A Hereditary Alteration in Kidneys of Mice with Chediak-Higashi Syndrome

The beige mouse is considered to be a homologue of Chediak-Higashi syndrome (CHS). Cytochemical and electron microscopic studies have revealed an inherited lesion in the kidneys of these mice. The alteration was confined to the distal segments (S3) of the proximal tubules and was characterized by the accumulation of numerous massive polysaccharide-rich granules. These granules were reactive for acid phosphatase and β-glucuronidase activities and were therefore considered to be lysosomes. Small numbers of lymphocytes were also observed in the perivascular spaces and within the tubules of the S3 segment. The fine structure of S3 cells was also markedly altered. In addition to the massive lysosomes, dense material was found associated with the brush border and was present in pinocytotic vesicles at the base of the brush border and between basal invaginations of the plasma membranes. Despite these changes, reabsorption of exogeneous peroxidase by S3 cells appeared to be normal. The presence of a congenital defect in the kidney of the beige mouse appears to provide a useful model for studying the morphology and function of the S3 region of the nephron.     

Corticoliberin, somatocrinin and amine contents in normal and parkinsonian human hypothalamus

We have compared hypothalamic contents of various neurotransmitters (dopamine (DA), norepinephrine and serotonin) and their metabolites (dihydroxyphenyl acetic acid, homovanilic acid, 5-hydroxyindoleacetic acid) in post-mortem human controls and parkinsonian hypothalami. Neurotransmitters and their metabolites were measured in 0.1 N HCl hypothalami extracts using electrochemical detection after high performance liquid chromatography. Using specific radioimmunoassays we have also measured corticoliberin and somatocrinin contents in these hypothalami. Despite a 50% decrease of DA contents in parkinsonian hypothalami, no variations of corticoliberin and somatocrinin contents were found: 16.6 +/- 1.78 pg/mg tissue in Parkinson disease vs 16.71 +/- 1.89 in controls for human corticotropin-releasing factor (hCRF 1-41) and 37.38 +/- 11 vs 45.16 for human growth-hormone-releasing factor (hGRF 1-44).     

Giant ragweed specific immunotherapy is not effective in a proportion of patients sensitized to short ragweed: analysis of the allergenic differences between short and giant ragweed

BACKGROUND: Short ragweed and giant ragweed pollen allergens are considered largely cross-reactive, and it is generally believed that 1 species is sufficient for skin testing and immunotherapy. However, in the area north of Milan (a zone widely invaded only by short ragweed), about 50% of patients submitted to injection specific immunotherapy with giant ragweed showed little or no clinical response, but showed an excellent outcome if they were shifted to short ragweed specific immunotherapy. OBJECTIVE: To investigate allergenic differences between short and giant ragweed. METHODS: IgE reactivity to short ragweed of sera from 16 patients allergic to ragweed was assessed by immunoblot before and after absorption with short and giant ragweed. Moreover, 41 ragweed-monosensitive patients underwent skin prick test with both ragweed species. RESULTS: In several cases, preabsorption of sera with giant ragweed extract was unable to inhibit IgE reactivity fully against both a 43-kd allergen and other allergens at different molecular weights in short ragweed. On skin prick test, short ragweed induced larger wheals than giant ragweed in the majority of patients, and 6 of 41 (15%) patients were strongly short ragweed-positive but giant ragweed-negative. The immunoblot with the serum from 1 of these subjects showed a strong IgE reactivity to short ragweed at about 43 kd in the absence of any reactivity to giant ragweed. CONCLUSION: Short and giant ragweed are not allergenically equivalent. Allergenic differences involve both the major allergens Amb a 1-2/Amb t 1-2 and some minor allergens. In patients allergic to ragweed, both diagnosis in vivo and immunotherapy should always be performed by using the ragweed species present in that specific geographic area.     

External quality control assessment in PCR diagnostics of dengue virus infections

BACKGROUND: Increased travelling to countries endemic for dengue fever (DF) demands efficient laboratory diagnostics. Nucleic acid amplification techniques (NAT) are now frequently used for rapid diagnosis of imported viral diseases. Different PCR systems are available. OBJECTIVES: In order to assess the quality of molecular diagnostics of dengue virus infections, an external quality assurance (EQA) in PCR diagnostics was conducted. Study design: A panel of 10 human plasma samples was prepared and spiked with dengue virus types DEN-1 to DEN-4. In addition, a 10-fold dilution series (1:10-1:10(4) ) of DEN-3 virus was included. The panel was pre-tested by nested RT-PCR, in-house real-time PCR, and a commercial real-time PCR kit. The samples were inactivated by gamma irradiation and shipped in freeze dried state. Thirteen laboratories, within the European network for the diagnostics of imported viral diseases (ENIVD) took part using either single-round, nested, or real-time RT-PCR methods. Two laboratories used two methods in parallel, summarising up to 15 comparable results. RESULTS: 33-100% correct results were achieved. All laboratories detected DEN-2 correctly, followed by DEN-1 (14 positive results of 15), DEN-3 (12/15) and DEN-4 (11/15). Testing of the serial dilution revealed low sensitivity in many labs, with results ranging from 33 to 80% of correctly tested samples. CONCLUSION: The EQA gives a feedback of the quality of the RT-PCR system used by each respective laboratory. The different test systems and amplification conditions demonstrate the importance of external quality control measures.     

Treatment options for severe lupus nephritis

Renal involvement in systemic lupus erythematosus is a common complication that significantly worsens morbidity and mortality. Landmark trials conducted by the National Institutes of Health established cyclophosphamide as the mainstay of therapy. Since then, the prognosis of patients with lupus nephritis has markedly improved, and 10-year survival rates now surpass 75%.These superior outcomes have come at the expense of adverse events such as serious infections and gonadal failure in a significant number of patients,and the relapsing nature of the disease continues to pose a problem. For thesereasons, new treatment protocols, such as mycophenolate mofetil induction or sequential therapies using azathioprine or mycophenolate mofetil in the maintenance phase, have been developed in recent years with the goal to maintain remission and reduce adverse events. In addition, ongoing research into the pathogenesis of lupus nephritis has confirmed the importance of B and T cell activation, leading to the identification of potential new therapeutic targets. This article discusses established and novel treatment options for patients with severe lupus nephritis corresponding to WHO classes III, IV, and V withIII or V with IV.     

Mild phenotype in two unrelated patients with a partial deletion of 21q22.2-q22.3 defined by FISH and molecular studies

We describe two unrelated patients with cytogenetically visible deletions of 21q22.2-q22.3 and mild phenotypes. Both patients presented minor dysmorphic features including thin marfanoid build, facial asymmetry, downward-slanting palpebral fissures, depressed nasal bridge, small nose with bulbous tip, and mild mental retardation (MR). FISH and molecular studies indicated common deleted areas but different breakpoints. In patient 1, the breakpoint was fine mapped to a 5.2 kb interval between exon 5 and exon 8 of the ETS2 gene. The subtelomeric FISH probe was absent on one homologue 21 indicating a terminal deletion spanning approximately 7.9 Mb in size. In patient 2, the proximal breakpoint was determined to be 300-700 kb distal to ETS2, and the distal breakpoint 2.5-0.3 Mb from the 21q telomere, indicating an interstitial deletion sized approximately 4.7-7.3 Mb. The 21q- syndrome is rare and typically associated with a severe phenotype, but different outcomes depending on the size and location of the deleted area have been reported. Our data show that monosomy 21q of the area distal to the ETS2 gene, representing the terminal 7.9 Mb of 21q, may result in mild phenotypes comprising facial anomalies, thin marfanoid build, and mild MR, with or without signs of holoprosencephaly.     

The Community Placement Scale: an adaptation of the Community Competence Scale for placement of the deinstitutionalized mentally ill

The Community Placement Scale (CPS), an abbreviated form of the Community Competence Scale (Anderten, 1979) suitable for placement of deinstitutionalized mental patients in the community, was developed in a combined sample of 87 subjects placed in the community in California and Missouri. Although the Community Competence Scale has shown considerable promise as a placement instrument with the deinstitutionalized mentally ill, a briefer measure is needed in order to increase acceptance by both patients and professional staff. Other improvements sought were determining the acceptability of items to placement personnel nationwide, eliminating nondiscriminating items, and heightening internal consistency reliability of subscales. In a series of discriminant analyses, remaining subscales were used to predict community placement with minimal and maximal degrees of structure. From these analyses, a measure that consisted of 5 subscales and 41 items and required approximately 20 minutes to administer was selected. This short form has many similarities to and a few important differences from the previously published short form.