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Biomedical subjects

G Stoica

Publications and source records attributed to G Stoica.

At least 73 records · Page 4Linked to original sources

Characteristics of normal rat mammary epithelial cells and N-ethyl-N-nitrosourea-induced mammary adenocarcinoma cells grown in culture.

The characteristics of normal mammary epithelial cells derived from Lewis and Sprague-Dawley rats and N-Ethyl-N-Nitrosourea (ENU)-induced mammary gland adenocarcinoma cells derived from Sprague-Dawley (CD) and Fisher (CDF) rats and grown in culture were compared. After collagenase treatment, the rat mammary epithelial cell aggregates were placed in a hormone-supplemented medium. The normal mammary epithelial cells (NE) attached to the surface of the dish within 50 hours, whereas the mammary adenocarcinoma cells (MA) attached within 24 hours and grew as cell multilayers. After the colonies of NE and MA cells became confluent, the culture system entered a steady state in which the cells from the upper layer were shed into the medium. The rate of proliferation and squame detachment in confluent cultures was increased by the presence of epidermal growth factor (EGF). Rhodanile blue staining and transmission electron microscopy showed that the shed cells were partially keratinized. In addition, cultured MA (but not normal) cells were able to grow in soft agar and form tumors when inoculated into appropriate hosts. The opposite was true in each case for the mammary adenocarcinoma cells. Karyotypes of normal and neoplastic rat epithelial cells revealed a hypodiploid modal number of chromosomes.

Adenocarcinoma↗

Decrease of serum immunoglobulin M levels in some diabetic patients.

Contradictory results have been published on serum immunoglobulin levels in diabetes. Our study population consisted of 26 "juvenile" IDDM patients (males/females 14/12, mean age 15.8 +/- 2.4 yrs), 42 "adult-onset" IDDM patients (25/17, 45.1 +/- 15.2 yrs), 62 NIDDM patients (27/35, 59.8 +/- 7.7 yrs), 128 controls. IgM has been measured by a highly standardized endpoint radial immunodiffusion. Since age and sex significantly influence serum IgM levels, we calculated Z values using the formula: log (Xobs:Xexp): SDexp, where Xobs is the measured IgM in any individual and Xexp and SDexp are the expected (geometric) mean and standard deviation of the log IgM values for each year of age in both sexes, as previously calculated by orthogonal polynomials from a large population of "laboratory controls" (n = 755; 10-70 yrs). These Z values (+/- SD) in juvenile IDDM (-0.442 +/- 0.988) and NIDDM (-0.559 +/- 1.215) were significantly lower (P = 0.035 and P less than 10(-3)) than in "laboratory controls" (0 +/- 1). Values in adult IDDM (-0.0225 +/- 1.213; P = 0.24) and in controls (-0.018 +/- 1.04) did not differ significantly from the "laboratory controls". The prevalence of diabetes within the four quartiles of the IgM distribution differed significantly from the one expected according to the null hypothesis (chi-square = 42.2; 3df; P less than 10(-4]. This is also applied to juvenile IDDM (P less than 0.05) and NIDDM (P less than 10(-4], but not to adult-onset IDDM. These results suggest that the low IgM levels may partly contribute to the poorly explained increase in susceptibility to infections in some diabetics.

Adolescent↗

Lectin binding sites in normal rat ovary and ENU-induced Sertoli cell tumors of the ovaries.

A panel of seven fluorescein isothiocyanate (FITC) labeled lectins were used to study the distribution of specific binding sites in histologic sections of rat ovaries and ENU-induced Sertoli cell tumors (SCT) of the ovaries. Ten SCT and 5 normal ovaries derived from Berlin Druckey IV (BD-IV) rats were examined by FITC lectins. The tissues examined were fixed in 10% buffered formalin and embedded in paraffin blocks. In normal ovaries, lectin binding sites were more uniform, ordered and consistent than in ovarian SCT where some lectin staining appeared disorderly inconsistent and varied with the degree of tumor differentiation. Two lectins, (from Triticum vulgaris [WGA] and Arachis hypogaea [PNA], uniformly stained the apices of the ovarian surface epithelium and subadjacent tunica vaginalis. The ovarian stroma, oocyte nucleus, follicular and granulosa-theca cells, stained uniformly strong with succinated Con A (from Con-canavalia ensiformis). Three lectins (from Triticum vulgaris, Ulex europeaus [UEA-1] and Arachis hypogeae) accentuated the basal lamina in the SCT and normal ovarian follicles. The zona pellucida was strongly labeled with lectin derived from Triticum vulgaris, Ricinus communis (RCA) and moderately with lectin derived from Arachis hypogeae. The oviduct ampulla exhibited an intracytoplasmic strong vesicular labeling with lectins derived from Triticum vulgare, Dolichos biflorus (DBA), Glycin max (Soybean-SBA) and Arachis hypogeae. The SCT cells showed an inconsistent, irregular labeling pattern with lectins derived from Ulex europaeus, Dolichos biflorus and Soybean mostly as a coarse granular cytoplasmic labeling. Neuraminidase digestion enhanced lectin staining with PNA in normal ovary and in SCT. This data provided at list of lectin markers for distinct components of the BD-IV rat ovary and ovarian SCT.

Animals↗

Lectin binding sites of cultured ovarian Sertoli cell tumors and follicular granulosa cells.

A panel of seven alkaline phosphatase labeled lectins was used to probe nitrocellulose electroblots of SDS-PAGE separated proteins from a primary culture of normal ovarian granulosa cells and an ENU-induced Sertoli cell tumor cell line (SCTL-I). Several additional lectin binding proteins were observed in silver stained SDS-PAGE gels as well as with lectins in SCTL-I. Succinated concanavalin A (Suc. Con A), Ricin communis agglutinin (RCA-I), Ulex europaeus agglutinin (UEA 1), Soybean agglutinin (SBA), Dolichos biflorus agglutinin (DBA) and Peanut agglutinin (PNA) stained more intensely in SCTL-I than normal granulosa cells. The same lectins as above, labeled with fluorescein isothiocyanate (FITC), were used to study the distribution of specific binding sites of tissue cultured cells grown in chamber/slides. Both normal ovarian granulosa cells and SCT cells exhibited strong peninuclear cytoplasmic labeling with Con A UEA-1 and WGA exhibited predominantly a nuclear and granular cytoplasmic staining pattern. SBA and DBA exhibited a strong coarse granular cytoplasmic labeling in granulosa cells and moderate granular cytoplasmic in SCT cells. In granulosa cells, Golgi regions stained strongly with PNA but weakly in SCT cells. RCA-I staining was negative in both cultures. Labeling of tissue cultured cells with lectins provides more details than histological sections of lectins binding sites at cellular structural levels.

Animals↗

The renal involvement in scleroderma. A clinical and morphologic study.

The main clinical, biologic, immunologic and morphologic changes characteristic of the sclerodermic nephropathy have been investigated during a mean period of 3.8 years in 21 patients with scleroderma, 19 women and 2 men, with a mean age of 36.1 years. The results obtained have revealed the frequent (38.1%) and early renal involvement, with constant arteriolar and glomerular lesions. Proteinuria was the most frequent (28.6%) and early sign of renal damage. The urinary sediment was poor and the immunologic investigations unconclusive. Dosage of urinary proteins by sensitive techniques (immunoquantitation) and renal biopsy have proved to increase the accuracy of studies for the detection of sclerodermic nephropathy in its initial stage.

Adolescent↗

DNA damage, repair, replication, and tumor incidence in the BDIV rat strain following administration of N-ethyl-N-nitrosourea.

Berlin-Druckrey (BD-IV) rats were used to evaluate the level of neoplastic transformation, initiation of DNA damage and repair following treatment with N-ethyl-N-nitrosourea (ENU). ENU, a potent neurocarcinogen in the Sprague-Dawley (CD) and BDIX rat strains, was a less potent neurocarcinogen when administered to 30 day old BDIV rats. ENU induced significantly higher levels of tumors of the nervous system, kidney, and liver in CD rats than in BDIV rats. Initial DNA damage was determined by quantitating and comparing the number of alkaline labile sites (ALS) and alkylation of [14C]ENU to deoxyguanosine in the brain, kidney, and liver of BDIV rats. A smaller percentage of ALS were lost from the DNA of the brain (10-15%) than from the kidney (19-27%) and liver (30%). Similarly, loss of 0(6)-ethylguanine was greatest in liver (100%), next in kidney (73%), and least in brain (23%) DNA during a seven-day period. Loss of N7-ethylguanine ranged between 23-44%. These levels of repair are similar to those previously observed in the more sensitive Sprague-Dawley rat. Cellular replication was highest in the liver and lowest in the brain of BDIV rats at 30 days of age and was inhibited to varying extents in all three tissues by ENU. These data indicate, that while there is a good correlation between organ sensitivity to ENU induced carcinogenesis and the persistence of DNA lesions and levels of DNA replication in the same strain of rat, there is no correlation across strains with different carcinogenic potential.

Animals↗

Microalbuminuria following exercise, an early sign of diabetic nephropathy.

Microalbuminuria after physical exercise is characteristic for the preclinical stage of diabetic nephropathy, permitting an early diagnosis of this severe complication of diabetes mellitus. In 24 patients with type I diabetes, 11 women and 13 men free of clinical and biological signs of renal damage, the presence of microalbuminuria has been investigated by radial immunodiffusion in the urines collected between 3 and 7 hrs in the morning, as well as after a 20-min rest following a moderate exercise of 75 watts during 20 min at the ergometric bicycle. The patients were distributed into four groups, according to the age of disease, and microalbuminuria was expressed in micrograms/min. Compared with the mean values recorded in normal subjects by the same method (6.8 micrograms/min), the level of microalbuminuria has been significantly higher in the cases evaluating since more than two years, in keeping with the time elapsed after onset, and particularly following exercise. No relationship could be established between the quality of metabolic control of diabetes and the levels of microalbuminuria after exercise.

Adolescent↗

Concentration of serum immunoglobulins in acute and chronic hepatic diseases. I. Serum-levels of IgG, IgA, IgM and IgD in young patients with viral hepatitis.

Concentrations of IgG, IgA, IgM and IgD were measured against WHO Reference Preparation 67/97 and British Standard 67/37 in sera from 105 patients with viral hepatitis and 110 "current" controls. To allow comparison at different ages and between sexes, constants previously determined on sera from a large "laboratory" group of controls were used to calculate "scores" for all Ig values. The patients' IgM scores were remarkably higher than those of controls and were bimodally distributed. About 68% of the patients had IgM scores more than 2 SD above the expected mean for laboratory controls. The distribution of IgG and IgA scores appeared unimodal, but schifted to the right of controls. The mean values of IgG and IgA scores were significantly greater in patients than in controls, and in female patients compared with males. Moreover, 16% (12 of 73) of the male and 47% (15 of 32) of the female patients had Ig G scores more than 2 SD above the expected mean. With regard to IgD, no significant difference between patients and controls was observed.

Acute Disease↗

Concentration of serum immunoglobulins in acute and chronic hepatic diseases. II. Viral hepatitis; time-dependent changes in immunoglobulin concentration.

Immunoglobulin (Ig) concentrations were determined on blood samples drawn of 6 occasions over a 2-month period from 38 young patients with viral hepatitis. The main and joint effects of sex and day factors on mean Ig levels were studied by using a 2-way ANOVA model. No distinct pattern of variation was observed for IgA, IgG and IgD, whereas the mean values of IgM showed a statistically significant variation throughout the study period. Female patients had significantly higher mean Ig values than males; for each Ig-class, however, the day-to-day variation was very similar in the two sexes, as reflected by an unsignificant sex-day interaction. The results suggest that serial measurements of IgM levels can be useful for identifying those patients at risk of developing chronic hepatitis and for an early detection of viral hepatitis in persons at very high risk of contracting this disease.

Acute Disease↗

Prevalence and patterns of hyperimmunoglobulinemia in acute viral hepatitis convalescents.

The 99th-percentile values of a large control group were used to determine the frequency and patterns of hyperimmunoglobulinemia (HIg) in 119 convalescents from viral hepatitis in whom Ig quantitation was performed on two occasions within 6 1/2 months after their acute episode. The mean levels of IgG, IgA and IgM, but not of IgD, were significantly higher in convalescents than in controls. There was no significant difference (p greater than 0.1) in the overall frequency of HIg (at least one Ig-class value greater than or equal to 99th percentile of controls) between the initial (30.2%; n = 119) and repeat (20.6%; n = 97) samples, though differences in the distribution of HIg patterns occurred between the two samples. At the time of repeat testing, 7 out of 77 subjects with normo-Ig, but 13 out of 20 with HIg had clinical and/or laboratory abnormalities (p less than or equal to 0.001).

Acute Disease↗

Neoplasms induced with high single doses of N-ethyl-N-nitrosourea in 30-day-old Sprague-Dawley rats, with special emphasis on mammary neoplasia.

Intraperitoneal administration of high doses (45, 90, and 180 mg/kg of ENU (N-ethyl-N-nitrosourea) to 30-day-old female Sprague-Dawley (CD) rats resulted in a high incidence (greater than 100%) of mammary tumors (MT), of which 95% were malignant. The mean induction time was 92 days for the high dose group. There was a definite dose-effect relationship. As the dose of ENU decreased the number of rats affected and number of tumors per rat decreased, but the survival time and mean induction time increased. At the time of death 7.5% of mammary tumors had metastasized to the lung. A variety of histological MT types were produced simulating breast tumors in women. In addition to MT, a number of rats developed primary tumors in other organs (brain, ovary, kidney, and hemic-lymphatic system). The high MT incidence, high rate of malignancy, short latent period, and the simulation of human breast tumor types suggest this experimental design to be a valuable animal model to study initiation, hormone dependency, and pathogenesis of mammary neoplasia.

Age Factors↗

Biologic variation of human immunoglobulin concentration. I. Sex-age specific effects on serum levels of IgG, IgA, IgM and IgD.

Data on a large, randomly selected population of apparently health subjects, aged 10 to 73 years, of both sexes were used to derive estimates of the reference intervals for serum levels of IgA, IgG, IgM, and IgD. The main effects of age and sex on the mean values were studied by the use of a two-way ANOVA model. Except for IgG that showed no sex dependencies, statistically significant sex and age-related differences in mean levels were found for each of the immunoglobulins studied. The mean concentrations of both IgA and IgD were higher in males than in females; an inverse relationship was identified for IgM. Serum levels of both IgG and IgA rose gradually with advancing age in either sex; by linear-regression analyses these age dependencies were found to be statistically significant for IgG in males and IgA in both sexes. The age-related changes in either IgM or IgD serum levels were more complex and fitteda quintic function better than a linear one. These results indicate that any interpretation of immunoglobulin values without appropriate consideration of the subject's age and sex is likely to be misleading.

Adolescent↗

Screening procedures for detection of hyperlipoproteinemia. I. Comparison of four turbidimetric methods for simultaneous determination of low- and very low-density lipoproteins.

In order to chose a reproducible and discriminatory method for use in mass screening for hyperlipoproteinemia, a comparison was made of four procedures of LDL and VLDL precipitation with polyanions in the presence of divalent cations. All the four methods (ie., heparin-Mn2+, heparin-Ca2+, heparin-Mg2+, and phosphotungstate-Mg2+) were applied simultaneously to aliquots from a single serum sample. Highly significant correlations were found when the results on 104 randomly selected sera were analyzed by matching every method with each of the other three techniques, indicating that all the four methods are really measuring the same analytes. The heparin-Mn2+ method, however, was more precise, selective and quantitative.

Humans↗

Criteria for immunosuppressive treatment (corticotherapy) in the early stage of chronic viral hepatitis.

Thirty-five patients showing quatitative deviations from normal of the M and G immunoglobulin (Ig) fractions were selected for study from a larger group of patients with viral hepatitis. In 15 of the 35 cases, most of which showed high IgM and/or IgG serum levels, moderate doses of prednisone were administered for 60 days. Determinations of Ig levels were performed before and after corticotherapy, two and four months respectively after the onset of the acute viral hepatitis. The rest of 20 patients were used as controls. In the cases in which the clinical and biological parameters indicated an improvement after treatment, the initial high IgM titers showed a tendency to decrease while in those with severe evolution, IgM levels increased. A similar behaviour of IgM titers, though less marked, was also noticed in the control group, of untreated patients. These variations are assumed to predict the further favourable of severe course of the disease; Ig variations and particularly the IgM ones, might be useful criteria for the selection of cases with high risk of developing chronic hepatitis, so that corticotherapy could be applied in the early stages, to prevent the progress to more severe forms of the disease.

Adolescent↗