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SUMMARYAn infectious recombinant human adenovirus type 5 (Ad5) vector, AdG12, which carries the glycoprotein gene of vesicular stomatitis virus (VSV) and expresses that gene in cultured HeLa cells was used to examine the host range of insert expression by human Ad vectors. The VSV glycoprotein was expressed in bovine, canine and murine cells when infected with AdG 12 in culture. These cell lines are respectively permissive, non-permissive and semi-permissive for human Ad5 replication. Administration of the AdG 12 vector to calves, piglets or dogs by either the subcutaneous or oral route resulted in the production of high titres of neutralizing antibodies to VSV. Mice injected intraperitoneally with the vector produced neutralizing antibodies and were protected against subsequent intravenous challenge with normally lethal doses of VSV. This work demonstrates the utility of human adenoviral vectors for antigen expression in a number of non-human cell lines and for the induction of an immune response to the delivered antigen in a number of species.

Tissue wet weight as well as total protein content, 5’-nucleotidase activity, alkaline phosphatase activity and Ca²⁺ accumulation associated with a plasma membrane fraction isolated from spontaneous hypertensive rats (SHR) and rats with deoxycorticosterone (DOC) induced hypertension were investigated. Enhanced alkaline phosphatase activity and reduced ATP-dependent Ca²⁺ accumulation preceded the development of hypertension in SHR and these effects were reversed by DOC withdrawal followed by lowering of blood pressure in DOC hypertension. Increased arterial tissue wet weight and 5’-nucleotidase occurred only at the later stage of hypertension in SHR and the increased tissue wet weight was not reversed by DOC withdrawal in DOC hypertension. These observations suggest that enhanced alkaline phosphatase and reduced ATP-dependent Ca²⁺ uptake may play a significant role in initiating hypertension, while increased arterial wet weight and 5’-nucleotidase activities may participate in the maintenance of hypertension.

The role of intrinsic nerves in the control of migrating myoelectric complexes (MMCs) was studied in seven conscious dogs, each implanted with a set of eight bipolar Trimel wire electrodes. Local areas, 3-5 cm long, were perfused close intra-arterially via an exteriorized heparinized Silastic cannula. Experiments consisted of giving bolus injections of atropine (20-50 micrograms), hexamethonium (20 mg), and tetrodotoxin (TTX; 3-30 micrograms) via the catheter at varying periods of time with respect to the arrival of phase III at the perfused site. Atropine and hexamethonium, given close intra-arterially immediately before the arrival of phase II at the perfused site, blocked its further propagation. Tetrodotoxin given locally also blocked the propagation of phage III, as above. After the block, TTX initiated a new phase III activity at, or distal to, the perfused site in 10 out of 14 perfusions. The new phase III activity propagated distally. This study shows that the mechanisms for the initiation and propagation of MMCs are built into the enteric plexus. Once an MMC is initiated, its propagation is achieved by proximal-to-distal excitation through the intrinsic cholinergic network of neurons. This study explains the lack of any significant changes in the propagation parameters of MMCs after vagotomy or celiac and superior mesenteric ganglionectomy.

Morphine was injected intravenously at various phases of the migrating myoelectric complex (MMC) cycle to study the oscillatory characteristics of MMCs by the premature initiation of phase IIIs. All injection timings were represented as a percentage of the normal MMC period at the most proximal duodenal electrode. During the initial 20% of the MMC cycle, the mechanism of initiation of MMCs was in an absolutely refractory state in the sense that a supramaximal dose of morphine (200-300 micrograms/kg) did not initiate a premature phase III. During the remainder of the MMC cycle, the control mechanism was in a relatively refractory state. As this state progressed, premature phase III activity was initiated with diminishing doses of morphine. This was called the relatively refractory state. The initiation of a premature phase III by morphine did not affect the phase III already in progress, except that its propagation velocity was increased. Truncal vagotomy did not affect the refractory characteristics of MMCs or the action of morphine. Only large doses of naloxone (2 mg/kg) blocked the above action of morphine. The study shows that the MMC cyclic phenomenon has the characteristics of relaxation oscillators that may result from enteric neural biological clocks. The period of these oscillators can be altered by stimulants such as morphine.

The projections of nerve fibres with immunoreactivity for the peptides enkephalin (ENK), gastrin-releasing peptide (GRP), neuropeptide Y (NPY), somatostatin (SOM), substance P (SP) and vasoactive intestinal peptide (VIP) were studied in canine small intestine by analysing the consequences of lesions of intrinsic and extrinsic nerves. Of peptides present in fibres supplying myenteric ganglia, GRP, SOM and VIP were in anally directed nerve pathways, whereas ENK and NPY were in orally directed pathways. Pathways ran for up to about 30 mm. SP fibres ran for short distances in both directions in the myenteric plexus. The circular muscle was supplied with ENK, NPY, SP and VIP fibres arising from the myenteric ganglia, whereas most mucosal SP and VIP fibres were deduced to arise from submucous ganglia. There were projections of fibres reactive for ENK, GRP, SOM, SP and VIP from myenteric ganglia to submucous ganglia. Antibodies to tyrosine hydroxylase were used to locate noradrenaline nerve fibres supplying the intestine; these fibres all disappeared when extrinsic nerves running through the mesentery to the small intestine were cut. It is deduced that there is an ordered pattern of projections of peptide-containing fibres in the canine intestine.

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