Advanced 1H Solid‐State NMR Spectroscopy on Hydrogels, 1

Summary: The nature of the pH dependent collapse of poly(methacrylic acid) (PMAA) hydrogels is investigated using recent ¹H solid‐state NMR methods. In aqueous solution, PMAA changes from an expanded conformation at high pHs to a compact contracted form at low pHs, where hydrogen bonds play a central role. In solid‐state ¹H NMR spectra, recorded under fast magic angle spinning (MAS), dried PMAA samples previously collapsed at low pHs show characteristic signals in the spectral region of the carboxylic acid protons. With the aid of 2D ¹H‐¹H double‐quantum (DQ) MAS NMR spectra, three signals can be distinguished at 8, 10.5 and 12.5 ppm, which are attributed to free carboxylic groups and two different types of hydrogen bonded forms, respectively. The 12.5 ppm signal arises from the hydrogen bond with the shortest H? H distance, corresponding to the form that is most stable with respect to increasing temperature and pH. The weaker hydrogen‐bonded form (with a signal at 10.5 ppm) requires a slightly lower pH, while the free acid signal (at 8 ppm) emerges under the most acidic medium. Moreover, the stabilities of the hydrogen‐bonded carboxylic acid dimers can be inferred from the proton‐proton distances within the dimers, i.e. (275 ± 5) pm and (295 ± 15) pm for the protons at 12.5 and 10.5 ppm, respectively, which are determined by means of DQ MAS sideband patterns. Both the stability of the hydrogen bonds and the acidity of the protons may be related to the stereochemistry and the conformation of the PMAA chains.

     

Isolation of human immunodeficiency virus (HIV) from plasma during primary HIV infection

Human immunodeficiency virus (HIV) has been isolated from plasma in 6 of 7 patients showing clinical symptoms of a primary HIV infection. Parallel cultures from peripheral blood mononuclear cells (PBMC) yielded virus in 5 patients. In one case, virus could only be isolated from the cerebrospinal fluid but not from peripheral blood. Detectable viremia was transient and preceded the appearance of HIV specific antibodies. After cessation of acute symptoms, the frequency of HIV isolations was similar to that of asymptomatic carriers (23 and 26%, respectively). The role of the immune response in terminating detectable viremia remains to be established.     

Effect of treatment with octreotide on the morphology of growth hormone—secreting pituitary adenomas: Study of 24 cases

Twenty-four acromegalic patients were treated with octreotide subcutaneously for periods of 3 to 6 weeks (group I, 12 cases) or 6 months (group II, 12 cases) before transsphenoidal surgery. Radiological studies performed in 19 patients before and at the end of this treatment period revealed no changes in 8 cases. In 8 other cases, a slight reduction in tumorsize was observed, and in 3 cases an important shrinkage was documented. At surgery, the adenomatous tissue appeared softer than in nonpretreated patients, facilitating the operation. Pathological examination revealed widening of perivascular spaces with accumulation of fibrous tissue and more crinophagy than in nonpretreated patients but failed to reveal morphologically pronounced cell involution as observed in prolactin-producing adenomas treated with dopamine agonists. No significant difference in frequency or extent of cellular changes was noted between the two groups. These morphological findings seem to be more consistent with a functional inhibition of growth hormone release than with cellular alterations induced by octreotide.     

Epstein-Barr virus-associated B-cell proliferations of diverse clonal origins after bone marrow transplantation in a 12-year-old patient with severe combined immunodeficiency

A 12-year-old boy with severe combined immunodeficiency who had been kept in a gnotobiotic environment since birth received bone marrow from a histoincompatible sibling in an attempt to reconstitute immunologic function. To prevent graft versus host disease, the donor's marrow was treated in vitro with monoclonal antibody and complement to remove alloreactive T cells. Eighty days after transplantation, the patient had a systemic illness characterized by fever, thrombocytopenia, gastrointestinal pain, and bleeding; he died on the 124th post-transplantation day. Postmortem examination revealed multiple tumor-like B-cell proliferations, recipient in origin, in numerous organs. Epstein-Barr virus (EBV) was isolated from the patient's pharyngeal secretions; EBV nuclear antigen was found in spontaneously transformed peripheral-blood lymphocytes, inflammatory cells from peritoneal fluid, and bone marrow cells; and EBV genomes were discovered in all tumor tissues. The donor's serum showed evidence of past EBV infection. Analysis of cellular immunoglobulin and immunoglobulin gene DNA from the tumors indicated both monoclonal and oligoclonal B-cell proliferations. These findings provide evidence for the evolution of EBV-induced polyclonal activation of B cells to oligoclonal B-cell proliferation and finally to monoclonal B-cell lymphoma.