Lymphocytes capable of mediating delayed-type hypersensitivity reactions accumulate within sponge matrix allografts

The rejection of sponge matrix allografts across H-2 barriers has generally been found to contain specifically sensitized cytotoxic T cells to donor alloantigen. There is one exception: sponge matrix allografts that differ only with respect to class II alloantigens do not contain specifically sensitized cytotoxic T cells. We therefore investigated the capacity of infiltrating cells removed from sponge matrix allografts to generate delayed hypersensitivity reactions after exposure to fresh alloantigen in a footpad assay. Cells infiltrating class I and II allografts were equally capable of eliciting delayed footpad reactions when injected with specific donor alloantigen into the footpads of naive responder strain mice. Allosensitized T-lymphocyte clones of helper or cytotoxic type were also capable of initiating delayed-type hypersensitivity (DTH) reactions in vivo. We conclude that rejecting allografts across class I or II alloantigenic barriers are infiltrated by cells capable of effecting DTH reactions, in addition to their capacity to exert specific helper or specific cytotoxic reactions. The results also support that both helper and cytotoxic T cells can participate in allospecific DTH reactions.     

Liver transplantation for severe Amanita phalloides mushroom poisoning

Amanita phalloides mushroom poisoning is an increasingly common and potentially lethal problem for which liver transplantation offers definitive therapy in selected patients. When significant liver dysfunction appears, early transfer to a liver transplant center is important to identify appropriate candidates and to begin the search for a donor organ. The clinical course of five severely poisoned patients, four of whom underwent liver transplantation, is reviewed. Indications for transplantation included primarily a markedly prolonged prothrombin time that was only partially correctable and a constellation of findings including metabolic acidosis, hypoglycemia, hypofibrinogenemia, and increased serum ammonia, following a marked elevation in serum aminotransferase levels. Unlike viral fulminant hepatic failure, grade III or IV hepatic encephalopathy, marked elevation of the serum bilirubin level, and azotemia were not indications for transplantation. Resected livers demonstrated hepatocyte viability of 0% to 30%. Manifestations of Amanita poisoning complicating preoperative and/or postoperative care included severe diarrhea, gastrointestinal hemorrhage, hypophosphatemia, bowel edema, and marrow suppression with lymphopenia, thrombocytopenia, and neutropenia. All five patients are well 1 year later. This largest experience with liver transplantation for Amanita poisoning further defines the early clinical and laboratory indications for, and the unique complicating features of, transplantation in this setting.     

Increasing incidence of coeliac disease in Sweden.

Changes in the incidence of coelic disease was studied among children born in Göteborg, Sweden, between 1970 and 1988. A total of 188 patients with coeliac disease were found. Of these, 83% were less than 2 years old at the time of their first duodenal biopsy and 74% of them have so far been verified according to the criteria of the European Society for Gastroenterology and Nutrition (ESPGAN). The cumulative incidence at 2 years of age/1000 liveborn infants increased significantly from 0.31 in the first birth cohort to 2.93 in the last. This increase could only partly be explained by improvements in detection. Weight for age at diagnosis was generally considerably below the reference value, but was slightly less affected towards the end of the period. The increase in incidence of coeliac disease is the first reported since the middle 1970s and makes the disease one of the most common chronic diseases among Swedish children.     

Nodular sarcoidosis of the liver and spleen: Appearance on MR images

Small nodular lesions in the liver and spleen have been reported as an infrequent manifestation of sarcoidosis. Five patients with this appearance on either dynamic contrast material—enhanced computed tomographic (CT) or ultrasound scans underwent magnetic resonance (MR) imaging with and without dynamic gadolinium enhancement. The lesions were relatively uniform in size, ranging from 0.5 to 1.5 cm. On CT scans, they were hypoattenuating relative to surrounding parenchyma. On MR images, the lesions were hypointense relative to background parenchyma with all sequences. No substantial enhancement was observed in the lesions, although lesion conspicuity decreased over time on serial postcontrast images. Lesion conspicuity was greatest on either T2-weighted fat-suppressed (T2FS) images or early-phase dynamic contrast-enhanced images. Abdominal adenopathy was seen in three of the five patients and was hyperintense relative to liver on T2FS images in two and intermediate in intensity in one patient.     

Reporting the results of human immunodeficiency virus testing

We conducted a pilot study of potential sources of incorrect laboratory reports of human immunodeficiency virus type 1 testing using blind proficiency testing. Sets of three serum samples, including one serum sample with negative reactions in antibody tests, one serum sample with positive reactions, and one that gave false-positive results with certain testing kits, were sent as routine patient specimens to testing laboratories. Half the laboratories reported the serum sample positive for human immunodeficiency virus antibodies as "indeterminate"; one laboratory rendered a final positive report without supplemental testing. On the report forms, the actual laboratory results were often obscured and intermingled with information, sometimes incorrect, such as identifying the agent as "HTLV-III" (human T-cell lymphotropic virus type III) and advising that a test with positive results is evidence of exposure to the virus. Many of these reports have the potential to confuse, rather than to enlighten, the requesting physician.     

Chloride distribution in Aplysia neurones

1. The intracellular Cl^- concentration (Cl_i) and the membrane potential (E_m) were measured in the medial pleural neurones of Aplysia under various experimental conditions designed to determine the Cl^- conductance of the neurones and investigate the possibility of an active Cl^- transport.

2. The magnitude of the Cl^- conductance of the cell depends on the experimental conditions.

3. In normal sea water, large changes of E_m produced by passing current across the cell membrane caused no change of Cl_i, suggesting that the Cl^- conductance was low. Similarly, moderate changes of E_Cl produced by decreasing Cl_o or increasing Cl_i had little or no effect on E_m.

4. A high Cl^- conductance was observed in high K_o or very low Cl_o. It was greatly reduced if the external Ca²⁺ was replaced by Co²⁺, or in the presence of tubocurarine, or if the experiment was performed on an isolated cell soma. The high Cl^- conductance is therefore attributed to the release of ACh and perhaps other transmitters from synaptic terminals.

5. High concentrations of tetraethylammonium ions or procaine induced a depolarization of the cell, but a decrease of Cl_i. The rate of fall of Cl_i was increased by lowering external K⁺ or raising external Ca²⁺, and was decreased by replacing external Ca²⁺ by Co²⁺.

6. NH₄⁺ ions applied externally had effects similar to those of K⁺ ions. In situations in which intracellular NH₄⁺ might be increased a fall in Cl_i was observed.

7. The changes of Cl_i caused by TEA, procaine, or internal NH₄⁺ occur against the driving force for passive Cl^- movements. They are still observed in isolated cell bodies, and cannot be attributed to the activation of synaptic channels.

8. Some interpretations of these anomalous Cl^- movements are discussed which could also account for the difference between E_Cl and E_m observed under normal conditions.

     

Genetic analysis of the CD28/CTLA4/ICOS (CELIAC3) region in coeliac disease

Abstract:  In order to extend our previous findings of genetic linkage to the CD28/CTLA4/ICOS region on chromosome 2q33 ( CELIAC3 ) in coeliac disease (CD), we have investigated 22 genetic markers in 325 Norwegian/Swedish multiplex and simplex CD families. We found both linkage and association with several markers, primarily in the multiplex material. We observed strong linkage disequilibrium (LD) between SNPs (Single Nucleotide Polymorphisms) within an LD block delimited by MH30 and D2S72. A haplotype of this region marked by the alleles −1147*T: + 49*A:CT60*G:CT61*A was significantly associated with CD, suggesting that one or more polymorphisms of this haplotype, possibly −1147*T, are involved in CD susceptibility. The CT60 SNP, a polymorphism found to be most strongly associated with some other immune-mediated diseases, was not associated with CD, as this SNP was part of both associated and non-associated haplotypes. Moreover, our results suggest that CELIAC3 harbours several independent loci contributing to CD susceptibility.     

Damaged chromatin does not prevent the exit from metaphase I in fused mouse oocytes

The presence of checkpoint mechanisms which are able to recognize damaged chromatin and thereafter to prevent exit from metaphase I has been investigated in giant mouse oocytes produced by fusion of a normal metaphase I oocyte with an equivalent oocyte with damaged chromatin. The presence of damaged chromatin did not prevent the onset of anaphase I in both sets of chromatin in the fused cells. Interestingly, fused or unfused cells containing only damaged chromatin failed to enter anaphase and persisted instead in a metaphase-like state. These results demonstrate the fragility of checkpoint controls in mammalian female germ cells.