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At least 163 records · Page 9Linked to original sources

Un-cross-linked fibrin substrates inhibit keratinocyte spreading and replication: correction with fibronectin and factor XIII cross-linking.

Wound repair is characterized by the presence of a fibrin-rich matrix, but the effect of fibrin on re-epithelialization remains unclear. In this study, we determined the effects of different fibrin matrices on cultured human neonatal keratinocytes. Using purified fibrinogen and fibrin gels generated by the enzymatic action of thrombin, batroxobin (it leads to retention of fibrinopeptide B), or Agkistrodon contortrix thrombin-like enzyme (ACTE; it leads to retention of fibrinopeptide A), we determined the effect of each of these matrices on keratinocyte morphology, attachment, spreading, and replication as compared to tissue culture plastic. Morphologically, keratinocytes seeded on fibrin surfaces were more rounded and formed three-dimensional structures. Specific cell attachment, as measured at either 37 degrees C or 4 degrees C, was not altered on the different fibrin substrates (P > .05) but was increased on fibrinogen and factor XIII cross-linked fibrin (P < .01). However, keratinocytes seeded on fibrin, regardless of the presence or absence of fibrinopeptides A or B, showed a marked decrease (up to 71%) in cell numbers by days 5 (P = .0357) and 10 (P = .0114). Keratinocyte spreading was decreased by 78.8% (P = .0006), 80.3% (P = .0001), and 89.2% (P = .0001) on thrombin-, batroxobin-, and ACTE-generated fibrin, respectively, but not on fibrinogen-coated dishes. However, either the addition of fibronectin or cross-linking of fibrin with factor XIII allowed full keratinocyte spreading to occur (P = .0002 and P = .0013, respectively). We conclude that fibrin inhibits keratinocyte spreading in the absence of other matrix or plasma proteins or cross-linking by factor XIII.

Cell Adhesion↗

Membrane proteins and proteomics: un amour impossible?

Proteome analysis implies the ability to separate proteins as a first step prior to characterization. Thus, the overall performance of the analysis strongly depends on the performance of the separation tool, usually two-dimensional electrophoresis. This review shows how two-dimensional electrophoresis performs with membrane proteins from bacteria or animal or vegetable cells and tissues, the recent progress in this field, and it examines future prospects in this area.

Animals↗

Commentary: adaptive immunity in the absence of innate immune responses? The un-Tolled truth of the silent invaders.

The development and expression of effective adaptive immunity is currently thought to hinge entirely upon inductor and effector mechanisms furnished by cells of the innate immune system. An obligate intracellular bacterium, the causative agent of human granulocytic anaplasmosis, apparently defies this dogma: in a mouse model of infection, Anaplasma phagocytophilum is controlled by specific lymphocyte immunity even in the absence of Toll-like receptor (TLR)2, TLR4, the TLR-adaptor protein MyD88, inducible nitric oxide synthase or the gp91 component of the NADPH oxidase complex. A. phagocytophilum infection biology raises some interesting questions about the development of resistance to innate defense strategies by vector-borne pathogens, and challenges our current bias concerning the relative importance and the mode of interaction of the innate and adaptive arms of infection control in vertebrates.

Anaplasma phagocytophilum↗

Characterization of HCV strains in an oncohematological pediatric department reveals little horizontal transmission but multiple introductions by un-screened blood products in the past.

Because several children were found infected with hepatitis C virus (HCV) at a pediatric oncohematological department in Vilnius, 474 children were tested for anti-HCV. Fifty-eight percent of 96 children treated with blood and plasma products manufactured before the introduction of anti-HCV screening of blood in Lithuania in 1994 were positive for anti-HCV versus 3.4% of those treated after 1994. The possible route of transmission for 45 of these was investigated by phylogenetic analyses within the NS5B region. Children treated before 1995 were infected with a multiplicity of strains of different subtypes, predominantly 1b found in 21 cases, 3a in 5 cases, 2 in 3 cases, 1a in 1 case, and not subtypeable genotype 1 strains in 2 cases. Children who had received blood products after 1994 were infected with only two subtypes, 1b in six and 3a in seven. Genetic analysis showed multiple introductions of HCV before 1995 and that horizontal spread between patients had occurred only to a minor extent at the department. However, two transmission chains involved children treated before 1995. Another chain involved five children treated after 1994. Since the most important risk factor for acquiring hepatitis C was blood products manufactured before the introduction of donor screening for anti-HCV, the spread between children would not have been revealed without molecular tools. These and the background strains provide the first reported sequence data on Lithuanian HCV strains. In general, these were shown to form autochthonous clades, except the 3a strains that were related to strains from the former USSR.

Blood Banks↗

Human insulin: much ado about hypoglycaemia (un)awareness.

The biological effects, hypoglycaemic symptoms, endocrine counterregulatory responses and glucose recovery following the injection of purified porcine and human insulin preparations were compared in a number of controlled clinical investigations and prospective clinical trials. In these studies involving healthy volunteers, Type 1 (insulin-dependent) diabetic patients on continuous subcutaneous insulin infusion or intensified conventional insulin therapy and insulin treated Type 2 (non-insulin-dependent) diabetic patients, no differences with regard to biological effects, counterregulatory responses, hypoglycaemic awareness or the long-term incidence of severe hypoglycaemia between porcine and human insulin preparations were identified. These data fail to confirm any specific risk of severe hypoglycaemia attributable to the use of human insulin preparations in the treatment of patients with diabetes mellitus.

Adult↗

[Peripartum cardiomyopathy-the (un)known obstetricalcardiologic emergency situation].

Peripartum cardiomyopathy (PPCM) is rare cardiac complication afflicting women during pregnancy or until 5 months post partum with the typical signs of acute cardiac failure. PPCM is similar to dilated cardiomyopathy (DCM) in terms of symptoms, histopathology and treatment but is characterized by a better outcome with a high rate of spontaneous normalization of left-ventricular size and function. The understanding of the etiology is limited. However, viral myocarditis and autoimmune factors might be involved in the development of PPCM. Clinically, PPCM shows pulmonary symptoms such as dyspnea, tachypnea and coughing. The diagnosis is finally established by echocardiography. It has to be assumed that PPCM is often undetected or misdiagnosed because of the low incidence, the unspecific symptoms and the fact that other pregnancy-related factors have similar clinical appearance. The treatment is also unspecific and similar to DCM and acute cardiac failure. The severity of the disease requires an interdisciplinary approach in a perinatal center with consequent follow-up of the patients for risk stratification including echocardiography.

Adult↗

On the applicability of a haplotype map to un-assayed populations.

The rationale for mapping all common haplotypes in our species relies on reports of the conservation of haplotype blocks across human populations. Recent findings indicate that these blocks may, at least in part, be a random artifact of genetic drift. This raises the concern that the latter process may challenge the general applicability of a human haplotype map to case-by-case population-specific association studies. We develop arguments indicating that even stochastic drift-originated blocks will, under many conditions, be shared across populations, supporting the utilization of a panhuman haplotype map.

Alleles↗

Analysis of the preS1 gene of hepatitis B virus (HBV) to define epidemiologically linked and un-linked infections in South Africa.

Analysis of the preS1 gene of hepatitis B virus was used to define two nosocomial outbreaks of HBV infection. In an outbreak in an oncology unit we had previously shown by single stranded conformational polymorphism (SSCP) analysis of a 189 bp fragment of the preS1 gene, that 52 children were infected with HBV strains that displayed only 5 different SSCP profiles. Sequencing of a 383 bp fragment encompassing the entire preS1 gene, revealed that isolates with same SSCP profile were identical in sequence across the entire preS1 gene, confirming that those patients with the same SSCP pattern had epidemiologically linked infections. A second outbreak involved 8 liver transplant patients from two different hospitals, 5 of whom were from the same hospital at which the oncology outbreak had occurred. Two of these 5 patients had HBV strains that were identical to strains from the oncology unit and nosocomial transmission probably accounted for the infections in these two, while diversity of both SSCP profiles and sequence data of remaining 6 patients supported the conclusion that they had not been infected from a common source. The donor liver is believed to be the most likely source of infection in these patients. HBV isolates from patients infected in the community were used as a standard for the general degree of preS1 sequence variation of local HBV strains. Phylogenetic analysis and comparison with reference HBV clones revealed that of 27 local HBV strains, genotypes A and D occurred most frequently and were identified in 14 and 12 patients respectively, while genotype C was detected in one patient.

Base Sequence↗