Availability of 4'galactosyllactose (O-beta-D-galactopyranosyl-(1----4)-O-beta-D-galactopyranosyl-(1----4)- D-glucopyranose) in rat

O-beta-D-Galactopyranosyl-(1----4)-O-beta-D-galactopyranosyl-(1----4)-D- glucopyranose (designated as 4'GL) is produced from lactose by Cryptococcus laurentii. The influence of chronic ingestion of 4'GL on body weight gain, organ weight, serum lipids, and liver lipids was investigated in rats. The body weight gains of the 5% and 10% 4'GL-diet groups were higher than that of the control group. Food intake and fecal dry weight were significantly increased (p less than 0.05) by 4'GL feeding. The 4'GL diet produced a significant increase (p less than 0.01) in the wet weight and contents of both the cecum and the colon. However, no significant increase was observed in the weight of the stomach, small intestine, liver, or other organs. The effects of 4'GL on serum and liver lipid levels were not observed in this experiment. The digestion of 4'GL was measured in vitro using the artificial gastric juice, alpha-amylase of human saliva, alpha-amylase of hog pancreas, and mucosa of rat intestine. 4'GL was not hydrolyzed by these enzymes. Long-term ingestion of 4'GL did not cause any induction of 4'GL hydrolyzing enzyme activity in the rat small intestine.     

Intra-operative administration of neocarzinostatin into the duodenal subserosa and levels found in the regional lymph nodes in pancreato-duodenal cancer

As an intraoperative chemotherapy treatment for the regional lymph nodes in resectable cases of pancreatoduodenal cancer, Neocarzinostatin (NCS) was administered in the duodenal subserosa and the NCS concentration was measured in the resected lymph nodes. Experiments: NCS 4,000 units (n = 4), or 10,000 units (n = 4) was administered into the duodenal subserosa of mongrel dogs, and 2 hours after administration, the lymph nodes of the mesentery root were resected. The NCS concentration in the lymph nodes was 0.21 U/g in the 4,000-U group and 1.39 U/g in the 10,000-U group. Clinical findings: NCS 10,000 U was administered into the duodenal subserosa in 6 cases of pancreatoduodenal cancer. The total number of resected lymph nodes was 49 and the mean NCS concentration was 5.65 U/g. According to site, the highest concentration was measured in lymph nodes from the anterior and posterior region of the pancreas head, which were near to the administration site. Also, NCS was well distributed in the lymph nodes in the hepatoduodenal ligament and mesentery root which lay in the direction of lymph flow. NCS concentration was high in lymph nodes resected 1 hour after administration. According to experimental reports of in vitro studies, an NCS concentration of more than 0.5 U/g is required to obtain an anticancer effect. This method is therefore considered to be useful as a form of intraoperative chemotherapy for the regional lymph nodes in pancreatoduodenal cancer.     

Association of sixty-one non-synonymous polymorphisms in forty-one hypertension candidate genes with blood pressure variation and hypertension.

We previously selected a group of hypertension candidate genes by a key word search using the OMIM database of NCBI and validated 525 coding single nucleotide polymorphisms (SNPs) in 179 hypertension candidate genes by DNA sequencing in a Japanese population. In the present study, we examined the association between 61 non-synonymous SNPs and blood pressure variations and hypertension. We used DNA samples taken from 1,880 subjects in the Suita study, a population-based study using randomly selected subjects. Analyses of covariance adjusting for age, body mass index, hyperlipidemia, diabetes, smoking, drinking, and antihypertensive medication revealed that 17 polymorphisms in 16 genes (APOB, CAST, CLCNKB, CTNS, GHR, GYS1, HF1, IKBKAP, KCNJ11, LIPC, LPL, P2RY2, PON2, SLC4A1, TRH, VWF) were significantly associated with blood pressure variations. Multivariate logistic regression analysis with adjustment for the same factors revealed that 11 polymorphisms in 11 genes (CAST, CTLA4, F5, GC, GHR, LIPC, PLA2G7, SLC4A1, SLCI8A1, TRH, VWF) showed significant associations with hypertension. Five polymorphisms in five genes, CAST(calpastatin), LIPC (hepatic lipase), SLC4A1 (band 3 anion transporter), TRH (thyrotropin-releasing hormone), and VWF (von Willebrand factor), were significantly associated with both blood pressure variation and hypertension. Thus, our study suggests that these five genes were susceptibility genes for essential hypertension in this Japanese population.     

The use of the polymerase chain reaction to map CD4+ T cell epitopes.

CD4+ T cells recognize processed exogenous antigen in the form of peptides bound to syngeneic major histocompatibility complex class II molecules on antigen-presenting cells. We have developed a novel and convenient method to synthesize and map CD4+ T cell epitopes of cloned antigens using polymerase chain reaction (PCR)-directed construction of genes expressing recombinant protein fragments. Unique restriction sites incorporated into the PCR primers were employed for the unidirectional cloning of gene fragments into a bacterial expression vector that can be induced to high-level expression. The bacterial lysate could be used directly in T cell proliferation assays. Overlapping recombinant fragments spanning the entire protein were generated and tested. The length of the sequence containing the epitope was further reduced by utilizing PCR to generate 3' truncations. Finally, a small number of overlapping peptides spanning a sequence of 39 amino acids were synthesized to identify a thirteen-amino acid peptide epitope within chicken transferrin that stimulates the T helper cell clone D10.G4.1. PCR-directed construction of fragments of antigen allows for optimal design of strategies for the mapping and analysis of CD4+ T cell epitopes.     

CT findings in panacinar emphysema]

We analyzed the CT images (in vivo) of 5 lobes (right middle lobe, 1; left lower lobe, 1; right lower lobe, 3) with panacinar emphysema (PAE) obtained at autopsy or thoracotomy for solitary lung tumor. The lobes were inflation-fixed by the method of Heitzman and sliced axially for a CT-pathologic correlative study. One lobe with mild PAE had normal appearance on CT; however, the other four lobes with PAE demonstrated low-attenuation areas (LAAs) of various shapes and sizes on CT. LAAs were locally distributed on CT slices in one lobe, dominant in the inner zones in two lobes, and diffuse in one lobe. Relatively normal to diminished vasculature was observed within the LAAs of four lobes. These CT findings differed significantly from those of centriacinar emphysema (CAE) as reported in other studies. We conclude that CT is useful in the clinical diagnosis of PAE and its differentiation from CAE.     

Intraosseous ganglion about to cause a fracture of the glenoid: a case report

Intraosseous ganglia of the glenoid are rare, and their etiology is unknown. This report describes a case of an intraosseous ganglion about to cause fracture of the glenoid. The patient was a 61-year-old woman with a painful left shoulder with a limited range of motion. Her symptoms did not improve after non-operative treatment. Arthroscopic examination showed a cartilage defect and erosion in the posteroinferior portion of the glenoid, behind which computed tomography (CT) showed a cystic lesion of the glenoid. There was no communication between the cyst and the joint space. The patient was treated by curettage and an autogenous cancellous bone graft from the iliac crest. Two years after the operation, the patient was almost free from pain, and CT showed good integration of the bone graft.     

Myrocin C, a new diterpene antitumor antibiotic from Myrothecium verrucaria. I. Taxonomy of the producing strain, fermentation, isolation and biological properties

A new diterpene antitumor antibiotic, myrocin C, has been isolated from the culture filtrate of a soil fungus, Myrothecium verrucaria strain No. 55. The antibiotic was effective against Gram-positive bacteria, fungi and yeasts, and prolonged the life span of mice bearing Ehrlich ascites carcinoma.     

Penicillamine-Induced Degenerative Dermatoses: Report of a Case and Brief Review of Such Dermatoses

We describe a case of elastosis perforans serpiginosa with additional findings of degenerative skin changes. A 20-year-old man with hepatolenticular degeneration, under prolonged treatment with D-penicillamine, presented with a circular or serpiginous arrangement of nuchal papules. Histopathologically, transepidermal channels were accompanied by granulomatous reactions, with several giant cells engulfing elastic fibers. In addition to these findings of a typical elastosis perforans serpiginosa, we observed scar-like skin changes inside the circular arrangement of the papules. At the scar-like tissue, we found electron-microscopical evidence of randomly aggregated thin collagen fibers with no tendency toward systemic combined bundle formation, which is a characteristic feature of normal collagen fiber formation. Pseudoxanthoma-elasticum-like changes were observed on his neck. On his axillae and groin, slight skin thickening and wrinkling were detected. The diagnosis of elastosis perforans serpiginosa does not represent all of the manifestations or the pathological background described above. The skin manifestations described here represent not only an elastosis but also a total degenerative dermatosis with over-healed collagenosis. Thus, those dermatoses should be summarized as one entity, penicillamine-induced degenerative dermatosis. After considering the pathogenic background and clinical similarities, we further propose to simplify the penicillamine-induced skin manifestations to three categories: acute sensitivity reactions, bullous dermatoses, and degenerative dermatoses.     

Mechanisms underlying the enhanced elevation of IL-1beta and TNF-alpha mRNA levels following endotoxin challenge in rat alveolar macrophages cultured with low-Mg2+ medium.

We have previously shown that interleukin (IL)-1beta and tumour necrosis factor (TNF)-alpha mRNA levels in rat alveolar macrophages are increased in by endotoxin (lipopolysaccharide; LPS)- stimulation and further enhanced by culturing with low-Mg2+ medium. We have now investigated the mechanisms of underlying this enhancement by using some specific signal transduction inhibitors. The enhanced elevation of both mRNAs levels was suppressed by pretreatment with TMB-8 (which inhibits calcium release from the endoplasmic reticulum) or dexamethasone (which inhibits nuclear factor [NF]-kappaB and activator protein [AP]-1), but not with verapamil or nifedipine (which inhibits calcium channels). The enhancment of IL-1beta, but not TNF-alpha mRNA levels, was suppressed by pretreatment with W-7 (which inhibits calmodulin), whereas the enhancement of TNF-alpha mRNA levels was suppressed by pretreatment with U73122 (which inhibits phospholipase C). Curcumin (an inhibitor of AP-1), suppressed the increases in both mRNAs induced by low-Mg2+ medium alone, but had no suppressive effect on the levels of either mRNA after LPS-stimulation in low-Mg2+ medium. Pyrrolidine dithiocarbamate (an inhibitor of NF-kappaB) prevented the elevation of TNF-alpha mRNA levels induced by low-Mg2+ medium without LPS-stimulation, but had no suppressive effect on IL-1beta mRNA levels. From these results, we conclude that the enhanced elevation of IL-1beta and TNF-alpha mRNA levels seen in LPS-stimulated alveolar macrophages in low-Mg2+ medium occurs partly via the same, and partly via different, signaling pathways.