Allografts of tumor nuclear transplantation embryos: differentiation competence.

The developmental potential of nuclei can be studied by nuclear transplantation. Although amphibian blastula nuclei and other early embryonic nuclei are totipotent, to our knowledge no nucleus from an adult cell has ever been shown to be totipotent by this procedure. Transfer of Lucké renal carcinoma nuclei into enucleated eggs results in prefeeding swimming tadpoles. Inasmuch as these tadpoles die, rescue of this pluripotential tissue was attempted by grafting fragments of triploid tumor nuclear transplant tadpoles to the tails of normal diploid Rana pipiens hosts. Grafts of tumor nuclear transplant tadpole tissue were histologically indistinguishable from grafts of normally fertilized embryos and developed normal-appearing structures such as complete eyes, well-differentiated neural tissues, kidney tubules, and gut epithelium. Moreover, histological differentiation in tumor nuclear transplant grafts was comparable to that observed in 50-day-old normal larvae. Grafting enhanced the survival of tumor nuclear transplant tissue from no more than 14 days as part of the donor tadpole to 40 days at which time the grafts were harvested as healthy tissue. Thus, both differentiation and survival of tumor nuclear transplant tissue were augmented with the grafting procedure. Cytophotometric analysis of ploidy was used to confirm the tumor origin of the donor tissue.     

Epikeratophakia without annular keratectomy

Nineteen patients (20 eyes) underwent epikeratophakia for correction of high myopia. In contrast to the conventional surgical method utilizing an annular keratectomy, no keratectomy was performed in these patients. The surgical procedure is discussed. Preliminary results (up to six months) indicate that the omission of an annular keratectomy has no effect on graft clarity or viability. The weighted-average percent correction over six months postoperatively was 102%.     

Immunomodulation of Delayed Hypersensitivity to Methylated Bovine Serum Albumin (MBSA) in Mice Using Subliminal and Normal Sensitization Procedures

Delayed hypersensitivity (DH) was induced in the footpads of mice sensitized to methylated bovine serum albumin (MBSA). The magnitude of this DH response increased with increasing sensitizing concentration of MBSA. Levamisole administered 1 hr prior to MBSA challenge stimulated the DH response and this was optimal using subliminal sensitizing concentrations of antigen. A number of antirheumatic agents, immunomodulators mediator antagonists and antiallergies were subsequently examined using the subliminal sensitizing concentration of MBSA. The same drugs were also evaluated using a normal sensitizing procedure. These studies indicate that the sensitizing concentration of antigen is critical in establishing whether a drug will stimulate or suppress a DH response.     

Cardiac arrhythmogenic action of benzo(a)pyrene in the rabbit

Rabbits treated with benzo(a)pyrene developed cardiac arrhythmias when exposed by inhalation to 8100 ppm trichloroethylene or 15000 ppm halothane to a greater extent and at lower doses of epinephrine challenge than did controls. Benzo(a)pyrene and 3-methylcholanthrene both increased the metabolism of trichloroethylene, but 3-methylcholanthrene did not increase its cardiotoxic effect. The basis of the arrythmogenic action of benzo(a)pyrene appears to be unrelated to its ability to induce xenobiotic metabolism.     

Electrophysiologic target localization in posteroventral pallidotomy

Summary The current interest in stereotactic posteroventral pallidotomy (PVP) for treating Parkinson's disease and the variability of published results have raised questions regarding techniques for target localization. In our technique the probe is guided to the optimum target at the most ventral pallidum and ansa lenticularis by macroelectrode stimulation of the internal capsule and optic tract from within the globus pallidus, with the thresholds providing a relative measure of the electrode proximity to these structures. We have characterized these localizing macroelectrode stimulation parameters in 57 posteroventral pallidotomies with consistent anatomic lesion placement, excellent outcome, and no complications.Using a 1.8 × 2.0 mm radiofrequency electrode for macroelectrode stimulation (RFG-3C, Radionics Inc.), minimum voltages (thresholds) to activate motor (at a frequency of 2 Hz) or visual (at a frequency of 100 Hz) responses as well as impedance measurements were obtained at the final target (Tf) and at distances proximal to Tf along the electrode trajectory. The visual and motor threshold voltages at Tf via our standard approach angles (50 ° above base plane, 20 ° from the sagittal plane), had a range of 1.0 to 1.5 V, and 2.0 to 3.5 V respectively. We also found that as the probe approaches Tf there is a significant decrease in voltage thresholds for motor (P<.0001) and visual (P<.0001) responses in an individual patient indicating that the probe is converging on these structures. Increases in impedance between Tf, 2–3 mm, and 4–5 mm proximal to Tf were also statistically significant (P<.0001). Microelectrode recording of electrophysiological neuronal activity at various points along the trajectory towards the target showed distinct firing patters providing identification of the globus pallidus externus and internus, ansa lenticularis, and optic tract.Macroelectrode electrophysiological stimulation within the target volume, inducing threshold responses in the internal capsule and optic tract, provides for accurate localization of the most effective PVP target in the ansa lenticularis. In unresponsive patients, the utilization of microelectrode recording for the identification of the pallidal borders and the optic tract improves safety.     

Convergence of occipital nerve and superior sagittal sinus input in the cervical spinal cord of the cat

Co-existence of facial and occipital pain may occur in occipital neuralgia, migraine and cluster headache; suggesting convergence of trigeminal and cervical afferents. Such convergence has been shown in humans and other animals, but the site and extent of this are uncertain. In anaesthetized adult cats, the superior sagittal sinus and occipital nerve were stimulated electrically, and extracellular recordings made in the dorsolateral area of the upper cervical cord using glass-coated tungsten electrodes. Of 49 units in 10 cats, 33 (67%) had input from the superior sagittal sinus and the occipital nerve. Thirteen (27%) had superior sagittal sinus input and 3 (6%) had occipital nerve input. Convergent receptive fields were identified mechanically in 7 units. These experiments in cats show convergent input from occipital nerve and superior sagittal sinus on dorsolateral area units in two-thirds of cases studied. This experimental site of trigeminocervical convergence may relate to referral of pain in occipital neuralgia and other headaches.     

Asymptomatic HIV infection does not cause EEG abnormalities: results from the Multicenter AIDS Cohort Study (MACS)

We conducted EEG testing in 200 asymptomatic homosexual men, half of whom were HIV seropositive. We chose to include half of the subjects because they were rated as impaired on a neuropsychological screening test. We used both traditional visual EEG interpretation and quantitative EEG analysis. Abnormal EEGs and borderline degrees of EEG slowing occurred in 32% of these men. These EEG changes were not related to HIV serostatus. EEG changes did correlate with the impaired neuropsychological test performance. Clinicians faced with abnormal EEG results or borderline EEG slowing in an asymptomatic HIV-seropositive patient should not attribute the EEG change to effects of the serostatus itself but should look for other causes.     

Nonsteroidal anti-inflammatory drugs (NSAIDs) and the kidney

In patients with PG-dependent renal function, NSAID administration constantly reduces GFR and RBF in a dose-dependent fashion. In this situation, the risk of overt acute renal failure is high and should be taken into proper account. In contrast, the incidence of NSAID-related renal structural alterations appears to be very low, yet the absolute number of patients may be significant considering the wide use of such drugs. Concerning the antiproteinuric effect of NSAIDs, the unfavourable ratio risk/benefit does not seem to support their indication in proteinuric nephropathies. The development of PGHS-2 selective inhibitors is promising, and may open new therapeutical strategies in the treatment of the progression of renal disease.      

Neurophysiological investigation of effects of the D-1 agonist SKF 38393 on tonic activity of substantia nigra dopamine neurons

The effects of the D-1 agonist SKF 38393 on tonic activity of rat substantia nigra pars compacta dopamine neurons were studied using extracellular, single-unit recording techniques. Unlike nonselective D-1/D-2 dopamine agonists or the D-2 agonist quinpirole, SKF 38393 did not inhibit dopamine neuronal activity when applied iontophoretically or when administered intravenously in doses up to 20 mg/kg to chloral hydrate-anesthetized rats. Moreover, pretreatment with SKF 38393 did not alter the inhibitory response of these neurons to apomorphine or the D-2 agonist quinpirole. However, in locally anesthetized, gallamine-treated, artificially respired rats, dopamine cell activity was significantly altered by i.v. administration of SKF 38393; firing rate increases and decreases were observed. Administration of the inactive enantiomer of SKF 38393, S-SKF 38393, did not induce similar changes in parallel experiments. These results support the idea that unlike D-2 autoreceptor stimulation, D-1 receptor stimulation does not exert a direct local effect on dopamine neurons in the substantia nigra pars compacta and suggest that D-1 receptor stimulation at sites postsynaptic to the dopamine cells may indirectly affect the activity of some dopamine neurons through long-loop feedback mechanisms.