CD16-expressing CD8alpha alpha+ T lymphocytes in the intestinal epithelium: possible precursors of Fc gammaR-CD8alpha alpha+ T cells

T lymphocytes normally express their Ag receptors in association with the CD3 proteins, which include CD3zeta. In CD3zeta eta(null) mice thymic and peripheral T lymphocytes do not express the TCR/CD3 complex on their surface due to retention in the endoplasmic reticulum of the remaining polypeptide chains. However, intestinal intraepithelial lymphocytes (iIEL) of CD3zeta eta(null) mice do express surface TCR, because the Fc epsilonRI gamma chain replaced the CD3zeta chain in the TCR/CD3 complex. Here we report that in a subset of CD8alpha alpha+ iIEL the presence of the Fc epsilonRI gamma chain could be accounted for by the surface expression of the Fc gammaRIII(CD16) complex. Because in wild-type (wt) mice only CD16+ iIEL coexpressed Fc epsilonRI gamma and CD3zeta, we concluded that the presence of Fc epsilonRI gamma was dictated by its required participation of CD16 complex. CD8alpha alpha+ iIEL bearing CD16 and B220 were also detected in the intestinal mucosa of RAG-2(null) mice from 12 days after birth onward. Two independent experimental settings were used in an attempt to demonstrate that CD16+ iIEL matured into CD16- T cells. First, in the RAG-2(null) mice, iIEL responded to in vivo administration of an anti-CD3epsilon mAb by progression to a more mature stage of development, characterized by a loss of CD16 and B220. Secondly, a conversion to CD16- iIEL occurred upon transfer of wt CD16+ iIEL into RAG-2(null) mice. We conclude from these experiments that in both RAG-2(null) and wt mice, a precursor/progeny relationship may exists between CD16+ B220+ CD8alpha alpha+ and CD16- B220- CD8alpha alpha+ iIEL.     

Epididymo-orchitis and Reiter''s disease. Two infrequent complications after intravesical bacillus Calmette-Guérin therapy

Two cases of adverse reactions to intravesical treatment with bacillus Calmette-Guérin are reported. The first patient presented with a severe suppurating epididymo-orchitis three months after his last treatment. The second patient developed Reiter's disease with arthritis of one knee and conjunctivitis 1 week after the fourth instillation.     

Inhibitory control over no-longer-relevant information: adult age differences

Hartmann and Hasher (1991) used a garden-path task in which younger and older adults generated the final word for each of a series of high-cloze sentences. Under instructions to remember the final word, the experiment included critical sentences for which the generated word was replaced by a new, to-be-remembered target. Using an implicit priming task, the first experiment replicated a basic finding: Younger adults showed priming only for the target words, whereas older adults showed priming for both the generated and target words. Two experiments explored the boundary conditions. One showed that an additional sentence that interpreted the new target word enabled older adults to narrow access to only the target word. The provision of additional time following the introduction of the new target word did not. Specific information, not more time, is required for inefficient inhibitory mechanisms to clear the recent past from memory.     

Genetic epidemiology of muscular dystrophies resulting from sarcoglycan gene mutations

BACKGROUND: The autosomal recessive limb-girdle muscular dystrophies (LGMDs) are a group of genetically heterogeneous muscle diseases characterised by progressive proximal limb muscle weakness. Six different loci have been mapped and pathogenetic mutations in the genes encoding the sarcoglycan complex components (alpha-, beta-, gamma-, and delta-sarcoglycan) have been documented. LGMD patients affected with primary "sarcoglycanopathies" are classified as LGMD2D, 2E, 2C, and 2F, respectively. METHODS: A geographical area in north east Italy (2,319,147 inhabitants) was selected for a genetic epidemiological study on primary sarcoglycanopathies. Within the period 1982 to 1996, all patients living in this region and diagnosed with muscular dystrophy were seen at our centre. Immunohistochemical and immunoblot screening for alpha-sarcoglycan protein deficiency was performed on all muscle biopsies from patients with a progressive muscular dystrophy of unknown aetiology and normal dystrophin. Sarcoglycan mutation analyses were conducted on all patient muscle biopsies shown to have complete or partial absence of alpha-sarcoglycan immunostaining or a decreased quantity of alpha-sarcoglycan protein on immunoblotting. RESULTS: Two hundred and four patient muscle biopsies were screened for alpha-sarcoglycan protein deficiency and 18 biopsies showed a deficiency. Pathogenetic mutations involving one gene for sarcoglycan complex components were identified in 13 patients: alpha-sarcoglycan in seven, beta-sarcoglycan in two, gamma-sarcoglycan in four, and none in the delta-sarcoglycan gene. The overall prevalence of primary sarcoglycanopathies, as of 31 December 1996, was estimated to be 5.6 x 10(-6) inhabitants. CONCLUSION: The prevalence rate estimated in this study is the first to be obtained after biochemical and molecular genetic screening for sarcoglycan defects.     

Genetic mapping of a major susceptibility locus for juvenile myoclonic epilepsy on chromosome 15q

The epilepsies are a group of disorders characterised by recurrent seizures caused by episodes of abnormal neuronal hyperexcitability involving the brain. Up to 60 million people are affected worldwide and genetic factors may contribute to the aetiology in up to 40% of patients. The most common human genetic epilepsies display a complex pattern of inheritance. These are categorised as idiopathic in the absence of detectable structural or metabolic abnormalities. Juvenile myoclonic epilepsy (JME) is a distinctive and common variety of familial idiopathic generalised epilepsy (IGE) with a prevalence of 0.5-1.0 per 1000 and a ratio of sibling risk to population prevalence (lambda(s)) of 42. The molecular genetic basis of these familial idiopathic epilepsies is entirely unknown, but a mutation in the gene CHRNA4, encoding the alpha4 subunit of the neuronal nicotinic acetylcholine receptor (nAChR), was recently identified in a rare Mendelian variety of idiopathic epilepsy. Chromosomal regions harbouring genes for nAChR subunits were therefore tested for linkage to the JME trait in 34 pedigrees. Significant evidence for linkage with heterogeneity was found to polymorphic loci encompassing the region in which the gene encoding the alpha7 subunit of nAChR (CHRNA7) maps on chromosome 15q14 (HLOD = 4.4 at alpha = 0.65; Z(all) = 2.94, P = 0.0005). This major locus contributes to genetic susceptibility to JME in a majority of the families studied.     

Mutations in purine nucleoside phosphorylase deficiency

PURPOSE: The aim of this study was to investigate the incidence of unexpected malignant uveal melanoma in the age of ultrasound diagnostics and to highlight the reasons for misdiagnosis. PATIENTS AND METHODS: All eyes were surgically removed and histologic examination was performed between 1981 and 1995. The eyes were investigated for the incidence of uveal melanoma, and the history of the unexpected malignant melanoma of the uvea or ciliary body highlighted. RESULTS: 225 (18.7%) eyes with malignant melanoma out of 2583 enucleated eyes were found. Eight (3.6%) of 225 were clinically unexpected. The clinical misdiagnoses were secondary angle closure or open angle glaucoma (6), retinal detachment (5), iritis (1), scleritis (1), cataract (4) and an intraocular mass that was believed to be a metastasis of a colon carcinoma. Seven of eight eyes were blind, and one eye had light perception only. The longest follow up before enucleation was 13 years. On three eyes diagnostic ultrasound was reportedly performed without specific diagnosis of uveal melanoma. Surgery was performed on four eyes for reasons of uncontrollable intraocular pressure or retinal detachment up to five years before enucleation. Histologic diagnoses were 3 epitheloid-type, 2 spindel-type and 3 necrotic melanoma of the uvea. Four eyes showed scleral invasion by tumor cells and one eye an invasion into the episcleral space. CONCLUSIONS: Even today the rate of unexpected uveal melanoma, according to our study is 3.6%. Therefore, all blind eyes without visualisation of the posterior pole should be examined with ultrasound in order to diagnose an uveal melanoma prior to enucleation.     

Leptin is present in human milk and is related to maternal plasma leptin concentration and adiposity

Leptin is elevated during pregnancy and may be involved in the regulation of milk production in women. Immunoreactive leptin was quantified in human milk by modified radioimmunoassay. Leptin concentration was higher in whole vs. skim milk fractions; however, leptin concentration was not correlated with percentage milk fat. Leptin concentrations in whole and skim milk were correlated with maternal plasma leptin concentrations, maternal body weight, body mass index, and tricep skinfold thickness, but not with plasma insulin concentration. These data provide the first evidence for the presence of leptin in human milk in the range of concentrations found in human plasma and indicate that the concentration of leptin in milk reflects maternal adiposity. Determining the biological role(s) of milk-borne leptin could add to our understanding of neonatal metabolism and the mechanisms underlying the development of body fat and obesity in humans.