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Biomedical subjects

J Gil

Publications and source records attributed to J Gil.

At least 199 records · Page 11Linked to original sources

Pituitary extract causes aggregation and differentiation of rat mammary tumor MTW9/Pl cells.

Alkaline pituitary extracts (PE) of the mammosomatotropic tumor MtTW10 differentiated cultured PRL-independent rat mammary tumor cells MTW9/Pl. Within 24 h, MTW9 cells growing in suspension began to aggregate and adhere to the plastic dish. Cultured dispersed MTW9 cells were undifferentiated, but PE treatment resulted in organoid aggregates that exhibited glandular luminal structures and periodic acid-Schiff-positive material consistent with basement membrane formation. Morphometric examination of organoids demonstrated a reduction in nuclear and cell perimeters compared to those of untreated cells. Electron microscopy showed that the treatment resulted in polarization, nuclear changes, junctional complexes, secretory spaces, microvilli, and basement membrane formation. A disaggregated undifferentiated tumor now appeared as a differentiated adenocarcinoma. PE induced expression of laminin and milk protein, but failed to increase fibronectin expression. Extracts of MTOM (a variant of MtTW10 which secretes little PRL) and bovine pituitary also produced aggregation and adhesion of MTW9. A number of tissue extracts, growth factors, and hormones failed to produce such aggregation. Laminin, but not fibronectin, produced aggregation and adhesion similar to those produced by PE. Cycloheximide inhibited the aggregation effect of PE, but not that of laminin. PE was mitogenic for MTW9, but inhibition of proliferation by vinblastine did not inhibit the aggregation induced by PE. These observations suggest that the pituitary contains a novel factor that stimulates matrix synthesis, resulting in differentiation, possibly laminin induced.

Animals↗

Immunotherapy of chronic active viral hepatitis B with propionibacterium granulosum KP-45 (a 5-year follow-up report).

In the period 1982 to 1984, 14 HBS-AG-positive patients with chronic active hepatitis B were treated monthly with a cell wall preparation (5 or 10 mg) of Propionibacterium granulosum KP-45 (PG), intravenously administered for a period of 6 to 10 months. All 14 patients were monitored by serological and biochemical tests as well as liver biopsy two, three and five years after completing immunotherapy with PG. During this period the patients received neither a specific antiviral, corticosteroid or interferon therapy, nor PG. Re-appearance of HBSAG or HBeAG was never seen in patients who were already free from the antigens one year after completing PG immunotherapy. During the 5-year follow-up, spontaneous improvement in serological and morphological (liver biopsy) parameters of chronic virus B hepatitis occurred in six patients. Five years after completion of PG immunotherapy, only four of the 14 patients showed trace amounts of serum HBSAG (carriers), and in two low levels of anti-HBeAG were present, while the whole group showed a decreasing tendency and serum anti-HBc was still detectable in six patients. HBeAG- and DNA-polymerase-positivity was absent in all patients. Microscopic examination of liver biopsies 5 years after PG immunotherapy showed mild symptoms of chronic hepatitis with inflammatory infiltration, non-active cirrhosis, but without massive periportal and/or multilobular necrosis and trace amounts of HBsAG and HBcAG in hepatocytes only in the four carriers. The remaining 10 patients were free of symptoms of active hepatitis and/or active cirrhosis, but all the patients had moderate to intensive fibrosis in their liver biopsies.

Adjuvants, Immunologic↗

Early in-vitro histological chondral differentiation.

In vitro chondrogenesis is possible in the chick embryo from stage 4 of Hamburger and Hamilton (1951), only 18-19 hours of incubation, before somite formation. In stage 4 of Hamburger and Hamilton (1951) the chondroblasts are placed laterally to the primitive streak and notochord cells are not necessary for cartilage differentiation.

Animals↗

Use of computerized interactive morphometry in the diagnosis of mammary adenoma and adenocarcinoma in dogs.

We attempted to define quantitative objective criteria for diagnosis of mammary adenoma and adenocarcinoma in dogs. To that end, correlation between diagnosis made by conventional histologic examination and morphometric descriptors, obtained by computerized histologic analysis, was assessed in biopsy specimens of mammary tissue from 63 dogs. We used 2 interactive computer procedures: one assessed mean nuclear perimeter, mean nuclear area, and circularity factor; and the other evaluated nuclear stratification and cell crowding. A data base was generated with 11 specimens from normal mammary tissue, 17 specimens from mammary adenoma, 18 specimens from low-grade mammary adenocarcinoma, and 15 specimens from mammary adenocarcinoma. The mean values of nuclear perimeter, nuclear area, nuclei per millimeter of basement membrane, and minimal distances from cells to basement membrane gradually increased from normal to high-grade malignancy. Distributions of nuclear areas and of minimal distances from cells to basement membrane were shifted in specimens from malignant tumors. Multivariate analysis confirmed the homogeneity of the diagnostic groups.

Adenocarcinoma↗

6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase in rat brain.

The concentration of fructose 2,6-bisphosphate in the brain remained stable during starvation and early stages of ischaemia, but decreased in diabetes or after lengthened ischaemia. 6-Phosphofructo-1-kinase activity was also decreased in diabetic and ischaemic animals, whereas 6-phosphofructo-2-kinase was not modified. The concentration of the bisphosphorylated metabolite seems to be remarkably constant under a wide variety of experimental conditions, suggesting that it plays an essential role in the basal activation of 6-phosphofructo-1-kinase. Purified 6-phosphofructo-2-kinase also showed fructose-2,6-bisphosphatase activity with an activity ratio similar to that of the purified heart isoenzyme. The brain enzyme also has a net charge similar to that of the heart isoenzyme. Its activity is not modified by sn-glycerol 3-phosphate, and it is more sensitive to citrate than the liver or muscle isoenzyme. Moreover, the enzyme from brain, similarly to that from heart and muscle, is not modified by the cyclic AMP-dependent protein kinase or protein kinase C. A near-full-length cDNA probe from liver hybridized with RNA from brain and heart. In both cases, a major band of 6.8 kb of RNA and a minor one of 4 kb of RNA were detected. All these properties support the hypothesis that brain contains a different isoenzymic form from that of liver and muscle, and it is probably related to the heart isoform.

Animals↗

Bombesin, vasopressin, and endothelin rapidly stimulate tyrosine phosphorylation in intact Swiss 3T3 cells.

The mitogenic neuropeptides bombesin and vasopressin markedly increased tyrosine and serine phosphorylation of multiple substrates in quiescent Swiss 3T3 fibroblasts, including two major bands of Mr 90,000 and 115,000. Tyrosine phosphorylation of these proteins was increased as judged by immunoprecipitation of 32Pi-labeled cells and immunoblotting of unlabeled cells with monoclonal antiphosphotyrosine antibodies, elution with phenyl phosphate, and phospho amino acid analysis. Phosphotyrosyl proteins generated by bombesin and vasopressin did not correspond either by apparent molecular weight or by immunological and biochemical criteria to several known tyrosine kinase substrates, including phospholipase C gamma, the microtubule-associated protein 2 kinase, GTPase-activating protein, or phosphatidylinositol kinase. The effect was rapid (within seconds), concentration dependent, and inhibited by specific receptor antagonists for both bombesin and vasopressin. The endothelin-related peptide, vasoactive intestinal contractor, also elicited a rapid and concentration-dependent tyrosine/serine phosphorylation of a similar set of substrates. These results demonstrate that neuropeptides, acting through receptors linked to GTP-binding proteins, stimulate tyrosine phosphorylation of a common set of substrates in quiescent Swiss 3T3 cells and suggest the existence of an additional signal transduction pathway in neuropeptide-induced mitogenesis.

1-Phosphatidylinositol 4-Kinase↗

Antigen shedding vs. development of natural suppressor cells as mechanism of tumor escape in mice bearing Ehrlich tumor.

C57BL/6J mice immunized with devitalized Ehrlich tumor (ET) cells produce high serum levels of IgM antibodies to ET cell-surface carbohydrates that are critical in the observed resistance against this tumor. However, this response is not found in ET-bearing mice at any stage of tumor development. Since previous studies had shown splenic natural suppressor (NS) cells in ET-bearers, their role in such IgM impairment was assessed. Here we show that tumor-bearers' spleen cells (TBSC) are unable to produce IgM in vitro in response to LPS, due to the presence of NS cells. Nevertheless, TBSC do produce IgM antibodies to ET cell-surface carbohydrates in increasing amounts as the tumor progresses. Yet these antibodies are not detected in sera of ET-bearers and are greatly decreased in immunized mice with a growing tumor. Moreover, increasing amounts of circulating carbohydrates, able to absorb most specific IgM, are found in ET-bearing sera associated with a large molecular size structure(s). These carbohydrates are also found in ET cell-culture supernatants and cell-free ascites fluid derived from this tumor, indicating their tumor origin. Taken together, our results indicate that lack of specific IgM antibodies in ET-bearing mice is not due to faulty production, but to in vivo absorption by carbohydrates shed from ET cells in increasing amounts as the tumor progresses. Thus, NS cells are unable to suppress this IgM production in vivo, despite the strong suppressor activity they show for many responses in vitro.

Animals↗

Correlation of nuclear morphometry and DNA ploidy in rectal cancer.

Several investigators have used morphometric measurements to determine differences in the nuclear size and shape of normal and neoplastic colorectal tissue. Changes in nuclear morphometric parameters have also been shown to correlate with prognosis in a variety of noncolorectal cancers. The association of nuclear morphometry with prognostic indicators in rectal cancer has not been well studied. Measurements of the nuclear area, perimeter, longest cord, and circularity factor from 39 primary rectal adenocarcinomas were compared with DNA content, degree of tumor differentiation, Dukes' class, and patient survival. Nuclear circularity was found to correlate with DNA ploidy. Nondiploid tumors with a DNA index greater than 1.3 had significantly more circular nuclei than tumors with diploid or near-diploid DNA content. There was no correlation between nuclear morphometry and Dukes' class or patient survival. Significant increases in DNA content of rectal cancers appear to be reflected by measurable changes in nuclear shape. Nuclear morphometric measurements may provide useful information in the study of the progression of neoplastic changes in colorectal cancer.

Actuarial Analysis↗

Mastoparan, a novel mitogen for Swiss 3T3 cells, stimulates pertussis toxin-sensitive arachidonic acid release without inositol phosphate accumulation.

Mastoparan, a basic tetradecapeptide isolated from wasp venom, is a novel mitogen for Swiss 3T3 cells. This peptide induced DNA synthesis in synergy with insulin in a concentration-dependent manner; half-maximum and maximum responses were achieved at 14 and 17 microM, respectively. Mastoparan also stimulated DNA synthesis in the presence of other growth promoting factors including bombesin, insulin-like growth factor-1, and platelet-derived growth factor. The synergistic mitogenic stimulation by mastoparan can be dissociated from activation of phospholipase C. Mastoparan did not stimulate phosphoinositide breakdown, Ca2+ mobilization or protein kinase C-mediated phosphorylation of a major cellular substrate or transmodulation of the epidermal growth factor receptor. In contrast, mastoparan stimulated arachidonic acid release, prostaglandin E2 production, and enhanced cAMP accumulation in the presence of forskolin. These responses were inhibited by prior treatment with pertussis toxin. Hence, mastoparan stimulates arachidonic acid release via a pertussis toxin-sensitive G protein in Swiss 3T3 cells. Arachidonic acid, like mastoparan, stimulated DNA synthesis in the presence of insulin. The ability of mastoparan to stimulate mitogenesis was reduced by pertussis toxin treatment. These results demonstrate, for the first time, that mastoparan stimulates reinitiation of DNA synthesis in Swiss 3T3 cells and indicate that this peptide may be a useful probe to elucidate signal transduction mechanisms in mitogenesis.

1-Methyl-3-isobutylxanthine↗

The role of Yersinia enterocolitica in appendicitis in the southwestern United States.

Infection with Yersinia enterocolitica had been associated with acute appendicitis in approximately six per cent of patients in northern European countries. However, the incidence of Y. enterocolitica in patients with appendicitis in this country is uncertain. Therefore, this study was undertaken to ascertain whether Y. enterocolitica is a possible infectious agent in appendicitis in the southwestern United States. Fifty prospective patients (35 men and 15 women) with an average age of 22.3 years (range 3 to 62 years) underwent appendectomy for presumed appendicitis. Portions of each specimen were cultured for Y. enterocolitica with highly selective media (Cefsulodin-Irgasan-Novobiocin [CIN] agar). Pathologically, 44 of the patients had appendicitis and 6 patients had normal appendices. Four of the 44 patients (9.1%) with appendicitis were found to be culture positive for Y. enterocolitica, while it was recovered from none of the normal appendices. This indicates that Y. enterocolitica may represent the major pathogen in acute appendicitis in a small, but distinct, portion of indigent patients within Los Angeles County as it does elsewhere in the world.

Acute Disease↗

[Septic pulmonary embolism, bacterial endocarditis and endocavitary pacemaker].

The number of patients carrying an endocavitary pacemaker is increasing every day. The presence of a foreign body in right cavities predisposes to the formation of thrombi that can be over infected from distal septic focci usually silent. When a pulmonary embolism is diagnosed in these patients, the initial study must include an echocardiographic exam in order to rule out the presence of an intracardiac thrombosis as the origin of the emboli. We present the case of a patient with and endocardiac pacemaker who was admitted with fever and repeated episodes of pulmonary embolism. Hemocultures were positive for proteus mirabilis and a electrocatheter thrombosis was demonstrated in bidimensional echocardiography. Proteus mirabilis was positive in cultures from the material obtained by cardiothomy and clinical evolution after surgery was satisfactory.

Aged↗

Porphyria cutanea tarda associated with autoimmune hypothyroidism, vitiligo and alopecia universalis.

The aetiology of porphyria cutanea tarda (PCT) has not been elucidated, but the possibility of an autoimmune mechanism has been proposed. We report a case of an unknown clinical combination of PCT with autoimmune hypothyroidism, alopecia universalis and vitiligo with thyroid and parietal cell circulating antibodies. This is highly suggestive of underlying autoimmune damage in this patient.

Adult↗

Unilateral absence of a pulmonary artery: congenital disease or embolic occlusion?

A young man with congenital absence of the left pulmonary artery is reported. A right aortic arch and normal pulmonary pressures essentially rule out an alternate diagnosis of occlusive chronic thrombus in the central pulmonary arteries. Recurrent or massive haemoptysis makes an exact knowledge of the pulmonary circulation advisable.

Adolescent↗

Inhibition of in vivo tumor growth by a monoclonal IgM antibody recognizing tumor cell surface carbohydrates.

We have shown previously that IgM from Ehrlich tumor (ET)-immunized mice, recognizing ET cell surface carbohydrates, protects control mice to a subsequent tumor challenge. The factors involved in such IgM-mediated protection were unknown, since it was independent of complement activation. Here, we have extended these in vivo studies by means of monoclonal IgM antibodies. Two of them (A10 and E1), strongly recognizing ET cells and with specificity to ET cell surface carbohydrates, were selected. The results show that A10 (but not E1 or unrelated IgM antibodies) is able to protect nonimmunized mice against ET growth. Protection by A10 was also seen by reducing 800-fold the initial dose; however, E1 was unsuccessful whatever the dose used. A10-mediated protection was observed in C3-defective mice (cobra venom factor treated) or in C5-deficient DBA/2, but not in silica-treated animals. Endotoxin removal did not affect the protection afforded by A10 while specific IgM depletion prevented any protective effect. In addition, the relationship between natural antibodies of IgM isotype recognizing ET cell surface carbohydrates and mouse strain resistance to this tumor is established. Similarly, this natural resistance seems to be complement independent but macrophage mediated. Therefore, these results indicate that some IgM molecules recognizing cell surface carbohydrates may participate in in vivo tumor suppression by a macrophage-dependent mechanism.

Animals↗