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Biomedical subjects

L Rocco

Publications and source records attributed to L Rocco.

At least 19 recordsLinked to original sources

Molecular and chromosomal analysis of ribosomal cistrons in two cartilaginous fish, Taeniura lymma and Raja montagui (Chondrichthyes, Batoidea).

We used silver nitrate staining, CMA3 and FISH to study the chromosomal localization of both the major ribosomal genes and the nucleolar organizer regions as well as that of the minor ribosomal genes (5S rDNA) in two species of Batoidea, Taeniura lymma (Dasyatidae) and Raja montagui (Rajidae). In both species, all the metaphases examined showed the presence of multiple NOR-bearing sites, while the gene for 5S rRNA proved to be localized on two chromosome pairs. Furthermore, one of the two 5S rDNA sites in T. lymma was shown to be co-localized with the major ribosomal cluster. The presence of multiple nucleolar organizer regions in the two species might be interpreted as being the result of intraspecific polymorphisms, or as a phenomenon of the amplified transposition of mobile elements of the genome. We also determined the nucleotide sequence of the 5S rRNA gene, consisting of 564 bp in R. montagui and 612 bp in T. lymma. We also found TATA-like and (TGC)n trinucleotides, (CA)n dinucleotides and (GTGA)n tetranucleotides, which probably influence gene regulation.

Animals↗

Chromosomal mapping and molecular characterization of ribosomal RNA genes in Lebias fasciata (Teleostei, Cyprinodontidae).

Chromosome location of major (18S, 5.8S and 28S) and 5S ribosomal RNA genes (rDNAs) was examined in Lebias fasciata collected from different Italian blackish-waters, using silver (Ag)- and chromomycin A3 (CMA3)-staining and/or fluorescence in situ hybridization (FISH). Both 18S and 5S rDNA probes for FISH were obtained with polymerase chain reaction-directed cloning from genomic DNA of the examined species. Nucleolar organizer regions (NORs) containing the major rDNAs showed intraspecific polymorphism in number as detected by Ag-and CMA3-staining and FISH with the 18S rDNA probe. On the other hand, 5S rDNA loci constantly occurred on one chromosome pair and co-localized with a pair of the major rDNA loci as evidenced by two-color FISH using the 5S and 18S rDNA probes. Sequential CMA3- and Ag-NOR staining and FISH revealed apparent inactivation of some NORs. The cloned 5S rDNA was found to contain some TATA-like sequences that might play an important role in the regulation of gene expression.

Animals↗

Selachian cytogenetics: a review.

The karyotype of Chondrichthyes is still the least investigated among vertebrates. Over the last 40 years, the karyotypes of 63 out of the 1100 known species (5.73%) have been described in literature, namely seven squalomorph, one squatinomorph, 20 galeomorph, 33 batoid and two holocephalian species. Generally, the diploid number ranges from a minimum of 28 to a maximum of 106 elements, with more frequent values observed between 50 and 100 chromosomes. None of the four superorders is characterized by a peculiar chromosome set or morphology; the number of uniarmed and biarmed elements is variable in all the karyotypes, and microchromosomes are often present. The general trend in all groups seems to be a progressive reduction of the telocentric chromosome number in the most specialized species, followed by the loss of the microchromosomes. Polyploidy, followed by diploidization events and Robertsonian rearrangements, might have played a key role in the karyological evolution of elasmobranch fish. Chondrichthyes have the largest genome sizes among vertebrates, with the exception of dipnoans and urodeles. In the whole class, the species examined vary greatly in size, from 3 to 34pg/N: the lowest values have been observed in holocephalians, while galeoids and batoids have a DNA amount ranging from 5 to 15 pg/N. Squaloids show heterogeneous DNA amounts, ranging from 8 to 34 pg/N. In more recent years, karyological studies have provided new data on the characterization of selachian karyotypes by C-banding, NOR staining, restriction enzymes in situ digestion and FISH with specific DNA probes, such as telomeric and SINE sequences.

Animals↗

(TTAGGG)n telomeric sequence in selachian chromosomes.

The distribution of telomeric sequence (TTAGGG)n in the genomes of Chondrichthian species at different stages of evolution was investigated both by DNA genomic hybridization, and by fluorescence in-situ hybridization (FISH) of metaphase chromosomes. The sequence is highly conserved in all the species examined. FISH revealed a label uptake only by the telomeres in Raja asterias. However, in Torpedo ocellata, we revealed pericentromeric and interstitial sequence localization on some chromosome pairs in addition to the hybridization signal on telomeres. These findings confirm that the karyotype evolution of these fish began by Robertsonian fusion.

Animals↗

Duration of vaginal retention and potential duration of antiviral activity for five nonoxynol-9 containing intravaginal contraceptives.

OBJECTIVE: The purpose of this study was to determine the vaginal retention of five nonoxynol-9 intravaginal contraceptives. METHOD: An open-label crossover study in 10 premenopausal volunteers was performed at an outpatient clinical research center. The outcomes are described utilizing the median and range. RESULT: At 8 h post-instillation, the median amounts of nonoxynol-9 present in the vagina were: Delfon 7.68 mg, Conceptrol 5.18 mg, Advantage 24 1.95 mg, VCF 1.74 mg, and Semicid 1.51 mg respectively. Our calculated theoretical minimal amount needed to protect against HIV infection is 2.00 mg. CONCLUSION: The best vehicle for retaining nonoxynol-9 in the vagina appears to be foam. Further research in the effectiveness of nonoxynol-9 in prevention of the spread of HIV infection should be directed toward the use of foam vehicles to deliver nonoxynol-9 to the vagina.

Administration, Intravaginal↗

Cloning and characterization of a repetitive DNA detected by HindIII in the genome of Raja montagui (Batoidea, Chondrichthyes).

A repetitive HindIII fragment of DNA from Raja montagui (Rajiformes) was cloned and sequenced for the first time in cartilaginous fishes. This element, which comprises approximately 5% of the whole genome of the spotted ray, is absent in long tandem arrays, being typical of satellite DNA. It appeared constituted by 311 AT-rich bp (61%). The clone was hybridized to the genomic DNA of species with varying phyletic distances, revealing a high degree of conservation.

Animals↗

NOR and heterochromatin analysis in two cartilaginous fishes by C-, Ag- and RE (restriction endonuclease)-banding.

Selachian chromosomes were investigated for the first time by C-, Ag- and RE (restriction endonuclease)-banding. A pair of NOR-bearing acrocentric chromosomes, as well as a third extra site, were demonstrated in two species of Torpedo. In situ digestion with restriction endonucleases revealed a peculiar arrangement of constitutive heterochromatin: in Torpedo ocellata the centromere never appeared C-banded, and was always digested by AluI, PstI, DdeI and HaeIII; in Torpedo marmorata, instead, heterochromatin was present in the centromere, and was not digested by the same enzymes. The occurrence of different types of centromeric heterochromatin suggests an involvement of highly repeated DNA fractions in the Robertsonian phenomena that occurred in chromosome rearrangements in the genus Torpedo.

Animals↗

Immunocytochemistry of carbonic anhydrase and non-radioactive detection of its RNA by in situ hydridization in the chick embryo membranous labyrinth.

An immunocytochemical study was carried out with the aim to localize carbonic anhydrase isozymes (CA I and CA II) in the chick membranous labyrinth. CA I and CA II were localized in the same cells and, during the early developmental stages, were diffusely present in the labyrinthine epithelium. At later stages, the sensorial epithelium of the maculae acusticae, crista ampullaris and papilla basilaris, as well as labyrinthine dark cells and the epithelium of the endolymphatic sac strongly stained by the immunocytochemical procedure. In 1-day and 1-week old chicks, CA was present in the same sites as at advanced embryonal stages. In order to detect mRNA for carbonic anhydrase II, in situ hybridization was also used. Strong hybridization signals were observed in the sensorial epithelium of the saccule, utricle and crista ampullaris, in the tegmentum vasculosum, the endolymphatic sac, the erythrocytes and the choroid plexus in embryos older than 10 days. This positivity persisted until the day after hatching. The authors discuss the significance of labyrinthine CA and, based on in situ hybridization results, suggest that melanocytes do not provide labyrinthine dark cells with enzyme protein.

Animals↗

Prevention of preeclampsia with low-dose aspirin in healthy, nulliparous pregnant women. The National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units.

BACKGROUND: Although low-dose aspirin has been reported to reduce the incidence of preeclampsia among women at high risk for this complication, its efficacy and safety in healthy, nulliparous pregnant women are not known. METHODS: We studied 3135 normotensive nulliparous women who were 13 to 26 weeks pregnant to determine whether treatment with aspirin reduced the incidence of preeclampsia. Of this group, 1570 women received 60 mg of aspirin per day and 1565 received placebo for the remainder of their pregnancies. We also evaluated the effect of aspirin on maternal and neonatal morbidity. RESULTS: Of the original group of 3135 women, 2985 (95 percent) were followed throughout pregnancy and the immediate puerperium. The incidence of preeclampsia was lower in the aspirin group (69 of 1485 women [4.6 percent]) than in the placebo group (94 of 1500 women [6.3 percent]) (relative risk, 0.7; 95 percent confidence interval, 0.6 to 1.0; P = 0.05), whereas the incidence of gestational hypertension was 6.7 and 5.9 percent, respectively. There were no significant differences in the infants' birth weight or in the incidence of fetal growth retardation, postpartum hemorrhage, or neonatal bleeding problems between the two groups. Subgroup analysis showed that preeclampsia occurred primarily in women whose initial systolic blood pressure was 120 to 134 mm Hg (incidence among such women, 5.6 percent in the aspirin group vs. 11.9 percent in the placebo group; P = 0.01). The incidence of abruptio placentae was greater among the women who received aspirin (11 women, vs. 2 in the placebo group; P = 0.01). CONCLUSIONS: Low-dose aspirin decreases the incidence of preeclampsia among nulliparous women, primarily through its effect in those who have elevated systolic blood pressure initially. This treatment does not decrease perinatal morbidity but increases the risk of abruptio placentae.

Abruptio Placentae↗

Chromosome markers and karyology of selachians.

Among vertebrates, chondrichthyans exhibit peculiar karyotypes and total amount and composition of DNA very different from those of tetrapods and teleosteans. Selachians have relatively large genome sizes (more than 30 pg/N), which are inversely related to the fraction rich in adenine-thymine. Moreover, they show a high chromosome number (2n = 60-100), decreasing in the most specialized species. The karyotypes of Scyliorhinus stellaris, Torpedo ocellata, and T. marmorata have been investigated by several techniques in order to distinguish particular genome fractions along the chromosome arms. C-banding appears to be positive in most telomeric regions in Scyliorhinus and at the interstitial level in the two torpedo species. Studies with restriction enzymes (RE) have just been started in selachians, employing ALU I and HIND III in Scyliorhinus stellaris. The former digests the whole chromosome except the telomeric regions, revealing patterns similar to the C-bands. The latter cuts the chromosomes into several interstitial regions, producing G-bands. Other RE are being studied, which will allow identification in situ of qualitative differences in the various DNAs.

Animals↗

[Liver cirrhosis. Survival of a homogeneous population].

The aim of the study was the evaluation of survival of 140 cirrhotic patients who had a liver biopsy between 1970 and 1987. It is interesting to point out that all the patients with cirrhosis were included in the study and that they were all coming from a limited geographic area. This justifies the limited drop-out (7/147 patients). The high survival rate could be due to the fact that only patients suitable to receive a liver biopsy were elected for the study. We found that factors critical for prognosis in the short term (6-12 months) are biochemical values such as prothrombin index, serum albumin, serum bilirubin, alkaline phosphatase, while the factors affecting long-term prognosis are age, sex, etiology of cirrhosis, high alcohol intake after biopsy, ascites and untreated portal hypertension.

Adult↗

Clinical evaluation of amoscanate in healthy male volunteers.

Single oral doses of amoscanate (4-isothiocyanato-4'-nitrodiphenylamine), an experimental antiparasitic agent, are highly effective in animals against the four major species of schistosomes which infect humans. Two prospective, randomized, double blinded, placebo controlled Phase I studies were designed to evaluate the tolerance and safety of the 5% aqueous suspension of 2-mu particles of amoscanate administered to healthy male volunteers. In addition to routine safety monitoring, particular attention was directed toward detecting hepatic, neurological, cardiovascular or ocular toxicity. Three of four men who received 3.5 mg/kg of amoscanate developed mild, reversible hepatotoxicity, which could not be unequivocably attributed to the drug. In the second study, of 1 mg/kg amoscanate, there was no statistically significant evidence of hepatotoxicity, although 1 of 12 drug recipients developed transient liver chemistry changes. Despite intensive monitoring, there was no evidence in either study of significant symptomatic complaints, or of neurological, cardiovascular or ocular toxicity. No mutagenic activity attributable to amoscanate was detectable in the urine. These results suggest that this formulation of amoscanate, at 1 mg/kg, is sufficiently well tolerated and safe to justify evaluation for efficacy in patients with schistosomiasis.

Adult↗

Cefotaxime compared with nafcillin plus tobramycin for serious bacterial infections. A randomized, double-blind trial.

In a prospective, randomized, double-blind study, we compared cefotaxime with nafcillin plus tobramycin in the treatment of serious bacterial infections. Of 195 patients with suspected or proven infections who were not neutropenic, definite bacterial infections were identified in 81; 34 of 38 patients given cefotaxime and 26 of 43 given nafcillin plus tobramycin (p less than 0.01) responded to treatment. The difference in response rates occurred primarily in patients with rapidly fatal underlying disease or with an infection outside the urinary tract. A logistic regression analysis showed that treatment with cefotaxime was still associated with a higher response rate after adjusting for several potential confounding factors. Among patients treated for 3 days or more, our criteria for nephrotoxicity were met in 2 of 68 (2.9%) given cefotaxime and 16 of 57 (28.1%) given nafcillin plus tobramycin (p less than 0.001). Prolongation of the prothrombin time and enterococcal colonization did not occur more frequently with cefotaxime. We conclude that cefotaxime may be more effective and less toxic than nafcillin plus tobramycin for patients with serious bacterial infections.

Adult↗

Acyclovir kinetics in end-stage renal disease.

Acyclovir (ACV) is almost entirely eliminated by the kidneys and has a terminal plasma half-life (t1/2) of 2 to 3 hr in subjects with normal renal function. To determine the drug's kinetics and tolerance in patients with severe renal failure, six anuric subjects on long-term hemodialysis were studied. Each received a 1-hr infusion of 2.5 mg/kg IV ACV. The kinetics are well described by a two-compartment open model. ACV terminal plasma t 1/2 and the total body clearance were 19.5 +/- 5.9 hr (mean +/- SD) and 28.6 +/- 9.5 ml/min/1.73 m2. Peak (end of infusion) and 8- and 24-hr plasma ACV concentrations were 37.5 +/- 23.3, 10.3 +/- 2.9, and 6.4 +/- 2.4 microM. Approximately 48 hr after the start of the infusion the subjects were hemodialyzed for 6 hr. The pre- and posthemodialysis ACV plasma levels were 2.74 +/- 1.38 and 1.11 +/- 0.60 microM. The terminal ACV t1/2 during hemodialysis was 5.7 +/- 0.85 hr. During hemodialysis paired arterial and venous samples showed that ACV was readily dialyzed, with a mean coefficient of extraction of 0.45 +/- 0.12. The dialysis clearance of acyclovir was 81.8 +/- 12.6 ml/min. None of the patients had any ACV-related adverse effects. Since ACV elimination is markedly reduced in end-stage renal failure and because ACV is readily hemodialyzible, dosage modification are needed to avoid cumulation and to replace dialyzed drug.

Acyclovir↗

Effects of probenecid on the pharmacokinetics and elimination of acyclovir in humans.

The effects of probenecid on the pharmacokinetics and renal clearance of acyclovir were studied in humans. Acyclovir (5 mg/kg) was given as a 1-h infusion to three volunteers with normal renal function both before and after oral administration of probenecid (1 g). The kinetics were well described by a two-compartment open model with zero-order infusion. The mean acyclovir concentrations at all time points after 1.0 h from the end of acyclovir infusion following probenecid administration were statistically higher than the corresponding mean acyclovir concentrations following the acyclovir infusion without probenecid administration. In the absence of probenecid, the renal clearance (248 +/- 80 ml/min per 1.73 m2) accounted for 83% of the total clearance (300 +/- 69 ml/min per 1.73 m2) and was almost threefold greater than the estimated creatinine clearance (90 +/- 48 ml/min per 1.73 m2). After probenecid administration, there was a 32% decline in renal clearance (248 to 168 ml/min per 1.73 m2; P less than or equal to 0.05), a 40% increase in the area under the curve (91.3 to 127.6 nmol.h/ml; P less than 0.05), and an 18% increase in the terminal plasma half-life (2.3 to 2.7 h; P less than 0.01). Although statistically significant, these effects due to the influence of probenecid probably have only limited clinical importance. In this study we confirmed that acyclovir is eliminated predominantly by renal clearance, both by glomerular filtration and tubular secretion; our results suggested that at least part of the tubular secretion is inhibited by probenecid.

Acyclovir↗

Gonadotropin responses following luteinizing hormone releasing hormone administration in normal subjects.

Synthetic luteinizing hormone releasing hormone (LHRH), 100 mug, was administered intravenously to 29 normal individuals. In male subjects, both baseline and peak LH response values showed minimal variations between subjects. The FSH baseline and response were more variable. In normal females the FSH and LH baseline values and response to LHRH infusion showed greater variation than that seen in male subjects, and this variation correlated with the phase of the menstrual cycle. In perimenopausal women with elevated baseline gonadotropins, the absolute LH peak values were comparable to those seen during the periovulatory period of the menstrual cycle, while FSH baseline and peak values were unmistakably higher than those observed in the normally menstruating women. Three women under gonadotropic suppression by three different drugs were investigated; megestrol suppressed the LHRH response more effectively than either diethylstilbestrol or an oral contraceptive. The LHRH stimulation test reflects only the ability of the pituitary cell to release gonadotropins. In a normal individual, however, some justifiable assumptions can be made regarding the immediate past synthesis and release versus accumulation of pituitary LH.

Diethylstilbestrol↗

Gonadotropin response to luteinizing hormone releasing hormone administration in secondary amenorrhea and galactorrhea syndromes.

Luteinizing hormone releasing hormone (LHRH), 100 mug, was administered to 60 patients with secondary amenorrhea. No side effects or adverse reactions occurred. Delayed FSH and LH peak outputs were observed in patients receiving LHRH subcutaneously rather than intravenously, but responses were otherwise comparable. The majority of patients with secondary amenorrhea had responses which fell into the 95% confidence limits of responses for normal ovulating women. Responses of patients with different forms of dysfunction may be similar, and patients with similar pathology may respond quite differently. The LHRH stimulation test may assist in the diagnosis of particular hypothalamic, pituitary, or gonadal dysfunction, but it must be used clinically in the context of a carefully integrated study.

Adenoma, Chromophobe↗