Mesenteric venous thrombosis--1911 to 1984

The objective of this study was to identify those patients in whom mesenteric venous thrombosis (MVT) is likely to develop and to review the pathophysiology, clinical presentation, diagnostic modalities, and patient outcome. We present a review of the literature from 1911 to 1984 with respect to 372 patients with MVT, including five of our own patients. Data on 99 of these patients were obtained from autopsy reports and were not included in the study. This disease is common in the sixth and seventh decades of life, with 81% of these older patients having associated illnesses. MVT involves segments of the small bowel, but rarely of the colon, with hemorrhagic infarcts rather than gangrene. This disease does not conform to a pattern, although a prodromal period of days or weeks of abdominal pain (which is usually out of proportion to physical findings), marked leukocytosis, and dehydration are all highly suggestive of MVT. Serosanguineous fluid obtained by means of peritoneal tap is a useful diagnostic tool. A high index of suspicion, early diagnosis, and prompt surgical intervention with the addition of anticoagulants seems to improve survival and reduce recurrence.     

expression of members of the heat-shock protein 70 family in the exoerythrocytic stages ofPlasmodium berghei andPlasmodium falciparum

Exoerythrocytic stages ofPlasmodium berghei cultured in HepG2-A16 hepatoma cells and those ofP. falciparum in human hepatocytes transplanted under the kidney capsule of CB-17/ICr scid/scid mice were used to evaluate expression of heat-shock-related stress proteins. Although undetectable in the sporozoites, the expression of proteins similar in sequence of a heat-shock protein of 70 kDa and a glucose-regulated protein of 78 kDa was markedly induced in the hepatic stages of malaria parasites. Expression of these proteins in the exoerythrocytic stages of the malaria parasite warrants a systematic evaluation of their potential role in eliciting cellular immune responses directed against infected hepatocytes.     

Differential susceptibility to experimental autoimmune neuritis in Lewis rat strains is associated with T-cell immunity to myelin antigens

Experimental autoimmune neuritis (EAN) is a CD4(+) T-cell-mediated inflammatory demyelinating disease of the peripheral nervous system (PNS) that serves as a model for Guillain-Barré syndrome (GBS) in humans. Various rat strains show different susceptibility to EAN. We examined PNS myelin-induced T- and B-cell responses and cytokine production in order to explore the mechanisms behind different EAN susceptibility in the three Lewis rat strains, Hannover, Charles River, and Taconic. Lewis rats of Hannover and Charles River strains exhibited a higher susceptibility to EAN than Lewis rats of the Taconic strain. The higher susceptibility was associated with increased inflammatory cell infiltrates and major histocompatibility class II expression as well as enhanced mitogenic (phytohemagglutinin-induced) and antigen-specific (P2 peptide 57-81-induced) lymphocyte proliferation compared with the Taconic strain. The Hannover strain also showed increased proinflammatory cytokine (interferon-γ and tumor necrosis factor-α) production in the PNS. Cross-cultures of T cells and macrophages from Hannover and Taconic rats revealed that the Hannover rats exerted the strongest priming function of T cells. In contract, the P2 peptide-induced antibody production was not different among the three Lewis rat strains. In conclusion, the differential susceptibility to EAN of Lewis rat strains is correlated primarily with T-cell immunity to myelin antigens.     

Haptoglobin: Old protein with new functions

When released from red blood cells (RBCs), hemoglobin (Hb) is extremely toxic due in large part to the redox activity of its heme center. Nature however, has provided a multitude of protective mechanisms that can detoxify free Hb effectively under physiological conditions. Chief amongst them is haptoglobin (Hp) which chaperones Hb subunits to the macrophages for safe degradation. Recent research on the interactions between Hb and Hp under oxidative conditions revealed that Hp specifically shields key amino acids on the Hb molecule, allowing the heme to consume oxidants and short-circuits the emerging and damaging radicals. Moreover, animal studies showed that the infusion of Hb complexed with Hp prevents Hb-induced systemic hypertension and tissue injury. It may prove necessary to explore these protective clearing mechanisms to counter the toxicity associated with free Hb when used as oxygen therapeutics in hemolytic anemias and in RBC storage lesions.     

A Kunitz protease inhibitor from Dermacentor variabilis, a vector for spotted fever group rickettsiae, limits Rickettsia montanensis invasion

A defining facet of tick-Rickettsia symbioses is the molecular strategy employed by each partner to ensure its own survival. Ticks must control rickettsial colonization to avoid immediate death. In the current study, we show that rickettsial abundance in the tick midgut increases once the expression of a Kunitz-type serine protease inhibitor from the American dog tick (Dermacentor variabilis) (DvKPI) is suppressed by small interfering RNA (siRNA). A series of in vitro invasion assays suggested that DvKPI limits rickettsial colonization during host cell entry. Interestingly, we observed that DvKPI associates with rickettsiae in vitro as well as in the tick midgut. Collectively, our data demonstrate that DvKPI limits host cell invasion by Rickettsia montanensis, possibly through an association with the bacterium.