Histamine is found in nerve cell bodies of the tuberomammillary nucleus in mammalian brain. This nucleus is prominent in human brain. Samples of human cerebelli obtained from neurosurgical operations were examined for the presence of histamine-containing nerve fibers. In all samples, a moderately dense network of histamine-immunoreactive fibers was seen in the molecular layer. These fibers ran parallel to the Purkinje cell layer after traversing it perpendicularly. Numerous fibers were also seen in the granular cell layer. The results suggest that the human cerebellar cortex receives a direct input from histamine-synthesizing hypothalamic neurons, as no other histamine-containing neurons have been found in human brain.

Aged↗

PubMed1993

Collaboration between growth factors and diverse chemical carcinogens in hepatocarcinogenesis of transforming growth factor alpha transgenic mice.

Transforming growth factor alpha (TGF-alpha) has been shown to induce liver tumors within 1 year in transgenic male mice in which this potent mitogen is overexpressed. To determine more precisely how TGF-alpha participates in multistep tumorigenesis of the liver, genotoxic (diethylnitrosamine or dimethylnitrosamine) and nongenotoxic (phenobarbital) chemical carcinogens were administered independently to TGF-alpha transgenic mice [line MT42 on a Crl:CD-1(ICR)BR background]. TGF-alpha overexpression dramatically accelerated carcinogen-induced hepatocarcinogenesis in MT42 males but not females. Interestingly, all three chemical agents were found to enhance strongly both hepatic tumor formation and progression in TGF-alpha transgenic male mice. In this study 100%, 90%, and 78% of transgenic males exposed to diethylnitrosamine, dimethylnitrosamine or phenobarbital, respectively, developed tumors between 24 and 32 weeks of age. Moreover, approximately 70% of tumor-bearing transgenic mice from each treatment group had hepatocellular carcinomas; no malignant lesions were found in any carcinogen-treated or untreated nontransgenic mice or in untreated MT42 mice at this age. These results demonstrate that chemical agents as diverse as nitrosamines and phenobarbital act as cocarcinogens with TGF-alpha in the livers of these transgenic mice, indicating that TGF-alpha possesses the unique ability to complement both initiation and promotion in hepatocarcinogenesis. Furthermore, because carcinogen-induced malignant conversion was restricted to transgenic mice, constitutive TGF-alpha overexpression may promote liver tumor progression as well.

Animals↗

PubMed1993

Localization of nitric oxide synthase-immunoreactive neurons in the solitary nucleus and ventrolateral medulla oblongata of the rat: their relation to catecholaminergic neurons.

The morphological relationship between nitric oxide (NO) and catecholamines in the solitary nucleus (SOL) and ventrolateral medulla oblongata (VLM) was studied by a double immunostaining method with antibodies against NO synthase (NOS), an NO-synthesizing enzyme, and tyrosine hydroxylase (TH), a catecholamine-synthesizing enzyme. Although NOS- and TH-immunoreactive neurons were widely distributed in the SOL and VLM, these immunoreactivities did not coexist in any single neurons. NOS-immunoreactive neurons formed clusters in some restricted regions, i.e. in the medial subnucleus of the SOL, where both NOS- and TH-immunoreactive neurons showed a complementary distribution. These findings suggest that NO-producing neurons constitute a subclass that is distinct from that of catecholaminergic neurons.

Amino Acid Oxidoreductases↗

PubMed1993

Expression of the CD15 antigen in hepatocellular carcinoma.

Expression of the CD15 antigen, which is one of the adhesion molecules, was studied immunohistochemically to investigate the mechanism of intrahepatic metastasis in 56 hepatocellular carcinomas (HCC). Twenty-nine percent (16 of 56) of the HCC expressed CD15. No noncancerous hepatocytes expressed CD15. CD15-positive HCC had histologic intrahepatic metastasis more often than did CD15-negative HCC; the difference was statistically significant (P < 0.02). The survival rate of patients with CD15-negative HCC was better than that of patients with CD15-positive HCC, although the difference was not statistically significant. The authors speculate that there is a relationship between the expression of CD15 and intrahepatic metastasis in HCC.

Antigens, CD↗

PubMed1993

Tyrosine kinase activity of the ret proto-oncogene products in vitro.

We investigated tyrosine kinase activity of the ret proto-oncogene products (proto-Ret proteins), using a cell lysate of NB-39-nu neuroblastoma cells. The 150 kDa and 170 kDa proto-Ret proteins immunoprecipitated with antibodies against their carboxy-terminal 20 amino acids were shown to be phosphorylated predominantly on tyrosine residues in immunocomplex kinase assay. The level of tyrosine phosphorylation of the 150 kDa proto-Ret protein was approximately 10-fold higher than that of the 170 kDa proto-Ret protein, although both proteins were expressed at similar levels in neuroblastoma cells. This result was confirmed by using a lysate of SK-N-MC human primitive neuroectodermal tumor cells transfected with the ret proto-oncogene. The kinase activity of proto-Ret proteins was significantly inhibited by antibodies against their kinase domain, indicating that these antibodies recognize crucial epitopes for the enzymatic activity. On the other hand, the proto-Ret proteins were not phosphorylated in vivo in NB-39-nu cells and SK-N-MC transfectants.

Amino Acids↗

PubMed1993

Association of expression of blood group-related carbohydrate antigens with prognosis in breast cancer.

BACKGROUND: It has been thought that carbohydrate antigens, especially Lewis (Le) blood group antigens, are cancer-related antigens. METHODS: The authors conducted immunohistochemical studies to investigate the expression of seven different types of Le carbohydrate antigens in breast cancer tissue and their usefulness as an indicator of the degree of malignancy and as a prognostic factor. RESULTS: When this expression was compared in the cancerous portion of 300 breast cancers and noncancerous mammary ductal epithelium in each of the patients, reduced expression of type 1 carbohydrate antigens and increased expression of type 2 carbohydrate antigens were found in the cancerous portions. No correlation was detected between the antigen expression and clinicopathologic factors. The prognosis of patients in whom type 2 carbohydrate antigens were increased in the cancerous portion, especially Lex (19.7% of patients) and sialyl Lex-i (20.3% of patients), was poorer than in patients in whom they were not increased (P < 0.01). CONCLUSIONS: The relative expression of type 2 carbohydrate antigens in breast cancer tissue seems capable of serving as a prognostic factor.

Antibodies, Monoclonal↗

PubMed1993

Oxygen-deficient barium lead oxide perovskites.

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Journal Article↗

PubMed1993

Neuropeptide Y innervation in the spinal nucleus of bulbocavernosus of the rat.

Immunoelectron microscopy combined with a retrograde tracing technique was carried out to examine the synaptic interaction between neuropeptide Y (NPY)-like immunoreactive (LI) axon terminals and spinal motoneurons innervating bulbocavernosus muscles. Cell bodies and proximal dendrites of these motoneurons were frequently found to receive synaptic inputs from NPY-LI axon terminals.

Animals↗

PubMed1993

L-Tyrosine-induced antinociception in the mouse: involvement of central delta-opioid receptors and bulbo-spinal noradrenergic system.

L-Tyrosine methyl ester (L-Tyr-OMe) produces naloxone-reversible antinociception in mice. This effect was characterized in the present study. L-Tyr-OMe administered s.c. at doses of 100-400 mg/kg elicited dose-dependent antinociception, which was antagonized by s.c. and i.c.v. naloxone at 1 mg/kg and 10 ng/mouse, respectively, but not by i.t. injection at 10 ng/mouse. The antinociceptive effect of systemic L-Tyr-OMe was also inhibited by naltrindole (0.1 mg/kg s.c.), a selective delta-opioid receptor antagonist, but was resistant to L-leucyl-L-arginine (3 micrograms/mouse i.c.v.), a kyotorphin (L-tyrosyl-L-arginine) receptor antagonist. This effect was reduced by i.t., but not by i.c.v., phentolamine at 0.1-1 microgram/mouse, while methysergide (10 microgram/mouse i.t.) and p-chlorophenylalanine (500 mg/kg s.c.) did not have such an inhibitory effect. L-Tyr-OMe, given i.c.v. and i.t. at 0.1-10 microgram/mouse, also produced dose-dependent antinociception, the latter effect being naloxone-reversible but resistant to i.t. phentolamine. These results suggest that L-Tyr-OMe (s.c.)-induced antinociception is mediated by central delta-opioid receptors and by the bulbo-spinal noradrenergic system, but not by the central 'kyotorphinergic' system, and that L-Tyr-OMe, when given i.t., produces antinociception via spinal opioidergic, but not noradrenergic systems.

Animals↗

PubMed1993

Recombinant human erythropoietin and hypophosphatemia in patients with cirrhosis.

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Blood Transfusion, Autologous↗

PubMed1993

Expression of blood group-related antigens in normal and malignant pancreatic tissue correlated with genotype of the patient defined by saliva glycoprotein.

BACKGROUND: Seven murine monoclonal antibodies (MoAb) detecting blood group antigens of the Lewis system and their sialylated derivatives were used to define their immunohistochemical distribution in normal and malignant pancreatic tissues. The specific blood group antigens studied included Lewis(a) (Le(a)), Lewisb (Leb), Lewisx (Le(x)), Lewis(y) (Le(y)), sialyl-Lewis(a) (s-Le(a)), sialyl-lacto-N-tetraose (s-LNT), and sialyl-Lewisx (s-Le(x)). METHODS: The expression of these antigens was analyzed by immunoperoxidase technique in pancreatic tissue of patients with (n = 27) and without (n = 19) pancreatic cancer. The genetic background of their secretor status and their Lewis phenotypes were determined by the enzyme-linked immunosorbent assay using purified salivary glycoprotein and MoAb against eight different blood group-related antigens (Le(a), Leb, Le(x), Le(y), H1, H2, A, B2), and the putative genotypes of the patients were classified as follows: SeLe, Sele, seLe, and sele. RESULTS: The following results were obtained: (1) In normal pancreas, Le(a), s-Le(a), s-LNT, and s-Le(x) were expressed in ducts, but their expression was restricted to the luminal side of the cytoplasm (cytoplasmic type with positive polarity). Leb and Le(y) showed similar patterns of expression in ducts and some parts of the acinus. In contrast, Le(x) was absent in most cases. (2) Expression of Leb was observed in normal pancreatic ducts in all 46 patients, regardless of their genotypes. Le(a) and s-Le(a) were not expressed in specimens from patients with the seLe and sele saliva phenotypes. (3) In pancreatic cancer, the following antigens were expressed cytoplasmically in the proportion of cases indicated: Le(a) (78%), Leb (85%), Le(x) (33%), Le(y) (44%), s-Le(a) (78%), s-LNT (89%), and s-Le(x) (85%). They also were detected in the surrounding stroma. This pattern of expression is distinct from that found in normal pancreatic tissue. Patients with Sele and sele genotypes did not express Le(a) or s-Le(a), except in one case. (4) Serum levels of carbohydrate antigen 19-9 (CA 19-9) were not elevated in patients with pancreatic cancer with the Sele and sele genotypes but were elevated in most patients with SeLe and seLe genotypes. CONCLUSION: The overall findings indicate that Lewis-related antigens act as pancreatic tissue-related antigens, depending in part on salivary phenotypes of the patient. With proper antigen selection and the determination of secretor status, these anti-blood group MoAb may be of clinical utility in the diagnosis of pancreatic cancer.

Antibodies, Monoclonal↗

PubMed1993

Low oxygen tension increases mRNA levels of alpha 1 (I) procollagen in human dermal fibroblasts.

Dermal fibroblasts exposed to low oxygen tension show upregulated synthesis of transforming growth factor-beta 1 (TGF-beta 1), an established stimulatory peptide in the formation of extracellular matrix proteins. In this report, procollagen synthesis was measured in cultures of confluent adult human dermal fibroblasts exposed to either standard (20%) or low (2%) oxygen tension. By Northern blot analysis the steady state levels of alpha 1 (I) procollagen mRNA were increased by 75 to 150% of control (standard oxygen) as early as 12 hours and more than 200% 96 hours after exposure of cells to low oxygen. Similar increases in procollagen mRNA levels were obtained in hypoxic fibroblast cultures in a collagen lattice. The stimulatory effect of hypoxia on procollagen mRNA levels in fibroblast monolayers was diminished by antibodies to TGF-beta, and could not be augmented further by the addition of TGF-beta 1, evidence that hypoxic fibroblasts may already be maximally stimulated by TGF-beta 1. We conclude that low oxygen tension enhances steady state mRNA levels of alpha 1 (I) procollagen, and that this effect is mediated at least in part by TGF-beta 1.

Antibodies↗

PubMed1993

P-glycoprotein expression in hepatocellular carcinoma.

In hepatocellular carcinoma cell lines, the intensity of staining with the monoclonal antibody C-219 to the multidrug-resistant gene (mdr1) product P-glycoprotein and the intensity of the band at a molecular weight of 170 KDa on Western blot were associated closely with resistance to Adriamycin but not with the resistance to cis-dichlorodiamine platinum (CDDP). In clinical specimens, noncancerous liver tissue was regularly stained with this antibody on the biliary canalicular front of the hepatocyte cell membrane. In liver cancer tissue, however, regular staining as in the noncancerous regions of the liver was observed in only 16% of the patients, irregular staining was seen in only 24%, and no staining was seen at all in 60%. Staining of P-glycoprotein with the C-219 antibody is technically simple and is useful for studying the role of P-glycoprotein in drug-resistant hepatocellular carcinoma.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1993

Distribution of adenosine deaminase binding protein in normal and malignant tissues of the gastrointestinal tract studied by monoclonal antibodies.

A mouse monoclonal antibody V-715 was raised against fresh colon cancer tissues. Biochemical analysis elucidated that the antigen defined was adenosine deaminase binding protein (ADBP). In colon cancer cell lines, V-715 was positive in 8 out of 16 differentiated cancers and in 2 out of 8 poorly differentiated cancers. In frozen sections, ADBP was expressed in 17 out of 33 differentiated colon cancers, but none of 4 poorly differentiated colon cancers. In normal colon, the expression was observed in epithelium. In gastric cancers, ADBP was expressed in 10 out of 15 differentiated cancers, but weakly or only heterogenously expressed in 2 out of 8 poorly differentiated cancers. In normal gastric mucosa, ADBP was mainly detected in the foveolar epithelium, but was weakly or not expressed in the deep gastric glands. Carcinoid tumors and malignant lymphoma of the stomach did not express ADBP. These results suggest that ADBP may act as a marker of enterocytic differentiation in normal and neoplastic gastrointestinal cells, and might be exploitable in clinical and pathological diagnosis of gastrointestinal cancers.

Adenocarcinoma↗