or stenosis), 2) postoperative arteriography was of any practical value in this situation. Images obtained were classified into 3 groups according to the quality of vascular visualization. Clinical results were also classified into 3 groups according to whether no, one or two cervical complications were present, respectively. Angiographic and clinical results were concordant in 8 cases and discordant in 7. No definite relationship between the quality of coloplasty vascularization and the quality of clinical outcome was found in this study, but results suggest that retromanubrium compression might play a major role in outcome as visualization of colonic vascularization was obtained in only 9 of 15 cases. When clinical results are poor, characteristic images of ischemia may help in determining the indication for reoperation.