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Biomedical subjects

H D Hall

Publications and source records attributed to H D Hall.

At least 19 recordsLinked to original sources

Effects of nerve growth factor on cyclocytidine-induced growth responses of sympathectomized parotid or parotid of partially desalivated rat.

Cyclocytidine (CC), a potent antitumor agent, caused a 2.4- to 3.9-fold increase in [3H]thymidine uptake of rat parotid gland after 3 days of daily administration of the CC in a dose of 500 mg/kg body weight. Gland weight also was increased. Ablation of the submandibular-sublingual glands prior to initiation of the CC regimen prevented the usual CC-induced increase in [3H]thymidine uptake but this inhibition was partially reversed when nerve growth factor (NGF) was administered with the CC; values for [3H]thymidine uptake into parotid DNA were 81, 54, and 73% of those of glands of intact CC-treated rats. Submandibular gland ablation did not prevent the usual CC-induced increase in parotid size, and administration of NGF had no effect. Sympathectomy of the salivary glands also inhibited the thymidine increase in parotid gland usually induced by CC but in addition it also inhibited the usual CC-induced increase in gland weight. NGF, however, failed to reverse the effects of sympathectomy on [3H]thymidine uptake or gland size: both remained at the same level observed in sympathectomized parotid not given NGF.

Ancitabine

Nerve growth factor effects on inhibition by submandibular gland ablation or autonomic denervation of activity-induced parotid growth.

Present data confirm our earlier report that an increase in [3H]thymidine incorporation into DNA of parotid gland occurs with reintroduction of solid chow to rats previously maintained on liquid diet; if, however, the submandibular-sublingual glands are removed prior to the dietary substitution, the increase is prevented (present data and [19]). In addition, present data show that administration of nerve growth factor (NGF) to partially sialoadenectomized rats during the 2-day period of dietary change from liquid to solid diet restores thymidine values to the high levels observed following the dietary change in intact animals. However, the increase in gland size that accompanied the change in dietary consistency was not prevented by prior submandibular gland ablation, and administration of NGF had no influence on gland size or cell size. The removal of both the sympathetic and parasympathetic nerves to the parotid gland prior to the dietary manipulation also suppressed [3H]thymidine incorporation into parotid, and values did not differ from chow controls. The data show that NGF, a submandibular growth factor, has a prominent role in regulation of the autonomically-mediated hyperplastic response. However, neither the submandibular gland nor NGF has an important role in regulation of the increase in gland size that also accompanies the dietary change.

Aging

Effects of selective denervation and nerve growth factor on activity-mediated growth of rat parotid gland.

A dietary change from all liquid to solid food is followed by an average increase of 200% in [3H]thymidine uptake into the parotid gland of rat. However, removal of either the parasympathetic (Px) or the sympathetic (Sx) innervation to the parotid gland prior to the dietary change resulted in a partial inhibition of the increase; values for the parasympathectomized gland were 51% of those of the innervated gland, and values of the sympathectomized parotid gland were 42% of those of the innervated gland. Removal of both autonomic nerves caused a complete inhibition. Initiation of nerve growth factor (NGF) injection (1 microgram/kg body wt, two times daily for the 2 days of chow refeeding) at the time of chow refeeding had no effect on completely or partially denervated glands, and thymidine values for the denervated parotid gland of rats given NGF did not differ statistically from those of rats not given NGF. With parasympathectomy, sympathectomy, and complete denervation, weight of parotid gland was decreased from that of innervated glands, and administration of NGF had no effect on the denervation-induced decreases. The data show that both branches of the innervation to parotid gland must be intact to ensure a maximal increase in thymidine uptake with the dietary change from liquid to solid food. The level of the enzyme, beta 1-4 galactosyltransferase, involved in proliferation, also depended on the presence of intact nerves. Enzyme activity of innervated parotid gland showed an average increase of 200% with chow refeeding of rats previously on liquid diet, but with Px, the average increase was 51% of that of the innervated parotid, and with Sx, it was 41%. NGF administration did not cause any change in levels of this enzyme in any Px or PxSx parotid gland and only a small change in Sx parotid; it did increase levels of this enzyme in parotid of rats without submandibular-sublingual glands.

Animals

Comparison of cyclocytidine and sympathetic nerve induced changes in norepinephrine and adrenoceptors in salivary glands.

Norepinephrine (NE) concentration of parotid and submandibular glands of young rats was reduced 51% and 39%, respectively at 1 h, and 60% and 47% at 2 h after i.p. administration of a single dose (500 mg/kg body weight) of the anti-tumor agent, cyclocytidine (CC). For adult rats, the reductions were 44% and 46%, respectively, at 1 h and 54% and 49% at 2 h. This decrease from controls was generally similar to the decrease induced following 1 and 2 h of electrical stimulation (square wave pulses of 4 V, 5 ms duration, and frequency of 16 Hz) of the sympathetic innervation to these glands (young rats, 59% and 58% at 1 h; 66% and 63% at 2 h; for adult rats, 51% and 55% at 1 h and 69% and 53% at 2 h for parotid and submandibular, respectively). The changes in density of beta-adrenoceptors induced by direct nerve stimulation also corresponded to the changes induced by CC (CC induced a decrease in parotid of 12%, compared with a decrease of 11% with electrical stimulation; a 15% and 18% reduction in number of beta-adrenoceptors of submandibular gland was found at 1 h after CC and electrical stimulation, respectively). Compelling evidence for the mechanism of CC action was thus established, showing that CC mimics effects of sympathetic nerve stimulation (inducing reduction in NE concentration and transient change in beta-adrenoceptor density) by causing release of NE from sympathetic nerve endings.

Ancitabine

Inhibition of activity-induced parotid growth by submandibular gland ablation or autonomic denervation.

When solid chow was reintroduced for 2 days to rats previously maintained on an all-liquid diet, [3H]thymidine incorporation into rat parotid gland was 2.4-4.4 times that of chow-fed or liquid-fed animals. When the submandibular-sublingual glands were removed before the change in diet from liquid to solid food, values for [3H]thymidine incorporation of parotid gland were not statistically different from those of chow-fed rats: the increase was completely prevented. The increase in gland size that accompanied the change in dietary consistency was not prevented by prior submandibular gland ablation; [3H]uridine incorporation was also not different from that of chow controls. The removal of both the sympathetic and parasympathetic nerves to the parotid gland before the dietary manipulation also suppressed [3H]thymidine incorporation into parotid, and values did not differ from chow controls. Moreover, the return to normal gland size (chow level) also was prevented by autonomic denervation. The data show an important role of the submandibular gland in regulation of the thymidine increase associated with the enhanced parotid activity that accompanies the change from liquid to solid diet. However, the submandibular gland does not have an important role in regulation of the increase in gland size that also accompanies the dietary change, whereas the autonomic nerves have an important role in regulation of hypertrophy and hyperplasia of parotid gland.

Animal Feed

Effects of varying frequency of sympathetic stimulation on chloride and amylase levels of saliva elicited from rat parotid gland with electrical stimulation of both autonomic nerves.

Simultaneous stimulation of the parasympathetic and sympathetic nerves to the parotid gland of rats elicited saliva at a rate dependent on the frequency of sympathetic stimulation when parasympathetic frequency was maintained at 16 Hz. The flow rate was lowest at 2 Hz (sympathetic), moderate at 5 Hz, and highest at 16 Hz. Cl concentration of the saliva evoked with stimulation of both nerves was highest at the highest frequency and flow rate (maintained at the level of 102 mEq/liter, for 35 min) and lowest at 2 Hz (declining from 40 mEq/liter initially to 28 mEq/liter). With sympathetic nerve stimulation alone, Cl concentration ranged from 27 to 58 mEq/liter when frequency was varied from 2 to 16 Hz, and with parasympathetic stimulation alone (16 Hz), it ranged from 132 to 124 mEq/liter. Amylase concentration of sympathetically elicited saliva was, in contrast, highest at 2 Hz (1.5 times the level at 5 Hz, and twice the level at 16 Hz), and nearly 18-38 times that seen with parasympathetic stimulation alone. The same pattern was found when both nerves were stimulated, and at 2 Hz (sympathetic), amylase concentration was 1.6 times the level at 5 Hz and 2.6 times the level at 16 Hz. When the two nerves were simultaneously stimulated, the total amount of amylase secreted over 35 min was twice as high as that observed with sympathetic nerve stimulation alone, at any frequency. The relation of frequency to norepinephrine concentration was examined. There was no consistent difference in norepinephrine concentration related to variation in frequency of sympathetic stimulation. Only when both nerves were stimulated at 16 Hz was there a statistically significant reduction in norepinephrine concentration of 46%. A relation between frequency of sympathetic stimulation, flow rate, amylase concentration, and Cl concentration was established, but these changes could not be directly correlated with quantitative differences in norepinephrine concentration.

Amylases

Modification of cyclocytidine-induced changes in [3H]thymidine incorporation and weight of parotid gland by partial sialoadenectomy.

Cyclocytidine (CC), a potent antitumor agent, caused a 2.3- to 5.0-fold increase in [3H]thymidine uptake of rat parotid gland after 3 days of daily administration of 500 mg/kg body wt. Gland weight also showed a 47-67% increase from that of controls. Ablation of the submandibular-sublingual glands prior to initiation of the CC regimen prevented the usual CC-induced increase in [3H]thymidine uptake, but did not inhibit the increase in gland size. It is postulated that CC-induced parotid hyperplasia requires an initial release of growth factors from the submandibular gland; however, enlargement of the parotid gland by CC is independent of such factors.

Ancitabine

Chloride concentration of rat parotid saliva evoked by electrical stimulation of parasympathetic or sympathetic nerves with or without antagonists.

Chloride (Cl) of saliva evoked by electrical stimulation of the parasympathetic nerve to parotid gland was from two to seven times higher than that elicited with sympathetic nerve stimulation; [Cl] remained elevated (125-135 mEq/liter) for 60 min of parasympathetic nerve stimulation, whereas Cl of sympathetically evoked saliva decreased from high levels of 58 to 15 to 20 mEq/liter. The administration of propranolol, the beta-adrenergic antagonist, 20 min prior to initiation of sympathetic nerve stimulation resulted in saliva with Cl of 100 mEq/liter; when phentolamine, the alpha-adrenergic antagonist was administered prior to sympathetic nerve stimulation, [Cl] was 48-35 mEq/liter. Values with the beta-agonist, isoproterenol, were about 35 mEq/liter, whereas phenylephrine, an alpha-adrenergic agonist, evoked saliva with Cl ranging from 113 to 85 mEq/liter. Flow rate was very high with parasympathetic nerve stimulation and low with sympathetic nerve stimulation, but [Cl] with beta-blockade was not flow dependent: flow was very low but Cl high. Cl secretion is principally regulated by activation of cholinergic and alpha-adrenergic receptors.

Adrenergic alpha-Antagonists

Audiometric assessment of patients with painful TMJ internal derangements: failure of audiometry to change following arthrotomy.

Thirteen patients with proven internal derangements of 16 temporomandibular joints were scheduled for arthrotomy. The patients' perception of otologic symptoms were recorded before surgery, and hearing was evaluated audiometrically both before and after surgery. There was no significant correlation between otologic symptoms and ipsilateral painful internal derangement of the temporomandibular joint. Perceived hearing loss was substantiated in only about half of the instances. Further, only about half of the ears with measured hearing loss (sensorineural) were associated with a painful internal derangement. Arthrotomy did not change any of the audiograms.

Adolescent

Autonomic receptors and cyclic nucleotides of rat parotid gland following simultaneous electrical stimulation of its parasympathetic and sympathetic nerves.

[3H]dihydroalprenolol and [3H]quinuclidinylbenzilate binding of membranes of rat parotid gland were generally unchanged after 10, 15, 30, or 60 min of simultaneous electrical stimulation of the parasympathetic and sympathetic nerves to the gland, although stimulation of either nerve separately caused nerve-specific changes in both. Concentrations of cyclic nucleotides of the gland were, however, increased significantly from levels of the unstimulated parotid gland. Cyclic GMP showed a 10-fold increase after 10 min of stimulation, whereas only a 2-fold increase in cyclic AMP was found at this time. The increases were maintained, albeit at reduced levels, at 15 and 30 min also but by 60 min both were not different from levels of the unstimulated gland. The increases induced by separate stimulation of each nerve were greater but nerve specific, and the changes induced with simultaneous stimulation tended to reflect a reigning influence of one nerve on the other.

Animals

Effects of electrical stimulation of the parasympathetic nerve on the levels of cholinergic muscarinic and beta-adrenergic receptors and cyclic nucleotides in rat salivary glands.

Density of muscarinic receptors of rat parotid gland, although unchanged after 5 or 10 min of stimulation of the parasympathetic nerve to the gland, showed a decrease of 23% following a 15-min period of stimulation. After 30 min the decrease was 19% but by 60 min density of receptors returned to within 5% of receptor density of the unstimulated gland; there was virtually no change in density of beta adrenoceptors at any time during the 60 min of stimulation. Markedly elevated (30-fold increase) levels of cyclic GMP appeared within 5 min after initiation of nerve stimulation and remained at this level at 10 min, but dropped from 90 to 46 pmol/mg total protein by 15 min, the time at which a decrease in muscarinic receptors first was evident. GMP levels continued to decrease but were still four times basal levels after 60 min of stimulation and did not return to normal concentration until 120 min. Cyclic AMP was generally unchanged. These changes in muscarinic receptors and cyclic GMP are apparently closely related to the kind of neural stimulation, unlike the condition when stimulation of the sympathetic nerve was employed.

Animals

Comparison of effects of surgical and chemical sympathectomy on beta adrenergic and muscarinic receptors of parotid gland of young and adult rats.

Surgical (removal of a superior cervical ganglion) or chemical [(administration of a single dose of 6 hydroxydopamine (6 OHDA) (50 mg/kg dose body wt)] sympathectomy of rats at 2 or 8 days of age resulted in an increase in [3H]DHA binding of membranes of parotid gland of young rats (age range 21 days to 48 days). The increase progressed with postnatal age; at 21 days of age (surgical sympathectomy), it was 13%; at 32 days of age with 6 OHDA, it was as much as 34%, but only 26% at 42 days of age with surgical sympathectomy. No change in [3H]QNB binding was observed at any postnatal ages following neonatal sympathectomy. Conversely, surgical sympathectomy of the parotid of adult rat resulted in little or no change in [3H]DHA binding at 1, 2, 3, or 4 weeks postdenervation, but [3H]QNB binding was reduced at all periods, with the reduction from control values at 2 weeks being 34%, and at the subsequent intervals, 24-26%. The increase in number of beta adrenoceptors of the parotid gland was not related to the kind of sympathectomy (chemical or surgical) or neonatal age at which it was done; however, duration of the denervation for 2-3 weeks was necessary for the receptor increase to occur. In the adult, however, the duration of the denervation was of no importance since change in number of beta adrenoceptors did not occur at 1, 2, 3, or 4 weeks after surgical denervation but did occur after only 1 week after of reserpine-induced denervation. QNB binding was decreased with surgical sympathectomy as well as reserpine-induced sympathectomy of adult parotid gland; norepinephrine concentration was decreased to levels of a few percent of innervated glands. The relation between development of glandular supersensitivity and increase in beta adrenoceptors is discussed.

Aging

Acute lung inflammation in rats induced by phorbol myristate acetate (PMA).

Intratracheal administration of PMA produces acute lung injury in part due to the generation of O2-derived free radicals. This study evaluated the role of the antioxidant enzyme superoxide dismutase (SOD) in PMA-induced lung injury in the rat. PMA was instilled into rats intratracheally (20-60 micrograms/kg), and the lungs were lavaged 4 hr later. Total number of cells recovered from lavage after PMA treatment was not different from the total number recovered from controls; lavagable PMNs increased in a dose-dependent manner. Albumin in lavage fluid (an index of lung vascular permeability) was significantly increased at 60 micrograms/kg PMA. SOD (10,000 U) + PMA (60 micrograms/kg) reduced the albumin level but significantly increased both total number of cells and number of PMNs recovered from lavage fluid. To investigate the possibility that SOD decreases the ability of PMNs to adhere, PMN aggregation was measured in vitro. The results indicated that 10,000 U SOD can inhibit PMA-induced aggregation by 50%. In contrast, aggregation to other stimuli (e.g., fMet-Leu-Phe, A23187) was unaffected by SOD. We conclude SOD prevents PMA-induced lung permeability and diminishes PMN adherence.

Animals

Muscarinic receptors of rat parotid gland enlarged by gland ablation and bulk diet. Effects of denervation.

The density of muscarinic binding sites was increased 10% in the rat parotid gland enlarged (2 times control) as a result of ablation of the submandibular-sublingual glands and maintenance of rats on bulk diet (50% inert cellulose plus 50% solid chow) for 4 weeks. When either the parasympathetic or sympathetic innervation to the gland was unilaterally removed at the time of submandibular-sublingual ablation and introduction of the bulk diet, the density of muscarinic receptors showed an even greater increase from levels of innervated glands of chow-fed controls (29%); with removal of both nerves, the increase was 39%. A 36% increase in cyclic guanosine monophosphate levels accompanied the increase in receptors of the enlarged gland, but when the parotid was denervated, there was no change in cyclic GMP. Absence of either or both nerves led to a maximal decrease of 24-29% in density of muscarinic receptors of parotid gland of chow-fed controls, but to no change in cyclic GMP levels. While autonomic influences mediate the changes in density of muscarinic receptors of parotid gland of chow-fed rats, some additional factor is apparently involved in their increase in the enlarged gland.

Animals

Further refinement and evaluation of intraoral vertical ramus osteotomy.

Eighty-nine patients were treated with a modified procedure for intraoral vertical ramus osteotomy. Complications were virtually eliminated except for damage to the inferior alveolar nerve. Acute nerve damage occurred in about 36% of operated sides. Seventy-four percent of these damaged nerves recovered fully by one year. Only 8% of operated sides had persistent diminished sensation, usually mild, of the lower lip and chin. It is concluded that this technique should be seriously considered for mandibular ramus osteotomies when the mandible is going to be retruded or minimally moved in any other direction.

Cephalometry