Mechanism of synaptic inhibition by noradrenaline acting at alpha 2-adrenoceptors.

The actions of agonists at alpha 2-adrenoceptors were investigated on single cells of the submucous plexus of the guinea pig small intestine. Intracellular recordings were made from neurons in vitro, and noradrenaline and other agonists were applied by adding them to the superfusion solution. The actions of noradrenaline released from terminals of sympathetic nerves was also studied by stimulating the nerves and recording the inhibitory postsynaptic current; this current can be mimicked by brief applications of noradrenaline from a pipette tip positioned within 50 micron of the neuron.

Direct observation of cold-shock effects in ram spermatozoa with the use of a programmable cryomicroscope.

Cryoinjury in individual ram spermatozoa was investigated in cells cooled at 10 degrees C/min on a programmable cryomicroscope. In physiological buffer and cryoprotective media, there was a smooth decline in sperm swimming speed with decreasing temperature; cooling in buffer caused a marked decline in the proportion of cells displaying forward progression, especially once the temperature fell below 16 degrees C. Spermatozoa cooled in the presence of rhodamine 123, a mitochondrial-specific dye, showed that abolition of sperm motility by cold shock in buffer was not due to mitochondrial inactivation.

Pregnancy in women with diffuse mesangial proliferative glomerulonephritis.

The clinical course of 168 pregnancies in 91 women with non-IgA diffuse mesangial proliferative glomerulonephritis has been analyzed. Twenty percent (33) of pregnancies resulted in fetal loss, 18% (31) in premature delivery and 62% (105) in a term infant. Maternal renal function declined, reversibly, in 3% (5) of pregnancies and in 48% (80) hypertension developed.

Pregnancy in women with primary focal and segmental hyalinosis and sclerosis.

Thirty-one pregnancies and post partum clinical course of 21 women with a diagnosis of primary focal and segmental hyalinosis and sclerosis have been analyzed. Forty-five percent (14) of pregnancies resulted in fetal loss, 39% (12) in premature delivery and 16% (5) in a term infant. Of 17 fetuses for whom birthweight was recorded, 29% (5) were small for gestational age.

Hormonal and behavioural detection of oestrus in blackbuck, Antilope cervicapra, and successful artificial insemination with fresh and frozen semen.

Hormonal detection of urinary pregnanediol-3 alpha-glucuronide proved an effective method of monitoring the progress of oestrous cycles in the blackbuck; observation of sexual behaviour in a vasectomized male was, however, a more practical procedure. Good correlation was observed between the occurrence of minimal pregnanediol concentrations in females and the maximal behavioural response by the male. On the basis of intervals between periods of behaviourally detected oestrus, a mean cycle length of 16.

The antitumor function of tumor necrosis factor (TNF), I. Therapeutic action of TNF against an established murine sarcoma is indirect, immunologically dependent, and limited by severe toxicity.

The ability of murine recombinant tumor necrosis factor (rTNF) and natural TNF in tumor-necrotizing serum (TNS) to cause regression of the SA1 sarcoma was investigated. We found that to cause regression of a 9-d SA1 sarcoma, near lethal quantities of rTNF and TNS had to be given to the host. However, even at these highly toxic doses, rTNF was not reliable at causing complete tumor regression.

The antitumor function of tumor necrosis factor (TNF) II. Analysis of the role of endogenous TNF in endotoxin-induced hemorrhagic necrosis and regression of an established sarcoma.

In agreement with the results of previous studies (1), it was shown that intravenous injection of endotoxin into mice bearing 9-d SA1 sarcoma resulted in a tumor hemorrhagic reaction that rapidly caused necrosis of most of the center of the tumor, and then the complete regression of the rim of living tumor tissue that survived the hemorrhagic reaction. The tumor hemorrhagic reaction was confined to the vascular bed of the tumor, and its rate and extent of development were measured in terms of the intratumor extravasation of 51Cr-labeled syngeneic red cells. The development of the hemorrhagic reaction was associated with the presence in the tumor over a 6-h period of endogenous TNF that was measured in terms of its capacity to kill L929B cells in vitro and identified by its susceptibility to neutralization with a monospecific, polyvalent anti-rTNF antibody.

The role of membrane-active lipids in the protection of ram spermatozoa during cooling and storage.

The interactions of ram spermatozoa with exogenous liposomes of varying composition were studied, with the aim of examining the mechanisms by which some lipids protect against cold-induced damage during cryostorage. Liposomes containing various preparations of phosphatidylcholine and cholesterol enhanced sperm survival during storage at 5 degrees C, both in terms of motility and acrosomal integrity. A membrane-fluidizing agent, A2C, was slightly deleterious in this respect.

Sublethal, whole-body ionizing irradiation can be tumor promotive or tumor destructive depending on the stage of development of underlying antitumor immunity.

It was shown that sublethal (500 rads), whole-body gamma-irradiation of mice bearing an established i.d. immunogenic tumor can result, after several days delay, in complete tumor regression and long-term survival, but only if radiation is given after the tumor is established and growing progressively.

Drug receptors on single enteric neurons.

There are many substances contained within enteric nerves which excite or inhibit other nerves when these substances are applied to single neurons. The actions of these substances and of drugs which mimic these actions is to open or close membrane ion channels. The effects on membrane potential are dependent on the nature of the ions which pass through the channel and whether the channel is opened or closed.

Effects of three mammalian tachykinins on single enteric neurons.

The effects of substance P (SP), substance K (SK) and neuromedin K (NMK) were compared on single neurons of the guinea pig myenteric plexus. The tachykinins depolarized all myenteric neurons with a rank order of potency SP greater than SK greater than NMK. In approximately 80% of neurons studies the depolarization was associated with an increase in membrane resistance: in 20% membrane resistance decreased.

Cellular mechanisms of opioid tolerance: studies in single brain neurons.

Intracellular recordings of membrane potassium current were made from rat locus coeruleus in vitro. The effects of agonists at mu-opioid receptors were studied on neurons from rats that had been chronically treated with morphine; these were compared with actions on neurons from control rats. Tolerance to the opioid-induced increase in potassium conductance was observed, and this was more pronounced for normorphine than for [Met5]enkephalin and [D-Ala2, Mephe4, Gly5-ol]enkephalin: experiments with the irreversible receptor blocker beta-chlornaltrexamine indicated that normorphine had lower intrinsic efficacy than [Met5]enkephalin and [D-Ala2 MePhe4, Gly5-ol]enkephalin.

Dopamine acts on D2 receptors to increase potassium conductance in neurones of the rat substantia nigra zona compacta.

1. Intracellular recordings were made from neurones in the substantia nigra zona compacta in slices of rat mesencephalon in vitro. The majority of neurones fired action potentials spontaneously at 0.

Potentiation of enkephalin action by peptidase inhibitors in rat locus ceruleus in vitro.

Intracellular recordings were made from locus ceruleus (LC) neurons in slices of rat pons. It has been shown previously that opioids inhibit firing and hyperpolarize LC neurons by activating mu-opioid receptors. Concentration-response curves were constructed by measuring the hyperpolarization, or outward current at -60 mV, caused by various opioid agonists added to the superfusing solution.

A non-adrenergic, non-cholinergic slow inhibitory post-synaptic potential in neurones of the guinea-pig submucous plexus.

1. Intracellular recordings were made from neurones in the submucous plexus of guinea-pig ileum and caecum. The responses to electrical stimulation of fibre strands entering the nodes of the plexus were studied.

Somatostatin increases an inwardly rectifying potassium conductance in guinea-pig submucous plexus neurones.

1. Intracellular recordings were made from neurones in the submucous plexus of the guinea-pig caecum and ileum. 2.

Membranous glomerulonephritis and pregnancy.

The clinical courses of 33 pregnancies in 24 patients with biopsy proven membranous glomerulonephritis have been analyzed. Twenty-four percent (8) of pregnancies resulted in fetal loss, 43% (14) in premature delivery and 33% (11) in a live birth after 36 weeks gestation. Maternal renal function declined during pregnancy in 9% (3) of the pregnancies and in 46% (15) hypertension developed.

Ouabain augments calcium-dependent potassium conductance in visceral primary afferent neurones of the rabbit.

1. The effects of ouabain (1 nM-100 microM) on the membrane properties of rabbit visceral primary afferent neurones (nodose ganglion cells) were studied with intracellular recordings and voltage-clamp techniques in vitro. 2.

Mu and delta receptors belong to a family of receptors that are coupled to potassium channels.

The effects of agonists at mu and delta opioid receptors were compared by measuring membrane currents under voltage clamp from neurons of the rat nucleus locus coeruleus and guinea pig submucous plexus. In each tissue, the appropriate selective agonist (Tyr-D-Ala-Gly-MePhe-Gly-ol for mu receptors in locus coeruleus or Tyr-D-Pen-Gly-Phe-D-Pen for delta receptors in submucous plexus) increased the conductance of an inwardly rectifying potassium conductance and strongly hyperpolarized the membrane. The properties of the potassium conductance affected by the two opioids could not be distinguished.

Single channels activated by acetylcholine in rat superior cervical ganglion.

1. The elementary currents flowing through single channels opened by acetylcholine were recorded in rat superior cervical ganglion neurones using patch-clamp methods. Acetylcholine (30 microM) was included in the patch electrode (cell-attached recordings) or applied by ionophoresis (outside-out configuration).

Persistent calcium-sensitive potassium current and the resting properties of guinea-pig myenteric neurones.

1. Intracellular recordings were made from neurones in the guinea-pig myenteric plexus which show a long-lasting after-hyperpolarization following the action potential (AH neurones). In most experiments membrane currents were measured using a single-electrode voltage clamp.

Vergence adaptive changes with varying magnitudes of prism-induced disparities and fusional amplitudes.

Vergence adaptation response monitored with various prism disparities demonstrated that the rates of adaptation decreased as the prismatic effect was increased. However, the amount adapted increased with the increase in the value of the prism until this value fell outside the fusional amplitude; the amount adapted then decreased. However, a large disparity can be adapted to with ease if the prismatic effect is increased gradually in small steps.