The effect of somatostatin analogue on glucose homeostasis in conscious dogs.

Our aim was to clarify the effect of a somatostatin analogue (octreotide) on glucose flux in conscious dogs. We monitored the effects with catheters in the portal vein, hepatic vein and femoral artery and Doppler flow probes on the portal vein and hepatic artery before and after oral glucose administration. A significant increase of portal vein plasma flow after oral glucose was completely suppressed by both 4 and 1 micrograms/kg octreotide.

Interaction between left-handed Z-DNA and polyamine - 3. The crystal structure of the d(CG)3 and thermospermine complex.

The DNA fragment, d(CG)3, was co-crystallized with N-(3-amino-propyl)-N-(5-aminopropyl)-l,4 -diaminobutane (thermospermine; PA(334)), a polyamine metabolized from the nucleic acid. By using a good crystal with dimensions of 0.5 x 0.

A candidate for cancer gene therapy: MIP-1 alpha gene transfer to an adenocarcinoma cell line reduced tumorigenicity and induced protective immunity in immunocompetent mice.

Purpose: To evaluate the possibility of cancer gene therapy by the gene delivery of chemokine, the effects of human macrophage inflammatory protein 1 alpha (hu-MIP-1 alpha), murine-macrophage inflammatory protein 1 alpha (mu-MIP-1 alpha), and human-interleukin 8 (hu-IL-8) on tumor progression and immunization were studied.

Methods: Cachexia-inducing and highly tumorigenic adenocarcinoma cells (cell line colon 26, clone 20) were transfected with either a control plasmid, hu-MIP-1 alpha, mu-MIP-1 alpha, or hu-IL-8 expression vector. The production of hu-MIP-1 alpha reached > 1.

Interaction between the left-handed Z-DNA and polyamine-2. The crystal structure of the d(CG)3 and spermidine complex.

This paper deals with the crystal structure of d(CG)3-spermidine complex. The DNA fragment, d(CG)3, was crystallized with N-(2-amino-propyl)-1,4-diamino-butane, PA(34), spermidine. The results of its X-ray crystallographic analysis showed many intermolecular contacts between d(CG)3 and spermidine, but the binding mode of spermidine to the d(CG)3 molecule is different from that of the d(CG)3 and N-(2-amino-ethyl)-1,4-diamino-butane [PA(24)] complex: a spermidine molecule bound to the d(CG)3 and its symmetrically related neighboring d(CG)3 molecules through the water molecules with hydrogen bonds, while one PA(24) molecule connected directly to one d(CG)3 molecule, but not to its neighboring d(CG)3 molecule.

Numerical chromosome alterations in colorectal carcinomas detected by fluorescence in situ hybridization. Relationship to 17p and 18q allelic losses.

This study concerns DNA ploidy, numerical changes of chromosomes 7, 8, 10, 17 and 18, and allelic losses at chromosomes 17p13.3 (flanking the p53 gene) and 18q21 (location of the DCC gene) in 31 freshly resected colorectal tumours. Cytological smears were used to determine DNA ploidy by image analysis, and chromosome numbers by fluorescence in situ hybridization (FISH) using chromosome-specific pericentromeric alpha-satellite DNA probes.

Are glomerular lesions alternatives to microalbuminuria in predicting later progression of diabetic nephropathy?

We inquired whether the type of diabetic glomerulosclerosis, diffuse or nodular, is of value as an alternative to microalbuminuria in predicting later progression of renal disease. To answer this question, we conducted a retrospective cohort study in eleven Japanese non-insulin-dependent diabetes mellitus patients with normo- to microalbuminuria. Nodular diabetic glomerulosclerosis was found in six patients, and diffuse diabetic glomerulosclerosis in five patients.

Translation initiation sites and relative activity of large and small forms of human choline acetyltransferase.

We have previously shown that translation of human choline acetyltransferase (ChAT) mRNA starts at least at two sites and produces two enzyme proteins with different molecular weights. In this study, translation initiation sites and relative activity of large and small forms of ChAT were determined by site-directed mutagenesis, followed by expression and immunoblotting analyses. The large and small forms were translated at the first and second ATG codons of ChAT cDNA, respectively, and the specific activity was almost the same between the two forms of the enzyme.

Localization of choline acetyltransferase and acetylcholine in the chorion of early human pregnancy.

This report concerns the activity of choline acetyltransferase (ChAT), and the localization of ChAT and acetylcholine (ACh) in the human chorion during the 5th to 10th weeks of gestation. Radio-enzyme, immunohistochemical, and in situ hybridization assays were used. We found that ChAT activity increases as a function of gestational age between the 5th and the 9th weeks of pregnancy.

Matrix metalloproteinase 9 (gelatinase B) is expressed in multinucleated giant cells of human giant cell tumor of bone and is associated with vascular invasion.

Human giant cell tumor (GCT) consists of multinucleated giant cells and mononuclear stromal cells, and is characterized by frequent vascular invasion without distant metastases. To study the role of matrix metalloproteinases (MMPs) in the vascular invasion, we examined production of MMP-1 (tissue collagenase), -2 (gelatinase A), -3 (stromelysin-1), -9 (gelatinase B), and tissue inhibitors of metalloproteinases (TIMP-1 and -2) in GCT. MMP-9 was highly and predominantly expressed in giant cells by both immunohistochemistry and in situ hybridization.

Studies on cerebral protective agents. IX. Synthesis of novel 1,2,3,4-tetrahydroisoquinolines as N-methyl-D-aspartate antagonists.

A series of 1,2,3,4-tetrahydroisoquinoline derivatives were synthesized and evaluated for anticonvulsant activity against intracerebro-ventriculas (i.c.v.

Immunohistochemical study on choline acetyltransferase in the spinal cord of patients with amyotrophic lateral sclerosis.

The authors developed a polyclonal antibody against a fusion protein containing 598 amino acids from a human choline acetyltransferase (ChAT) cDNA and 12 amino acids derived from an expression vector, and examined immunohistochemical reactivity for ChAT in large motor neurons (30 microns and more in somal minimal diameter) of the lumbar spinal cords of four patients with amyotrophic lateral sclerosis (ALS) and of four control cases. In controls, the number of large neurons included in the tissue with a total thickness of 100 microns ranged from 74 to 105 (average 87). About 60-90% (average 80%) of the neurons were positively stained in their perikarya with an anti-human ChAT antibody.

Human MCAF gene transfer enhances the metastatic capacity of a mouse cachectic adenocarcinoma cell line in vivo.

Purpose: To evaluate the effect of monocyte chemotactic and activating factor (MCAF/MCP-1/JE) on tumor progression and metastasis.

Methods: Cachexia-inducing adenocarcinoma cells (cell line colon 26, clone 20) were transfected with either a control plasmid or MCAF expression vector. Spontaneous lung metastases were determined in mouse.

An Unusual Case of Multiple Gastric Carcinoids Associated with Diffuse Endocrine Cell Hyperplasia and Parietal Cell Hypertrophy.

We describe a case of multiple gastric carcinoid tumors in a 47 year-old Japanese man. The patient had markedly elevated serum gastrin levels (>800 pg/mL), which were suppressed by secretin-pancreozymin administration. In the partial gastrectomy specimen, a total of 19 carcinoids arose from diffuse linear and micronodular hyperplasia of the oxyntic mucosal endocrine cells.

Studies on cerebral protective agents. VIII. Synthesis of 2-aminothiazoles and 2-thiazolecarboxamides with anti-anoxic activity.

Various 2-aminothiazoles (2a-s and 3a-g) and 2-thiazolecarboxamides (4a-h), possessing a nitrogenous basic moiety at the C-2 position of the thiazole ring, were prepared and tested for anti-anoxic (AA) activity in mice. Among them, N-[2-(4-morpholinyl)ethyl]-4-(3-trifluoromethylphenyl)-2- thiazolecarboxamide hydrochloride (4e, FR108143) (minimum effective doses of 3.2 mg/kg i.

Immunohistochemical study on collagenous proteins and biophysical analysis of crystals in extraskeletal chondroma.

The immunohistological distribution of collagen types I, II, III, and VI in five cases of extraskeletal chondroma was examined and compared with that in six cases of enchondroma. In addition, the composition of crystals deposited in three cases of extraskeletal chondroma were biophysically analyzed with special attention to the relationship between the collagen types of the matrix and the crystal deposition. In extraskeletal chondroma, immunoreactivity of type II collagen in the extracellular matrix and type VI collagen in the pericellular area, which were strongly and diffusely recognized in the normal hyaline cartilage and enchondroma, was diminished.

Prevention of endotoxin shock by an antibody against leukocyte integrin beta 2 through inhibiting production and action of TNF.

Septic shock remains a serious disorder associated with high mortality. Accumulating evidence indicates that TNF is a major and essential mediator of endotoxin shock. We report here that administration of an antibody against CD18 dramatically reduced endotoxin-induced shock in rabbits as revealed by prevention of severe hypotension, metabolic acidosis and a pathological change suggestive of disseminated intravascular coagulation with concomitant inhibition of elevation of plasma TNF activity.

Integrin distribution in gastric carcinoma: association of beta 3 and beta 5 integrins with tumor invasiveness.

Immunolocalization of a variety of integrins using monoclonal antibodies against beta 3, beta 5, alpha 3 beta 1 and alpha 6, and polyclonal antibodies against vitronectin receptor (alpha v beta 3) and beta 1 were investigated on PLP-fixed paraffin sections of 19 cases of advanced gastric carcinomas. The beta 5 integrin, which pairs only with the alpha v subunit, was positive in seven cases (37%), and was associated closely with scirrhous invasion (P < 0.05).

Immunolocalization of desmoglein and intermediate filaments in human oral squamous cell carcinomas.

Background: Information is limited as to how to predict the malignant behavior of the oral squamous cell carcinomas. The invasive and metastatic phenotype of the carcinoma cells may be related to changes in the expression of desmosomal and cytoskeletal proteins.

Methods: To investigate the expression of desmoglein, cytokeratins, and vimentin, 22 biopsy specimens of oral squamous cell carcinomas were examined by immunohistochemistry.

Conformational studies on the four stereoisomers of the novel anticholinergic 4-(dimethylamino)-2-phenyl-2-(2-pyridyl)pentanamide.

To interpret differences in the anticholinergic activity among the four stereoisomers of 4-(dimethylamino)-2-phenyl-2-(2-pyridyl)pentanamide (1-4), we performed conformational studies using the semiempirical molecular orbital method. The structures of the global minimum-energy conformations obtained for 1-4, however, could not explain the different activities, particularly in terms of distances between the essential pharmacophores. We thus implemented superimposition studies, using the energetically stable conformations of the most active stereoisomer, 1(2S,4R), as a template.

Interleukin-1 and its naturally occurring antagonist in peritoneal dialysis patients.

We have assessed the levels of interleukin-1b (IL-1b) and interleukin-1 receptor antagonist (IL-1RA) in both serum and peritoneal dialysate effluents (PDE) from nineteen continuous ambulatory peritoneal dialysis patients (CAPD) without peritonitis and three CAPD patients with peritonitis. IL-1 beta and IL-1RA were tested using a specific ELISA immuno-assay. Fifteen normal healthy volunteers severed as control.

Matrix metalloproteinase 7 (matrilysin) from human rectal carcinoma cells. Activation of the precursor, interaction with other matrix metalloproteinases and enzymic properties.

Matrix metalloproteinase 7 (MMP-7) has been purified as an inactive zymogen of M(r) 28,000 (proMMP-7) from the culture medium of CaR-1 human rectal carcinoma cells. The NH2-terminal sequence of proMMP-7 is Lys-Pro-Lys-Pro-Gln-Glu, which is identical to that of matrilysin. The zymogen is activated by 4-aminophenylmercuric acetate (APMA), yielding an intermediate form of M(r) 21,000 and an active species of M(r) 19,000 which shows the new NH2-terminal sequence of Tyr78-Ser-Leu-Phe-Pro-Asn-Ser.

Localization of matrix metalloproteinase 9 (92-kilodalton gelatinase/type IV collagenase = gelatinase B) in osteoclasts: implications for bone resorption.

Background: Matrix metalloproteinase 9 (MMP-9, 92-kD gelatinase/type IV collagenase = gelatinase B) is a member of the MMP gene family and implicated in tissue destruction in the various pathophysiologic conditions. Our previous study showed that MMP-9 purified from human fibrosarcoma cells can cleave the cross-link-containing NH(2)-terminal telopeptides of the alpha 2 chain of type I collagen and collagen types III, IV, and V as well as gelatins.

Experimental Design: To investigate the role of MMP-9 in bone resorption we have examined its localization in the human bone tissues by immunohistochemistry and in situ hybridization.

Agents for the treatment of overactive detrusor. VIII. Synthesis and pharmacological properties of 4,4-diphenyl-2-cycloalkenylamines including FK584 and 3,3- or 4,4-diphenylcycloalkylamines.

This article describes the synthesis of 4,4-diphenyl-2-cycloalkenylamines (3, 5a) including FK584 (S(-)-3a) and 3,3- or 4,4-diphenylcycloalkylamines (2, 4, 5b) and their inhibitory activities against detrusor contraction. The order of inhibitory activity (i.v.

Covalently-bound human C4b dimers consisting of C4B isotype show higher hemolytic activity than those of C4A in the C3-bypass complement pathway.

The ability to form a covalent dimer of human C4b was investigated with purified isotypes C4A and C4B, and antibody-sensitized liposomes supplemented with C1. In this system, no C4A or C4B formed a complex with the antibody or C1. Whereas both C4A and C4B isotypes formed dimers to a similar extent, C4B formed an ester-linked dimer and C4A an amide-linked dimer.

Pulmonary vasculitis with hypereosinophilia and episodic pulmonary hypertension: report of three siblings.

Three siblings with eosinophilia who developed pulmonary hypertension are reported. They consisted of a 3 year old boy (case 1), a 9 year old boy (case 2) and a 13 year old girl (case 3), all of whom died within an 18 month period of severe episodic attacks of pulmonary hypertension and the resultant low cardiac output. Marked peripheral eosinophilia was found in cases 1 and 2, and mild eosinophilia in case 3.