Therapeutic and diagnostic applications of minor histocompatibility antigen HA-1 and HA-2 disparities in allogeneic hematopoietic stem cell transplantation: a survey of different populations.

Minor histocompatibility antigens (mHags) HA-1 and HA-2 are encoded by biallelic loci, with immunogenic variants, HA-1H and HA-2V, which induce strong HLA-A2-restricted alloreactive T-cell responses, and nonimmunogenic counterparts, HA-1R and HA-2M, which represent functional null alleles that are poorly presented by HLA class I molecules. HA-1 and HA-2 are potential targets of selective graft-versus-leukemia and graft-versus-tumor reactivity after allogeneic hematopoietic stem cell transplantation (HSCT); however, these applications are restricted to a limited number of patients. Here, we show that a far more frequent application of HA-1 and HA-2 disparity relies on their use as markers for the state of host chimerism after allogeneic HSCT. We have determined allelic frequencies of 29.3% and 70.7% for HA-1H and HA-1R, respectively, and of 83.7% and 16.3% for HA-2V and HA-2M, respectively, in >200 healthy individuals from northern Italy. Similar frequencies were observed in nearly 100 patients affected by hematologic malignancies or solid tumors, thus showing that HA-1 and HA-2 variability are not associated with the presence of cancer. On the basis of these data, we predict that HA-1 and HA-2 can be used in 32.8% and 23.5% of Italian transplant patients, respectively, as markers for the state of host chimerism, whereas exploitation of disparity for these mHags for targeted immunotherapy will be possible in 10.7% and 1.1% of Italian patients, respectively. Retrospective HA-2 typing of bone marrow aspirates obtained from a patient during complete remission or recurrence of acute myeloid leukemia after haploidentical HSCT showed the feasibility of using HA-2 as a surrogate marker for disease monitoring. Because of an apparent north-south gradient for HA-1 allelic frequencies, with higher frequencies for the HA-1H variant reported in white populations from Southern Europe as compared with Northern Europe and North America, the diagnostic applicability of HA-1 disparity will be slightly more frequent in transplant patients from the north. Taken together, our data show that determination of HA-1 and HA-2 variability can be an important parameter for the selection of allogeneic stem cell donors, in particular for patients affected by hematologic malignancies without a tumor-specific molecular marker.     

An unusual variant of composite lymphoma: a short case report and review of the literature

We recently encountered an unusual case of composite lymphoma arising in a 73-year-old man with a history of follicular small cleaved cell lymphoma. The neoplasm was composed of follicular small cleaved cell lymphoma and nodular sclerosing Hodgkin disease within a single groin lymph node. In addition to morphologic evidence, the immunologic studies performed in this case demonstrated the simultaneous occurrence of 2 separate lymphocytic proliferations. To the best of our knowledge, only one such histologic type has been reported in the literature.1 Hodgkin lymphoma can develop in patients with non-Hodgkin disease and vice versa, especially after treatment. The simultaneous occurrence of Hodgkin disease and non-Hodgkin lymphoma in a single lymph node is extremely rare. In this article, the relationship between Hodgkin disease and non-Hodgkin lymphoma is explored, possible explanations for the occurrence of composite lymphoma are discussed, and the literature is reviewed.     

Orthopoxvirus DNA: strain differentiation by electrophoresis of restriction endonuclease fragmented virion DNA.

Procedures were developed for purifying intact intracytoplasmic poxvirus particles from infected cells and for isolating DNA from virions by equilibrium centrifugation in sodium diatrizoate density gradients. The buoyant density of twelve closely related orthopoxviruses purified in these gradients was determined to be 1.25 g/ml, and that of the isolated virion DNAs was 1.1 g/ml. Virion DNA from each of the 12 selected prototype and wild-type viruses was cleaved with three separate site-specific restriction endonucleases, Hin d III, Sal I, and Bam HI, and the fragments (molecular weights 0.5 × 10⁶ to 20 × 10⁶) were separated by agarose gel electrophoresis. Characteristic DNA fragment migration patterns observed in the gels permitted classification of the viruses. By comparing profiles of Hin d III cleaved DNAs we were able to group the viruses into 4 species: cowpox, vaccinia, monkeypox (2 isolates), and variola (8 isolates). Viruses from variola major infection could be differentiated from viruses from variola minor infection. Isolates within species (strains) were also differentiated, mainly by comparing the gel electrophoresis profiles of Sal I digested DNA from the viruses.     

Mediastinal hibernoma: a case report

Hibernomas are rare benign tumours that arise most often in adults from the remnants of fetal brown adipose tissue. They usually affect muscle and subcutaneous tissue and are asymptomatic and slow growing. The distribution of this tumour follows the sites of persistence of brown fat. Out of more then 100 cases described in the word literature only three hybernomas were mediastinal. A recent clinicopathological study of 170 cases from the Armed Forces Institute of Pathology confirmed the exceptionality of the intrathoracic location. This report describes a very rare case of mediastinal hibernoma in a young man.     

Multifunctional microcapsules for pancreatic islet cell entrapment: design,preparation and in vitro characterization

Great advances in cell transplantation have been made, including the recent, remarkable success in pancreatic islet transplantation for the treatment of type 1 diabetes mellitus. Unfortunately, the transplanted cells are very susceptible to oxidative stress that cause severe damage to either allo- or xenogeneic islets upon graft in diabetic patients. Consequently, the transplanted islet functional life span is significantly shortened. The aim of this study was to examine the possible effects of antioxidants on in vitro cultured adult rat islets, and to evaluate the effects of a prolonged-release formulation, in form of cellulose acetate (CA) microspheres, on Vitamin D(3) activity. Isolated rat islets, both free and entrapped in microspheres were treated with Vitamin D(3). The effects of the vitamin were studied at 3, 6 and 9 days of in vitro cell culture. According to insulin secretory patterns, treatment with Vitamin D(3) of both free and CA entrapped microspheres, increased the insulin output as compared to untreated controls. Such positive effects were confirmed under islet static incubation with glucose at day 6. These results suggest that pancreatic islets can be advantageously treated with anti-oxidising vitamins before implantation, and speculatively, with the help of special delivery systems, throughout the islet cell life span, in the post-transplant time period.     

Reliability of a single urine culture in establishing diagnosis of asymptomatic bacteriuria in adult males.

Fifty-nine asymptomatic men without catheters of ileal-loop bladders, who were attending a urology clinic and were incidentally discovered to have 100,000 or more Enterobacteriaceae per ml ("significant bacteriuria") in a clean voided urine sample, were prospectively evaluated. To identify these 59 patients, 5,876 urine samples, collected exclusively from men, had been subjected to quantitation and identification. A repeat urine culture performed on these patients invariably confirmed the results of the initial culture. The reproducibility of a single urine culture containing significant bacteriuria occurred independently of the tissue source of infection, as determined by the antibody-coated-bacteria immunofluorescence test. We conclude that a single urine culture obtained from a cooperative man can establish the diagnosis of asymptomatic bacteriuria.