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Biomedical subjects

R Ramirez

Publications and source records attributed to R Ramirez.

At least 55 records · Page 3Linked to original sources

Macroscopic effects of percutaneous trigeminal ganglion compression (Mullan's technique): an anatomic study.

After the use of Mullan's technique, macroscopic changes take place on the gasserian ganglion and the surrounding structures. These changes were studied on 20 trigeminal nerves of 10 fresh adult cadavers. Changes took place on the dura as well as in the neural elements. There was compression on the ganglion and on the trigeminal nerve, and there were changes in the position of the trigeminal root, with shortening of its cisternal segment. When the balloon was inflated to capacity (0.75-1.0 ml), dural stretching in an area of 15 x 10 mm took place. This stretching of the dura extended from the lateral wall of the cavernous sinus to the level of the porus trigemini. Despite these important mechanical effects, we never found a rupture or tear on the dura or the trigeminal nerve fibers. We discuss the relationship between mechanical effects and clinical results.

Adult↗

Cell aggregation and apoptosis induced by hemodialysis membranes.

During hemodialysis, circulating mononuclear cells can be stimulated to different degrees, depending on membrane biocompatibility. Cell activation usually leads to aggregation and proliferation. It may also result in apoptosis if cells are subjected to abnormal activation. This may be the case of cells exposed to bioincompatible hemodialysis membranes. The study presented here evaluates the effects of two hemodialysis membranes, with different degrees of biocompatibility, (Cuprophan (CU; Lundia IC 5N; GAMBRO, Sweden) and polyacrylonitrile (AN69; Biospal 3000S, Hospal, France)) on aggregation and apoptosis of circulating human mononuclear cells and the human mononuclear cell line (THP-1). The results showed that 2-h incubation with CU, a bioincompatible membrane, produces cell aggregation of both peripheral mononuclear cells and THP-1 cells (35% and 54%, respectively). After 48 h of incubation with a CU membrane, apoptotic death was observed in 32% of THP-1 cells and in 45% of normal peripheral mononuclear cells. Neither cell aggregation nor apoptosis was observed after incubation with the AN69 membrane. CU membrane-induced apoptosis was inhibited by Staurosporrin (Sigma, St. Louis, MO) a protein kinase C (PKC)-inhibitor, suggesting that cell apoptosis induced by the CU membrane is mediated by a PKC-dependent cell activation. Furthermore, cell prestimulation with phorbol 12-myristate 13-acetate, an activator of PKC, results in a increase in the percentage of THP-1 cell death by apoptosis after CU exposure (53%). Our study indicates that CU membranes induce mononuclear cell activation, leading to cell apoptosis.

Acrylic Resins↗

The Vitek immunodiagnostic assay for detection of immunoglobulin M toxoplasma antibodies.

We compared the Vitek immunodiagnostic assay for detection of immunoglobulin M (IgM) toxoplasma antibodies (VIDAS TXM) with an IgM enzyme-linked immunosorbent assay (ELISA) which we developed. A total of 407 serum samples from 391 adults were used for this study. We also examined 17 serial serum samples from four women who had seroconverted during gestation. We observed a sensitivity of 99.5%, a specificity of 93%, a positive predictive value of 93.6%, a negative predictive value of 99.5%, and a global agreement of 96.3%. In each case of seroconversion the VIDAS TXM became positive at the same time as did the IgM ELISA.

Adult↗

Operating room cost awareness committee. A model for collaboration.

Kaiser Santa Rosa (KSRO), a small facility in the Kaiser Permanente health maintenance organization, was found to have an unfavorably high non-payroll cost per surgical hour as compared with other Kaiser facilities. An Operating Room Cost Awareness Committee was formed to address the problem and has now become a standing committee at KSRO. The committee is composed of surgeons, nurses, materiel management personnel and administrative representatives. Through a spirit of cooperation and the authority to approve and deny all OR supply requests, the committee has been able to bring its OR costs in line with other Kaiser facilities.

California↗

T-cell receptor J beta I/J beta II locus rearrangements concurring with a complex chromosomal aberration in an HTLV-1 positive T-cell lymphoma.

Human T-lymphotropic virus type I (HTLV-1) integration has been associated with the development of adult T-cell leukemia/lymphoma (ATL). Recently, a correlation between T-cell receptor (TCR) gene rearrangements and chromosomal aberrations has been implicated in this leukemia. We present a case of HTLV-1 infected adult T-cell lymphoma that initially presented with a normal karyotype and germline J beta I/J beta II loci. As the disease evolved to the aggressive stage, a complex chromosomal rearrangement with a duplication of chromosome 6p23-->pter translocated to a derivative chromosome 16, was identified by molecular cytogenetic techniques. The nature of this complex abnormality would have been difficult to determine if only conventional banding techniques were performed. Rearrangement involving one J beta allele was also detected at that time. After initiation of chemotherapy, no germline J beta loci were detected, suggesting a possible second rearrangement involving this locus that was homologous. Although no known immune response genes are located at the breakpoints involved in this abnormality, the chromosomal aberration concurred with the initial J beta rearrangement.

Adult↗

HLA class II-mediated aggregation is associated with the proliferation of B lymphocytes.

We have studied the role of LFA-1 antigens in human B lymphocyte aggregation, proliferation, and Ig production induced by a short stimulation via class II antigens. Cell stimulation with either bacterial superantigens or anti-DR mAbs rapidly induced homotypic cell aggregation. In response to IL-4, an increase in cell proliferation and Ig production was observed only when aggregation preceded addition of IL-4. The involvement of LFA-1 molecules in class II-induced aggregation was supported as LFA-1-deficient cells or B cells incubated with anti-LFA-1/ICAM-1 mAbs failed to aggregate after stimulation. The association between aggregation and subsequent Ig production and proliferation was further supported as, after IL-4 stimulation, in both LFA-1-deficient cells and B cells incubated with anti-LFA-1 mAbs, class II-mediated signals failed to increase Ig production or cell proliferation. These data suggest that in class II-stimulated cells, LFA-1-dependent aggregation has a major role in IL-4-dependent Ig production and proliferation of B cells.

B-Lymphocytes↗

Role of specific immunoglobulin E in diagnosis of acute toxoplasma infection and toxoplasmosis.

Toxoplasma immunoglobulin E (IgE) antibodies were evaluated in an immunosorbent agglutination assay (ISAGA) and an enzyme-linked immunosorbent assay (ELISA) to determine their usefulness in the diagnosis of acute infection with Toxoplasma gondii. IgE antibodies were not detected in serum specimens from otherwise seronegative individuals, individuals with chronic toxoplasma infection, or infants without congenital toxoplasmosis. In contrast, they were detected in pregnant women who seroconverted during gestation (100% by ELISA, 63% by ISAGA), patients with toxoplasmic lymphadenopathy (96% by ELISA, 88% by ISAGA), infants with signs of congenital toxoplasmosis which prompted serologic testing in the postnatal period (92% by ELISA, 67% by ISAGA), children and adults with toxoplasmic chorioretinitis (36% by ELISA, 18% by ISAGA), and adult patients with AIDS and toxoplasmic encephalitis (33% by ELISA, 25% by ISAGA). In many of the serum specimens, the titer of IgE antibodies detected by the ISAGA were close to or at the positive cutoff value. The duration of detectable IgE antibodies in patients with acute infections varied considerably among individuals but showed a trend toward a briefer duration by the ISAGA than by the ELISA. These results reveal that recrudescence of IgE antibodies in patients with reactivated chronic infection (toxoplasmic chorioretinitis and toxoplasmic encephalitis) may be useful diagnostically and that demonstration of toxoplasma IgE antibodies is a useful adjunct to currently available serologic tests for the diagnosis of acute toxoplasma infection and toxoplasmosis.

Acute Disease↗

[Cardiotoxicity of anthracyclines].

The only factor limiting the use of anthracyclines (very powerful antimitotic antibiotics) is their cardiotoxicity. The cardiac involvement is irreversible, dose-dependent and may be detected at an early stage by non-invasive (echocardiography, myocardial scintigraphy) or invasive investigations (endomyocardial biopsy). The mechanism of cardiac toxicity involves the oxidative metabolism of the cardiac myocyte and liberation of oxygen free radicals and is different from the antitumoral effect. Protocols of administration over 6 to 24 hours have enabled the use of higher total doses and the reduction of cardiotoxicity without affecting the therapeutic efficacy. The use of "antioxidants" such as ICRF 187 has given promising results in myocardial protection. The strategy of surveillance (screening) of cardiotoxicity, of the mode of administration of the anthracyclines, results from the essential coordination of the efforts of the chemotherapist, taking into account the pathology, the sensitivity of the tumor to anthracyclines therapy, enabling personalization of the prescription and the abandon of the concept of maximal dosage.

Adolescent↗

Evidence for a viral superantigen in humans.

Superantigens bind class II major histocompatibility proteins and stimulate powerful proliferative responses of T lymphocytes bearing particular V beta sequences as part of their alpha beta antigen receptor. Exogenous bacterial superantigens are responsible for food poisoning and toxic shock syndrome. Murine virus-encoded self-superantigens induce clonal deletion of T lymphocytes. Although superantigen-like properties have been suggested for human immunodeficiency virus-1, no viral superantigen has been identified in humans. Here we report that the nucleocapsid of the rabies virus is an exogenous superantigen specific for V beta 8 human T lymphocytes which binds to HLA class II alpha-chains.

Antigen-Presenting Cells↗

Mechanisms involved in NK resistance induced by interferon-gamma.

Human tumor cell lines were treated with interferon-gamma (IFN-gamma) and then used as target cells in NK assays to measure their ability to form conjugates and stimulate the production of NK cytotoxic factors (NKCF) and to determine their susceptibility to NKCF lysis. K562 and cell lines RS1, RS3, RS7, CAC, and CAP2, obtained from solid brain tumors, were used as targets, and peripheral blood lymphocytes (PBL) from normal donors were used as effector cells. IFN-gamma-treated cell lines had a decreased susceptibility to NKCF lysis and a decreased ability to induce the release of these factors without affecting target-effector cell binding. These results were not due to changes in HLA class I antigen expression, given that the level of HLA class I antigens on the tumor cell lines was not affected, the only exception being K562. In an attempt to further clarify the possible influence of HLA class I expression on K562, IFN-gamma-pretreated K562 cells were separated into HLA class I positive and HLA class I negative subsets for the NK assays. The results showed that both populations behaved similarly upon target-effector conjugate formation, whereas the HLA class I positive population showed a reduced susceptibility to lysis by NK cells and NKCF. Thus, these results establish that NK resistance induced by IFN-gamma is mediated by blocking the target cell's ability to activate NK cell triggering and release of NKCF and by blocking its susceptibility to lysis by these factors. This analysis helps to clarify not only the NK process but also the controversial regulatory effect of IFN in NK lysis.

Cell Adhesion↗

HLA class-II-mediated homotypic aggregation: involvement of a protein tyrosine kinase and protein kinase C.

Homotypic aggregation of B-lymphocytes, B-cell lines and class-II-positive T cells via HLA class II molecules was examined. Signaling via DR antigens induced rapid aggregation in a dose- and time-dependent manner, maximum and stable aggregation was induced within 20 minutes. On the contrary, rapid signaling via DP or DQ required prestimulation with either PMA or anti-sIg. Aggregation was temperature and energy dependent. [Ca2+] and [Mg2+] concentrations and an intact cytoskeleton were required while neither mRNA or protein synthesis were required. Furthermore, FACS analysis revealed that aggregation was not directly correlated with cell surface expression of HLA class II molecules. Our results demonstrate that aggregation was mediated through a protein tyrosine kinase (PTK)-dependent pathway that preceded activation of protein kinase C (PKC) and failure to generate either the PTK signal or the PKC signal prevented aggregation. The contribution of a tyrosine kinase was further demonstrated by the total inhibition of aggregation following treatment with an anti-CD45 mAb.

Antibodies, Monoclonal↗

A sensitive radioisotopic assay of myo-inositol: its application to rat pancreatic islets.

A radioisotopic procedure for the assay of myo-inositol is presented. It is based on the generation of NADH from NAD+ in the reaction catalyzed by myo-inositol dehydrogenase and the subsequent NADH-dependent conversion of 2-[U-14C]ketoglutarate to 14C-labeled L-glutamate in the reaction catalyzed by glutamate dehydrogenase. This method was applied to the measurement of myo-inositol in rat pancreatic islets. The myo-inositol islet content was decreased when the animals were fed a diet deprived of myo-inositol. When incubated in the absence of exogenous D-glucose, pancreatic islets, like parotid cells, released myo-inositol in the incubation medium. Over 90 min of incubation, a rise in extracellular D-glucose concentration increased the myo-inositol islet content, which was decreased, however, after incubation in the presence of carbamylcholine. These findings indicate that the myo-inositol content of islets is affected by nutritional and other environmental factors.

Animals↗

Evaluation of glipizide and glyburide in a health maintenance organization.

OBJECTIVE: To determine if there was a difference in the long-term glycemic control, average daily dose, and cost of therapy in patients with noninsulin-dependent diabetes mellitus (NIDDM) treated with glyburide and glipizide in a health maintenance organization (HMO). DESIGN: Retrospective evaluation of medical and pharmacy records. SETTING: Multispecialty group practice HMO. PATIENTS: 140 NIDDM patients being treated with either glyburide (n = 70) or glipizide (n = 70) were randomly selected from the populations of patients receiving either drug using computerized pharmacy records. MAIN OUTCOME MEASURE: Mean daily doses and blood glucose measurements (fasting blood glucose, random blood glucose, hemoglobin A1C) were stratified in 3-month periods from the time the drug therapy was started or the patient first presented to the clinic for a total of 18 months. Long-term glycemic control was defined as fasting blood glucose less than 8.33 mmol/L (150 mg/dL). RESULTS: The groups were comparable with regard to age (53.4 y glyburide, 56.7 y glipizide), gender (43 M:27 F glyburide, 47 M:23 F glipizide), race (38 W/16 B/16 H glyburide, 45 W/16 B/9 H glipizide), concurrent medical conditions, adverse effects, and compliance. Long-term glycemic control was similar in both groups. Although the number of subjects who were controlled (by definition) tended to be greater in the glyburide group, no clinical or statistical difference was found. There was no statistical difference in mean daily dose between the ethnic groups, but the small numbers preclude further analysis. The glipizide group had a larger percentage increase in dose within the first year than did the glyburide group; however, the percentage increase from the 3-month dose was similar after 18 months (22.7 percent glyburide, 27.5 percent glipizide.) Average daily cost of therapy, based on mean daily dose, was slightly lower for glyburide-treated patients. CONCLUSIONS: If glycemic control is similar with glyburide and glipizide, as seen in this study, economic considerations regarding choice of therapy and formulary inclusion may be appropriate.

Adult↗

Collagenase-inhibitory activity in deposit and resorption phases of guinea pig carrageenin granuloma.

The levels of collagenase inhibitor, both free and bound to metalloproteinases, were evaluated at 7 days [deposit phase (DP)] and 14 days [resorptive phase (RP)] of evolution of the subcutaneous carrageenin-induced granuloma in the guinea pig. The level of free collagenase inhibitor was considerably higher in the supernatant of DP granulomas (7.95 +/- 1.53 U/mg protein) as compared to that of RP granulomas (2.53 +/- 0.41 U/mg protein). When the samples were heated at acid pH to release the inhibitor from metalloproteinase-inhibitor complexes, free inhibitor was recovered in both phases. However, the units of recovered collagenase inhibitor were several fold higher in all RP granulomas in comparison with DP granulomas (6.88 +/- 2.46 vs 1.5 +/- 0.53). Therefore, DP and RP tissues exhibited similar total amount of tissue inhibitor. By HPLC, collagenase inhibitor activity was localized in a fraction consistent with the size of TIMP. These results suggest a different balance of collagenase and collagenase inhibitor during the evolution of the granuloma; an excess of inhibitor over metalloproteinases appears to predominate during the phase of collagen accumulation contrasting with an inverse situation when the granuloma is healing.

Animals↗

Assay of 3-hydroxybutyrate in the picomolar range.

A radioisotopic procedure for the assay of 3-hydroxybutyrate is presented. It is based on the measurement of NADH, generated in the 3-hydroxybutyrate dehydrogenase reaction, through the conversion of 2-[U-14C]ketoglutarate to 14C-labeled L-glutamate in the presence of beef liver glutamate dehydrogenase. The assay is linear in the range of 2.5 to 20.0 pmole/sample and about 100-times more sensitive than previous methods. The procedure proved useful for the measurement of 3-hydroxybutyrate in liver samples not exceeding 25 micrograms wet weight.

3-Hydroxybutyric Acid↗

Sera from patients with colon, breast and lung cancer induce resistance to lysis mediated by NK cytotoxic factors (NKCF).

Natural killer (NK) cells are involved in the antitumoral immunologic mechanism. These cells act through the release of cytotoxic molecules defined as NK cytotoxic factors (NKCF). Inhibitory factors of NK and NKCF mediated lysis have been described in in vitro assays. This study evaluates the induction of resistance to NKCF cytotoxicity by sera from 27 patients with colon, breast and lung cancer. Addition of these sera to the cytolytic assay where K562 cells and concentrated NKCF were used, induced resistance to NKCF mediated cytotoxicity in 21 cases (77%). The sera from the group with metastasis blocked NKCF lysis more markedly than the group with local tumours. However, no differences were observed when the groups with colon, breast and lung cancers were compared. This blocking effect was not found to be related to gamma interferon (IFN) levels. In a previous study, we described a tumour factor (NK-RIF) produced by human cell lines derived from metastatic adenocarcinomas. This factor blocked lysis of tumour target cells by NK cells. Consequently, it is proposed that the release of similar tumour factors with a capacity to induce resistance to NKCF may be involved in tumour growth and metastatic spreading in in vivo.

Breast Neoplasms↗

Cellular immunity in current active pulmonary tuberculosis.

A group of 10 patients with recently diagnosed pulmonary TB were studied and compared to 10 bacillus Calmette-Guérin (BCG) immunized healthy individuals. Cellular immune mechanisms were explored in vitro utilizing fresh and precultured peripheral blood mononuclear cells exposed to PHA, PPD, and recall antigens (SK/SD and CA). Proliferative assays were also carried out in the presence of either each patient's serum (autologous serum) or cocultured with CD3(+)-depleted adherent cells. Serum measurements of soluble interleukin-2 (IL-2) receptor and synthesis of IL-2 generated by mononuclear cells stimulated with PPD and SK/SD were also performed. Patient sera were able to inhibit autologous as well as allogeneic cell responses, and a significant adherent cell suppressive effect was observed. As a whole the group of patients showed decreased blast transformation to PPD, preserved proliferative responses to other recall antigens, and a low PPD-induced generation of IL-2. Furthermore, as possible evidence of preactivated T cells, these patients demonstrated high soluble IL-2 receptor serum levels. Early compromise of specific cell-mediated immunity, including IL-2 abnormalities, may be of significance in newly diagnosed pulmonary TB.

Adult↗