INAUGURAL ARTICLE by a Recently Elected Academy Member:From oligonucleotide shapes to genomic SELEX: Novel biological regulatory loops

The SELEX method and oligonucleotide combinatorial chemistry discovery process yields high-affinity/high-specificity ligands for virtually any molecular target. Typically, the enormous starting libraries used in the SELEX process contain 10¹⁴–10¹⁵ sequences. We now ask if the smaller sequences, complexity of extant organisms, and evolutionary history provide useful interactions between oligonucleotides and at least some unexpected targets. That is, do organisms contain a robust “linkage map” between their oligonucleotides and proteins and/or small molecules that enriches life?     

Improving self-care among older patients with type II diabetes: the "Sixty Something..." Study.

A 10-session, self-management training program was designed specifically for persons over 60 years of age having Type II diabetes. It targeted social learning variables, especially problem-solving skills and self-efficacy, found to be related to diabetes self-care in earlier correlational research. One hundred two adults were randomized to immediate or delayed intervention conditions. At posttest, subjects in the immediate intervention condition showed significantly greater reductions in caloric intake and percent of calories from fat than control subjects. The intervention also produced greater weight reductions and increases in the frequency of glucose testing than did the control condition. Improvements among immediate intervention subjects were generally maintained at a 6-month follow-up. Intervention results from subjects receiving delayed intervention closely replicated those for immediate intervention subjects. We conclude that a relatively short-term program can improve self-management skills of older diabetic adults, and that there is an important need for such interventions.     

HELLP Syndrome: an Often Unrecognized Complication of Preeclampsia

We describe a case of preeclampsia with the HELLP (Haemolysis, Elevated Liver enzymes, Low Platelets) syndrome and highlight the delayed diagnosis due to its nonspecific presentation. This syndrome is associated with significant maternal and perinatal mortality and morbidity and we discuss the importance of early recognition of the condition, aggressive management and a multidisciplinary approach.     

Physiologic comparison and validation of Stairobic stepping with bench stepping.

To compare the oxygen cost of submaximal exercise on the Stairobic stepping (SS) machine with bench stepping (BS), 12 healthy men and women (mean age 23 years) underwent six different five minute exercise bouts that were randomly assigned. Tests were conducted using standard open circuit calorimetry. SS at 40 and 60 st/min was equal to BS at 20 st/min and SS at 80 st/min was equal to BS at 30 st/min for VE and RER. VO2 was equal at 20 st/min (BS) and 60 st/min (SS), and 30 st/min (BS) and 80 st/min (SS). Stairobic MET (SM) displayed values over-estimated actual MET (AM) values at the two lowest SS rates and under-estimated the AM value at the highest SS rate. Forty-eight observations of the MET response of SS were conducted and analyzed (BMDP2R) in a forward stepping solution. The multiple regression equation calculated for AM was: AM = -0.567 + -0.012 (WT) + 0.063 (rate) + 0.612 (SM) with an adjusted R2 of 0.82 and a SEE of 0.90. The physiologic cost of BS was approximately equal to SS at two to three times the BS rate of stepping.     

TGFβ-1 regulation of VEGF production by breast cancer cells

Background: Angiogenesis is essential for tumor growth and metastasis. Vascular endothelial growth factor (VEGF) is the most potent angiogenic factor identified to date. TGFβ-1 acts as an indirect angiogenic agent. Methods: VEGF and TGFβ-1 were measured in the serum of breast cancer patients and agematched controls and in tumor tissue of cancer patients by ELISA. VEGF protein and mRNA expression by breast tumor cell lines were examined, and the effect of TGFβ-1 on VEGF production in these cells was assessed. Results: VEGF levels were significantly higher (P=.03) in the serum of patients with breast cancer compared to age-matched controls. A positive correlation was found between serum (r=0.539) and tumor tissue (r=0.688) levels of VEGF and TGFβ-1. Metastatic MDA-MB-231 breast cancer cells produce more VEGF than do the primary BT474 cells. TGFβ-1 significantly (P<.05) increased production of VEGF. Conclusions: Breast cancer cells constitutively produce VEGF protein and mRNA. There is a relationship between VEGF and TGFβ-1 levels in breast cancer patients, and TGFβ-1 regulates VEGF expression by breast cancer cells. Presented at the 50th Annual Cancer Symposium of the Society of Surgical Oncology, Chicago, Illinois, March 20–23, 1997.     

CNS mycosis fungoides: CT and MR findings.

Mycosis fungoides (MF) is a malignant T-cell lymphoma that primarily involves the skin, but may, in its advanced stages, metastasize to internal organs. From autopsy series, CNS involvement of MF can be seen in 14% of patients. We describe the CT and MR findings in three patients with CNS metastases. The images showed various manifestations of CNS MF, including parenchymal homogeneously intensely enhancing masses and ependymal enhancement. The CSF and biopsy results were eventually diagnostic in all three cases. One patient was treated prior to pathologic diagnosis, the other two were treated after diagnosis. The tumor improved following treatment in two patients. Although the imaging findings of CNS MF are nonspecific, they can be the first evidence of the disease.     

Induction of major histocompatibility complex class II glycoproteins by interferon-gamma: attenuation of the effects of restraint stress.

The effect of restraint on the activation of macrophages was evaluated based on the induction of I-A expression following injection of viable Mycobacterium bovis (strain BCG) or treatment in vitro with recombinant interferon-gamma (rIFN-gamma). We found that restraint suppressed the induction of I-A expression when applied just prior to or at the same time as the injection of the microorganisms but had no effect if applied after the injection of the Mycobacteria. The effect of stress was attenuated by increasing the number of microorganisms or by incubating macrophages from stressed mice with higher doses of rIFN-gamma. The suppressive effect of restraint does not appear to be associated with uptake, processing or presentation of antigen but rather to an alteration in the response of the macrophages to rIFN-gamma.