Mouse homologues of the human AZF candidate gene RBM are expressed in spermatogonia and spermatids, and map to a Y chromosome deletion interval associated with a high incidence of sperm abnormalities

An RNA-binding motif (RBM) gene family has been identified on the human Y chromosome that maps to the same deletion interval as the 'azoospermia factor' (AZF). We have identified the homologous gene family (Rbm) on the mouse Y with a view to investigating the proposal that this gene family plays a role in spermatogenesis. At least 25 and probably >50 copies of Rbm are present on the mouse Y chromosome short arm located between Sry and the centromere. As in the human, a role in spermatogenesis is indicated by a germ cell-specific pattern of expression in the testis, but there are distinct differences in the pattern of expression between the two species. Mice carrying the deletion Yd1, that maps to the proximal Y short arm, are female due to a position effect resulting in non-expression of Sry ; sex-reversing such mice with an Sry transgene produces males with a high incidence of abnormal sperm, making this the third deletion interval on the mouse Y that affects some aspect of spermatogenesis. Most of the copies of Rbm map to this deletion interval, and the Yd1males have markedly reduced Rbm expression, suggesting that RBM deficiency may be responsible for, or contribute to, the abnormal sperm development. In man, deletion of the functional copies of RBM is associated with meiotic arrest rather than sperm anomalies; however, the different effects of deletion are consistent with the differences in expression between the two species.      

Anticipatory control of hand and eye movements in humans during oculo-manual tracking

Anticipatory activity of hand and eye has been examined during oculo-manual tracking of a constant velocity visual target with a hand cursor. Both target and cursor were presented briefly (< 480 ms), but repeatedly, at regular inter-stimulus intervals (ISI). In Expt 1, the build-up of hand and eye responses was examined for target velocities varying from 10–40 deg s⁻¹ with an ISI of 2.4 s. The velocity 100 ms after target onset (i.e. prior to visual feedback) for both hand and eye ( V ₁₀₀) progressively increased over the first four presentations but then attained a steady state (SS). SS V ₁₀₀ values for eye and hand increased in proportion to target velocity and were thus predictive of forthcoming movement. Hand velocity exceeded eye velocity but both exhibited similar anticipatory trajectories. In Expt 2, target velocity was constant (40 deg s⁻¹) but ISI varied from 0.48–3.74 s. Subjects made anticipatory eye movements for all ISIs but hand movements were often reactive at the longest ISI. If the target failed to appear as expected, subjects initiated predictive hand and eye responses with timing appropriate for the prevailing ISI. In Expt 3, predictive responses were compared with responses to randomised presentation. Peak hand velocity was greater in the randomised mode than in the predictive condition, whereas the converse was true for peak eye velocity. This difference is discussed in terms of the mechanisms of positional error correction in hand and eye. Results provide evidence of similar anticipatory mechanisms in hand and eye, using storage of velocity and timing to achieve rapid prediction of target motion.     

Heart rate reactivity and heart period variability throughout the first year after heart transplantation

Heart rate reactivity to mental stress is substantially blunted early after heart transplantation, suggesting that the loss of neural modulation limits the cardiovascular response to mental stress. We tested whether reactivity to mental stress recovers during the first year after heart transplantation. Hemodynamic and respiratory responses to mental arithmetic challenge were studied in 20 heart transplant recipients 3, 6, and 12 months after surgery. A normal comparison group was studied at equivalent intervals. Heart rate reactivity to mental arithmetic was significantly reduced in the cardiac transplant group compared to the normal subjects. This effect persisted up to 1 year after transplantation. Heart period variability in the heart transplant recipients was minimal in all three-test sessions. The findings suggest that no functional reinnervation or other compensatory adaptation occurs up to 1 year after heart transplantation.     

Studies of Antibody to Herpes Simplex Virus Fcγ-Binding Protein gE in Patients with Rheumatoid Arthritis, Juvenile Rheumatoid Arthritis and Normal Controls

IgG antibody to gE, the Fc gamma-binding herpes simplex 1 (HSV-1) viral glycoprotein, was studied in 49 rheumatoid arthritis (RA) patients and 43 normal controls. Antibody to gD, another important HSV-1 antigen, was assayed in parallel. No difference between RA patients and normal controls was found in levels of anti-gE antibody measured by reactivity of IgG F(ab')2 fragments reacting with gE coated to ELISA plates. No difference in anti-gD antibody was recorded between normals and patients with RA. Levels of IgG anti-IgE antibody did not correlate with quantitative elevations of serum rheumatoid factor (RF) in RA patients. When IgG anti-gE and anti-gD were assayed in 20 patients with juvenile rheumatoid arthritis and 22 children controls, no significant differences were noted. However, when individual RFs from patients with RA were tested for reactivity against a panel of affinity-isolated F(ab')2 antibodies to gE, some evidence for individual autospecificity was obtained. Four of 20 monoclonal IgM RFs produced from RA patients' B cells showed marked elevations of reactivity with some RA patients' F(ab')2 antibodies to gE. All four of the monoclonal RFs showing this specificity were derived from RA synovial tissue B cells. These findings may provide support for the concept that some RFs in patients with RA show individual specificity for internal image determinants of IgG antibodies to viral Fc gamma-binding proteins.     

Olfactory threshold in Parkinson''s disease.

Olfactory threshold to differing concentrations of amyl acetate was determined in 78 subjects with idiopathic Parkinson's disease and 40 age-matched controls. Impaired olfactory threshold (previously reported by others) was confirmed in Parkinsonian subjects compared with controls. There was no significant correlation between olfactory threshold and age, sex, duration of disease, or current therapy with levodopa or anticholinergic drugs. In a sub-group of 14 levodopa-treated patients with severe "on-off" fluctuations, no change in olfactory threshold between the two states was demonstrable. Olfactory impairment in Parkinson's disease may involve mechanisms that are not influenced by pharmacologic manipulation of dopaminergic or cholinergic status.     

EFFECT OF NITROGLYCERNE-INDUCED HYPOTENSION ON CANINE SPINAL CORD BLOOD FLOW

Twenty-four mongrel dogs were anaesthetized with pentobarbitoneand morphine sulphate. Neuromuscular blockade was achieved usingpancuronium. Spinal cord blood flow was measured using the radionuclidemicrosphere and hydrogen washout methods before, during, andfollowing nitroglycerine-induced hypotension. Heart rate, meanarterial pressure, cardiac output, pulmonary capillary wedgepressure, and acid-base balance were determined with each measurement.Mean arterial pressure was reduced by 50%. Spinal cord bloodflow, as measured by the microsphere method, increased duringthe period of hypotension, whereas values obtained using thehydrogen washout method were not significantly different fromthose at normotension. No significant change in spinal cordblood flow was detected by either method after the applicationof spinal distraction. Nitroglycerine acts predominantly onvenous capacitance vessels and it is postulated that perfusionpressure, and therefore flow, is maintained despite a reductionin arterial pressure. Presented in part at the Anual Meeting of the American Societyof Anesthesiologists, October 1985, San Francisco, California. ^*Shackleton Department of Anaesthetics, Southampton GeneralHospital, Shirley, Southampton, Hants SO9 4XY. Section of Orthopedic Surgery, Madison, Wisconsin.     

The Effects of Magnetic Resonance Imaging on Implantable Pulse Generators

The effects of magnetic resonance imaging were assessed on four dual chamber and two single chamber pulse generators. The tests were performed with a resistive, water-cooled magnet operating at 0.15 T. The 6.4-MHz radiofrequency (RF) field was operated at a maximum power of 1,000 watts with a period adjusted from 130 to 500 ms. Reed switch closure occurred in all six pulse generators tested when placed near the entrance of the magnetic resonance imaging scanner, and the generators reverted to asynchronous operation unless programmed to the "magnet off" mode. None of the pulse generators exhibited any alterations in programmed parameters or in the ability to be reprogrammed after RF pulsing. When the RF field was turned on, there was no change in the asynchronous paced cycle length in four pulse generators; however, during RF scanning there was rapid cardiac stimulation at the RF pulse period in one single chamber and one dual chamber pulse generator.     

Nasogastric and intravenous infusions of (+)-4-propyl-9-hydroxynaphthoxazine (PHNO) in Parkinson's disease.

(+)-4-propyl-9-hydroxynaphthoxazine (PHNO) is a new dopamine agonist which is capable of producing a sustained response in parkinsonian patients with "on-off" fluctuations when given as a continuous infusion either nasogastrically or intravenously. These data suggest that a sustained release formulation of PHNO may provide a significant, new treatment for patients with "on-off" fluctuations.