Mevalonic acidemia: First case of Japan

Summary Mevalonic acidemia is a rare metabolic disorder due to mevalonate kinase deficiency which affects the biosynthesis of cholesterol and nonsterol isoprenes. We report the first case of Japan. The clinical course is characterized by intrauterine growth retardation, postnatal growth failure, intractable diarrhea, liver dysfunctions and death at three months of age. Dysmorphic features including triangular face, protrusion of forehead, hypertelorism, low set ears and micrognathism were noted. High mevalonic acid level was found by GC/MS.     

Chromosome 1q terminal deletion resulting fromde novo translocation with an acrocentric chromosome

Summary Distal deletion of chromosome 1q has been reported in nearly 30 patients, all being associated with a deletion ranging from the 1q42 or q43 band to 1qter region. Here, we describe a girl with 1q terminal deletion resulting from an unbalancedde novo translocation t(1;D or G)(q44; p11), as revealed by the presence of a satellited feature and an NOR-stained region at the tip of 1q. We suggest that most of the phenotypic abnormalities seen in patients with 1q distal deletion are attributable to the monosomy for band 1q44.     

Ectopic expression of activated Stat6 induces the expression of Th2-specific cytokines and transcription factors in developing Th1 cells

Stat6 is critical for IL-4-mediated Th2 cell development, but its molecular mechanism remains unclear. Here we constructed Stat6:ER, a Stat6-estrogen receptor fusion protein that can be activated by 4-hydroxy-tamoxifen, independently of IL-4 and endogenous Stat6. Retrovirus-mediated introduction of Stat6:ER into developing Th1 cells induced Th2-specific cytokines and suppressed IFNgamma production in a 4-HT-dependent manner and in the absence of IL-4. It also induced GATA-3 and c-maf expression and downregulated IL-12Rbeta2 chain expression. Its decreased ability to induce the Th2 phenotype with progressing Th1 cell commitment correlated with a decreased induction of GATA-3 and c-maf. This study indicates that Stat6 functions upstream of GATA-3 and c-Maf to induce Th2 development.     

Heterotopic gastric mucosa of the small intestine in laboratory beagle dogs

Out of the 365 young laboratory beagle dogs which were used in 17 toxicity bioassays, 15 cases (4.1%) were diagnosed as having congenital heterotopic gastric mucosa of the small intestine. Its incidence in the male dogs (12 cases out of 187) was higher than in the female dogs (3 cases out of 178). Grossly, the lesions were seen as an ulcerous focus of the small intestine, 25 cm to 88 cm proximal to the ileocecal valve. All of the lesions were quite similar histologically and electron microscopically to the normal gastric mucosa, which are composed of the surface mucous cells, chief cells, parietal cells, mucous neck cells and basal granulated cells of the stomach. And consequently, they were considered to be that of a congenital heterotopic tissue in the small intestine. The only morphological characteristic of these lesions different from the regular gastric mucosa was an association with the tubular structure seen in the basal region of these mucosal layers. These cells were considered to be of mucous-secreting cell origin because of secreting type III mucous evident from paradoxical concanavalin A or periodic acid Schiff stains. They seemed to be protecting the surrounding intestinal mucosa from gastric acid.     

Activation of lymphokine genes during stimulation of cloned T cells

To study the regulation of lymphokine production by T lymphocytes, we have characterized the activation of lymphokine genes in T cells by measuring the levels of lymphokine mRNA in cloned murine T lymphocytes after stimulation. Lymphokine mRNA was not detected in cells taken after seven days of maintenance culture. Following stimulation of T helper lymphocytes L2 and AD9.1 with concanavalin A, lymphokine mRNA appeared, reached peak levels and disappeared over a 43-h time period. A single stimulation event resulted in the induction of mRNA for interleukin 2 (IL 2), IL 3 and interferon gamma. Maximal mRNA levels were generally found at 6 h in the T helper lymphocytes, but could occur as late as 18 h. The lymphokine genes were expressed coordinately; however, in these cloned cells, IL 2 mRNA levels appeared to be lower than the other two mRNAs. Lymphokine titers in the supernatant fluids paralleled the appearance of mRNA but IL 2 titers began to fall after 12 h probably because of utilization of this lymphokine by the activated cells. In the cytolytic T lymphocyte, L3, qualitatively similar kinetics were found after stimulation by lectin or a clonotypic antibody with peak mRNA levels occurring later (18 h) with the antibody. These studies indicate a single stimulating event activates the lymphokine genes of T cells in a coordinate manner; the appearance of the lymphokines in supernatant fluids represents de novo synthesis of these proteins but the levels of lymphokines measured in supernatant fluids reflects both production and utilization rates, and exposure to IL 2 at the time of stimulation is not essential for the production of other lymphokines.     

Hypothalamic laterality in regulating gonadotropic function: unilateral hypothalamic lesion and ovarian compensatory hypertrophy

Regardless of the side of hemiovariectomy, unilateral lesion placed in the right-side medial anterior hypothalamus suppressed ovarian compensatory hypertrophy, but the lesion made in the left side failed to suppress it. This suggests the presence of a hypothalamic laterality in regulating gonadotropin secretion.     

Effect of an endogenous satiety substance, 2-buten-4-olide, on gastric acid secretion and experimental ulceration in rats

The involvement of a feeding-related endogenous sugar acid, 2-buten-4-olide (2-B4O) on central regulation of gastric acid secretion, and its antiulcer effects on several gastric and duodenal experimental ulcer models were investigated in rats. Spontaneous gastric acid secretion was not affected by 2-B4O at doses below 10 mg/kg. The peripheral secretagogue-stimulated gastric secretions were significantly increased by pretreatment with 2-B4O. Gastric acid secretion induced by 2-deoxy-D-glucose (2-DG) was significantly suppressed by pretreatment with 2-B4O at doses between 0.1 and 100 mg/kg. Gastric and duodenal ulcerations induced by cold stress plus indomethacin, restraint and water immersion stress, pylorus ligation or cysteamine were also inhibited by pretreatment with 2-B4O. The results suggest that antiulcer effects of 2-B4O are due to suppression of gastric acid secretion via reduction of activity of the vagus nerve and gastric-related hypothalamic neurons. Thus, 2-B4O may be useful for treatment of gastroduodenal ulcer.     

A common Ile796Val polymorphism of the human SREBP cleavage-activating protein (SCAP) gene

We identified a new common amino acid polymorphism of isoleucine/valine at codon 796 in exon 16 of the gene for human sterol regulatory element binding protein (SREBP) cleavage-activating protein (SCAP), a central regulator of lipid synthesis and metabolism in animal cells. It can be detected as an MslI restriction fragment length polymorphism. The allelic frequencies were: isoleucine (A) allele, 0.57 and valine (G) allele, 0.43. This polymorphism may be useful for genetic studies of disorders affecting intracellular lipid metabolism and hyperlipidemia. Received: August 17, 1999 / Accepted: August 19, 1999     

Distribution of 5'-nucleotidase activity in greater omentum of rats

The aim of the present study is to demonstrate the cellular basis of 5'-nucleotidase (5'-Nase) activity in the greater omentum of rats. Enzyme histochemistry for 5'-Nase showed that lymphatic vessels in the omentum as well as lymphocytes in the milky spots were positively stained. Electron microscopic observation revealed-5'-Nase activity at the luminal surface of the lymphatic endothelial cells, pinocytotic vesicles in the endothelial cells and the surface of fibroblasts located at the intercellular space of adipose cells. Fibroblasts extended long cytoplasmic processes toward adipose cells and inflammatory cells. These findings suggest that lymphatic endothelial cells as well as fibroblasts in the omentum may play an important role in regulation of metabolism and immune mechanisms in the greater omentum by supplying adenosin.     

Two cases of a renal epithelial tumour resembling immature nephron

Summary Two cases of renal epithelial tumours are reported in females aged 46 and 66 years respectively. In spite of the large size of the tumours, neither invasive growth nor metastasis was observed. Histologically, the tumours were composed of immature epithelial cells forming tubules with abortive glomeruloid structures. Electron microscopy of tumour cells revealed poorly developed polarity and intracytoplasmic organelles. They showed similar immunohistochemical reactions to those of developing nephrons, particularly to those of the S-shaped body. The nuclear DNA content of the tumour cells was almost euploid. We conclude that the lesions were epithelial tumours of the kidney histologically mimicking developing renal parenchyma.