New alleles in the B44 family including B*44022, B*44032, B*4411, B*4420, B*4421, B*4424, and B*8301

Seven new HLA-B locus alleles have been described. B*44022 and B*44032 are silent substitutions altering known alleles. B*4411 carries a unique Bw4-like epitope. B*4420, B*4421, and B*4424 carry new combinations of motifs previously observed in other alleles. B*8301 appears to be the result of the replacement of exon 2 from B*4402 with exon 2 from B*5603.     

Systemic autoimmune disease induced by dendritic cells that have captured necrotic but not apoptotic cells in susceptible mouse strains

Systemic lupus erythematosus (SLE) is an autoimmune disorder of a largely unknown etiology. Anti-double-stranded (ds) DNA antibodies are a classic hallmark of the disease, although the mechanism underlying their induction remains unclear. We demonstrate here that, in both lupus-prone and normal mouse strains, strong anti-dsDNA antibody responses can be induced by dendritic cells (DC) that have ingested syngeneic necrotic (DC/nec), but not apoptotic (DC/apo), cells. Clinical manifestations of lupus were evident, however, only in susceptible mouse strains, which correlate with the ability of DC/nec to release IFN-gamma and to induce the pathogenic IgG2a anti-dsDNA antibodies. Injection of DC/nec not only accelerated disease progression in the MRL/MpJ-lpr/lpr lupus-prone mice but also induced a lupus-like disease in the MRL/MpJ-+/+ wild-type control strain. Immune complex deposition was readily detectable in the kidneys, and the mice developed proteinuria. Strikingly, female MRL/MpJ-+/+ mice that had received DC/nec, but not DC/apo, developed a 'butterfly' facial lesion resembling a cardinal feature of human SLE. Our study therefore demonstrates that DC/nec inducing a Th1 type of responses, which are otherwise tightly regulated in a normal immune system, may play a pivotal role in SLE pathogenesis.     

Evaluation of a Selective Transport Medium for Gastric Biopsy Specimens To Be Cultured for Helicobacter pylori

Since the means of culturing Helicobacter pylori may not be available in some laboratories, prolonging the survival of this organism during transportation is a major concern in terms of improving detection rates. A selective transport medium was evaluated for the preservation of H. pylori from 254 gastric biopsy specimens collected from a rural area in China where culturing is not feasible. Gastric biopsy specimens were inoculated in sterile broth consisting of brain heart infusion (BHI) broth, horse serum, and yeast extract supplemented with vancomycin, amphotericin B, and nalidixic acid (VAN). Of the 254 biopsy specimens, 238 were identified by histology to have H. pylori infection. Total rates of recovery of H. pylori from the H. pylori-positive gastric biopsy specimens stored in the BHI-VAN broth ranged from 76 to 46% after storage of specimens for 5 to 9 days. In conclusion, the selective medium is useful for prolonging the survival of H. pylori in gastric biopsy specimens for which immediate culture is not feasible.     

An immunohistochemical study of neuronal and glial cell reactions in retinae of rats with experimental glaucoma

Glaucoma is a common disease seen in the eye clinic, but its associated pathological processes, especially the role of glial cells in glaucomatous retinae, are still under debate. The aim of the present work was to study the responses of astrocytes, Müller cells and microglia in retinae of rats with experimental glaucoma. Glaucoma was induced in adult male Wistar rats by cauterizing limbal-derived veins and the changes in glial fibrillary acidic protein (GFAP), OX42, OX18, OX6 and EDI expression were studied by immunohistochemical staining. Neuronal cell viability was studied by immunostaining with the neuronal nuclei (NeuN) antibody. In the experimental glaucomatous eyes, a significant drop in the number of NeuN-positive neurons was observed from 7 days postoperation and beyond in both the ganglion cell layer and inner nuclear layer. The expression of GFAP and OX42 was increased during the first 2 months after operation and reduced in rats at 3 and 4 months. OX6 and OX18 immunoreactivity was induced in some microglia of both glaucomatous and sham-operated control eyes. Possible mechanisms of the reaction of astrocytes, Müller cells and microglia in neuronal degeneration following glaucoma are discussed.     

Ontogeny of the transition from killer to caregiver in dwarf hamsters (Phodopus campbelli) with biparental care

Biparental Phodopus campbelli and uniparental P. sungorus juvenile litters (2 males, 2 females) both consumed amniotic fluid and placenta during the birth of younger siblings. Three days later, P. campbelli juveniles were most responsive to a displaced younger sibling. Thus, P. campbelli are responsive to pups as juvenile alloparents and as new parents; however, at intervening ages, infanticidal attack (bite) was seen. At 5, 7, 9, 11, or 13 weeks of age, male and female P. campbelli were given a 5-min test with an unrelated, 3-day-old, anesthetized pup. Females attacked more often than males, yet pup-retrieval rates did not differ. Female aggression increased with age and was replaced by retrieval behavior 3 days after parturition. Male attack ceased after a birth, but parental behavior did not increase, remaining below the rate for new fathers tested with their own awake pup. Over repeated testing, behavior in one test did not predict behavior in another. Transitions from caregiving alloparent to infanticidal adult and back to parental care were clear in females, but less discrete with this stimulus paradigm in these highly paternal males.     

Eighty consecutive cases of gamete intra-Fallopian transfer

Eighty patients with the main problems of unexplained infertility,oligospermia and endometriosis were treated with gamete intraFallopiantransfer (GUT). From 80 treatment cycles, 29 women conceived(36.3%). Of these, four were biochemical pregnancies and thereforethe clinical pregnancy rate (25/80) was 31.2%. There were sixsets of multiple pregnancies, a multiple pregnancy rate of 24%.Three women (12%) miscarried. The pregnancy rates in the patientswith unexplained infertility, oligospermia and endometriosiswere 33.3, 16.7 and 38.5%, respectively. The transfer of fouroocytes appears to increase the pregnancy rate without increasingthe risk of multiple pregnancy. The presence of in-vitro fertilizationof excess oocytes after GIFT did not correlate with the finaloutcome of GIFT     

Reactive hemophagocytic syndrome: a study of 7 fatal cases

Reactive hemophagocytic syndrome is a clinico-pathologic entity characterized by systemic proliferation of non-neoplastic histiocytes showing phagocytosis of hemopoietic cells, resulting in blood cytopenia. It is best known to be associated with virus infection, but other associated diseases have also been implicated. The clinical and pathological findings of 7 fatal cases are described. The syndrome affected both sexes of a wide age range, and all patients had fever. Significant laboratory findings were blood cytopenia, abrupt drop in the blood cell counts, deranged liver function tests and abnormal coagulation profile. The associated diseases were diverse: two patients had bacterial infection; two had peripheral T-cell lymphoma; one had disseminated undifferentiated carcinoma of the ovary; one had both tuberculosis and disseminated nasopharyngeal carcinoma, and one had no obvious underlying disease. It is postulated that lymphokines secreted by lymphoid cells or tumor cells may be responsible for the systemic activation of histiocytes. The differential diagnosis from malignant histiocytosis is discussed.     

Recombinant alpha2(IV)NC1 domain inhibits tumor cell-extracellular matrix interactions, induces cellular senescence, and inhibits tumor growth in vivo

Cellular interaction with the extracellular matrix is thought to be a critical event in controlling angiogenesis and tumor growth. In our previous studies, genetically distinct noncollagenous (NC) domains of type-IV collagen were shown to interact with integrin receptors expressed on the surface of endothelial cells. Moreover, these NC1 domains were shown to inhibit angiogenesis in vivo. Here, we provide evidence that a recombinant form of the alpha2(IV)NC1 domain of type-IV collagen could bind integrins alpha1beta1 and alphavbeta3 expressed on melanoma cells and inhibit tumor cell adhesion in a ligand-specific manner. Systemic administration of recombinant alpha2(IV)NC1 domain potently inhibited M21 melanoma tumor growth within full thickness human skin and exhibited a dose-dependent inhibition of tumor growth in nude mice. Interestingly, alpha2(IV)NC1 domain enhanced cellular senescence in tumor cells in vitro and in vivo. Taken together, these results suggest that recombinant alpha2(IV)NC1 domain is not only a potent anti-angiogenic reagent, but it also directly impacts tumor cell behavior. Thus, alpha2(IV)NC1 domain represents a potent inhibitor of tumor growth by impacting both endothelial and tumor cell compartments.     

Virion stability and aphid vector transmissibility of Cucumber mosaic virus mutants

The physical stability of virions of Cucumber mosaic virus (CMV) mutants was investigated to determine if relative stability correlated with efficiency of aphid transmission. Virion stability was evaluated by a urea disruption assay and by testing the infectivity of virus following purifications. All viruses were infectious when purified using a low salt buffer without organic solvent, whereas two of seven viruses were less stable and inactivated following purification with a high salt buffer and chloroform. These two viruses were both reassortants derived from the spontaneous transmission-defective mutant CMV-M (F1F2M3 and F1F2M3-L129P). F1F2M3 was relatively unstable, being disrupted between 0 and 1 M urea versus the wild-type CMV-Fny (F1F2M3) that was destabilized at 3-4 M urea. Modifications of F1F2M3 at three amino acid positions (129, 162, 168), singly or in combination, increased the relative stability of virions. A second class of transmission-defective CMVs with engineered mutations in the betaH-betaI surface loop of the CMV-Fny capsid protein (CP) exhibited near wild-type levels of stability. Lastly, a single Pro to Leu substitution at CP position 129 of CMV-Fny (F1F2M3-P129L) conferred the induction of necrosis in tobacco plants and reduced aphid transmissibility, but did not markedly alter the physical stability of virions. Thus, only among CMV-M derivatives harboring the CP mutation of Thr to Ala at position 162 were increases in stability correlated with restoration of transmissibility by the aphid Aphis gossypii.