Biohybrid artificial pancreas. Long-term function of discordant islet xenografts in streptozotocin diabetic rats

DNA sequences are presented for two members of the wheat Em gene family. The sequences correspond to the two linked genes at the Xem-1AL locus. Comparisons of these sequences with that of another wheat Em gene and two Em cDNA clones reveals substantial homology within the protein-coding regions, and the presence in the 5'-flanking regions of the genomic sequences of motifs characteristic of ABA-responsive cis-acting elements.     

Primary structure of Beijing duck apolipoprotein A-1

The primary structure of Beijing duck apolipoprotein A-1 was determined by sequencing peptide fragments derived from tryptic and endoproteinase Asp-N digestion of the protein, and alignment with homologous chicken apo A-1. All of the peptide fragments were isolated by high-pressure liquid chromatography (HPLC) with a Vydac C18 column using a trifluoroacetic acid (TFA) buffer system. The N-terminus of the protein was determined to be aspartic acid by directly sequencing 52 residues of the intact protein. The C-terminus was alanine. The protein contains 240 amino acid residues. By analysis of the whole protein and its tryptic peptides, a six amino acid (Arg-Tyr-Phe-Trp-Gln-His) prosegment was determined. No cross-reactivity between duck and human apo A-1 with a goat antiserum against human apo A-1 was found. Sequence analysis of apo A-1 of other species indicates that amino acid substitutions in rat are more extensive than in other mammals. Isoleucine residues in apo A-1 are inversely correlated to the homology of human to other species, except dog.     

The use of below-knee percutaneous transluminal angioplasty in arterial occlusive disease causing chronic critical limb ischemia

PURPOSE: To determine the efficacy, safety and long-term results of crural artery percutaneous transluminal angioplasty (PTA) in limbs with chronic critical limb ischemia (CLI). METHODS: Patients undergoing crural artery PTA due to CLI were followed at regular clinic visits with ankle brachial pressure index (ABPI) measurements. PTA of the crural arteries was attempted either alone (n = 39) or in combination with PTA of the superficial and/or popliteal artery (n = 55) in 86 limbs (82 patients and 94 procedures) presenting with CLI. The ages of patients ranged from 37 to 94 years (mean 72 years). The indications for PTA were rest pain in 10 and ulcer/gangrene in 84 limbs. RESULTS: A technically successful PTA with at least one crural level was achieved in 88% of cases (n = 83). Cumulative primary clinical success rates at 6, 12, 24, and 36 months were 55%, 51%, 36%, and 36%, respectively. Cumulative secondary clinical success and limb salvage rates at 36 months were 44% and 72%, respectively. CONCLUSION: PTA of the crural arteries might be considered the primary choice of treatment in patients with CLI and distal lesions with localized stenosis or segmental short occlusions.     

Ultrasonographic imaging of canine mammary tumours

Two-hundred-and-fifteen embryos recovered from 76 donor ewes from flocks endemically infected with sheep pulmonary adenomatosis (SPA) and mated with uninfected rams were transferred to 131 uninfected recipients under strict sanitary conditions using International Embryo Transfer Society protocols. The recipients and their progeny were kept in a closed, isolated SPA-free flock. Thirty-eight of 51 progeny from SPA-positive donors and 55 of 74 progeny from donors in which no lesions of SPA were detected survived for at least five years after birth. In a similar study 11 embryos from four uninfected donors mated to an SPA-infected ram were transferred to seven recipients, and four of five progeny born to four recipients survived for at least five years. No evidence of SPA was found in the recipients or their progeny by embryo transfer in either study. On the basis of clinical and pathological criteria, it is concluded that embryo transfer can be used to provide an effective barrier against the transmission of SPA from donors from infected flocks, whether or not the parents show clinical signs of the disease.     

Estrogen receptor accessory proteins augment receptor-DNA interaction and DNA bending

The human Cu/Zn superoxide dismutase (hSOD-1) gene, catalyses the dismutation of O2 to H2O2 and O2. It is located on chromosome 21 in q22.1 and is overexpressed in Down's syndrome (DS) patients. These patients present various abnormalities including mental retardation, congenital heart disease, immunological deficits and premature aging. In order to explore the potential role of SOD-1 overexpression in DS, we have generated two lineages of transgenic mice for the hSOD-1 gene and studied, at the ultrastructural level, the effect of hSOD-1 overexpression on the thymic microenvironment. Modification of the cellular architecture and morphology associated with a lipidic invasion, signs of a premature involution of the thymus, were observed in both lineages. A rupture of the filamentous network in the extracellular and probably also in the intracellular matrix was first observed. These results correlate the thymic alterations visualized in light microscopy, on the thymus from DS patients, and raise the question of the relationship between the SOD-1 overexpression and the different morphological alterations associated with the premature thymic involution observed in SOD-1 transgenic mice. They suggest that thymic and immunological impairments present in DS patients may be related to the SOD-1 gene dosage effect.     

Seroepidemiology of emerging tickborne infectious diseases in a Northern California community

A seroprevalence and risk factor study of emerging tickborne infectious diseases (Lyme disease, ehrlichiosis, and babesiosis) was conducted among 230 residents of a semirural community in Sonoma County, California. Over 50% of residents reported finding a tick on themselves in the preceding 12 months. Samples from 51(23%) residents were seroreactive to antigens from one or more tickborne disease agents: 1.4% to Borrelia burgdorferi, 0.4% to Ehrlichia equi, 4.6% to Ehrlichia chaffeensis, and 17.8% to the Babesia-like piroplasm WA1. Only 14 (27%) of these seroreactive residents reported one or more symptoms compatible with these diseases. Seroreactivity was significantly associated with younger age (<16 years), longer residence in the community (11-20 years), and having had a physician's diagnosis of Lyme disease. In northern California, the risk of infection with these emerging tickborne diseases, particularly in children, may be greater than previously recognized.     

Diagnosis of hereditary hemochromatosis with molecular analysis of DNA in patients with anti-HCV positive liver cirrhosis. Clinical case

A case of hereditary hemochromatosis in a patient affected by anti-HCV positive liver cirrhosis is described. The difficulties for an exact diagnosis are underlined. Really, it can be particularly difficult to make a differential diagnosis between hereditary hemochromatosis and secondary hemochromatosis, if liver cirrhosis has already been found. Practically, at this stage of disease, the histological and clinical aspects of these two forms become completely interchangeable. Moreover, diagnostic difficulties increase when, at the same time, the patient presents more causes of potential liver damage. In this case report, the DNA-analysis, obtained by polymerase chain reaction amplification and enzymatic digestion, allows to make the diagnosis of hereditary hemochromatosis, because it showed the presence of two genetic mutations, considered responsible for the disease. Both the hereditary hemochromatosis and the HCV infection, had greatly contributed to the development of liver cirrhosis. In the future, DNA-analysis by amplification with polymerase chain reaction, can assume relevant importance for the screening of affected patients' first grade parents too. It could permit an early diagnosis of hereditary hemochromatosis and then to start a timelier and more efficacious therapy, to prevent an irreversible histological damage.     

Substance P regulates somatostatin expression in inflammation

Substance P (SP) and somatostatin (SOM) are made at mucosal surfaces and sites of inflammation. There is a SP/SOM immunoregulatory circuit that modulates the IFN-gamma response in murine schistosomiasis. SP enhances, while SOM decreases, IFN-gamma secretion. Various inflammatory mediators induce macrophages to make SOM, but no known factor limits this expression. It was discovered that SP regulates SOM synthesis. Splenocytes from normal, uninfected mice cultured with LPS, IFN-gamma, or IL-10 for 4 h strongly expressed SOM mRNA, but failed to do so in the presence of SP. The inhibition with 10(-9) M SP was > 85% shown by quantitative PCR. Also, splenocyte SOM content decreased from 1048 +/- 275 to < 10 pg/4 x 10(8) cells following SP exposure. Immunohistochemistry identified SOM solely within splenic macrophages following cytokine stimulation. Mice infected with Schistosoma mansoni form granulomas in the liver and intestines resulting from deposition of parasite eggs in these organs. The granulomas contain macrophages that make SOM constitutively. SP at 10(-8) M decreased SOM mRNA expression > 90% in dispersed granuloma cells cultured for 4 h or longer. Specific SP receptor antagonists blocked SP suppression of SOM expression in splenocytes and dispersed granuloma cells, showing that an authentic SP receptor mediated the regulation. Additional studies revealed that IL-4 antagonized the SP effect in the spleen. It is concluded that in granulomas and splenocytes from mice with schistosomiasis and in splenocytes from uninfected animals that 1) SP inhibits macrophage SOM induction and ongoing expression at the mRNA and protein levels acting through the SP receptor, and 2) IL-4 can antagonizes this SP effect.