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Biomedical subjects

C Russo

Publications and source records attributed to C Russo.

At least 91 records · Page 5Linked to original sources
PubMed1995

Oxytocin receptor gene expression in the rat uterus during pregnancy and the estrous cycle and in response to gonadal steroid treatment.

It is well established that uterine oxytocin receptors (OTRs) are strongly up-regulated immediately before parturition as well as in response to estrogen (E2) administration. Progesterone (P4), on the other hand, induces a rapid down-regulation. We recently cloned the rat OTR gene and characterized its expression in the rat uterus. In this study, we examined the regulation of OTR messenger RNA (mRNA) levels in rat uterus during pregnancy, the estrous cycle, and in response to gonadal steroid treatment. OTR mRNA levels increased more than 25-fold during gestation: 4.5-fold during the first 21 days and 6-fold within 24 h between day 21 and the onset of parturition. Uterine OTR mRNA levels fell rapidly by 85% within 24 h following parturition. By in situ hybridization, OTR mRNA was localized specifically to the longitudinal and circular layers of the myometrium but was not detected in the endometrium. During the estrous cycle, OTR mRNA levels increased 2-fold between metestrus and proestrus, whereas oxytocin (OT) binding rose more than 10-fold within this same interval. Treatment of ovariectomized rats with E2 lead to a significant increase in both OTR mRNA levels (4.4-fold) and OT binding (< 6-fold). Cotreatment with P4 strongly reduced OT binding by 75% (P < 0.01) but did not significantly affect the E2-induced rise in OTR mRNA (11% decrease, P > 0.1). Our data suggest that the increased expression of OT binding sites observed at the onset of labor and at proestrus is mediated, at least in part, by an E2-induced up-regulation of OTR gene expression. However, it also appears that OTR mRNA levels are not the sole determinants of uterine OT binding. Specifically, P4-mediated OTR down-regulation cannot be explained by an effect on OTR mRNA accumulation and may involve novel mechanisms acting at translational or posttranslational levels.

Animals↗
PubMed1995

[The multiple-organ failure syndrome in acute pancreatitis. Its pathogenesis and treatment].

Multiple organ system failure (MOSF) is a severe clinical process that causes progressive renal and liver failure. Acute pancreatitis (AP) can cause MOSF. Several series document high mortality rate from necrotizing forms is associated with MOSF. The authors observed 199 cases of acute necrotizing pancreatitis in 10 years, with a mortality rate of 14.1%. MOSF occurred in 14 cases, resulting in death in 100% of affected patients. In AP, MOSF follows hemodynamic abnormalities suspected to be secondary to activation of kinins system and other vasoactive peptides that are responsible for pathogenetic mechanism of disease. Similar hemodynamic abnormalities can be observed in septic shock. Then many authors suppose causes of MOSF in AP are local (abscess, infection of pancreatic necrosis) and systemic septic complications or translocation of enteric bacteria or their endotoxins from the gut lumen. So it is important to provide prophylactic use of antibiotics that are effective against expected bacteria and also achieve a therapeutic concentration in pancreatic tissue and juice. Fluid replacement, nutritional support and other therapeutic strategies must be employed to prevent MOSF. When the MOSF is clearly developed, medical and surgical measures are unuseful and the mortality rate is very high also in an intensive care unit.

Acute Disease↗
PubMed1995

Gonadal steroid regulation of oxytocin and oxytocin receptor gene expression.

By Northern blot analysis and in situ hybridization, we have determined that, at term, the rat uterine epithelium represents a major site of oxytocin (OT) gene expression. OT mRNA levels increase > 150-fold during pregnancy and, at term, exceed hypothalamic OT mRNA by a factor of 70. By cryoultramicroscopy, OT immunoreactivity was localized to transport vesicles in the apical compartment of uterine epithelial cells. Estrogens (E) act as a strong inducer of uterine OT gene expression in vivo, and this effect is potentiated 7-fold by concomitant progesterone (P) administration. We have also cloned the rat OT receptor (OTR) gene and developed a polymerase chain reaction (PCR)-based assay to measure OTR mRNA. Whereas OTR mRNA is strongly induced by E, P does not potentiate but slightly attenuates the E-induced rise. However, E-induced OT binding is completely reversed by concomitant P administration, suggesting an additional post-transcriptional effect of P. The mechanisms of E-induction of the uterine OT gene remain unclear, inasmuch as the OTR gene promoter does not contain a classical estrogen response element (ERE). Moreover, transfection analysis of a 3.1 kb OTR gene promoter fragment linked to a luciferase reporter gene indicates that promoter activity is induced 5-fold by calcium ionophore A23187 but not by E.

Animals↗
PubMed1995

Omega-3 polyunsaturated fatty acid supplements and ambulatory blood pressure monitoring parameters in patients with mild essential hypertension.

OBJECTIVE: To evaluate the effects of low doses of omega-3 polyunsaturated fatty acids on ambulatory blood pressure monitoring parameters in a group of mild essential hypertensives. PATIENTS: We studied 24 consecutive essential hypertensive patients from our outpatient clinic with mild hypertension (diastolic blood pressure < or = 105 mmHg), no previous treatment for 4 weeks at least and no other disease. METHODS: After a 3-month run-in period, the patients entered an intervention phase and were given 3 g omega-3 polyunsaturated fatty acids (85% eicosapentaenoic and docosahexaenoic acid concentrate) daily for 4 months; this phase was followed by a 4-month washout period. Ambulatory blood pressure monitoring was performed at the end of each phase; erythrocyte membrane fatty acids were assessed to check compliance. RESULTS: After 4 months of treatment, erythrocyte omega-3 polyunsaturated fatty acids significantly increased but average systolic and diastolic blood pressure and the heart rate did not significantly change; no significant variations were recorded in blood pressure or heart rate variability (assessed as blood pressure and heart rate SD) nor in the diurnal blood pressure rhythm. After washout, a significant decrease was observed in erythrocyte omega-3 polyunsaturated fatty acids but the ambulatory blood pressure monitoring parameters were not substantially modified. CONCLUSIONS: The present data show that low doses of omega-3 polyunsaturated fatty acids as a single treatment are not effective in lowering blood pressure or the heart rate in mild essential hypertensive patients, despite a significant change in fatty acid cell membrane composition. Nor does this treatment seem likely to affect blood pressure variability or the diurnal rhythm.

Blood Pressure↗
PubMed1994

Clonal populations of T cells in normal elderly humans: the T cell equivalent to "benign monoclonal gammapathy".

To determine whether T cells, like B cells, can become clonally expanded in normal individuals as a function of age, we compared the T cell V beta repertoire of cord blood to that of peripheral blood from normal donors over 65 yr of age. T cells from elderly subjects contained expanded subsets (greater than the mean+three standard deviations) of T cell receptor (TCR) V beta populations. These expanded subsets were observed primarily among CD8, but not CD4 cells, represented up to 37.5% of all CD8 cells, and were present in most elderly subjects. An expanded V beta 5.2/3 CD8 subset and a V beta 6.7a CD8 subset from separate donors were analyzed by reverse transcriptase-polymerase chain reaction, cloning and sequencing of the TCR beta chain VDJ junction. In both cases the expanded subsets were mono- or oligoclonal while control CD4 populations were polyclonal. Using two-color flow cytometry it was possible to identify the expanded V beta 6.7a subset as CD8+ CD28-CD11b+ cells. In three of five random old subjects similar expansions of V beta subsets were found specifically in the CD8+ CD28- subpopulation, an interesting subset of cytotoxic T lymphocytes, known to lack proliferative responses to TCR stimuli. It is common practice to use the demonstration of clonality as a diagnostic indicator for T cell lymphoma/leukemia. In view of the high frequency of expanded T clones of T cells in normal elderly subjects the diagnostic usefulness of this test should be reexamined.

Aged↗
PubMed1994

Serum HLA class I levels in elderly humans. Utilization in following the response to influenza vaccine.

Some healthy elderly people (30%-40%) do not respond to influenza vaccination. Subjects who respond to influenza vaccination show a significant increase in serum HLA class I levels 2 weeks after immunization. In the present study, serum HLA class I levels were measured prior to vaccination and 4 and 6 weeks after vaccination. The responders (HAI titers > or = 40) had higher prevaccination HLA class I levels (2.03 +/- 0.12 microgram/ml) than nonresponders (HAI titers < 40) (1.57 +/- 0.14 microgram/ml) (P = 0.03). The responders' sHLA levels remained stable at 4 (1.98 +/- 0.12 microgram/ml) and 6 (2.13 +/- 0.12 microgram/ml) weeks postvaccination. In contrast, nonresponders' sHLA levels increased at 4 weeks (1.85 +/- 0.18 microgram/ml) but declined to prevaccination levels at 6 weeks (1.59 +/- 0.16 microgram/ml). Lymphocytes isolated from the responders (n = 4) 4 weeks after vaccination had a higher in vitro proliferative response (mean SI = 20) than lymphocytes from nonresponders (n = 4, mean SI = 6.4) to the influenza vaccine. This proliferative response was significantly inhibited (mean SI = 6.3, P = 0.04) in the responders by the addition of an anti-HLA class I mAb and was associated with increased cell surface expression of HLA class I molecules. Two forms of sHLA class I molecules of relative mass of M(r) 42,000 and 40,000 were immunoprecipitated from the serum of nonresponders whereas only the M(r) 40,000 form was detected in the sera of young controls and of elderly responders.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Active infective endocarditis: surgical approach.

From January 1982 to December 1991, 65 interventions were performed in 61 patients with active infective endocarditis (IE): 32 on native valves (Group 1) and 33 on prosthetic valves (Group 2). In Group 1, 23 patients had a known previous valve disease; major preoperative clinical complications occurred in 16 patients (50%); 84% were in NYHA classes III and IV. In Group 2 major preoperative clinical complications occurred in 13 patients (44.8%); 86% were in NYHA classes III and IV. The mean time interval between the onset of hemodynamic impairment of varying degrees and surgery was 13 +/- 15 days for Group 1, and 8 +/- 11 days for Group 2. In all cases, the native valves or prostheses were replaced by mechanical valve prostheses. Particular procedures were performed in three patients in Group 1 and five patients in Group 2. In Group 1 there were 8 hospital deaths (25%) and 11 (34.4%) non-fatal complications. In Group 2 there were 9 deaths (31%) and 14 (48.3%) non-fatal complications. Risk factors for hospital death were "preoperative low cardiac output syndrome" and "time interval between the onset of cardiac failure and surgery" in Group 1, "cardiac failure+sepsis" in Group 2, "time interval between the onset of cardiac failure and surgery" and "particular procedures" in all 61 patients. Sepsis alone and the type of pathogenic agent does not significantly affect the risk of death. The recurrence of acute IE was 12.6% in Group 1, and 20% in Group 2. The incidence of reintervention was 12.6% in Group 1 and 35% in Group 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Vaccine immune response and side effects with the use of acetaminophen with influenza vaccine.

The purpose of this study was to determine whether acetaminophen impairs the immune response to influenza vaccine. Influenza vaccine is an under-utilized preventive measure, partly because of the unfounded perception that fever and myalgias frequently follow vaccination. While acetaminophen may decrease these infrequent side effects, it may also alter the immune response to vaccination. We compare the effect of acetaminophen with placebo on the humoral immune response to the 1991-1992 commercially available influenza vaccine. We studied 60 healthy, elderly subjects from a geriatric clinic and 20 infirm, elderly subjects from a nursing home. The subjects were randomly assigned to receive placebo or acetaminophen (1,000 mg every 6 h) for 2 days. Acetaminophen did not depress or enhance the immune development of serum hemagglutination inhibition antibody to the three vaccine antigens. The systemic side effects of fever and myalgia were uncommon in both groups. The healthy elderly subjects mounted a significantly better immune response to the influenza virus A/Taiwan/1/86 (H1N1) vaccine strain than did the infirm elderly subjects (geometric mean titer, 115 versus 51; P = 0.003). The functional activity score obtained by using the chronic healthy evaluation component of the Acute Physiology and Chronic Health Evaluation system could be used to distinguish the healthy from the infirm elderly (scores of 1.27 versus 3.75, P < 0.001). Acetaminophen neither depressed nor enhanced the serum antibody response to the vaccine in the healthy and infirm elderly subjects studied.

Acetaminophen↗
PubMed1994

Germline mutations of the p53 tumor suppressor gene in children with osteosarcoma.

PURPOSE: We investigated the possibility that a significant proportion of children with osteosarcoma harbor germline mutations of the p53 tumor suppressor gene and, therefore, this subgroup of pediatric cancer patients should be considered for large-scale predictive testing. PATIENTS AND METHODS: Genomic DNA extracted from peripheral-blood leukocytes from 235 unselected children with osteosarcoma from 33 institutions were screened for the presence of germline p53 mutations using constant denaturant gel electrophoresis (CDGE). Exons 5 through 8 were evaluated in all patients and exon 2 and exon 9 were analyzed in 59 and 95 patients, respectively. Those samples that showed aberrant migration on CDGE were sequenced or analyzed by restriction enzyme digestion of polymerase chain reaction (PCR) products to confirm the nature of the gene alteration. RESULTS: In 18 samples, CDGE showed fragments of the p53 gene with altered electrophoretic mobilities compared with wild-type p53. DNA sequencing showed that 11 samples had an identical, previously described polymorphism. The other seven contained heterozygous p53 mutations located in exon 5 (n = 3), exon 6 (n = 1), exon 7 (n = 1), and exon 8 (n = 2). Six alterations were missense mutations and one was a nonsense mutation. Three of these patients had first-degree relatives with cancer. One of these three kindreds had a family history consistent with Li-Fraumeni syndrome (LFS). CONCLUSION: We identified germline p53 mutations in seven of 235 (3.0%) children with osteosarcoma. Four of these mutations were found in patients who did not have first-degree relatives with cancer. Although genetic transmission of the altered p53 gene could not be tested in this survey because of how it was designed, it is possible that predictive testing for p53 mutations could identify unaffected relatives of gene carriers who also have a high risk for the development of cancer. This study provides evidence for the importance of considering children with osteosarcoma for predictive testing for germline p53 mutations.

Base Sequence↗
PubMed1994

[Aortic valve replacement in old age. The results and follow-up echo-Doppler study of the prostheses].

BACKGROUND: To analyze the results of aortic valve replacement in elderly patients and to evaluate the hemodynamic performance of valvular prostheses, we have retrospectively studied the patients 70 years of age or older, who consecutively underwent aortic valve replacement in our Center. METHODS: From January 1988 to December 1992, a series of 112 patients aged 70 to 88 years (mean 74.8 +/- 3.8 years) underwent aortic valve replacement; 49.1% of patients were male; aortic valvular lesion was: stenosis in 65.2%, insufficiency in 9.8% and mixed stenosis and insufficiency in 25.0%. In 73.2% isolated valve disease was present; in 25.0% coronary artery disease was associated. Preoperatively 58.9% were in New York Heart Association class III, and 29.5% were in class IV. Concomitant extracardiac diseases were present in 73.2%. The types of valve prostheses employed were: mechanical tilting disc (28 cases), mechanical bileaflet (40 cases), bioprosthesis (44 cases). A significantly favourable relationship between body surface area and size of prostheses was evident. RESULTS: Overall hospital mortality was 8.9% (5.4% for elective isolated aortic valve replacement) with significant difference (p = 0.006) related to criteria for surgical indication (elective 6.4%, urgent 10.0%, emergency 37.5%). Valvular lesion, age, sex, associated coronary artery bypass surgery, the values of peak and mean aortic valve gradient, the relative wall thickness and the presence of extracardiac disease have not been identified as risk factors for hospital mortality. The mean follow-up of the 102 discharged patients is 27.1 +/- 16.5 months (range 2 to 64 months). Eight late deaths (7.8%) occurred; the overall actuarial freedom from all deaths (excluding hospital mortality) was 95.6 +/- 2.2% at 1 year and 88.6 +/- 4.0% at 3 and 5 years. Five non fatal valve related complications occurred: hemorrhage in 4 cases (1.8% pt/yr) and hemolysis in 1 case (0.4% pt/yr). Ninety-seven percent of patients were found to be in NYHA functional class I or II. Comparative echocardiographic evaluation of the prostheses showed significant differences in mean gradient: regarding 21 mm size lower in bileaflet than in tilting disc and regarding 23 mm size lower in bileaflet than in tilting disc or bioprostheses. CONCLUSIONS: Aortic valve replacement has proved to be safe and effective in the elderly population and is considered the procedure of choice for aortic valve disease. Although we consider mandatory to choose the valve substitute matching different physiopathological and psychological attitudes of individual patient, mechanical prostheses and particularly bileaflet type for size < or = 21 mm should be preferred.

Aged↗
PubMed1993

Age-dependent appearance of non-major histocompatibility complex-restricted helper T cells.

T cells which recognize antigen in association with self major histocompatibility complex (MHC) molecules are positively selected within the thymus. This results in skewing of the T-cell repertoire toward the recognition of antigenic peptides presented by self MHC molecules. While the thymus gland involutes at a relatively young age, bone marrow function and the size of the peripheral T-cell pool are maintained with age. We have investigated the MHC restriction of helper T-cell function for B-cell production of specific antibody in mice of different ages. Splenic helper T cells from 2- to 3-month old mice immunized with phosphocholine-keyhole limpet hemocyanin conjugate were MHC-restricted as defined by their capacity to induce phosphocholine-specific antibody synthesis by syngeneic but not by allogeneic B cells. In contrast, splenic T cells from immunized 18- to 20-month-old mice induced specific anti-phosphocholine antibodies by both syngeneic and allogeneic B cells. No evidence of polyclonal immunoglobulin synthesis was detected. The ability of T cells from old mice immunized with phosphocholine-keyhole limpet hemocyanin to induce phosphocholine-specific antibody synthesis by B cells from allogeneic mice was inhibited by T cells from immunized young mice. These findings suggest that non-MHC-restricted T-cell helper activity in old mice results from the loss of T cells, present in young mice, which suppress non-MHC-restricted helper cells.

Aging↗
PubMed1993

Effect of age on the expressed B cell repertoire: role of B cell subsets.

Aged humans and experimental animals are impaired in their responses to most foreign antigens although they produce greater amounts of autoantibodies. We have examined the effect of age on the production of antibodies to a prototypic foreign antigen, sheep erythrocytes (SRBC), and to a prototypic autoantigen, bromelain-treated mouse erythrocytes (BrMRBC), in young and old mice before and after immunization with SRBC. Old mice express more anti-BrMRBC plaque-forming cell (PFC) antibodies before and an even greater number after immunization with SRBC than young mice. Conversely, old mice produce far fewer anti-SRBC PFC than young mice following immunization with SRBC. We hypothesized that the differences in the responses of old mice to BrMRBC and SRBC reflects differences in the activity of CD5+ and CD5- B cells. To test this hypothesis we immunized young and old mice with foreign antigens reported (and confirmed in our studies) to stimulate CD5+ B cells [TNP-ficoll and phosphorylcholine-keyhole limpet hemocyanin (KLH)] or CD5- B cells (SRBC and TNP-KLH). We found that the PFC response of old mice to antigens mediated by CD5+ B cells was equal to or greater than that of young mice. In contrast the PFC response of old mice induced by antigens mediated by CD5- B cells was only 10% that of young mice. Thus it appears that the immune response of old mice is well maintained for antigens which elicit a CD5+ B cell response but not for those which elicit a CD5- B cell response.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1993

Increased serum HLA class I molecule levels in elderly human responders to influenza vaccination.

Increased cell surface expression and serum levels of HLA class I molecules have been shown to occur in normal elderly humans. Elderly subjects (65 years and older) generally also have a poorer response to influenza vaccine than younger adults. Some 30 to 40% of elderly subjects do not respond to influenza vaccination. Sera from 20 elderly subjects with a positive response to influenza vaccine (HAI antibody titer > 40) and 20 subjects who did not respond (HAI antibody titer < 40) were randomly selected and the levels of soluble HLA class I molecules determined before and after vaccination. The subjects who responded had higher serum HLA class I levels both before and after vaccination than did non-responders. Two weeks after vaccination non-responders showed similar serum HLA class I levels (1.78 mg/ml +/- 0.62) as compared to prevaccination levels (1.73 mg/ml +/- 0.49). The responders showed significantly higher levels of soluble HLA class I molecules following vaccination (2.64 mg/ml +/- 0.99) as compared to pre-vaccination (2.08 mg/ml +/- 0.85, p = 0.00001). Our results suggest that measuring soluble HLA class I molecules in the serum may be useful in assessing the adequacy of response to influenza vaccination in the elderly population.

Aged↗
PubMed1993

Posterior annuloplasty in the surgical treatment of mitral insufficiency.

One hundred and twenty-nine patients underwent posterior mitral annuloplasty with a Gore-Tex tube for mitral regurgitation between January 1982 and June 1991. The hospital mortality was 1.5% (CL = 0.5%-2.5%). The overall survival of hospital survivors was 96.5% +/- 2.7% at five and 86.2% +/- 7.6% at nine years, freedom from cardiac death was 99.1% +/- 0.9% and 95.2% +/- 3.9%, respectively. The actuarial freedom from embolism was 96.1% +/- 2.3% at five and 88.5% +/- 5.5% at nine years. The freedom from endocarditis (one patient) was 100% and 92.6 +/- 7.1%, respectively. Reoperation was necessary in six cases between one and 72 months after the operation (mean 38.5 +/- 30.5 months). The etiology of the valvular insufficiency was rheumatic in all reoperated cases. The freedom from reoperation was 94.1% +/- 3.2% at five and 87.2% +/- 5.6% at nine years. There was no mortality at reoperation. Of the 117 patients alive at the end of follow up and not requiring reintervention, 113 (96.6%) showed good functional improvement and were in NYHA functional class I or II. We conclude that both the immediate and long-term results of reconstructive surgery using the technique of inserting a half-ring on the posterior mitral annulus compare favorably with those obtained using other annuloplasty methods.

Actuarial Analysis↗
PubMed1993

Enhancement of glycine release from human brain cortex synaptosomes by acetylcholine acting at M4 muscarinic receptors.

Synaptosomes prepared from fresh specimens of human cerebral cortex were labeled with [3H]glycine ([3H]Gly) and distributed in parallel superfusion chambers. Exposure to 15 mM KCl evoked a tritium overflow which was largely prevented by 10 mM Mg++, suggesting a consistent component of Ca(++)-dependent [3H]Gly release. Acetylcholine (ACh; 1-100 microM), added during K(+)-depolarization, increased the release of tritium in a concentration-dependent manner (maximal effect, 60%; EC50 = 7 microM). Oxotremorine (1-100 microM) mimicked ACh. The effect of 10 microM ACh was insensitive to the nicotinic antagonist mecamylamine (100 microM), but it was blocked by the muscarinic antagonist atropine (0.1 microM). Three muscarinic receptor antagonists, pirenzepine, AF-DX 116 (11-[12-[diethylamino-methyl]-1-piperidinyl]acetyl-5-11-dihydro -6H-pyrido-[2-3-b][1,4]benzodiazepine-6-one) and himbacine, endowed with relative selectivity for various muscarinic receptor subtypes, prevented with differential affinities the effect of 10 microM ACh. Himbacine was the most potent antagonist of ACh, its pA2 (8.34) being 20- or 50-fold higher than that of pirenzepine (7.27) or AF-DX 116 (6.65). It is concluded that: 1) ACh can increase the release of Gly in human cerebral cortex; 2) the interaction occurs through muscarinic receptors which resemble most the M4 subtype; and 3) considering that Gly is required to activate the N-methyl-D-aspartate glutamate receptor, the ACh-evoked Gly release may represent a linkage between cholinergic and glutamatergic transmission, two systems strongly implicated in cognitive processes.

Acetylcholine↗