Development of the amygdalohypothalamic projection in the mouse embryonic forebrain.

The amygdalohypothalamic projection, a major component of the stria terminalis, is involved in the conduction of emotional and olfactory information integrated in the amygdala to the hypothalamus to elicit emotional reactions. Despite the extensive studies on functional aspects of the amygdaloid complex, developmental mechanisms of the amygdala and related structures are still poorly understood. To investigate the development of the amygdalohypothalamic projection in the mouse embryonic brain, carbocyanine dye was applied to the amygdala to label the growing axons anterogradely and to the hypothalamus to label the amygdaloid neurons retrogradely. The initial outgrowth of the stria terminalis was found to be as early as E11.5. The pathway crossed in a saddle over the internal capsule, another prominent connection in the developing forebrain of the mammalian embryo. Bipolar immature neurons were distributed along the stria terminalis at the telencephalo-diencephalic boundary, and the internal capsule was also surrounded by these cells. These cells expressed immunoreactivities to calretinin and the lot-1 antigen which has been shown to be involved in guidance of the developing lateral olfactory tract. Ultrastructural analysis revealed an adherens-like junction between the stria terminalis and the apposed cells, implying contact-mediated guidance. These results suggest that, in the development of the stria terminalis, the axonal outgrowth is guided by a mechanism similar to that of the developing lateral olfactory tract, a major amygdalopetal connection.

Chemical composition and antifungal properties of essential oils of three Pistacia species.

The chemical composition of essential oils obtained from the leaves of Pistacia vera, Pistacia terebinthus, Pistacia lentiscus and the resin of Pistacia lentiscus were analyzed by GC and GC-MS. alpha-Pinene, beta-pinene, limonene, terpinen-4-ol and alpha-terpineol were found to be the major components. The antifungal activities of the above oils and P. lentiscus resin (total, acidic and neutral fractions) against the growth of three agricultural pathogens, Pythium ultimum, Rhizoctonia solani and Fusarium sambucinum were evaluated. Some doses of P. terebinthus, P. vera and P. lentiscus leaf oils and total and neutral fraction of P. lentiscus resin significantly inhibited the growth of R. solani. However, all samples did not show antifungal activity against P. ultimum and F. sambucinum, but increased the growth of F. sambucinum.

Sesquiterpene coumarins from the roots of Ferula assa-foetida.

From the chloroform extract of the roots of Ferula assa-foetida, two sesquiterpene coumarins designated assafoetidnol A and assafoetidnol B were isolated, in addition to six known compounds, gummosin, polyanthin, badrakemin, neveskone, samarcandin and galbanic acid. The structures of the sesquiterpenes new compounds were established by spectroscopic methods.

Monoterpene coumarins from Ferula ferulago.

Two monoterpene coumarins, designated ferulagol A and B, as well as three known monoterpene coumarins and three sesquiterpene lactones were isolated from the chloroform extract of the roots of Ferula ferulago. The structures of ferulagol A and B were determined to be 7-[(E)-3'-hydroxy-3',7'-dimethyl-4',6'-octadienyloxy]coumarin and 7-[(3'Z,5'E)-7'-hydroxy-3',7'-dimethyl-3',5'-octadienyloxy]coumarin, respectively.

An eudesmanolide and a carotane from Ferula sinaica.

Re-examination of the chemical constituents of the leaves of Ferula sinaica afforded a new eudesmanolide and a new carotane. The structures were elucidated by spectroscopic methods.

Expression of the zinc finger gene fez-like in zebrafish forebrain.

Anterior-posterior (A-P) patterning in the neuroectoderm is established during gastrulation in zebrafish and amphibians. We isolated a novel zinc-finger gene fez-like (fezl) from zebrafish, which displays sequence similarities to Xenopus Fez. The fezl transcripts were detected in the anterior edge of neuroectoderm, the prospective dorsal forebrain, from the late gastrula (80% epiboly stage) to the mid-segmentation period. fezl was also expressed in the ventral forebrain overlying the prechordal plate at these stages. The expression of fezl was enhanced in embryos expressing the Wnt inhibitor Dkk1 and reduced in embryos expressing Wnt8b. The expression in the ventral forebrain was eliminated in the one-eyed pinhead mutant and the antivin RNA-injected embryos, which lack the prechordal plate. Radiation hybrid mapping revealed that the fezl gene is localized to linkage group 11.

A 37-kDa peroxidase secreted from liverworts in response to chemical stress.

A peroxidase was purified from the culture medium of a suspension culture of Marchantia polymorpha (liverwort) after treatment with bornyl acetate, which acts as a chemical stress agent to the cells. The peroxidase was characterised as a glycoprotein of molecular mass 37-kDa having a pl of about 10 and an optimal pH of 6.5. The peroxidase was thermally stable at 50 degrees C for up to 60 min. The partial amino acid sequence of the peroxidase was determined and found to be dissimilar to the amino acid sequences of other higher plant peroxidases. The oxidative polymerization of lunularin by this peroxidase was examined and the formation of a dimer, a trimer and a tetramer was demonstrated by negative ion Fast Atom Bombardment (FAB)-mass spectroscopy of the reaction products.

Clinical application of biodegradable rib connecting pins in thoracotomy.

BACKGROUND: To assess the usefulness in rib reconstruction of biodegradable connecting pins made of polylactide (PLA), PLA rib pins were compared with conventional non-absorbent aluminous ceramic rib pins (alumina rib pins) in terms of their ability for fixing and healing of cut ribs in thoracic surgery. METHODS: There were 13 cases of rib fixation after thoracotomy using PLA rib pins and 11 cases using alumina rib pins, all of which were inserted into the medulla of the stump of the ribs that had been cut at thoracotomy to secure a larger surgical field. The observation period was 6 months after the operation. RESULTS: The degree of vertical shift of the ribs connected with PLA rib pins was significantly reduced compared with the degree using alumina rib pins. In chest radiographs clear zones around the pins, indicating a delay in bone neogenesis, were observed frequently around the alumina rib pins but were absent around the PLA rib pins. Osteosynthesis using PLA rib pins was significantly more favorable than with alumina rib pins. CONCLUSIONS: These results demonstrated that the PLA rib pin was superior to the alumina rib pin for fixing and healing of the cut rib.

[A case of far-advanced gastric cancer treated with neoadjuvant combination chemotherapy of UFT, low-dose CDDP and leucovorin, followed by subtotal gastrectomy with curative intent].

We herein present a case of a 70-year-old man with the tentative diagnosis of far-advanced gastric cancer supposed to be beyond surgical intervention. Neoadjuvant chemotherapy enabled us to perform subtotal gastrectomy with curative intent. The man was admitted to our hospital with the chief complaint of poor appetite. Because preoperative examinations revealed a mass adjacent to the portal vein and common bile duct, which was suspected to be lymphnode metastasis or gastric cancer directly invading those vital structures, 4 weeks of neoadjuvant combination chemotherapy (NACC) (CDDP 10 mg/body, day 1 through day 5/week, UFT 600 mg/body, every day, Leucovorin 15 mg/body, every day) was given with resultant curative resection of the tumor one month after completion of NACC.

Impaired duodenal bicarbonate secretion in diabetic rats. Salutary effect of nitric oxide synthase inhibitor.

We previously reported the impaired HCO3- secretion and the increased mucosal susceptibility to acid in the duodenum of streptozotocin (STZ)-induced diabetic rats. In this study, we investigated the salutary effect of the NO synthase inhibitor L-NAME (NG-nitro-L-arginine methyl ester) on these changes and compared it with those of insulin. Animals were injected streptozotocin (STZ: 70 mg/kg, ip) and used after 1, 3-4, and 5-6 weeks of diabetes with blood glucose levels of > 300 mg/dL. Under urethane anesthesia the HCO3- secretion was measured in the proximal duodenal loop using a pH-stat method and by adding 10 mM HCl. L-NAME (20 mg/kg x 2) or insulin (4 units/rat) was administered sc for 4-5 weeks, starting 1 week after STZ treatment. The duodenal HCO3- secretory responses to various stimuli such as mucosal acidification (10 mM HCl for 10 min), 16,16-dimethyl prostaglandin E2 (dmPGE2: 10 micrograms/kg, i.v.), and vagal stimulation (0.5 mA, 2 ms, 3 Hz) were significantly decreased in STZ-treated rats, depending on the duration of diabetes. Repeated administration of L-NAME, starting from 1 week after STZ treatment, significantly reduced blood glucose levels toward normal values and restored the HCO3- responses to various stimuli in STZ rats, the effects being similar to those observed after supplementation of insulin. Diabetic rats developed duodenal lesions after perfusion of the duodenum with 150 mM HCl for 4 h, but this ulcerogenic response was significantly inhibited by the repeated treatment with L-NAME as well as insulin. We conclude that L-NAME is effective in ameliorating hyperglycemic conditions in STZ-diabetic rats, similar to insulin, and restores the impaired HCO3- secretion and the increased mucosal susceptibility to acid in diabetic rat duodenums.

A case of bilateral reversible thalamic lesions.

We describe a case of bilateral reversible thalamic lesions with no neurological deficits and a good prognosis. The lesions appeared as low-density areas on CT and high-intensity areas on T2-weighted MR imaging, and resolved within 1 month, suggesting that the cause was edema.

Effective 30-hour preservation of canine lungs with modified ET-Kyoto solution.

BACKGROUND: With the aim of developing a preservation solution that can preserve donor lungs reliably for a long time, we prepared a modified ET-Kyoto solution by adding N-acetylcysteine, nitroglycerin, and dibutyryl adenosine 3', 5'-cyclic phosphate to the previously reported ET-Kyoto solution, which contains trehalose, gluconate, and hydroxyethyl starch. In this study, we examined the efficacy of modified ET-Kyoto solution in 30-hour lung preservation. METHODS: Twenty five pairs of adult mongrel dogs were divided into four groups. Donor lungs were flushed with modified ET-Kyoto solution (n = 9), with ET-Kyoto solution (n = 6), with University of Wisconsin solution group (n = 6), or with ET-Kyoto solution plus the solvents of nitroglycerin (ethanol and propylene glycol) (n = 4), then stored at 4 degrees C for 30 hours. All animals were treated with prostaglandin E1. Left lungs were transplanted and reperfused for 6 hours. RESULTS: With respect to arterial oxygen tension, peak inspiratory pressure, and wet-to-dry lung weight ratio, modified ET-Kyoto solution was significantly superior to ET-Kyoto solution. The modified ET-Kyoto solution was significantly superior to University of Wisconsin solution with respect to survival rate, arterial oxygen tension, and wet-to-dry lung weight ratio. Ultrastructural findings supported these results. CONCLUSIONS: These results suggest that modified ET-Kyoto solution is superior to University of Wisconsin solution for 30-hour lung preservation.

Parabolic flight experiments on physiological data acquisition and processing technologies using small jet aircraft (MU300).

The parabolic aircraft flight provides a short low gravity environment for approximately 20 seconds, which may not be sufficient for a research on the physiological phenomenon induced by actual weightlessness in space. However, the method is still useful to reveal essential and characteristic feature of physiological signs, and is available for testing hardware and also training of crew member during altered gravity. This paper reports the summary of parabolic flight experiments recently conducted as a NASDA program (1990-1992). The program is providing opportunities in low gravity research with small jet aircraft for researchers and agencies. The flight experiments in the life science area have been conducted mostly focused on a physiological changes and basic methodology which may be effective under the altered gravity condition. In this study, the following research team, NASDA, Research Institute of Environmental Medicine, Nagoya University, Toyohashi University of Technology, Tokyo Metropolitan Hospital, Torey Research Center and JSUP were involved and coordinated for the research.

Effect of granulocyte colony-stimulating factor on hematopoietic recovery after peripheral blood progenitor cell transplantation.

To examine the effect of granulocyte colony-stimulating factor (G-CSF) on hematopoietic recovery after high-dose chemotherapy and peripheral blood progenitor cell transplantation (PBPCT), 20 patients with hematologic malignancies were divided into two groups. One group was given G-CSF at a daily dose of 50 micrograms/m2 subcutaneously, the other received no G-CSF. Neutrophil recovery was accelerated in the G-CSF treated patients and exceeded 0.5 x 10(9)/l at a median of 10 days post-PBPCT compared with 14 days in the control group (p < 0.01). This reduction led to a decrease in antibiotic use and a trend toward fewer febrile days in the G-CSF treated group.

Autoimmune thrombocytopenia following peripheral blood stem cell autografting.

A 22-year-old woman diagnosed as AML (M3) received myeloablative chemotherapy followed by autologous peripheral stem cell transplantation (PBSCT). Rapid hematopoietic reconstitution occurred. By day 10, the neutrophil count was > 0.5 x 10(9)/l and the platelet count > 50 x 10(9)/l. The platelet count was 145 x 10(9)/l on day 20. Purpura developed on the anterior chest and legs on day 50, at which time the platelet count fell to 17 x 10(9)/l. The BM was hypocellular with an increase in megakaryocytes. Platelet-associated IgG (PAIgG) was 88.1 ng/10(7) platelets (normal range 9-25 ng/10(7)); a diagnosis of idiopathic thrombocytopenic purpura (ITP) was made. Prednisolone administration led to an increase in the platelet count and a decrease in PAIgG. Analysis of lymphocyte subsets revealed an increased number of CD3+ gamma/delta T cells. It is postulated that the thrombocytopenia in this case was due to an autoimmune mechanism such as ITP.

Studies on absorption, distribution, excretion and metabolism of ginseng saponins. VIII. Isotope labeling of ginsenoside Rb2.

To clarify the pharmacokinetics of absorption, distribution and excretion of ginsenoside Rb2 (Rb2), one of the major saponins of the root of Panax ginseng, following oral administration to rats, a tritium (3H) labeling of Rb2 was examined. The C-12 position of Rb2 was labeled with 3H-sodium borohydride (3H-NaBH4) and 12-3H Rb2 and 12-3H-epi Rb2 was synthesized. This method of specific position labeling of Rb2 may be applicable to other ginsenosides. In the near future, the pharmacokinetics of Rb2 in rats may be clarified with 3H labeled Rb2.

[Mechanism of synergism and clinical results of sequential methotrexate and 5-fluorouracil in the treatment of gastric cancer].

Mechanism of synergism and clinical results of methotrexate and 5-fluorouracil (MTX/5-FU) combination therapy for gastric cancer were studied. The response rate against poorly differentiated gastric cancers was 35% in this treatment. This treatment also showed a remarkable effect against cases with pleural and abdominal effusion caused by cancerous disseminations. A promising result was obtained by this treatment as neoadjuvant and postoperative chemotherapy against Borrmann type 4 gastric cancer. A greater dependence on the de novo pathway of pyrimidine synthesis against poorly differentiated gastric carcinoma, which was estimated by the fact that the thymidylate synthetase/thymidine kinase ratio was significantly higher in poorly differentiated gastric cancer than in well differentiated cancer, may potentiate therapeutic results of this treatment.

Anticancer activity of free gamma-linolenic acid on AH-109A rat hepatoma cells and the effect of serum albumin on anticancer activity of gamma-linolenic acid in vitro.

The cytotoxicity of gamma-linolenic acid (C18:3n-6) against rat hepatoma AH-109A cells and the effect of bovine serum albumin (BSA) on its toxicity were examined in culture. The proliferation of AH-109A cells, evaluated by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay, was significantly suppressed by gamma-linolenic acid above 5 micrograms/ml concentration in serum-free culture medium. However, its toxicity was reduced by supplement of BSA. Similar observation of reduced toxicity by BSA was shown by the method of trypan blue dye exclusion and a colony formation assay. The cytotoxicity of gamma-linolenic acid was correlated closely with the concentration of unbound (free) gamma-linolenic acid. Production of thiobarbituric acid reactive material, one of the indicators of lipid peroxidation, was stimulated by gamma-linolenic acid and inhibited by BSA. These results suggested that the presence of albumin suppressed the cytotoxicity of the free fatty acid.

Carbazomycins G and H, novel carbazomycin-congeners containing a quinol moiety.

Carbazomycins G (I) and H (II), new congeners of the carbazomycin complex, have been isolated from the culture broth of Streptoverticillium ehimense. They have proved to contain a unique quinol moiety in the molecule. Their structures have been elucidated by mass and NMR spectrometries and X-ray crystallographic analysis. Carbazomycin G showed moderate antifungal activity against Trichophyton species.

Biologically active constituents of leaves and roots of Aloe arborescens var. natalensis.

Several biologically active substances, such as aloenin (1), magnesium lactate, aloe-emodin (4), barbaloin (5), and succinic acid, were found to be contained in the leaf juice of Aloe arborescens Mill. var. natalensis Berger, which has widely been used in domestic medicines. Aloenin (1) and magnesium lactate were elucidated to exhibit an inhibitory action on the gastric juice secretion of rats. Various constituents other than the above bioactive substances were found in the leaves and the roots of the plant.