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Biomedical subjects

M Pagano

Publications and source records attributed to M Pagano.

At least 181 records · Page 10Linked to original sources
PubMed1990

Early and late germinal matrix hemorrhage may have different antecedents.

The time of occurrence of germinal matrix hemorrhage (GMH) in preterm babies might convey information about risk. We compared the risk profile of babies whose GMH was evident on a cranial ultrasonogram before the 12th postnatal hour (i.e., early GMH) to that of babies whose GMH did not become evident until after that time (i.e., late GMH). Overall, the two groups were similar. Babies with early GMH, however, were more likely to have been born after a course of labor (p = 0.03), for the first measurement of arterial blood pH to have been less than 7.2 (p = 0.02), and to have received bicarbonate (p = less than 0.00001). These findings lend support to the view that the risk profiles of early and late GMH are not identical, and also to the view that intranatal and immediate postnatal factors contribute to the early onset of GMH in susceptible babies.

Acidosis↗
PubMed1990

Correlation between islet cell antibodies and anti-cytomegalovirus IgM and IgG antibodies in healthy first-degree relatives of type 1 (insulin-dependent) diabetic patients.

To investigate whether cytomegalovirus (CMV) infection may be related to islet cell antibodies (ICA) production and/or to insulin-dependent diabetes mellitus (IDDM) development, we have analyzed the prevalence of anti-CMV, IgM, and IgG antibodies and of ICA in 80 healthy siblings of IDDM patients (HSIDDP) and in 60 control subjects with negative familiar anamnesis of IDDM. HSIDDP and controls were also typed for HLA-A-B-C and DR antigens. IgM and IgG anti-CMV were detected by an ELISA method, whereas the ICA assay was performed by standard indirect immunofluorescence on 5-microns unfixed sections of human pancreas. HLA-A-B and C antigens were studied by standard microlymphocytotoxicity; DR antigens were also studied by a standard microlymphocytotoxicity on a B-enriched lymphocyte population. Our results indicate a significant association (P less than 0.0001) between high titers of anti-CMV IgG antibodies and ICA in HSDIDDP, whereas no correlation was found between the presence of any HLA-A-B-C and DR antigens and the prevalence of anti-CMV IgM and IgG antibodies and/or ICA. Thus, these data may support the hypothesis that a chronic CMV infection may be associated with ICA production whereas other factors seem to be needed for the complete development of type 1 diabetes.

Adolescent↗
PubMed1990

Enhanced percentage of CD5+ B lymphocytes in newly diagnosed IDDM patients.

The percentage of CD5+ B lymphocytes, the prevalence of islet cell antibodies (ICA) and of anti-insulin autoantibodies (IAA) and HLA-A-B-C and DR antigens were studied in 32 newly diagnosed insulin-dependent diabetes mellitus (IDDM) patients, in 12 non-insulin-dependent diabetes mellitus (NIDDM) patients and in 12 healthy subjects. The percentage of CD5+ B lymphocytes ranged from 18% to 51.2% (mean 40.3 +/- 11%) in IDDM patients, whereas in NIDDM patients and in controls it ranged from 20% to 25.2%, (mean 21.3 +/- 4.1%) and from 16% to 24%, (mean 19.3 +/- 1.9%), respectively (P less than 0.01 vs. NIDDM patients and vs. controls). There was no correlation between a higher percentage of CD5+ B lymphocytes and the presence of ICA and/or IAA, and their titres, and/or of any HLA-A-B-C and DR antigens. Thus, an enhanced percentage of CD5+ B lymphocytes may be present in newly diagnosed IDDM patients; the possible role of this cell type in the pathogenesis of IDDM needs further investigation.

Adolescent↗
PubMed1990

Hydration during the first days of life and the risk of bronchopulmonary dysplasia in low birth weight infants.

We conducted a case-control study of antecedents of bronchopulmonary dysplasia (BPD) in 223 infants enrolled in a prospective, randomized clinical trial of phenobarbital prophylaxis for intracranial hemorrhage. The trial took place at three Boston neonatal intensive care units between June 1981 and April 1984. The 76 babies with BPD had radiographic evidence of the condition and required oxygen therapy for 28 days or more. All 147 control babies survived until day 28 of life without meeting either of these criteria for BPD. Compared with control infants, those with BPD received greater quantities of total, crystalloid, and colloid fluids per kilogram per day in the first 4 days of life. In addition, infants with BPD generally had a net weight gain in the first 4 days of life in contrast to the normal pattern of weight loss seen in control infants. Finally, the infants with BPD were more likely to be given a clinical diagnosis of patent ductus arteriosus and to have received furosemide on days 3 and 4 of life. From these observations we infer that early postnatal phenomena such as excessive fluid therapy may be important in the pathogenesis of BPD.

Blood Pressure↗
PubMed1990

Intraocular pressure in a healthy population: a survey of 751 subjects.

Intraocular pressure (IOP) in a healthy population residing in the urban area of Naples, Italy was measured. The IOP was recorded in the early morning. A total of 751 subjects (367 men and 384 women) (1502 eyes) was examined twice on two different days using a Goldmann tonometer mounted on a Haag-Streit slitlamp. Age ranged from 6 to 89 years. We found a slight and not significant IOP increase with age and that the age-related IOP increase was more evident in women.

Adolescent↗
PubMed1990

Maternal glucocorticoid therapy and reduced risk of bronchopulmonary dysplasia.

Because of substantial clinical and laboratory evidence of the efficacy of glucocorticoids in the treatment of acute pulmonary surfactant deficiency in preterm newborns, we explored the hypothesis that maternal antenatal glucocorticoid receipt is followed by reduced risk of bronchopulmonary dysplasia (BPD). A sample of 223 intubated infants weighing less than 1751 g birth weight provided 76 infants with BPD (defined by both oxygen requirement and compatible chest radiograph) and 147 who had neither BPD characteristic by day 28 of life. When compared to babies who received a complete and timely course of antenatal glucocorticoids, those whose mothers received no glucocorticoids were at prominently increased risk of BPD (odds ratio = 3.0; 95% confidence interval = 1.1, 8.2). Babies whose mothers received a partial course of glucocorticoids were not at increased risk of BPD (odds ratio = 1.3; 95% confidence interval = 0.4, 4.3). Stratification by gender and birth weight at 1 kg showed a benefit of therapy in all strata except that of extremely low birth weight male infants. These data support the hypothesis that maternal antenatal glucocorticoid therapy offers very low birth weight infants protection against BPD.

Adult↗
PubMed1990

[Digestion in vitro of basal membrane, bovine lens capsule, by human liver lysosome cathepsins B, H and L and ascitic fluid tumor cathepsin B from ovarian adenocarcinoma].

Lysosomal cysteine proteinases, cathepsins B, H and L, and tumor cathepsin-B-like protease, are capable of digesting bovine lens capsule, a typical basement membrane, in vitro. Cathepsins L and H proved most active in the pH range 5.0-7.0, whereas cathepsin B and cathepsin B-like protease showed greatest activity at pH 3.0. The process was slow and involved binding of the proteases to the basement membrane. These proteases, of which some are produced by malignant cells, may contribute to tumor spread and progression to metastatic disease.

Adenocarcinoma↗
PubMed1990

Gamete intrafallopian transfer in a woman with tubal occlusion. A case report.

Gamete intrafallopian transfer (GIFT) is usually performed when at least one fallopian tube is normally patent. We used GIFT in a case of bilateral tubal occlusion. The patient, who had primary ovarian failure, was enrolled in our GIFT program since it was assumed that her tubes were normally patent. Unexpectedly, at laparoscopy both tubes turned out to be distally occluded; nevertheless, GIFT was carried out by piercing the tubal wall. At this writing the patient had reached the 11th week of a normal intrauterine gestation and was still undergoing hormone replacement therapy.

Adult↗
PubMed1990

"In vitro" digestion of intact bovine lens capsules by four human lysosomal cysteine-proteinases.

We have examined the biochemical degradation of an isolated basement membrane matrix (bovine lens capsule) by human liver cathepsins B, H and L and the cathepsin B-like proteinase from malignant ascitic fluid. This study was carried out using two different methods: The first strategy was to follow the liberation of soluble proteins and peptides as a function of time at different pHs. Then the digestion products were characterized, as collagen IV, fibronectin and laminin fragments, using monospecific polyclonal antibodies and a quantitative dot-blot analysis. From these results, the ability of the four proteinases to digest "in vitro" intact bovine lens capsule in the physiological pH range is demonstrated. Cathepsin L is the most powerful against the three membrane components studied. As shown by electroelution and immunochemical quantitation, the digestion would be a consequence of proteinases binding to the capsule. With intact basement membrane as a substrate a "in vitro" molecular analysis of this digestion process was possible by these methods. On this basis, the "in vivo" secretion of cysteine proteinases during malignancy would be related to the local basement membrane dissolution associated with tumor invasion.

Animals↗
PubMed1989

Short-term effects of carbon monoxide exposure on the exercise performance of subjects with coronary artery disease.

Patients with atherosclerotic cardiovascular disease may be adversely affected by the presence of carboxyhemoglobin, even at low concentrations. We investigated the effects of carbon monoxide exposure on myocardial ischemia during exercise in 63 men with documented coronary artery disease. On each test day, subjects performed two symptom-limited incremental exercise tests on a treadmill; the tests were separated by a recovery period and 50 to 70 minutes of exposure to either room air or air containing one of two concentrations of carbon monoxide (117 +/- 4.4 ppm or 253 +/- 6.1 ppm). The order of exposure was assigned randomly. On each occasion, neither the subjects nor the study personnel knew whether the subjects had been exposed to room air or to one of the concentrations of carbon monoxide. Exposure to room air resulted in a mean carboxyhemoglobin level of 0.6 percent, exposure to the lower level of carbon monoxide resulted in a carboxyhemoglobin level of 2.0 percent, and exposure to the higher level of carbon monoxide resulted in a level of 3.9 percent. An effect of carbon monoxide on myocardial ischemia was demonstrated objectively by electrocardiographic changes during exercise. We observed a decrease of 5.1 percent (90 percent confidence interval, 1.5 to 8.7 percent; P = 0.02) and a decrease of 12.1 percent (90 percent confidence interval, 9.0 to 15.3 percent; P less than or equal to 0.0001) in the length of time to a threshold ischemic ST-segment change (ST end point) after carbon monoxide exposures that produced carboxyhemoglobin levels of 2.0 percent and 3.9 percent, respectively. The length of time to the onset of angina decreased by 4.2 percent (90 percent confidence interval, 0.7 to 7.9 percent; P = 0.054) at the 2.0 percent carboxyhemoglobin level and by 7.1 percent (90 percent confidence interval, 3.1 to 10.9 percent; P = 0.004) at the 3.9 percent carboxyhemoglobin level. Significant dose-response relations were found in both the change in the length of time to the ST end point (P less than or equal to 0.0001) and the change in the length of time to the onset of angina (P = 0.02). We conclude that low levels of carboxyhemoglobin exacerbate myocardial ischemia during graded exercise in subjects with coronary artery disease.

Adult↗
PubMed1989

The glycosylation state of the precursors of the cathepsin B-like proteinase from human malignant ascitic fluid: possible implication in the secretory pathway of these proenzymes.

We have investigated the structure of the carbohydrate moiety of the precursors of the cathepsin B-like proteinase (PCBt). The largest precursor has an apparent molecular size (Mr) of 45-47 Kd and it contains 3 N-linked oligosaccharide chains which were Endo beta N acetylglucosaminidase H (Endo H)-resistant forms. On the other hand, these chains were sequentially removed by Endo beta N acetylglucosaminidase F (Endo F). Both results indicate a complex type structure for these oligosaccharides. As usual in these cases, sialic acids were also found. In the deglycosylated state, PCBt has a Mr value of 36 Kd closely related to the 35.9 Kd Mr for human Pro CB, deduced from the cDNa sequence. These findings may explain the extracellular location of PCBt in malignancy: complex oligosaccharides are in most cases associated with secretory or membrane bound glycoproteins. On the contrary, mannose-rich types are involved in the lysosomal routage.

Adenocarcinoma↗
PubMed1989

Surrogate human fallopian tubes for overcoming tubal infertility.

A procedure has been devised in order to establish a pregnancy in a patient with severe, untreatable tubal infertility who had unsuccessfully undergone tubal reconstructive surgery and repeated in-vitro fertilization procedures. This technique, which involves a volunteer, fertile woman, results from the combination of two infertility treatments: namely gamete intra-Fallopian transfer and uterine flushing. The gametes of the infertile couple were introduced into the distal tube of a synchronized volunteer woman; after 5 days, the embryos, recovered by lavage of the volunteer's uterus, were transferred into the patient's uterus with a resulting pregnancy and delivery.

Adult↗
PubMed1989

[Pro-cathepsin D can activate in vitro pro-cathepsin B secreted by ovarian cancers].

A precursor form of cathepsin B (Mr 45-47 kd) was purified from ascitic fluids of patients with ovarian adenocarcinomas. Following pepsin activation, this precursor produced a 33 kd cathepsin B-like proteinase closely related to lysosomal cathepsin B. A similar activation was found using the 52 kd pro-cathepsin D secreted by the MCF7 human breast cancer cells. This activation was a time, dose and pH dependent process. These results suggest that the 52 kd pro-cathepsin D may be involved in the early steps of the "metastatic cascade", activating pro-cathepsin B in an acidic environment.

Adenocarcinoma↗
PubMed1989

Acute effects of carbon monoxide exposure on individuals with coronary artery disease.

The purpose of this study was to determine, using more objective evidence than that reported in previous studies, whether or not exposures to carbon monoxide that produce approximately 2% or 4% blood carboxyhemoglobin levels cause an exacerbation of myocardial ischemia during a progressive exercise test. The objective measurements were based on the development of electrocardiographic evidence of ischemia. In addition, time to onset of angina pectoris was studied. Male subjects, ages 35 to 75, with stable exertional angina pectoris and positive exercise treadmill tests with reproducible ischemic ST-segment changes in their electrocardiograms, were studied. In addition, each subject fulfilled at least one of the following criteria of coronary artery disease: angiographic evidence of at least a 70% occlusion of one or more major coronary artery; prior documented myocardial infarction; or a positive exercise thallium test. Each subject was evaluated on four separate occasions, a qualifying visit and three blinded test visits, which involved exposure (in random order) to air without added carbon monoxide and to air that contained carbon monoxide concentrations calculated to produce approximately 2.2% or 4.4% carboxyhemoglobin, measured by gas chromatography, at the end of the exposure period. These immediate postexposure target levels were set 10% higher than the desired postexercise carboxyhemoglobin levels of 2.0% and 4.0% because exercise while breathing room air results in loss of carbon monoxide. The actual one-minute postexercise levels reached were 2.0% +/- 0.1% (mean +/- standard error of the mean) and 3.9% +/- 0.1%. On each test day, the subject performed a symptom-limited exercise test on a treadmill, was exposed for approximately one hour to air or to one of two levels of carbon monoxide in air, and then performed a second exercise test. Time to the onset of ischemic ST-segment changes and time to the onset of angina were determined for each exercise test. The percent difference for these endpoints on the pre- and postexposure exercise tests was determined, and then the results on the 2%-COHb-target day and the results on the 4%-COHb-target day were compared to those on the control day. Data from the 63 subjects who completed the three test visits and met all protocol criteria were analyzed. There were 5.1% (p = 0.01) and 12.1% (p less than or equal to 0.0001) (trimmed mean) decreases in the time to development of ischemic ST-segment changes after the 2%- and 4%-COHb-target exposures, respectively, compared to the control day.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1988

Immunohistochemical and biochemical study of a cathepsin B-like proteinase in human colonic cancers.

An immunohistological study was carried out on 51 human colorectal adenocarcinomas and eight samples of histologically normal colonic mucosa removed far from tumors, using anti-rabbit cathepsin B and anti-human cathepsin B immunoglobulins. Positive reactions were obtained on tumor cells and macrophage-like cells. However, as these immunoglobulins could not discriminate between cathepsin B and cathepsin B-like proteinases, and as they cross-reacted with cathepsins H and L, a partial characterization of the proteinase activities was performed in order to identify the type of enzyme present in the positive cells. The levels of cathepsins H and L were very low in extracts of colorectal tumors and normal colonic mucosa. A peculiar cathepsin B-like proteinase activity with pH optimum at 6.8 was found in tumor extracts together with the lysosomal cathepsin B, whereas normal colonic mucosa showed only cathepsin B activity (pH optimum, 6.0). These results indicate that lysosomal cathepsin B is responsible for staining of macrophage-like cells found in the lamina propria of colonic mucosa and in the peritumoral stroma. Immunohistochemical staining of colonic tumor cells observed in 29/51 cases seems on the other hand to be primarily due to a cathepsin B-like proteinase. Three colonic tumor cell lines, Colo-205, HT-29, and SW-1116, were also studied using the same methods. These cells produced a latent cathepsin B-like proteinase which, after activation, was similar to that found in tumor extracts. This latent proteinase was detected mainly in the culture media. The cultured colonic tumor cells, after staining by anti-cathepsin B antibodies, showed strongly positive granules. In conclusion, this work demonstrates that malignant colonic cells are the source of a cathepsin B-like proteinase, with optimal activity near neutrality. Its secretion into the extracellular space indicates furthermore, that it may be an important component of the "proteinase cascade" associated with tumor invasion and metastasis.

Cathepsin B↗