The effects of intranasal application of low dose buserelin in women with hypothalamic amenorrhea]

Low doses of the Gn-RH agonist (buserelin, 30 micrograms) were given intranasally to 14 women with clomiphene ineffective hypothalamic amenorrhea three times daily for three weeks in order to study pituitary responses and to induce follicular maturation and ovulation. Clomiphene ineffective hypothalamic amenorrhea patients were classified into two groups by LH-RH stimulation test before the treatment. Group 1 was defined as having basal serum LH and FSH levels lower than 1.5 mIU/ml, LH and FSH peaks lower than 3mIU/ml by LH-RH stimulation test. Group 2 consisted of cases other than those in Group 1. While a significant increase in basal LH and FSH (p less than 0.01, p less than 0.001) and improvement in pituitary response to LH-RH stimulation test were observed in group 1, the basal levels of LH and FSH did not increase significantly and pituitary response to a LH-RH stimulation test was decreased in group 2. It is suggested that pituitary priming occurred in group 1 and pituitary desensitization occurred in group 2. None of 14 patients showed signs of follicular maturation during or after the treatment. The results demonstrated that the biphasic pituitary response to intranasal buserelin spray and the limit of its therapeutic use for the treatment of hypothalamic amenorrhea.     

Polymorphisms in ADAM33 are associated with allergic rhinitis due to Japanese cedar pollen

BACKGROUND: A recent report provided evidence that a disintegrin and metalloprotease domain 33 (ADAM33), a member of the ADAM family, is a novel susceptibility gene in asthma linked to bronchial hyper-responsiveness. However, there has been no investigation of the genetic role of ADAM33 variants in nasal allergy. OBJECTIVE: The purpose of this study was to test the association between ADAM33 polymorphisms and Japanese cedar pollinosis (JCPsis), a most common seasonal allergic rhinitis in Japan. METHODS: We conducted a case-control association study among a Japanese population, involving 95 adult individuals with JCPsis and 95 normal healthy controls. A total of 22 single-nucleotide polymorphisms (SNPs) in ADAM33 were genotyped using PCR-based molecular methods. RESULTS: Six SNPs of ADAM33 gene, three in introns (7575G/A, 9073G/A and 12540C/T) and three in the coding region (10918G/C, 12433T/C and 12462C/T), were strongly associated with JCPsis (P = 0.0002-0.022 for absolute allele frequencies) and most of the SNPs were in linkage disequilibrium with each other. A higher frequency of the common alleles of these SNPs was noted for the subjects with JCPsis in comparison with healthy controls. We also identified a haplotype associated with the disease susceptibility. In addition, associations were found between ADAM33 polymorphisms and various cedar pollinosis phenotypes including clinical severity, eosinophil counts in nasal secretion and allergen-specific IgE levels in sera, but not total serum IgE levels. CONCLUSION: These results indicate that polymorphisms in the ADAM33 gene are associated with susceptibility to allergic rhinitis due to Japanese cedar pollen, but the functional relationship still needs clarification.     

Clinical Course and Autopsy Findings of a Patient with Clival Chordoma Who Underwent Multiple Surgeries and Radiation during a 10-Year Period.

The management of clival chordoma remains problematic. We present the case of a 48-year-old woman with clival chordoma who underwent multiple surgeries and radiation therapy, including gamma knife stereotactic radiosurgery (GK-SRS), during a 10-year clinical course. The tumor was initially removed by gross total resection via the trans-sphenoidal approach, followed by external linac radiation therapy. The tumor recurred at the clivus 5 years after the initial operation. After repeated trans-sphenoidal removal of recurrent tumors, she twice underwent GK-SRS for a tumor remnant adjacent to the brainstem. Although this part of the tumor was controlled by GK-SRS, there was further tumor extension toward the sphenoid and maxillary sinuses. Ultimately, lower cranial nerve dysfunction developed due to tumor extension into the lower part of the clivus and the patient died of respiratory failure. Autopsy revealed the tumor to extend from the lower clivus to the bilateral middle fossae. The lower part of the tumor extended to the nasal cavity and to the posterior wall of the pharynx, resulting in compression of the upper pharyngeal region. The tumor around the jugular foramen compressed the lower cranial nerves bilaterally. Tumor cells did not, however, invade the intradural space microscopically. Although chordoma is not biologically malignant, this tumor can show massive extension with destruction of bony structures and extracranial invasion of connective tissues. Therefore, the optimal treatment strategy is to remove the tumor mass as extensively as possible, including normal bony structures and connective tissues surrounding the tumor, using skull base surgical techniques.     

Mechanism of toxic action of fluoride in dental fluorosis: whether trimeric G proteins participate in the disturbance of intracellular transport of secretory ameloblast exposed to fluoride

In enamel fluorosis model rats treated with sodium fluoride, secretory ameloblasts of incisor tooth germs exhibited disruption of intracellular trafficking. We examined whether heterotrimeric G proteins participated in the disruption of vesicular trafficking of the secretory ameloblast exposed to fluoride, using immunoblotting and pertussis toxin (IAP)-induced adenosyl diphosphate (ADP)-ribosylation for membrane fractions of the cell. Immunoblotting of crude membranes, post supernatants of the ameloblast, with anti-G_i3/o and anti-G_s antibodies showed that G_i3 or G_o proteins existed in the secretory ameloblast, but G_s protein did not. Immunoblotting of the subcellular membrane fractions indicated that the G_i3 or G_o proteins were located in the Golgi membrane, but were not in the rough endoplasmic reticulum (rER) membrane. Autoradiograph of IAP-induced ADP-ribosylation, however, showed the existence of IAP-sensitive G proteins both in rER and Golgi membranes. Fluoride treatment decreased the G proteins bound to both membranes. These findings indicate that different G proteins, both of which are IAP-sensitive, are present in the rER and Golgi apparatus, and suggest that these G proteins participate in the disturbance of intracellular transport of the secretory ameloblast exposed to fluoride. Received: 24 June 1998 / Accepted: 8 September 1998     

Neuronal responses in monkey anterior putamen during operant bar-press behavior

Single neuron activity was recorded in the monkey anterior putamen to compare visuomotor-related responses during operant bar-press behavior with visual discrimination of objects. Of 615 neurons recorded 9.8% ( ) responded to the presentation of food during forced delay of access to the bar. Of these 60 neurons, 38 were also tested with nonfood, and 19 of these responded to the nonfood objects regardless of the following movement. The amplitude of the visual-related responses of some differential neurons was graded for different objects to reflect the relative degree of preference for the food presented. However, these responses disappeared in reaction time tasks in which the bar could be accessed for pressing immediately upon presentation of an object. The visual response latency of differential neurons ranged from 50 to 700 ms (mean ± SD, 386 ±211 ms), which was longer than that of the nondifferential responses (207 ± 204 ms). These results suggest that anterior putamen neurons might participate in estimation of visual information that could be related to forecasting movement.