Eperythrozoon coccoides I. Effect on the Interferon Response in Mice

Eperythrozoon coccoides is a common blood parasite of rodents and the etiological agent of a chronic infection present in many mouse colonies. After primary infection, mice develop a parasitemia and anemia followed by a chronic, latent infection. During the acute phase of infection, mice manifest a striking suppression of interferon production in response to induction with Newcastle disease virus, Chikungunya virus, and poly I:C. These data suggest that the reticuloendothelial system involvement with this agent is associated with impairment of the interferon response. The enhanced susceptibility of E. coccoides-infected animals to certain viral infections may be related to this suppression of interferon production.     

Sequence comparison of human and yeast telomeres identifies structurally distinct subtelomeric domains

We have sequenced and compared DNA from the ends of three human chromosomes: 4p, 16p and 22q. In all cases the pro-terminal regions are subdivided by degenerate (TTAGGG)n repeats into distal and proximal sub- domains with entirely different patterns of homology to other chromosome ends. The distal regions contain numerous, short (<2 kb) segments of interrupted homology to many other human telomeric regions. The proximal regions show much longer (approximately 10-40 kb) uninterrupted homology to a few chromosome ends. A comparison of all yeast subtelomeric regions indicates that they too are subdivided by degenerate TTAGGG repeats into distal and proximal sub-domains with similarly different patterns of identity to other non-homologous chromosome ends. Sequence comparisons indicate that the distal and proximal sub-domains do not interact with each other and that they interact quite differently with the corresponding regions on other, non- homologous, chromosomes. These findings suggest that the degenerate TTAGGG repeats identify a previously unrecognized, evolutionarily conserved boundary between remarkably different subtelomeric domains.      

Genital herpesvirus hominis infection in mice. I. Development of an experimental model.

Pregnant female mice, after intravaginal inoculation with Herpesvirus hominis (HVH) type 2, developed vaginitis on days 5 to 7 after virus challenge, followed by hunching and hind limb paralysis on days 7 to 9 and death from encephalitis on days 9 to 11. After initial replication in the mucous membranes of the genital tract, virus spread to the spinal cord and ascended to involve the brain. Viremia or replication of H. hominis type 2 in the liver or spleen was not detected. Virus was cleared from vaginal secretions by days 8 to 10 after infection. Pregnant mice were more susceptible to the infection than nonpregnant mice. This experimental infection in female mice provides a model for genital herpesvirus infection and for herpesvirus infection and for herpesvirus encephalitis in which one can evaluate potentially promising antiviral chemotherapeutic agents.     

Field matching of electron beams using plastic wedge penumbra generators.

We describe the use of polystyrene wedges to match adjacent electron beams with improved dose uniformity. These wedges were designed to increase the penumbra width at the field junction from about 1.5 to about 3.5 cm, to achieve dose uniformity. Measurements using thermoluminescent dosimeters (TLD) and therapy localization film showed that the use of polystyrene wedges (penumbra generators) produced only a small increase (less than 3%) in the surface dose and a small increase (less than 1%) in the x-ray contamination. Without wedges at the field junction, lateral mismatching of beam edges by 2 or 3 mm may introduce high dose variations (120% or more or 50% or less). Similar 2-3 mm set-up errors did not cause more than +/- 5% dose variations when plastic wedges were used to match the fields. These wedges are particularly useful when matching fields of different beam energies or matching fields on curved surfaces, such as the chest wall.     

Tissue culture of isolated human glomeruli

Glomerular cells have been grown in a reproducible manner from 5 normal human kidneys. A technique is described which combined mechanical disruption of renal cortex and microdissection, and provides large numbers of pure glomeruli within 30--45 mintues. Histological examination shows this technique produces intact glomeruli without cell disturbance. During tissue culture, glomeruli attach to the flask and the intrinsic cells migrate onto the flask and divide. Variations of culture conditions have shown that glomeruli are robust without fastidious culture requirements. Intact kidney tissue can be left at 4 degrees C for perios up to 24 hours prior to isolated of individual glomeruli without affecting subsequent cellular growth in culture. They grow in most commonly used media although the cells require 20% foetal calf serum for optimum growth. Their pH optimum is between 7.0 and 7.4 with temperature optimum of 37 degrees C. as glomeruli must attach prior to cell growth, minimum movement is critical to promote optimum growth. Under these optimum conditions a regular and predictable growth of cells of two distinct types, has been observed over 14 days; one of these types is probably epithelial.     

Treatment of resistant malignant lymphoma with cyclophosphamide, total body irradiation, and transplantation of cryopreserved autologous marrow

Twenty-seven patients with malignant lymphoma in whom primary chemotherapy had failed and the prognosis was poor were treated with cyclophosphamide, total body irradiation, and transplantation of cryopreserved autologous marrow. The median time to recovery of more than 500 neutrophils per microliter and more than 10,000 platelets per microliter was 18 and 24 days, respectively. Complete remission was achieved in 15 patients (56 per cent), five of whom were in continuous remission at this writing 19 to 71 months after transplantation without further therapy and one of whom was alive in a subsequent remission at 20 months. Fifteen patients died of lymphoma, three of interstitial pneumonitis, two of sepsis, and one of congestive heart failure. This experience shows that intensive therapy and autologous-marrow transplantation can produce prolonged remissions in patients with malignant lymphoma in whom conventional chemotherapy has failed.     

The use of successive blood-pressure measurements to estimate blood-pressure variability

Multiple daily, self-determined blood-pressure measurements were obtained from 254 hypertensive patients for 1 month. In an effort to establish a practical and reliable technique for estimating blood-pressure variability, standard deviations from three (at one time of day) or nine (throughout the day) successive self-determinations were compared with a reference value, taken to be the standard deviation for the entire month (252 determinations per subject). Neither the standard deviation of three measures taken on one occasion nor that of nine measures taken throughout the day correlated well with the reference value (average R₃=.21 for SBP, .20 for DBP; average R₉=.39 for SBP, .38 for DBP). However, when a sample consisting of 12 measures (taken three at a time, at the same time of day, weekly for 4 weeks) was used, the average correlation rose to .60 for SBP and .54 for DBP. Thus, it appears that 12 samples taken in this way provide a reliable estimate of the standard deviation for an entire month, and it is suggested that this sampling technique also would enhance the reliability of conclusions drawn from assessments of the prognostic value of blood-pressure variability.     

Comparison of benign and malignant insulinoma

BackgroundHow malignant insulinomas present relative to benign insulinomas is unknown.MethodsA single-institution retrospective study identified patients with insulinoma. Malignancy was defined by distant metastases, positive lymph node(s), T stage of 4, direct invasion into surrounding peripancreatic tissue, or presence of lymphovascular invasion. Wilcoxon Rank Sum tests and Kaplan-Meier analysis were used.ResultsA total of 311 patients were identified: 51 malignant and 260 benign. Patients with malignant insulinoma presented with higher levels of insulin, proinsulin, and c-peptide. Malignant lesions were larger: 4.2 ± 3.2 vs 1.8 ± 0.8 cm in benign lesions, p < 0.01. Overall survival at 5 years was 66.8% vs 95.4% for malignant and benign insulinoma respectively, p < 0.01.ConclusionsLarger size of insulinoma and increased serum β-cell polypeptide concentrations were associated with malignancy. Malignant insulinoma has poorer survival. Further work-up to rule out malignancy may be indicated for larger pancreatic lesions and for patients with higher pre-operative insulin and pro-insulin.