Prevention of diabetes in BioBreeding/Worcester rats with monoclonal antibodies that recognize T lymphocytes or natural killer cells

Diabetes-prone BioBreeding/Worcester (BB/Wor) rats received thrice weekly injections of mAb against antigens expressed on the surface of all T cells (OX19), cytotoxic/suppressor, and NK cells (OX8), helper/inducer cells (W3/25, OX35, OX38), and Ia+ cells (OX6, 3JP, OX17). Treatment with OX8 or OX19 achieved stable reductions of splenic and peripheral blood NK cells and helper/inducer T lymphocytes, respectively, and protected against diabetes. OX19 injections also prevented lymphocytic insulitis, thyroiditis, and the synthesis of autoantibodies to thyroid colloid and smooth muscle antigens. OX8 injections reduced splenic NK-mediated YAC-1 cell lysis, but did not prevent insulitis, thyroiditis, or autoantibody synthesis. Injections of mAb specific for antigens on the surface of helper/inducer cells, and for cells expressing IaE antigens provided marginal protection against diabetes without reductions of phenotypic subsets. These findings suggest that pancreatic beta cell destruction in the spontaneously diabetic BB/Wor rat is mediated by the combined action of NK and helper/inducer cells.     

The computer as a diagnostic consultant, with emphasis on use of laboratory data

In this preliminary study concerning the applicability of expert computer systems, such as INTERNIST-I, to providing advice to clinical pathologists regarding patients' diagnoses and the pertinence of performing further laboratory tests, 32 complex cases, drawn from Case Records of the Massachusetts General Hospital, were analyzed diagnostically by computer, on the basis of clinical laboratory data only. Half (16 cases) were diagnosed correctly, but in 15 of the rest no diagnostic conclusion could be reached. However, no diagnostic errors were made. The study provides preliminary evidence that expert computer systems can be useful to clinical pathologists and clinical internists in guiding the laboratory workup of patients toward correct diagnosis.     

Periodic lateralized epileptiform discharges (PLEDs): a possible role for metabolic factors in pathogenesis

Periodic, lateralized, epileptiform discharges (PLEDs) in the electroencephalogram have been reported in association with a variety of structural lesions of the brain. Although a great deal of attention has been directed to the neuropathological basis of PLEDs, little emphasis has been placed on the functional basis of this EEG syndrome. In this paper, we reported a patient with multiple systemic problems whose EEG showed PLEDs. However, radiological and pathological studies revealed no neuropathological basis for the occurrence of this EEG syndrome. Thus, we presented evidence that metabolic factors may play a part in the pathogenesis of PLEDs.     

Use of frequency-modulated radiofrequency pulses in MR imaging experiments

With increasing field strength for whole-body MR scanners there is a need for rf pulses of higher bandwidth to perform selective excitation or inversion. AM pulses will have to become shorter thus leading to an enormous requirement for the peak power of the power amplifier. To reduce these requirements the use of frequency modulation is investigated. The effect of pulses based on a linear frequency sweep on the spin system is analyzed by calculation and computer simulation. It turns out that the nonlinear phases induced by those pulses may compensate each other, that therefore spin-echo experiments as usual in MR imaging may be performed, and that the required peak power may be reduced by up to a factor of 50.     

Pseudo-endophthalmitis caused by intravitreal lipid transudation in association with proliferative diabetic retinopathy and hyperlipidemia

A 20-year-old woman with a 13-year history of insulin-dependent diabetes mellitus presented with a history of malaise, fever, a non-healing ulcer of the great toe, and an insect bite incurred during recent travel to a foreign country. Milky white infiltrates accompanied by inflammatory cells located within close proximity to neovascular fronds in both vitreous cavities led to the suspicion of bilateral metastatic endophthalmitis. Studies conducted during hospitalization failed to show evidence of systemic blood born infection. A diagnostic vitrectomy in one eye failed to grow organisms, though lipid laden macrophages were identified by electron microscopy. The clinical appearance improved in both eyes during her hospitalization coincident with improved diabetic control. It was later concluded that the milky white infiltrates were associated with hyperlipidemia as a consequence of poorly controlled diabetes and a familial tendency toward hyperlipidemia.     

Comparison between the iontophoretic and passive transport of thyrotropin releasing hormone across excised nude mouse skin

Thyrotropin releasing hormone [L-proglutamyl-L-histidyl-L-proline amide (TRH)], a tripeptide with molecular weight of 362 and a pKa of 6.2, was used as a model peptide for in vitro passive and iontophoretic diffusion cell studies using excised dorsal nude mouse skin. The results indicate that both the charged and uncharged TRH fluxes across the excised tissue were greater than those obtained by passive diffusion alone. The steady-state flux of both the uncharged and charged TRH was directly proportional to the applied current density, with flux being greater for the uncharged TRH. Additional studies on the transport of methylene blue indicate that transport may be occurring through pores, and that positive ions are preferentially passed through the skin. These results imply that the steady-state flux of TRH is primarily due to a direct, electrically induced ion motion and convection. A practical implication of these results is that it may be possible to enhance and control the transdermal delivery of peptides.