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Neuro-urological studies were performed on 9 patients with a spinal arteriovenous malformation (S-AVM). The micturitional history revealed that all 9 patients had voiding symptoms, obstructive in 9 and irritative in 3 patients. All patients still had obstructive symptoms after treatment of S-AVM. Six of the 9 patients had a large volume of residual urine before treatment; 5 showed urinary retention. Four of the 5 patients (80%) for whom urodynamic studies were performed before treatment had micturitional dysfunction; 2 patients had detrusor hyperreflexia, 1 with detrusor external urethral sphincter dyssynergia (DSD) and 1 with a normal sphincter, 1 patient had an autonomous bladder with DSD and 1 patient had an atonic bladder with DSD. Only 1 patient had a normal bladder and sphincter. Findings of the urodynamic studies after treatment in 9 patients showed detrusor hyperreflexia in 3 patients (2 with DSD and 1 with normal sphincter), autonomous bladder in 1 patient with DSD, atonic bladder in 4 patients (2 with DSD, 1 with incompetent sphincter and 1 with normal sphincter) and normal bladder with normal sphincter in 1 patient. Lower urinary function after treatment of S-AVM was improved in 2 patients, unchanged in 4 patients and worsened in 3 patients.The above results showed 80% of S-AVM had a severe neuropathic bladder manifested mainly by disturbance of micturition. Treatment of S-AVM does not necessarily improve the lower urinary tract function.

The effect of pituitary factor on the constitutive and inducible levels of hepatic phenobarbital (PB)-inducible major cytochrome P-450, P-450b and P-450e, in male and female rat livers was studied by immunoblot analyses. Although only trace amounts (approximately 4 pmol/mg protein) of P-450b and P-450e were detected in untreated adult rats, hypophysectomy increased the contents of P-450b and P-450e 58- and 14-fold, respectively, in male rats and 118- and 30-fold, respectively, in female rats. The increases were also observed in treatment with dexamethasone, which suppressed the pituitary function. Treatment with PB increased more effectively the hepatic contents of P-450b and P-450e, but their contents were still 4-fold higher in the male than the female. Treatment of hypophysectomized female rats with PB increased the contents of P-450b and P-450e 4-fold higher than the contents in PB-treated nonhypophysectomized female rats. Consequently, the sex-related difference in their contents was reduced less than 1.4-fold in the hypophysectomized rats treated with PB. Similar results were also obtained from the quantitation of microsomal O-pentylresorufin O-depentylation and testosterone 16 beta-hydroxylation. Either intermittent injection or continuous infusion of human growth hormone, but not of ovine prolactin, into hypophysectomized male and female rats decreased the contents of both cytochromes. These results indicate that growth hormone acts as a repressive factor for the constitutive and inducible levels of P-450b and P-450e in a manner different from the regulation of P-450-male and P-450-female.

Background: Asthma has been recognized as a chronic inflammatory disorder of the airway. We have investigated the relationships among the activation markers on lymphocytes, eosinophils, their serum products in the peripheral blood, and the variability of airway obstruction in childhood asthma. Methods: Twenty-two patients with atopic asthma (mean age, 12 years) were treated regularly and asked to measure their peak expiratory flow (PEF) twice daily for 7 days. Peripheral venous blood was obtained on day 8. Results: The absolute counts of CD4 T lymphocytes expressing the activation marker CD25 in the peripheral blood on day 8 correlated significantly with the values of the coefficient of variation (CV) of both morning PEF (p<0.01) and night PEF (p<0.05) obtained over 7 days, but those of CD8+/CD25+ T lymphocytes, those of CD23+ B lymphocytes, and the serum concentrations of soluble CD25 did not. The absolute counts of peripheral blood eosinophils also demonstrated a significant correlation with the CV values of both morning PEF (p<0.01) and night PEF (p<0.05). Conclusion: CD4 T-lymphocyte activation and increased counts of eosinophils in peripheral blood correlate with CV of PEF in patients with asthma, suggesting that CV of PEF is a good marker for assessing not only the variability of airway obstruction but also the degree of airway inflammation

Suppression of two major phenobarbital-inducible cytochrome P-450s, P450IIB1 and P450IIB2, by thyroid hormone was studied and compared with growth hormone (GH)-induced suppression in rats in vivo and hepatocytes in primary culture in vitro. Treatment of adult male rats with 50 micrograms/kg triiodothyronine (T3) reduced the constitutively expressed amounts of P450IIB1 (up to 1 pmol/mg of protein) and P450IIB2 (2-5 pmol/mg of protein) to 42% and 3% of their levels in nontreated controls. Thyroidectomy increased the hepatic contents of P450IIB2 (to levels of 50-80 pmol/mg of protein) and, to a lesser extent, P450IIB1 (1-5 pmol/mg of protein) in male and female rats. Supplement of T3 to thyroidectomized rats reversed the increased contents to levels similar to those observed in normal rats. Hypophysectomy also increased both P450IIB1 and P450IIB2 protein, and their levels in both sexes were similar to that of P450IIB2 in thyroidectomized rats. Treatment of hypophysectomized rats with T3 as well as human GH suppressed hepatic contents of P450IIB1 and P450IIB2. In a hepatocyte culture including 2 mM phenobarbital, T3 and GH suppressed both P450IIB1 and P450IIB2. Other thyroid hormone derivatives, including thyroxine, D-T3, and reversed T3, also showed suppressive effects, in parallel with the potencies for their stimulatory action that have been reported. These results indicate that thyroid hormone may suppress both P450IIB1 and P450IIB2 by a direct effect on the liver, but not by an indirect effect through the modulation of pituitary GH synthesis. The high susceptibility of hepatic P450IIB2 to thyroid hormone-induced suppression also indicates that constitutive and phenobarbital-induced levels of P450IIB2 are suppressively regulated preferentially by thyroid hormone, in contrast to the high susceptibility to GH of P450IIB1 in rat liver. In addition, a difference in the suppressive mechanisms of thyroid hormone and GH was suggested by the difference in susceptibility to cycloheximide.

The mechanism of the suppression of an ethanol-inducible cytochrome P-450 (P-450DM/j) by pituitary hormone has been studied in rats. The hepatic content of P-450DM/j protein quantitated by Western blots was low but was 2-fold higher in male than female untreated rats (75 and 34 pmol/mg of protein, respectively). The content was increased 2.6-fold (male) and 5.6-fold (female) by hypophysectomy and the sex-related difference was abolished. Treatment of hypophysectomized rats with human growth hormone (hGH), but not with prolactin, reversed the increased amounts of P-450DM/j protein. The hGH-induced suppression was more effective with the continuous infusion than intermittent injection. The hepatic level of P-450DM/j mRNA, determined by the use of a 23-mer oligonucleotide probe, was also changed by hypophysectomy and/or hGH-treatment, largely in parallel with the changes in the content of P-450DM/j protein and microsomal p-nitrophenol and aniline hydroxylations. These results suggest that growth hormone exerts the suppressive effect on P-450DM/j through a somatogenic receptor-mediated process. In another growth hormone-depleted condition, diabetes, the hepatic level of P-450DM/j mRNA was also increased to a level similar to that in hypophysectomized rats, but the protein content was 2- to 3-fold higher in diabetic than hypophysectomized rats. These results indicate, in addition to the reduction of serum growth hormone level, the presence of another stimulatory factor, which acts translationally or posttranslationally in livers of diabetic rats. On the other hand, coordinate changes in the level of P-450DM/j protein and the mRNA in hypophysectomized rats indicate that growth hormone acts rather directly and suppresses the level of P-450DM/j mainly at a pretranslational step in rat livers.

The regulatory mechanism of hepatic sulfation of N-hydroxyarylamine and N-hydroxyarylamide by endocrine factors has been studied in rats. The cytosolic sulfations of N-hydroxy-2-acetylaminofluorene (N-hydroxy-AAF) and 2-hydroxyamino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (N-hydroxy-Glu-P-1), which were determined by the reductive formations of 2-acetylaminofluorene and Glu-P-1, were seven to nine times and three times higher, respectively, in male than female rats. Hypophysectomy of male rats decreased their activities to 23% and 41% of the levels of the untreated animals, respectively. Intermittent treatment of hypophysectomized male and female rats with human growth hormone (hGH) significantly increased their sulfating activities of both compounds. Infusion of hGH also enhanced the sulfating activity of N-hydroxy-AAF but not of N-hydroxy-Glu-P-1. The sulfating activity of N-hydroxy-AAF was also decreased by castration at neonate and was increased by the administration of testosterone propionate to gonadectomized male and female rats. Testosterone propionate and estradiol benzoate had no effect on hypophysectomized rats, but estradiol benzoate repressed the sulfating activities of N-hydroxy-AAF and N-hydroxy-Glu-P-1 in hGH-treated hypophysectomized male rats. These results indicate that sex steroids elicit their effects on the sulfations of N-hydroxyl-aryl compounds through modulating the action of growth hormone at hypothalamus-pituitary and hepatic levels in rat livers.

The possible interaction among different sensory units in the frog tongue was studied using several single papillae dually innervated by the medial and lateral branches of the glossopharyngeal (IXth) nerve. The afferent activity in one branch exposed to NaCl stimulation of the papilla revealed marked inhibition after antidromic electrical stimulation (100 Hz, 30 s, and 3 V) of the other branch. The degree of inhibition depended on the number of sensory responses observed in the electrically stimulated branch as well as the nature of the stimulated sensory units. Statistical analysis suggested that antidromic activation of gustatory units conducting the responses to NaCl and quinine and slowly adapting mechanosensitive units produced a large antidromic inhibition amounting to 19-25%, but that of gustatory units conducting the responses to acetic acid and rapidly adapting mechanosensitive units gave rise to only a slight inhibition. To examine the differential effects of these sensory units in antidromic inhibition, antidromic impulses were evoked by chemical stimulation of the adjacent papilla neuronally connected with the dually innervated papilla under study. Antidromic volleys of impulses elicited by NaCl or quinine stimulation produced a large inhibition of the afferent activity in the other branch, as induced by NaCl stimulation of the dually innervated papilla. Plausible mechanisms of synaptic interaction in peripheral gustatory systems are considered.

Effect of growth hormone (GH) on the age-related changes in hepatic cytochrome P450 (P450) was studied using GH-deficient dwarf and parental Sprague-Dawley rats. Microsomal testosterone (T) T2 alpha- and T2 beta-hydroxylations were lower in livers of mature male dwarf rats than the normals, whereas T16 beta-hydroxylation was rather higher in male dwarf rats. Although T2 alpha-, T2 beta-, T6 beta-, T16 alpha- and T16 beta-hydroxylations were barely detectable in senescence normal rats (24 months old), considerable levels of T6 beta-, T16 alpha- and T16 beta-hydroxylations were maintained in senescence dwarf rats (after 22 months old). These results are caused by the alteration of specific P450 forms including CYP2B1, CYP2B2, CYP2C11 and CYP3A2 in dwarf rats. Appearance of male-specific CYP2C11 and CYP3A2 and high levels of CYP2B1 and CYP2B2 in female dwarf rats indicate the role of pituitary GH on liver of normal rats. However, the additional role of a factor other than GH was suggested on the sex-related differences and age-associated alterations of specific P450 contents in dwarf rats. CYP2C11 appears in dwarf female rats with the same developmental profile as observed in normal male rats. This form appears apparently with the development of GH receptor in livers, suggesting the possibility that a factor independent from androgen and GH governs the ontogeny of this P450 in the liver. A female-specific protein, CYP2C12, in normal rat livers, also appeared in both sexes of senescence dwarf rats, suggesting the role of non-GH factor on the expression of this P450 in liver.

The connecting tubule (CNT), a segment interposed between distal convoluted tubules and collecting ducts, is a well defined segment in the rabbit nephron and have been shown to contain adenylate cyclase activity which is responsive to the beta agonist isoproterenol (ISO) and the nonselective beta blocker propranolol. We examined whether ISO also increased cAMP levels in the intact microdissected CNT in the presence of 1-methyl-3-isobutyl-xanthine and, in particular, which subtype of beta adrenoceptors was stimulated. ISO increased cAMP contents in a dose-dependent way (ED50 approximately equal to 10(-7) M) and the maximal stimulation was achieved at 1 microM ISO. Norepinephrine also elevated cAMP content in the CNT to the same extent as ISO. The increase in cAMP stimulated by ISO and norepinephrine was inhibited by 1 microM propranolol but not by 1 microM phenoxybenzamine. ISO-induced cAMP increased was blocked by the beta-1 antagonist metoprolol and also by the beta-2 antagonist ICI-118551 independently in a dose-dependent manner, and maximal inhibition was observed at 1 microM of both antagonists. These results indicate that both beta-1 and beta-2adrenoceptors appear to be located in the rabbit CNT and both can be positively coupled to adenylate cyclase to generate cAMP accumulation.

In order to clarify the expression of cytochrome P450 and glutathione S-transferase in human esophagus, 41 samples of human esophagus with squamous-cell carcinoma were investigated by immunoblot analysis and enzyme assays. Cytochrome P450 1A2/1 was clearly expressed in microsomes, and the amount in samples with tumorous tissue was significantly greater than that in samples without tumourous tissues or in liver; cytochrome P450 2B6 and 3A4/3 were expressed polymorphically. Aryl hydrocarbon hydroxylase activity was detected in microsomes and was greater in samples from smokers than non-smokers. Patients who both smoked and drank alcohol, however, had activity similar to that of patients without these habits. Glutathione S-transferase M1 and A1/2 protein existed polymorphically in cytosol, and glutathione S-transferase P1-1 was detected in all samples. The frequency of expression of the glutathione S-transferase A1/2 protein was greater in patients with M1 protein than in those without; no difference in the expression was seen for glutathione S-transferase P1-1. Neither smoking nor drinking influenced the expression or activity of glutathione S-transferase. Our data support the idea that some carcinogens can be directly activated or inactivated in human esophageal epithelium.

The depressant action of antidromic volleys of impulses on gustatory nerve signals from the tongues of bullfrogs was studied. Electrical stimulation of the glossopharyngeal nerve at a rate of 100 Hz for 10 s and at supramaximal intensity slightly depressed the integrated glossopharyngeal nerve responses to quinine and to mechanical taps to the tongue. The same antidromic stimuli resulted in a 30-40% reduction in the responses to salt, acid, water, and warmed saline, but depressed greater than 80% of the afferent impulses firing spontaneously. The magnitude of responses to quinine and NaCl and the number of spontaneous discharges decreased gradually with an increase in either the frequency or the duration of antidromic stimuli. Similar results were obtained with intensities above the threshold for exciting gustatory and slowly adapting mechanosensitive fibers. The time required to recover from termination of the antidromic stimuli to two-thirds of the maximal amount of depression ranged between 6 and 7 min, with no significant differences among the depressions. The possible mechanisms involved in the antidromic depression of gustatory nerve signals are discussed.