Sex differences in blood protein patterns: a computer-assisted electrophoretic analysis of mid-molecular weight range proteins of human serum.

We have studied the sexual dimorphism of human serum proteins between the ranges of approximately 60,000 and 150,000 daltons using computerized imaging and densitometry. Methodology is presented, based on the TEXAC computer system for the detection, segmentation and integration of protein bands. The results are discussed in terms of potential future applications in computerized medical diagnosis.

Circulatory effects on osmotic water exchange in Rana pipiens.

Tritiated water (3H2O) exchange was shown to be more sensitive to circulatory changes than to arginine vasopressin (ADH)-induced permeability changes. Reducing the circulation (sciatic artery ligation) and increasing the circulation (severing the sciatic nerve) caused the 3H2O exchange in frog legs to decrease from 6.0 +/- 1.3 (5) to 3.5 +/- 0.5 and increase from 6.0 +/- 0.7 (10) to 8.6 +/- 0.6 ml.h-1, respectively. In contrast injection of ADH caused a negligible increase in 3H2O exchange from whole frogs, while at the same time causing a significant increase in osmotic water exchange from 0.22 +/- 0.08 (6) to 0.63 +/- 0.13 (6) g.100 cm-2.h-1.200 mosM-1. Circulatory changes in whole frogs were produced by inducing a diving bradycardia that was less pronounced in a bath aerated with oxygen than with air. The bradycardia caused a reduction in skin circulation, as measured by 3H2O exchange, from 0.210 +/- 0.007 (16) to 0.17 +/- 0.006 (16) ml.h-1.cm-2 in air mixed media and from 0.149 +/- 0.009 (16) to 0.135 +/- 0.011 (16) in oxygen mixed media. Diving bradycardia was also found to affect osmotic water uptake which decreased from 0.61 +/- 0.05 (16) to 0.39 +/- 0.03 (16) g.100 cm-2.h-1.200 mosM-1 in air mixed media and from 0.61 +/- 0.05 (16) to 0.51 +/- 0.04 (16) in oxygen mixed media. The results indicate that circulation affects osmotic water exchange.

Effects of carbamazepine on muscle tone in the decerebrate cat.

Previous studies, which have demonstrated that carbamazepine (CBZ) possesses direct muscle spindle suppressant activity, suggest that CBZ may have therapeutic value in the treatment of hypertonic disorders characterized by high fusimotor drive. The effects of CBZ on motor tone in the midcollicular decerebrate cat were therefore examined. CBZ, in a concentration-dependent manner, reduced muscle tone, as measured by the force necessary to overcome hyperextension. Significant depression was first observed at a serum concentration of about 25 micrograms/ml, whereas 50% depression occurred at about 40 micrograms/ml. These effects could not be attributed to the hypotensive effect of the drug. CBZ produced little or no effect on spontaneous gamma motoneuron activity recorded in teased ventral roots of segmentally deafferented spinal cords of decerebrate animals; chlorpromazine, however, was effective in suppressing such activity. In the same preparations, CBZ reduced polysynaptic but had little effect on monosynaptic spinal reflexes evoked by dorsal root stimulation. The drug also shortened the duration of the pause in spontaneous gamma motoneuron activity after dorsal root stimulation. Serum concentrations which diminished extensor rigidity in decerebrate cats induced mild to moderate intoxication in intact unanesthetized cats. This was characterized by ataxic gait, sedation and hypotonia. These experiments indicate that CBZ may be of value alone or adjunctively in the reduction of some forms of muscle hypertonicity.

Description and analysis of the myotonolytic effects of phenytoin in the decerebrate cat: implications for potential utility of phenytoin in spastic disorders.

Phenytoin (DPH) was evaluated for its capacity to reduce several motor manifestations of decerebrate rigidity in the cat. In doses of the order of 40 to 50 mg/kg i.v., DPH diminished the force necessary to collapse the hyperextended limbs; at about half this dose range, the drug reduced gamma-motoneuron discharges; at still lower doses the drug profoundly depressed mechanical and electromyographic responses evoked by stretch from both forelimb and hindlimb extensor muscles. Serum levels of DPH associated with substantial reduction in electrical and mechanical manifestations of the extensor hypertonus were of the same order conventionally encountered when the drug is administered to humans for acute seizure management. The data are supportive of a centrally and peripherally mediated muscle relaxing effect of the drug in states where muscle spindle involvement is a contributing factor, and may help to explain further the utility of DPH in the treatment of spasticity.

The effects of phenytoin and lidocaine on a proprioceptor of the cockroach, Blaberus discoidalis: a simple method for discriminating between inhibitors of sensory transduction and axonal conduction.

Three linearly aligned tibial tactile spines of the cockroach Blaberus discoidalis were stimulated by a mechanically driven glass probe. A "window" was cut at the base of the central spine and various concentrations of phenytoin, lidocaine and colchicine were applied. Colchicine, phenytoin and a low concentration of lidocaine selectively inhibited stimulus-evoked discharges from the central spine, while lidocaine in higher concentrations inhibited discharges from the central and distal spines. We conclude that phenytoin and colchicine suppress afferent discharges by their ability to interfere with sensory transduction, while lidocaine suppresses afferent responses by interfering with axonal conduction as well as sensory transduction.

Albumin obscures sex differences in blood protein patterns of rats and humans.

Sex related differences in the blood protein patterns of male and female rats and humans have been studied by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. In rats, a prominent band of mol.wt. 74000--78000 is seen in females in far greater quantity than in males, castrated males or ovariectomized females. A secondary band of 100000 is seen under non-reducing conditions in female rats that is absent in males. In humans, bands of 92000 and 88000 mol.wt. appear to be variable in concentration in men although relatively constant in women. The above differences are observable only if serum albumin is removed from the samples before electrophoresis. The results suggest that each sex has its own characteristic blood protein pattern.