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Biomedical subjects

R Valenzuela

Publications and source records attributed to R Valenzuela.

At least 73 records · Page 4Linked to original sources
PubMed1984

Correlation between potency of calmodulin inhibitors and effects on cellular levels and cytotoxic activity of doxorubicin (adriamycin) in resistant P388 mouse leukemia cells.

The relationship between potency of phenothiazine and naphthalene-sulfonamide calmodulin inhibitors and their effects on cellular levels and cytotoxic activity of doxorubicin was evaluated using the doxorubicin-sensitive and greater than 100-fold doxorubicin-resistant P388 mouse leukemia model system. In cytotoxicity studies using cell counts based on proliferation following a 24-hr drug exposure and in survival based on colony formation in soft-agar after a 2-hr drug exposure, the calmodulin inhibitors significantly enhanced the cytotoxic effects of doxorubicin in the resistant but not parent-sensitive P388 cells. However, survival in soft-agar (based on colony formation) following long-term drug exposure (approximately 120 hr) revealed that the cytotoxic effects of doxorubicin were significantly increased by the calmodulin inhibitors in both sensitive and resistant P388 cells. Laser flow cytometry studies on single-cell doxorubicin levels indicated that treatment with doxorubicin in the presence of trifluoperazine had no effect on drug levels in sensitive cells but significantly enhanced cellular accumulation and retention of doxorubicin in resistant cells. Furthermore, unlike treatment with doxorubicin alone, in the presence of trifluoperazine, heterogeneity in cellular drug levels in the resistant P388 cells was not observed. Among the various calmodulin inhibitors effective in enhancing cellular levels and cytotoxic effects of doxorubicin in the resistant P388 cells, chlorpromazine was approximately two-fold less potent than trifluoperazine or prochlorperazine and only N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide but not N-(4-aminobutyl)-2-naphthalenesulfonamide was active.

Agar↗
PubMed1984

Immunophenotypic characterization of acute leukemia by immunocytology.

The potential for specific immunophenotypic characterization of the acute leukemias has been enhanced greatly by the development of monoclonal antibodies. Currently, this immunologic data is obtained most commonly by flow cytometric analysis or cellular cytotoxicity assays. The former is an expensive technic that lacks morphologic evaluation unless cell sorting is performed. The latter precludes morphologic assessment by the nature of the assay. The authors have developed an immunostaining procedure utilizing cytospin preparations and immunoperoxidase methods that are relatively inexpensive and allow simultaneous assessment of the immunologic markers and cellular morphology. Although a comparison of flow cytometry and immunocytology revealed quantitative differences for individual cell surface markers, the "qualitative" immunologic phenotype of the leukemic population was virtually identical by the two technics.

Acute Disease↗
PubMed1984

Weighted criteria for the diagnosis of systemic lupus erythematosus.

The preliminary American Rheumatism Association (ARA) criteria for classification of systemic lupus erythematosus (SLE) were evaluated for sensitivity and specificity in 87 patients with SLE and 73 without SLE from a rheumatology population. Using these data, Bayes' theorem was employed to weight the criteria so that a scoring system could be developed, allowing more accurate use of the criteria in diagnosis. Combinations of serologic test results were evaluated in a similar manner. Comparison of weighted scores with criteria counts showed greater sensitivity and specificity of the former whether the 1971 or modified 1982 ARA criteria were used. Weighted criteria may be more useful in clearly defining patient populations for studies of SLE.

Antibodies, Antinuclear↗
PubMed1984

A simple semiquantitative radiometric measurement of antithyroglobulin antibodies in human serum. Comparison with hemagglutination method.

A simple solid-phase radiometric assay for the measurement of thyroglobulin autoantibodies (TgRA) was developed and evaluated. The assay is semiquantitative, and the results were expressed as a ratio between sample versus negative control (normal human serum). In 59 normal subjects, the mean ratio was 0.93 +/- (SD) 0.34. Thyroglobulin antibodies by radiometric assay, by hemagglutination (TgHA), as well as microsomal antibodies by hemagglutination (MCHA) were measured in 41 patients with a histopathologic diagnosis of Hashimoto's thyroiditis (n = 22), adenomatous goiter (n = 10), carcinoma (n = 5), adenoma (n = 4), and in 59 patients without histopathologic diagnosis of thyroid disease. In patients with Hashimoto's thyroiditis, TgRA, TgHA, and MCHA were positive in 54, 31, and 81% of patients, respectively. 1 patient had positive TgRA with negative MCHA levels, and 2 had negative antibody titers by all methods. Thyrotropin-stimulating hormone levels were elevated (greater than 10 microU/ml) in 17 of these patients. Our results suggest that although the TgRA method is more sensitive than TgHA for detecting thyroglobulin antibodies, its diagnostic sensitivity is not equal to that of MCHA.

Autoantibodies↗
PubMed1983

A lymphocytotoxic factor(s) in plasma of patients with minimal change nephrotic syndrome: partial characterization.

The incidence, relationship to clinical disease, and physical characteristics of a plasma cytotoxic factor(s) were studied in steroid-responsive minimal change nephrotic syndrome (MCNS) and other renal diseases. Plasma activity was found in 76% of 67 children with MCNS and in 67% of 9 children with focal segmental sclerosis (FSS). Of 31 normal adults and children and 7 adults with membranous glomerulonephritis, only 1 individual had toxic plasma. In MCNS, degree of plasma activity was not related to clinical disease, prednisone dosage, or serum levels of IgG or alpha-2-macroglobulin. The active factor(s) was found more frequently in plasma than in serum, was heat stable and nondialyzable by selected filtration, and was approximately 100,000 to 300,000 molecular weight. By DEAE column chromatography, activity coincided with fractions containing IgA and IgM but not IgG. While the nature of the plasma factor(s) has not been identified, these data indicate that MCNS plasma may adversely affect lymphocyte viability by a slow process of cytotoxicity requiring 24 or more hr, and that such plasma activity occurs frequently in children with MCNS and also with the more severe FSS.

Adolescent↗
PubMed1983

A histochemical approach to the differentiation of lichen planus from lupus erythematosus.

A histochemical technic utilizing a maleimide-derived fluorochrome for the detection of disulfide bonds in subepidermal hyaline bodies is described. Lichen planus and the skin lesions of lupus erythematosus, which may have similar clinical, histologic, and immunofluorescent presentations, tend to demonstrate different patterns of reactivity with this reagent. This technic, then, may be used to distinguish between these two cutaneous disorders.

Diagnosis, Differential↗
PubMed1983

Characterization of blood mononuclear and cultured cells in hairy cell leukemia.

The nature of neoplastic cells in hairy cell leukemia (HCL) is still controversial. Most reports favor derivation from B cells, but some have suggested origin from monocytes/histiocytes, T cells, or even a hybrid Ig-bearing lymphocyte with phagocytic activity. We established a new cell line from peripheral blood of a patient with typical HCL. The morphologic, immunocytochemical, and functional properties of the new cell line were identical with the patient's original HC. Both cell types demonstrated the irregular, fine cytoplasmic projections characteristic of HC, were weakly phagocytic, markedly positive for tartrate-resistant acid phosphatase, and had variable nonspecific esterase reactivity. Low percentages of EAC-rosetting cells were found (8% original specimen and 6% cultured cells) and a minute amount of IgG, IgA, and IgM were synthesized by the new cell line. A small proportion of cells (13% original specimen and 12% cultured cells) bore SIg when stained with F(ab)2-fragment polyvalent antiserum. Our observations indicated that HC were a slowly proliferating cell population with immunochemical and functional characteristics of both B and monocyte/histiocytic cells.

Aged↗
PubMed1982

Membranous glomerulonephritis associated with industrial mercury exposure. Study of pathogenetic mechanisms.

The nephrotoxicity associated with mercury may be manifested as either acute tubular necrosis or an immune complex glomerulonephritis, depending upon the conditions under which the patient is exposed to the metal. Two patients with industrial exposure to mercury developed the nephrotic syndrome due to membranous glomerulonephritis. A multidisciplinary approach was used to define more precisely the pathogenetic mechanisms involved in the production of the glomerular lesion. Although glomeruli were normal by light microscopy, immunohistochemical studies demonstrated confluent finely granular epimembranous deposits of IgG and C3. This distribution was confirmed at the ultrastructural level with immunoelectron microscopy. High resolution elemental analysis of electron dense inclusions in tubular epithelial phagolysosomes demonstrated energy dispersion spectra characteristic of coexisting mercury and selenium. Eluates from the biopsy material were not immunoreactive against normal rat or human kidney. There was no immunoreactivity of epimembranous deposits with antibodies having renal tubular epithelial antigen or urinary uromucoid specificity. These observations suggest that a distinctive immunopathologic lesion is associated with mercury-associated membraneous glomerulonephritis, that the role of the metal itself may only be coincidental, and that the involved antigen remains unknown. Prednisone therapy had no documented persistent beneficial influence upon the level of proteinuria in one patient who has been lost to follow-up. In one patient not treated with steroid therapy, withdrawal of exposure to the metal resulted in disappearance of mercury from body fluids and clinical remission.

Adult↗
PubMed1982

Immunonephelometric quantitation of central nervous system IgG daily synthesis in multiple sclerosis. Clinical evaluation using predictive value theory.

With a laser nephelometric immunoassay and an empirical formula for the quantitation of central nervous system (CNS) daily IgG synthesis, we studied prospectively a population of 101 individuals divided into four groups: 31 normals, 25 patients with definite multiple sclerosis (DMS), 18 patients with probable or possible multiple sclerosis (PMS), and 27 patients with neurologic disease other than multiple sclerosis (NMS). By the Kruskal-Wallis, test the results of the DMS and PMS patients were significantly different from the normals and NMS patients (P less than 0.0003). Considering normals, DMS, and NMS patients only, the sensitivity of the test was 96%, the specificity was 98%, the positive predictive value was 96%, the negative predictive value was 98%, and the efficiency was 98%. Based on our study data, we applied the predictive value theory to different hypothetical populations (our Neurology Ward, Northeastern U. S., and patients with optic neuritis and chronic progressive myelopathy). In all these situations, the test gave a diagnostic efficiency for multiple sclerosis greater than 95%.

Adult↗
PubMed1982

Value of central nervous system IgG daily synthesis determination in the diagnosis of multiple sclerosis.

Using laser beam immunonephelometry, we confirmed the value of Tourtellotte's formula in the diagnosis of MS. Moreover, since immunonephelometry presents several advantages, including simplicity, rapidity, and precision, it is a promising technique for the diagnosis of MS. Complicated measurements are not necessary. Determinations take only minutes. The results are reproducible. Mathematics manipulations are simple with readily available computers.

Adult↗
PubMed1982

Improved white blood cell functions: additional effects of membrane plasmapheresis.

The changes in cellular functions were analyzed in 4 rheumatoid arthritis and 2 biliary cirrhosis patients. Impaired T-cell functions (low lymphocyte transformation reactivity (LTR) to Con A), seen in one cirrhosis patient before MP, improved with MP. MP also removed inhibitory factor(s) for LTR from the plasma of this patient. RA patients tended to have decreased Con A response and enhanced PWM response. MP enhanced LTR in 2 patients, but lowered LTR in patient who had been taking immunosuppressive drugs. Changes in lymphocyte populations occurred and included a substantial increase of T cells. A primary effect was an increase of helper T-cells. During MP, early leukopenia accompanied by complement activation and secondary leukocytosis were observed. Phagocytic PMNs activated by this process had significant augmentation of their O-2 generating activity as measured by chemiluminescence. This was evident in severe RA and in 2 cirrhosis patients with low phagocytic cell function before MP. This activation of phagocytes by MP may lead to additional beneficial effects by further lowering MMs such as immune complexes from plasma. A better understanding of these phenomena is necessary to assess the overall therapeutic response to MP, especially in patients where cellular mechanisms are important in pathogenesis of their disease.

Adult↗
PubMed1981

Light chain nephropathy.

In 13 specimens of renal tissue from 11 patients, deposits of monoclonal immunoglobulin light chains and continuous granular electron-dense material within tubular basement membranes and in association with the glomerular basement membrane were identified. All but one patient were men n the fifth to seventh decades of life, and each presented with azotemia and features of glomerular rather than tubulointerstitial disease. Osteolytic bone lesions occurred in only three patients, and a bone marrow plasmacytosis greater than 30 percent consistent with plasma cell myeloma was identified in only four patients. Light chain distribution in the nephron was confirmed with immunoelectron microscopy and was not associated with deposition of other serum proteins such as immunoglobulin heavy chains, complement, transferrin, alpha 2 macroglobulin and albumin. The electron dense deposits differed in distribution and character from those associated with membranoproliferative glomerulonephritis type II (dense deposit disease), amyloidosis, cryoglobulinemia, macroglobulinemia and benign monoclonal gammopathy. Serum from six of these patients did not bind to normal human or rat renal parenchyma in vitro. Kappa light chain nephropathy was characterized by predominant linear tubular basement membrane kappa deposits, and nodular mesangial and linear glomerular basement membrane kappa immunostaining. Lambda light chain nephropathy was characterized by linear lambda glomerular basement membrane and tubular basement membrane immunostaining. Manifestations of glomerular dysfunction dominated the clinical presentation of light chain nephropathy, and most patients did not have typical features of multiple myeloma. The diagnosis was predicated upon thorough immmunohistologic assessment of renal biopsy material.

Adult↗
PubMed1981

Comparison of alternative chromogens for renal immunohistochemistry.

Renal immunomicroscopy using enzyme labeled reagents has been shown to be a reliable method for the identification of immunoglobulins and complement in the routine evaluation of glomerular disease. However, the potential carcinogenicity of benzidine derivatives used in the procedure represents a major disadvantage of the technique. With a series of 55 renal biopsy specimens evaluated by light microscopy, immunofluorescence, and electron microscopy from patients with a variety of renal diseases, a study was done comparing aminoethylcarbazole and the Hanker-Yates reagent (p-phenylenediamine and pyrocatechol), chromogens chemically unrelated to benzidine. Aminoethylcarbazole was not suitable for renal immunomicroscopy, since in cases of antiglomerular basement membrane disease the color reaction product was finely granular at high magnification. Specimens immunostained with the Hanker-Yates reagent yielded permanent water insoluble reaction products and immunomicroscopic patterns identical to the results observed with immunofluorescence in all cases. To our knowledge, no carcinogenic properties have been identified for p-phenylenediamine or pyrocatechol. The Hanker-Yates reagent may be used routinely for renal enzyme immunomicroscopic studies with no currently identified carcinogenic hazard to laboratory personnel.

3,3'-Diaminobenzidine↗
PubMed1981

Ultrastructural study of tissue and peripheral blood neutrophils in human renal allograft recipients. A clinicopathological description of an unusual abnormality discovered in three cases.

This report describes an unusual striking ultrastructural abnormality of neutrophils in three human renal allograft recipients. The abnormal neutrophils showed the presence of numerous elongated nuclear and cytoplasmic inclusions measuring up to 1.6 by 0.1 mu in greatest dimensions. Although the definite nature and functional significance of these inclusions are unknown, we suggest that they may represent an acquired neutrophil disorder. The three patients had serious infectious complications.

Adult↗
PubMed1981

The ocular pigmentary disturbance of human Chédiak-Higashi syndrome. A comparative light- and electron-microscopic study and review of the literature.

The ultrastructure of the ocular pigment abnormality of human Chédiak-Higashi syndrome is described. The presence of giant abnormal melanosomes, probably the end result of the fusion of smaller abnormal organelles, was the most striking pathologic finding. This defect involved both optic cup and neural crest-derived melanocytes; the former were affected more severely. Giant lysosome-like organelles were also observed.

Chediak-Higashi Syndrome↗
PubMed1981

Acid phosphatase staining pattern as an indicator of T-cell acute leukemia.

Acid phosphatase staining pattern has been variably advocated and discouraged as an indicator of T-cell differentiation of acute lymphoblastic leukemias. This study indicates that acid phosphatase staining pattern will correlate with the results of E rosette testing in both T-cell and non-T, non-B acute lymphoblastic leukemias in over 90% of cases. Acid phosphatase staining pattern may reliably be used to indicate T-cell differentiation in acute lymphoblastic leukemia in cases where insufficient material for E rosette testing is available.

Acid Phosphatase↗
PubMed1981

Primary ultrastructural diagnosis of cryoglobulinemic glomerulonephritis.

A 58-year-old woman suffering from epistasis was found to be hypertensive. Hypocomplementemia associated with normal serum creatinine level, erythrocytosis, microscopic hematuria, proteinuria, and normal serum immunoglobulin levels and immunoelectrophoresis results led to a renal biopsy. Light microscopy disclosed mesangial hypercellularity and accumulation of eosinophilic material in capillary loops and in the mesangium. Immunomicroscopy disclosed coarsely granular to globular deposition of IgG, IgM, and C3 in similar distribution. Electron microscopy demonstrated electron-dense mesangial and subendothelial deposits consisting of interlacing fibrillar bundles associated with infiltration of acute inflammatory cells characteristic of cryoglobulinemic glomerulonephritis. After the biopsy, the presence of circulating IgG-IgM cryoglobulins was documented. Substructure of the in vitro cryoprecipitate and the immune complexes in the kidney was very similar. These observations illustrate the importance of continued routine ultrastructural assessment in evaluation of renal biopsy material.

Cryoglobulins↗