Electromyogram biofeedback training for daytime clenching and its effect on sleep bruxism.

Bruxism contributes to the development of temporomandibular disorders as well as causes dental problems. Although it is an important issue in clinical dentistry, no treatment approaches have been proven effective. This study aimed to use electromyogram (EMG) biofeedback (BF) training to improve awake bruxism (AB) and examine its effect on sleep bruxism (SB). Twelve male participants (mean age, 26·8 ± 2·5 years) with subjective symptoms of AB or a diagnosis of SB were randomly divided into BF (n = 7) and control (CO, n = 5) groups to undergo 5-h daytime and night-time EMG measurements for three consecutive weeks. EMG electrodes were placed over the temporalis muscle on the habitual masticatory side. Those in the BF group underwent BF training to remind them of the occurrence of undesirable clenching activity when excessive EMG activity of certain burst duration was generated in week 2. Then, EMGs were recorded at week 3 as the post-BF test. Those in the CO group underwent EMG measurement without any EMG BF training throughout the study period. Although the number of tonic EMG events did not show statistically significant differences among weeks 1-3 in the CO group, events in weeks 2 and 3 decreased significantly compared with those in week 1, both daytime and night-time, in the BF group (P < 0·05, Scheffé's test). This study results suggest that EMG BF to improve AB tonic EMG events can also provide an effective approach to regulate SB tonic EMG events.

Normalization of low biotinidase activity in a child with biotin deficiency after biotin supplementation.

We report findings in a Japanese boy with severe skin rash attributable to biotin deficiency. The patient had an intracranial malformation and developed biotin deficiency due to tube feeding with a single formula for over one year. Results of urinary organic acid analysis were consistent with multiple carboxylase deficiency, and low biotinidase activity was also observed. After biotin supplementation, the skin rash improved and biotinidase activity normalized. We speculate that biotin is one regulating factor in the biosynthesis of biotinidase.

Microwave thermotherapy for benign prostatic hyperplasia with the Dornier Urowave: response durability and variables potentially predicting response.

OBJECTIVES: To evaluate the clinical efficacy and durability of transurethral microwave thermotherapy (TUMT) in the treatment of benign prostatic hyperplasia. The clinical variables useful in predicting outcome were identified. METHODS: From October 1996 to March 2000, 58 patients with symptomatic benign prostatic hyperplasia were treated with TUMT using the Urowave device. Treatment outcome was evaluated by the International Prostate Symptom Score (IPSS), quality-of-life assessment score, and urodynamic investigation. The patients were divided into those having a good and poor response on the basis of the degree of IPSS decrease at 3 months. RESULTS: The mean IPSS significantly decreased from 19.2 at baseline to 13.3 at 3 months (P <0.0001). The mean quality-of-life score changed from 4.6 at baseline to 2.9 at 3 months (P <0.0001). No statistically significant differences in peak flow rate, postvoid residual volume, Schäfer's obstruction scale, or detrusor pressure at peak flow were noted before or after TUMT. The pretreatment IPSS of the good response group was significantly higher than that of the poor response group (P=0.017). A more significant difference was obtained for the obstructive score (P = 0.002), and no difference was observed in the irritative score (P = 0.631). The Schäfer grading scale score of the good response group was significantly smaller than that of the poor response group (P = 0.047). CONCLUSIONS: TUMT with the Urowave was effective in eliminating symptoms associated with benign prostatic hyperplasia, but did not markedly improve the objective voiding parameters. Patients with urodynamically less obstructive symptoms but subjectively more obstructive symptoms are therefore probably good candidates for TUMT.

Acute normovolemic hemodilution for radical prostatectomy: can it replace preoperative autologous blood transfusion?

BACKGROUND: Although preoperative autologous blood donation (PAD) is accepted as a standard of care for radical prostatectomy, it is costly, time-consuming and has risks associated with blood storage. Acute normovolemic hemodilution (ANH) is reported to be less expensive and to preserve blood components more effectively than PAD. In the present study, the efficacy and safety of these two autologous blood-collection techniques were compared. METHODS: The study included 16 consecutive patients scheduled for radical prostatectomy. The first eight patients underwent conventional preoperative autologous blood donation of 400 mL 1 week before the operation (PAD group) and the second eight patients underwent acute normovolemic hemodilution followed by immediate operation (ANH group). All blood collected was transfused in the perioperative period. Preoperative and postoperative hematocrit levels in these two groups were compared. RESULTS: There were no differences in preoperative hematocrit, time of operation or operative blood loss between the two groups. In the ANH group, 1080 +/- 160 mL of blood were collected. The postoperative hematocrit level did not differ significantly between the groups. No patient in either group received allogeneic blood transfusion or experienced an adverse event directly related to blood transfusion. CONCLUSION: The two blood-conservation strategies resulted in similar postoperative hematologic outcomes. Given its advantages, which include lower cost, lower risk and higher convenience, ANH is one of the procedures that may replace conventional PAD for use in radical prostatectomy.

Impact of interventional therapy for benign prostatic hyperplasia on quality of life and sexual function: a prospective study.

PURPOSE: Treatment for benign prostatic hyperplasia (BPH), including minimally invasive therapy, can impair the quality of life. We prospectively determined the impact of 4 different interventional therapies on quality of life and sexual function. MATERIALS AND METHODS: A total of 173 patients were prospectively evaluated between February 1995 and August 1997. Treatment modalities consisted of standard transurethral resection of the prostate in 55 cases, transurethral microwave thermotherapy in 34, interstitial laser coagulation of the prostate in 42 and transurethral needle ablation in 42. Disease specific quality of life was assessed using the International Prostate Symptom Score quality of life assessment index and BPH impact index. In addition, a self-reporting questionnaire was completed before and 3 months after treatment to determine the impact on sexual function. RESULTS: All 4 treatment groups showed significant improvement in the symptom score, International Prostate Symptom Score quality of life assessment score and BPH impact index score. Satisfaction with treatment was highest in patients treated with transurethral resection or laser coagulation. A mild to moderate decrease in erectile function was noted in 26.5%, 18.2%, 18.4% and 20.0% of the transurethral resection, microwave thermotherapy, laser coagulation and needle ablation groups, respectively, but there was no significant difference of mean pretreatment and posttreatment erectile function or libido scores in any group. Ejaculation loss or severe decrease in ejaculate volume was reported by 48.6%, 28.1%, 21.6% and 24.3% of the patients, respectively. Interestingly, 20 of the 44 patients (45. 5%) with loss of ejaculation or severe decrease in ejaculate reported deterioration of the sex life, while only 2 (3.6%) of the 56 without any change in ejaculate volume reported such deterioration. The association of ejaculatory dysfunction with an adverse impact on sexual activity was highly significant (p <0.0001). CONCLUSIONS: Significant improvement in quality of life could be achieved with the present assessed interventional therapies. There was no significant change in sexual desire or erectile function with these therapies. Posttreatment sexual dysfunction appears to be mainly related to impaired ejaculatory function. Urologists should provide proper counseling regarding the possibility of this complication even in patients receiving minimally invasive treatment.

Chronic treatment with FK506 increases p70 S6 kinase activity associated with reduced nitric oxide synthase activity in rabbit hearts.

FK506, an immunosuppressant, modulates phosphorylation of nitric oxide (NO) synthase, and induces cardiac hypertrophy in clinical settings. Having recently reported that chronic treatment with an inhibitor of NO synthase induces cardiac hypertrophy associated with the activation of 70-kD S6 kinase (p70S6K), which plays an important role in cardiac hypertrophy by regulating protein synthesis, we investigated the effects of chronic administration of FK506 on NO synthase and p70S6K activities in hearts. Twenty rabbits were divided into four groups: untreated rabbits, those treated with low-dose FK506 (0.10 mg/kg), those treated with medium-dose FK506 (0.20 mg/kg), and those treated with high-dose FK506 (0.40 mg/kg). FK506 was administered intravenously twice a day. After 4 weeks of treatment with FK506, calcium-dependent NO synthase activity in myocardium in the high-dose FK506 group was lower (P < 0.05) than in the untreated group. p70S6K activity in myocardium in the high-dose group was higher (P < 0.05) than in the untreated group. There was a significant (P < 0.05) inverse correlation between NO synthase and p70S6K activities in myocardium. However, the endothelial-dependent vasodilation of aortic rings or plasma levels of NO metabolites during experimental protocols did not differ among the groups studied. These findings suggest that chronic treatment of FK506 activates p70S6K and reduces NO synthase activity in rabbit hearts. Reduced NO synthase and/or activated p70S6K activities in hearts might contribute to the cardiac hypertrophy observed in some patients receiving FK506.

Effects of transforming growth factor beta-1 and all-trans-retinoic acid on androgen-induced development of neonatal mouse bulbourethral glands in vitro.

Effects of transforming growth factor beta-1 (TGF-beta1) and all-trans-retinoic acid (All-trans-RA) on development of bulbourethral glands (BUGs) of neonatal mice were investigated in vitro. BUGs from 0-day-old male mice were cultured for 6 days in serum-free, chemically defined medium containing transferrin and bovine serum albumin, supplemented with 5alpha-dihydrotestosterone (DHT; 10-8 M) and insulin (10 microg/mL) alone or in combination. Prior to culture, BUGs from 0-day-old mice consisted of a simple epithelial rudiment encapsulated by mesenchyme. Epithelial growth and ductal branching occurred in BUGs cultured in medium containing DHT and insulin or DHT alone, but epithelial branching did not occur in BUGs cultured in the presence of insulin alone. Addition of TGF-beta1 at concentrations of > 5 ng/mL (0.2 x 10-9 M) to medium containing both insulin and DHT, inhibited the expected increase in overall size of BUGs, epithelial area and ductal branching in a dose-dependent manner. TGF-beta1 also decreased [3H]-thymidine labelling indices of both epithelium and mesenchyme. TGF-beta1 at 10 ng/mL elicited these inhibitory effects on BUGs cultured in medium containing DHT alone. Addition of All-trans-RA (10-8 to 10-6 M) to the medium containing DHT plus insulin, or DHT alone did not exert significant effects on either overall size of BUGs or epithelial growth and ductal branching. All-trans-RA at 10-6 M decreased the [3H]-thymidine labelling index of mesenchyme of BUGs cultured in medium with DHT plus insulin or DHT alone, but did not decrease the [3H]-thymidine labelling index of epithelium. The present results indicate that TGF-beta1 inhibits androgen-induced epithelial and mesenchymal growth as well as epithelial morphogenesis of BUGs from neonatal mice. Such an inhibitory effect of TGF-beta1 is not mimicked by All-trans-RA at physiological concentrations.

Changes in nasal responsiveness to histamine and to specific antigen after laser surgery.

An initial treatment with several kinds of anti-allergic medicines is useful for reducing nasal allergy symptoms in patients suffering from Japanese cedar pollinosis during the pollen season. Since laser surgery before the pollen season seems to have a preventive effect as well, it would be of interest to know the time course of changes in the nasal reactivity to specific and non-specific stimuli after laser surgery. In this study, we investigated the changes in the nasal reactivities to specific antigen and histamine after CO2 laser surgery. The nasal reactivities to both specific antigen and histamine were enhanced 2 weeks after the laser surgery. On the other hand, they were significantly reduced after 4 weeks. Our data strongly suggest. therefore. that laser surgery must be done more than 4 weeks before the start of the pollen season to avoid temporary enhancement of nasal allergy symptoms.

Stem cell factor augments Fc epsilon RI-mediated TNF-alpha production and stimulates MAP kinases via a different pathway in MC/9 mast cells.

Mast cells express the receptor tyrosine kinase kit/stem cell factor receptor (SCFR) which is encoded by the proto-oncogene c-kit. Ligation of SCFR induces its dimerization and activation of its intrinsic tyrosine kinase activity leading to activation of Raf-1, phospholipases, phosphatidylinositol 3-kinase, and extracellular signal-regulated kinases. However, little is known about the downstream signals initiated by SCFR ligation except for activation of extracellular signal-regulated kinases. The murine mast cell line, MC/9, synthesizes and secretes TNF-alpha following the aggregation of high affinity Fc receptors for IgE (Fc epsilonRI). Ligation of SCFR or Fc epsilonRI on MC/9 cells resulted in the activation of all three MAP kinase family members, extracellular signal-regulated kinases, c-Jun amino-terminal kinase (JNK), and p38. Stem cell factor (SCF)-induced activation of JNK and p38 was insensitive to wortmannin, cyclosporin A, and FK506 whereas activation of these kinases through Fc epsilonRI was sensitive to these drugs. Coligation of SCFR augmented Fc epsilonRI-mediated activation of MAP kinases, especially JNK activation, and SCF augmented Fc epsilonRI-mediated TNF-alpha production in MC/9 cells, although SCF alone did not induce TNF-alpha production. This augmentation by SCF was regulated at the level of transcription, at least in part, since the promoter activity of TNF-alpha was enhanced following addition of SCF. These results demonstrate that SCF can augment Fc epsilonRI-mediated JNK activation and cytokine gene transcription but via pathways that are regulated differently than the ones activated through Fc epsilonRI.

Late phase response in nasal mucosa closely correlated with immediate phase reaction and hyperreactivity to histamine.

It has been suggested that the onset of the late phase response (LPR) and hyperreactivity to non-specific stimuli occurs in the lower airway. However, its relationship in the nose has not yet been studied. This study was designed to examine the mechanism of LPR and the relationship between LPR and hyperreactivity. A total of 25 Japanese cedar pollinosis patients participated in this study. On the first visit, the frequency of sneezes, weight of nasal discharge, and the nasal airway resistance (NAR) were time-dependently measured without antigen challenge. The histamine reactivity was observed after 12 h. The same protocol was used during the second to fourth visits. The frequency of sneezes, weight of nasal discharge, and NAR were measured continuously for 12 h after antigen challenge, and nasal reactivity to histamine was observed. The percent change of NAR during immediate phase response (IR) and during LPR showed a significant correlation. The frequency of sneezes and weight of nasal discharge induced by histamine were both significantly higher in the positive than in the negative LPR group. These results suggest that the chemical mediators and inflammatory cells inducing nasal swelling during IR cause, directly or indirectly, nasal swelling during LPR, and induce hyperreactivity to histamine.

Effects of methylcobalamin on the proliferation of androgen-sensitive or estrogen-sensitive malignant cells in culture and in vivo.

Methylcobalamin is one of the coenzymatically active cobalamin derivates and required for the activity of the cytoplasmic enzyme methionine synthetase catalyzing the methylation of homocysteine into methionine. The effect of methylcobalamin on the proliferation of malignant cells has been examined. Methylcobalamin inhibited the proliferation of androgen-sensitive SC-3 cells (a cloned cell line from Shionogi mouse mammary tumor, SC115) in culture at the concentration of 100-300 micrograms/ml. An inhibitory activity of methylcobalamin on the proliferation was also observed in other cell lines (estrogen-sensitive B-1F cells from mouse Leydig cell tumor and MCF-7 cells from human mammary tumor) at the concentration of 500 micrograms/ml. Moreover, large doses of methylcobalamin injected intraperitoneally (100 mg/kg body weight/day) were non-toxic and suppressed the tumor growth of SC115 and B-1F cells in mice fed a vitamin B12 deficient diet. These results show that methylcobalamin inhibits the proliferation of malignant cells in culture and in vivo and propose the possibility of methylcobalamin as a candidate of potentially useful agents for the treatment for some malignant tumors.

Inhibitory effects of retinoic acids on androgen-dependent development of neonatal mouse seminal vesicles in vitro.

The effects of retinoic acids (RAs) on development of seminal vesicles (SVs) of neonatal mice were investigated in vitro. SVs from 0-day-old male mice were cultured for 2-6 days in serum-free, chemically defined medium containing transferrin and BSA supplemented with 5alpha-dihydrotestosterone (DHT; 10(-8) M) and insulin (10 microg/ml), alone and in combination. Before culture, SVs from 0-day-old mice consisted of an unbranched epithelium surrounded by mesenchyme. SVs cultured in medium with DHT plus insulin or DHT alone formed numerous epithelial branches after day 2 of culture, whereas epithelial branching did not occur in SVs cultured with insulin alone. All-trans-RA or 13-cis-RA (10(-9)-10(-6) M) added to medium containing DHT plus insulin or DHT alone inhibited epithelial branching in a dose-dependent manner. This inhibitory effect was reversible after removal of the retinoids from the medium on day 4 of culture. These RAs also decreased [3H]thymidine labeling indexes of both epithelium and mesenchyme of SVs cultured in medium with DHT plus insulin or DHT alone and inhibited the increase in their protein contents. 9-Cis-RA was less inhibitory than all-trans-RA or 13-cis-RA on epithelial branching, [3H]thymidine labeling indexes of epithelium and mesenchyme, and protein content of SVs cultured in medium with DHT and insulin. In the absence of DHT (insulin alone), all-trans-RA did not affect either the [3H]thymidine labeling indexes of epithelium and mesenchyme or the protein content of cultured SVs. Reverse transcriptase-PCR demonstrated strong expression of transcripts for mouse RA receptors (RARalpha, RARgamma, and RXRalpha), with lower levels of expression of RARbeta, RXRbeta, and RXRgamma in neonatal SVs. The present results indicate that RAs reversibly inhibit androgen-dependent development of neonatal mouse SVs, most likely through RARs.

Danazol concentrations in ovary, uterus, and serum and their effect on the hypothalamic-pituitary-ovarian axis during vaginal administration of a danazol suppository.

OBJECTIVE: To determine danazol concentrations in the ovary, uterus, and serum during daily vaginal administration of a danazol suppository and to examine its effect on the hypothalamic-pituitary-ovarian axis. DESIGN: Sampling of tissues after vaginal or oral administration of danazol and sampling of blood during control and danazol-administration menstrual cycles. SETTING: Outpatient volunteers and inpatients at a public hospital. PARTICIPANTS: Thirty patients who were to undergo hysterectomy and oophorectomy because of uterine leiomyoma and eight regularly menstruating volunteers. INTERVENTIONS: Danazol was administered as a vaginal suppository (100 mg) or orally (400 mg). MAIN OUTCOME MEASURE: Danazol concentrations in the ovary, uterus, and serum, and serum E2 and P levels. RESULTS: Danazol concentrations in the ovary and uterus after daily vaginal administration of a suppository containing 100 mg danazol were comparable to those after daily oral administration of 400 mg danazol, but the serum danazol concentration was much lower. Menstrual cycle patterns of serum E2 and P levels were normal during daily vaginal administration of a danazol suppository. CONCLUSION: Daily administration of a suppository containing 100 mg danazol produces high ovarian and uterine concentrations but low serum concentrations, and no effect was detected on the hypothalamic-pituitary-ovarian axis.

Apoptosis of acinar cells in the pancreas of rats fed on a copper-depleted diet.

Male Fischer 344 rats weighing 80-90 g were fed on a copper-depleted diet supplemented with 0.6% triethylenetetramine tetrahydrochloride (a copper chelator), and the death of pancreatic acinar cells of these rats was investigated morphologically and biochemically. The weight of the pancreas of these rats decreased from 3 weeks after feeding, and concomitantly the percentage of dead acinar cells increased to the maximum in about the 5th week and decreased subsequently. These dead acinar cells showed light microscopic and electron microscopic characteristics of apoptosis. Furthermore, the electrophoretic pattern of DNAs extracted from the pancreas having many dead acinar cells showed a ladder-like distribution, characteristic of apoptosis. The present results indicate that feeding of rats on a copper-depleted diet supplemented with a copper chelator results in apoptosis of acinar cells of the pancreas.

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency: diagnosis by acylcarnitine analysis in blood.

Medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency is a disorder of fatty acid catabolism, with autosomal recessive inheritance. The disease is characterized by episodic illness associated with potentially fatal hypoglycemia and has a relatively high frequency. A rapid and reliable method for the diagnosis of MCAD deficiency is highly desirable. Analysis of specific acylcarnitines was performed by isotope-dilution tandem mass spectrometry on plasma or whole blood samples from 62 patients with MCAD deficiency. Acylcarnitines were also analyzed in 42 unaffected relatives of patients with MCAD deficiency and in other groups of patients having elevated plasma C8 acylcarnitine, consisting of 32 receiving valproic acid, 9 receiving medium-chain triglyceride supplement, 4 having multiple acyl-coenzyme A dehydrogenase deficiency, and 8 others with various etiologies. Criteria for the unequivocal diagnosis of MCAD deficiency by acylcarnitine analysis are an elevated C8-acylcarnitine concentration (> 0.3 microM), a ratio of C8/C10 acylcarnitines of > 5, and lack of elevated species of chain length > C10. These criteria were not influenced by clinical state, carnitine treatment, or underlying genetic mutation, and no false-positive or false-negative results were obtained. The same criteria were also successfully applied to profiles from neonatal blood spots retrieved from the original Guthrie cards of eight patients. Diagnosis of MCAD deficiency can therefore be made reliably through the analysis of acylcarnitines in blood, including presymptomatic neonatal recognition. Tandem mass spectrometry is a convenient method for fast and accurate determination of all relevant acylcarnitine species.

Definition of the roles for iron and essential fatty acids in cell cycle progression of normal human T lymphocytes.

A serum-free cell culture system for human T lymphocytes was used to investigate the synthesis and metabolism of several important cell cycle-regulated proteins (p62c-fos, p110Rb, and p34cdc2 and its homologs) and the possible roles of iron and essential free fatty acids in regulating cell cycle progression. Following stimulation with phorbol dibutyrate (PDB) and ionomycin under serum-free conditions, resting T cells entered the cell cycle, as evidenced by a burst of synthesis of p62c-fos and an increase in the amount of the p33 homolog of the cdc2 kinase. However, in the absence of other additions, cells were arrested in the G1 phase of the cell cycle. Supplementation of the medium with two components, iron and linoleic acid (LA), permitted activated cells to progress through the G1 phase of the cycle and initiate DNA synthesis. Under these conditions p110Rb became phosphorylated and p34cdc2 was synthesized similar to T cells proliferating in normal serum-containing medium. The addition of iron, without LA, had little effect on activated cells; however, the addition of LA, in the absence of added iron, had profound effects. RNA accumulated to levels characteristic of cells at the G1/S interface, phosphorylation of p110Rb was almost complete, and p34cdc2 was synthesized, although at lower levels than in proliferating cells. However, no DNA synthesis was detected; under these conditions the cells appeared to be blocked at or near the G1/S border. Since there was a possibility that some component of the cell culture system could provide "trace" amounts of iron, and also to further delineate the role of iron in this system, cells were activated in medium containing LA and deferoxamine (10 microM), a chelator of iron. The accumulation of p34cdc2 was now reduced to nearly undetectable levels although phosphorylation of p110Rb was not substantially affected. It therefore appears that synthesis of p34cdc2 requires a low amount of iron, a finding which may define a possible regulatory point in the cell cycle for iron before its well-recognized role in regulating S phase entry by acting as a cofactor for the enzyme ribonucleotide reductase.

Marked nitrosation by stimulation with lipopolysaccharide in ascorbic acid-deficient rats.

Marked formation of N-nitrosothioproline (N-nitrosothiazolidine-4-carboxylic acid) by stimulation with Escherichia coli lipopolysaccharide (LPS) was demonstrated in ascorbic acid-deficient mutant rats (osteogenic disorder syndrome rats; ODS rats) unable to synthesize ascorbic acid. The amounts of urinary nitrate and N-nitrosothioproline excretion after thioproline administration was measured in ODS rats with and without ascorbic acid supplement before and after the injection of LPS. LPS caused marked increase of urinary nitrate excretion in both groups. Urinary N-nitrosothioproline excretion increased 6-fold after LPS injection in ODS rats not supplied with ascorbic acid, but supplement with ascorbic acid markedly decreased the excretion of N-nitrosothioproline.

Decrease of nitrate biosynthesis in scorbutic mutant rats unable to synthesize ascorbic acid.

The effect of ascorbic acid deficiency on the urinary excretion of nitrate was investigated using a mutant strain of rats (osteogenic disorder syndrome rats; ODS rats) unable to synthesize ascorbic acid. The amount of urinary nitrate excreted by ODS rats with or without ascorbic acid supplementation were measured before and after the intraperitoneal injection of Escherichia coli lipopolysaccharide (LPS). Urinary nitrate excretion increased markedly after LPS injection. Urinary nitrate excretion by ODS rats not supplied with ascorbic acid was significantly less than that of those supplied with ascorbic acid both before and after LPS injection. These results show that ascorbic acid enhances both LPS-stimulated and constitutive nitrate production in vivo.

[Nasal allergy and leukotriene. 2. Kinetics of peptide leukotrienes and inflammatory cells in nasal lavage fluid after antigen challenge].

The purpose of this study is to clarify the role of peptide leukotrienes (LTs) on the onset of characteristic hyperreactive nasal symptoms of nasal allergy by observing the time course of the correlation among degrees of nasal symptoms, and by observing the amount of chemical mediators and the number of inflammatory cells in the nasal lavage fluid after nasal antigen challenge in subjects with Japanese cedar pollinosis during off season. Sneezing was terminated within 10 minutes and nasal discharge within 2 hours. However, time course change of the percent increase of nasal airway resistance showed dual response consisting of immediate and late phase responses. The peak of the former was seen at 30 minutes and the latter was at 7 hours after provocation. The significant increase of eosinophils in the nasal lavage fluid was observed during both the immediate and the late phase responses, but during the late phase response, the increase was more prominent. Basophilic cells definitely increased during the late phase response. The amount of LTs in the nasal lavage fluid increased significantly during both the immediate and the late phase responses. In contrast, the level of histamine increased significantly only during the immediate phase response. Considering that LTs, especially LTD4, has potent and persistent effect on causing swelling of nasal mucosa, LTs may play important role in causing nasal obstruction during both the immediate and the late phase responses after antigen challenge. On the other hand, the role of histamine may be confined to cause the hyperreactive nasal symptoms during the immediate phase response.(ABSTRACT TRUNCATED AT 250 WORDS)

Augmentation of aromatase activity by FSH in ovaries of fetal and neonatal mice in organ culture.

The stimulative effect of FSH on aromatase activity was investigated in ovaries of fetal (on days 17 and 18 of gestation) and neonatal mice (on days 0, 3, 6 and 9 after birth). Two to six ovaries, were cultured for 48 h in 2 ml of Medium 199 supplemented with insulin (5 micrograms/ml) and [1 alpha, 2 alpha, 6 alpha, 7 alpha, beta-3H]4-androstene-3,17-dione (0.35 microM) in the presence or absence of porcine FSH (0.5 units/ml) and the amount of [3H]oestradiol-17 beta and [3H]oestrone produced was estimated. In the presence of FSH, aromatase activity per ovary, which was found in all fetal and neonatal ovaries examined, increased with age. In the absence of FSH, however, the production of oestrogens could be demonstrated only in ovaries from 3- to 9-day old mice. FSH increased the aromatase activity by up to 10-fold. In spite of the stimulative effect of FSH on aromatase activity, FSH exerted no significant effect on DNA synthesis of the ovaries. The formation of primordial follicles could not be observed histologically in ovaries of fetal mice on day 17 of gestation, although the ovaries of 6- and 9-day old mice contained multilayered follicles. These results show that FSH stimulates the aromatase activity of the mouse ovary even before the formation of primordial follicles and that the stimulative effect of FSH on ovarian aromatase is not due to the proliferation of ovarian cells.