Brain-derived neurotrophic factor modulates glucagon secretion from pancreatic alpha cells: its contribution to glucose metabolism.

AIM: Brain-derived neurotrophic factor (BDNF) reduces plasma glucose levels in obese db/db diabetic mice and is speculated to produce its effects via the hypothalamus, the regulatory centre of satiety and the autonomic nervous system. The potential effect of BDNF directly on peripheral endocrine organs, however, remains to be clarified. Here we report the effects of BDNF on hormonal secretion from pancreatic islets of Langerhans using their isolated culture. METHODS AND RESULTS: In an immunohistochemical study, mouse pancreatic alpha cells were stained specifically with the anti-TrkB (a specific receptor for BDNF) antibody. After 7 days culture of isolated islets of the normal mouse pancreas, 10 ng/ml BDNF decreased the secretion of glucagon per 6 h significantly less than that of the control (p = 0.016). In contrast, there were no significant changes in insulin secretion or glucagon and insulin contents in the islets cultured under the same conditions. In vivo administration of BDNF (10 mg/kg/day) to normal mice for 7 days significantly decreased their food consumption (p < 0.05). The fasting plasma glucose levels were decreased on day 7 compared with day 1 more significantly in BDNF-treated mice (p = 0.043) than in pair-fed control mice (p = 0.14). In newborn BDNF-knockout mice, fasting plasma glucose levels increased in the order of homozygote, heterozygote and wild type (p = 0.033). No apparent immunohistochemical abnormality was observed for pancreatic glucagon in the BDNF-knockout mice. CONCLUSION: These data suggest that BDNF affects glucose metabolism not only with its anorectic effect but also with modulated glucagon secretion from pancreatic alpha cells.

Malignant melanoma of mandibular gingiva; the usefulness of fat-saturated MRI.

Case report of a histologically validated malignant melanoma affecting the mandibular molar gingiva in a 31-year-old woman. Tumour was evaluated by magnetic resonance (MR) imaging at 1.5-T, spin-echo 3 mm slice thickness with T1-weighted and fat-saturated T1-weighted images. The fat-saturated T1-weighted images demonstrated the lesion more clearly than conventional T1-weighted images.

Osteogenic sarcoma of the prostate.

A 76-year-old man was treated with bilateral orchiectomy, estramustine phosphate and pelvic irradiation for prostate cancer. Osteogenic sarcoma of the prostate developed 18 months after the treatment. Postmortem examination revealed that the tumor was 8 cm in diameter and had infiltrated into the bladder and rectal walls and had resulted in peritoneal dissemination. There was no distant metastasis. Macroscopically, the tumor was ashen, firm and relatively homogenous and diffusely spread. Histologically, it was composed of spindle and pleomorphic cells, which were making osteoid with calcification. There was no ordinary tubular formation as shown in adenocarcinoma of the prostate. No positive immunostaining for prostate-specific antigen, epithelial membrane antigen and cytokeratin (AE-1, AE-3) were confirmed. Positive immunostaining for nonepithelial marker vimentin was confirmed. The ultimate diagnosis was osteogenic sarcoma of the prostate.

Parapelvic neurofibroma of the kidney.

We report the first case of neurofibroma causing obstruction by external compression of the upper renal pelvis. A 33-year-old woman reported a 1-year history of dull lumbar pain on the right side. A right renal parapelvic cyst was suspected. The patient underwent retroperitoneoscopic exploration. The right renal parapelvic lesion was identified as a soft tissue tumor. The tumor was removed with a retroperitoneoscopic procedure. Histopathological findings revealed neurofibroma.

Calcitonin-producing pancreatic somatostatinoma: report of a case.

A 59-year-old woman was hospitalized due to a 1-year history of diarrhea and weight loss. Echography and computed tomography of the abdomen revealed a 10 x 7 cm solid mass in the tail of the pancreas and gallstones, while selective celiac angiography revealed the presence of a hypervascular mass. High levels of somatostatin and calcitonin were detected in the plasma, 70 pg/ml (normal range <28 pg/ml) and 5550 pg/ml (normal range 37 +/- 8 pg/ml), respectively. This tumor was thus removed by means of a distal pancreatectomy and a splenectomy. After the pancreatic tumor was removed, the elevated levels of plasma somatostatin and calcitonin returned to the normal ranges, and the persistent diarrhea also dramatically disappeared. A postoperative immunohistochemical study showed the tumor cells to be diffusely positive for somatostatin and calcitonin. These results clearly indicate this patient to be a case of calcitonin-producing pancreatic somatostatinoma.

[Bronchial hypersensitivity and development of bronchial asthma in children with atopic dermatitis].

Using histamine inhalation tests, we followed changes in bronchial hypersensitivity in 48 children with atopic dermatitis (AD) who were nonasthmatic on their initial visit. Twenty-three of these subjects became asthmatic during the follow-up period. The respiratory thresholds to histamine RT-Hist) of children with AD were widely distributed, ranging from 156 to more than 5000 micrograms/ml. There was a statistical difference in RT-Hist, as those who became asthmatic showed lower levels (< or = 625 micrograms/ml) at 2-6 yr of age. The percentage of peripheral eosinophil counts and IgE level was significantly elevated in those who became asthmatic. Subjects who developed asthma were more likely to have had positive D.p. RAST when they were less than 2 yr of age. The development of asthma in children with AD showed no significant relationship with family history of bronchial asthma.

[Bronchial hypersensitivity to histamine in asthmatic children longitudinal study from first visit to remitted state].

In order to examine the changes in bronchial hypersensitivity, histamine inhalation tests were evaluated in 27 asthmatic children who remitted. The respiratory threshold to histamine (RT-Hist) 2-3 yrs after remission was higher than in the initial test, in their worst periods of the asthma and just before remission (p < 0.001, p < 0.001, p < 0.005, respectively). Eleven subjects (40.7%), showed no improvement of bronchial hypersensitivity 2-3 yrs after remission (RT-Hist was 1250 micrograms/ml or lower). In this group, the asthma score per year two and three years before symptom-free state was higher than in the group with improved bronchial hypersensitivity (p < 0.05). There was no significant difference between % fall of FEV1.0 in RT-Hist in the worst periods of the asthma and 2-3 yrs after remission. FEV1.0/VCP, %V50, %V25 and V25/Ht 2-3 yrs after remission were higher than those in the worst periods of the asthma.

The effect of uvulonodular lesions on horizontal optokinetic nystagmus and optokinetic after-nystagmus in cats.

The effect of uvulonodular lesions on horizontal optokinetic nystagmus (OKN) and optokinetic after-nystagmus (OKAN) was investigated in alert cats. A lesion in each of 6 cats was made by suction-ablation under anesthesia. In the 3 cats with only a uvular lesion, both the initial slow phase velocity and the time constant of OKAN were unchanged. In the remaining 3 cats whose lesions included the nodulus as well as the uvula, the time constant of OKAN was markedly prolonged, but the initial slow phase velocity of OKAN was not affected. The postoperative average time constant of OKAN increased from the normal value of 9 s to about 40 s. In contrast, OKN parameters (the steady-state velocity and the rising time constant) were not affected by uvular or uvulonodular lesions. These results strongly suggest that the nodulus is involved in the velocity storage mechanism and might control the discharge characteristics of the velocity storage integrator.

Facial nerve enhancement in Gd-MRI in patients with Bell's palsy.

The diagnostic value of a contrast enhanced MRI in patients with Bell's palsy was investigated. It was a characteristic finding that the internal acoustic meatal segment of the facial nerve was enhanced only on the affected side. The signal intensity ratio of the geniculate ganglion and the tympanic segment was significantly higher on the affected side than on the normal side. The severity of the facial palsy and the results of physiological examinations showed no relation to the results of MRI scans. Gd enhanced MRI thus appears to provide some useful findings for estimating the affected region of Bell's palsy, whereas it is not considered to be valuable in the diagnosis of severity.

Cystic lymphangioma and plunging ranula treated by OK-432 therapy: a report of two cases.

Among head and neck angiotumors, cystic lymphangioma occurs in infancy in most cases and it is rare in adulthood. Plunging ranula is one of the diseases which need to be distinguished from lymphangioma, though operation is the first choice therapy for both of these. In the present study, we report on 2 cases in whom we conducted intralesional injection of OK-432 for cervical lymphangioma and ranula found in 20 and 35 year-old female patients. We obtained excellent improvement. First of all, we punctured the tumors and sucked out the liquid content as much as possible, and then used OK-432 in the same volumes to those drawn out. No swelling was observed in either patient after 1 month, and cysts disappeared in CT 4 and 12 months after injection, respectively; at present, the prognosis is satisfactory, without recurrence. The intralesional injection of OK-432 is considered an effective method, as the speed of complete disappearance by this therapy is high. Cosmetically it is superb, leaving no lesions in the skin of the injection site.

Splenic hemangiosarcoma with sinus endothelial differentiation.

A case of primary splenic hemangiosarcoma where the tumors entirely replaced the spleen is reported. Histologically, the splenic tumors consisted of two major components: (i) solid and nodular areas, in which spindle cells (SC) were arranged in interlacing fascicles; and (ii) vasoformative areas, in which vascular lining cells (VC) closely resembled normal splenic sinus endothelial cells (SSEC) in shape. Both SC and VC were immunoreactive with the markers of vascular endothelial cells (EC) including SSEC, JC70, von Willebrand factor, OKM5, vimentin MAb and Ulex europaeus-1 lectin. The tumor cells were positive for OKM5 MAb as well as normal SSEC and sheathed arterial EC, but other vascular EC in normal spleen were negative. Enzyme-histochemically, the tumor cells and normal SSEC revealed naphthol AS-D acetate esterase activity but no reaction for ALPase, whereas normal vascular EC other than SSEC in the spleen were positive for the latter but negative for the former. These studies revealed that the tumor cells expressed the same phenotype as normal SSEC. To the present author's knowledge this is the first report demonstrating sinus endothelial differentiation of splenic hemangiosarcoma, enzyme- and immuno-histochemically.

[Efficacy of continuous isoproterenol inhalation therapy for severe asthma attacks in younger children].

The aim of this study was to evaluate the efficacy of continuous isoproterenol inhalation therapy for severe asthma attacks in younger children, compared with its efficacy in older children. We used l-body isoproterenol (Proternol L) in 31 children with 42 episodes of severe attacks. They were divided into two group according to age: 20 cases under 6 years old (Group A), and 22 cases over 7 years old (Group B). All of the patients except for one in Group B, eventually improved with this therapy. Wood's clinical scores for Group A were significantly higher than those for group B (p < 0.01). In 22 cases whose scores were 5-6, their SpO2 values at the onset of this therapy were 90.8 +/- 3.17 in group A and 92.4 +/- 3.82% in group B. The improvement time of group A (13.6 +/- 16.2 hours) was significantly longer than that of group B (2.5 +/- 5.66, p < 0.01). The nebulized isoproternol doses for group A were 0.47 +/- 0.168 and for group B 0.26 +/- 0.096 mg/kg/saline 500 ml. The dose for group A was significantly higher than that for group B (p < 0.01). We concluded that continuous isoproterenol inhalation therapy was effective even in younger children. But the degree of efficacy was slightly lower in younger children, although they inhaled higher doses of isoproterenal than older children.

[Efficacy of early use of continuous isoproterenol inhalation therapy for severe asthma attacks in children].

The aim of this study was to evaluate the efficacy and safety of continuous isoproterenol inhalation therapy for asthma attacks in children. We used l-body isoproterenol (Proternol L) in 22 children with 32 episodes of severe attacks. One of them did not respond to this therapy, and two had complications (atelectasis and pneumothorax). Twenty-nine cases were divided into three subgroups according to their clinical scores; A) scores less than or equal to 4, which meant that they were in the early stage of severe attack (n = 9), B) scores 5-6, which meant impending respiratory failure (n = 17), C) scores greater than or equal to 7, which meant respiratory failure (n = 3). The values of SpO2 at the start of this therapy were 94.8, 91.5, 82.0%, respectively. The more severe their attacks were, the lower their SpO2 levels were. The periods until their scores became zero were 0.78, 6.3, 17.2 hours, respectively. There were significant differences between each period respectively (p less than 0.001, p less than 0.01). Heart rates decreased when their symptoms improved, and other adverse effects were not detected. These results suggest that this therapy is effective and safe for children with severe asthma attacks, especially in the early stage.

Re-evaluation of hydatidiform mole by DNA fingerprint method: the discrepancy in the diagnoses by pathological finding and the DNA fingerprint method.

Ten cases of hydatidiform mole (HM) were analysed by the DNA fingerprint method. DNA samples were prepared from HM tissue of HM and maternal and paternal bloods, followed by digestion with HaeIII restriction endonuclease, applied to agarose gel, and then transferred to a nitrocellulose filter. The filter was hybridized using mini-satellite DNA as a probe. A case of partial HM diagnosed by histological findings was revealed to be complete HM using DNA fingerprinting. The case was suggested to be a twin pregnancy with a cHM and an abortion, because the DNA fingerprint of hydropic tissue showed a paternal pattern and that of the non-hydropic tissue did not show such a pattern. DNA fingerprinting was considered to be useful in distinguishing complete HM from partial HM.

Effect of uvulonodular lesions on optokinetic nystagmus and optokinetic after-nystagmus in cats.

To investigate the effect of uvulonodular lesions on horizontal optokinetic nystagmus (OKN) and optokinetic after-nystagmus (OKAN), 6 cats were tested before and after lesions made by ablation under anesthesia. In the 3 cats with only uvular lesion, the initial slow phase velocity and the time constant of OKAN were unchanged. In the remaining three cats whose lesions included not only the uvula but also the nodulus, the time constant of OKAN was markedly prolonged, and the initial OKAN velocity was not affected. The postoperative average time constant of OKAN increased from normal value of 9 s to about 40 s. In contrast, OKN was unchanged in all of the 6 animals. These findings indicate that the nodulus may contribute to the discharge characteristics of the velocity storage integrator.

Discrepancy in the diagnoses of hydatidiform mole by macroscopic and microscopic findings and the deoxyribonucleic acid fingerprint method.

Ten cases of hydatidiform mole were analyzed by the deoxyribonucleic acid fingerprint method. Deoxyribonucleic acid samples were prepared from hydatidiform mole tissue of hydatidiform mole and maternal and paternal blood. A case of partial hydatidiform mole diagnosed by histologic findings was revealed to be complete hydatidiform mole by deoxyribonucleic acid fingerprinting.

Sialates and negative charge on the surface of syncytiotrophoblastic cells of full-term placentae in toxemic patients.

In the syncytiotrophoblastic surface of the toxemic full-term placentae, the sialates and their consequent negative charging were studied by both electron microscopic histochemistry (Ferritin method) and Western blot analysis. Evidence is presented showing (1) that the reactions with both the ferritin labelled Limulus Polyphemus Agglutinin (LPA-ferritin), specific to sialates, and the cationized ferritin, specific to a negative charge, decrease in the specimens of toxemic placentae, (2) that the density of sialates in placentae of severe gestational proteinuria or/and hypertension is statistically lower than that of severe gestational edema, and (3) that there is no difference between the blotted bands in normal placentae and toxemic ones regardless of the severity of the toxemia. These results indicate that the reduction of the surface negative charging is demonstrated in toxemic syncytiotrophoblasts and appears to be secondary to the decrease in the amount of sialate.

46,XY pure gonadal dysgenesis with gonadoblastoma.

A case of gonadoblastoma on one side in streak gonads in a phenotypic female with chromosomal 46,XY pattern is described. The histopathological resemblance between gonadoblastoma and sex cord tumor with annular tubules is discussed. The high serum testosterone level, being unrelated to the administration of human chorionic gonadotropin is valuable for the diagnosis of gonadoblastoma in an individual with dysgenetic gonads. Gonadoblastoma is frequently very small in size and is located in ectopic regions, so that laparotomy with biopsy has been stressed. The hormonal supplement for a postgonadectomized girl is also discussed.