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Biomedical subjects

S Skinner

Publications and source records attributed to S Skinner.

35 records · Page 2Linked to original sources
PubMed1994

The contributions of renin and vasopressin to the adaptation of the Australian spinifex hopping mouse (Notomys alexis) to free water deprivation.

Xeric-adaptation was studied during 28 days of total water deprivation (TWD) in Notomys alexis. Beyond 7 days, the initial reductions in body weight and increases in haematocrit, plasma renin and juxtaglomerular (JG) cell morphological activity returned to normal. Mus musculus showed similar changes at 7 days but could not be maintained thereafter. TWD decreased the blood pressure of Notomys but endogenous angiotensin and vasopressin did not support pressure to a greater extent than controls, as revealed by selective antagonists. The normal morphology of the JG apparatus in Notomys was similar to other rodents. Fluid volume and blood pressure maintenance during TWD in Notomys do not depend upon enhanced activities of the renin-angiotensin and antidiuretic hormonal systems.

Adaptation, Physiological↗
PubMed1994

The mammalian zona pellucida: its biochemistry, immunochemistry, molecular biology, and developmental expression.

Many studies of the molecular and biochemical aspects of mammalian fertilization have focused on the interaction of the spermatozoa with the zona pellucida (ZP). The zona pellucida, a unique extracellular matrix surrounding the mammalian oocyte, is formed during ovarian follicular development. Following ovulation of the mature ovum, the spermatozoa must bind to and penetrate this matrix before the fertilization process is completed and the male and female genetic information combine. Although numerous models for this interaction have been proposed, the complete process has yet to be elucidated. The precise mechanisms by which these interactions occur also vary markedly among different mammalian species, making it more difficult to establish a unified model. To a great extent, the study of the molecules involved in these interactions have been limited because small numbers of female gametes are available for these studies. The recent development of techniques to isolate large numbers of zonae pellucidae as well as advances in immunological and molecular biology techniques have permitted the detailed characterization of ZP proteins. Although there is a paucity of information on the post-translational modification and extracellular processing of these molecules which result in matrix formation, a number of properties have been elucidated allowing better correlation between the structure and function of different ZP proteins among species. This review reflects these studies in relation to protein nomenclature and the molecular complexity of ZP antigens.

Animals↗
PubMed1993

Selective localization of a radioiodinated phospholipid ether analog in human tumor xenografts.

Administration of [125I]-rac-1-O-[12-(m-iodophenyl)dodecyl-2-O-methylglycero-3- phosphocholine (NM-294) to athymic mice implanted with human tumors of several histologies, including adenocarcinoma of the ovary and colon, melanoma and small-cell carcinoma of the lung, resulted in excellent images of the tumors by gamma camera scintigraphy. Images of the tumor were obtained at 5 days or more postinjection, by which time nearly all background activity had cleared from the liver and gastrointestinal tract. Tumor-to-blood ratios at this time were quite high and ranged from approximately 8:1 (melanoma) to 30:1 (ovarian carcinoma), which is consistent with the scintigraphic images obtained in all human tumor models. Lipid extraction of the liver and tumor at 13 days postinjection showed that most of the radioactivity in these tissues remained associated with the parent compound, with only a small amount retained by the liver. Appropriately radioiodinated NM-294 has substantial potential as a tumor-avid radiopharmaceutical.

Adenocarcinoma↗
PubMed1992

Selective localization of radioiodinated alkylphosphocholine derivatives in tumors.

We have designed and synthesized two radioiodinated analogs of hexadecylphosphocholine in order to evaluate their tumor imaging potential. 12-(m[125I]iodophenyl)dodecyl phosphocholine (NM-324) and hexadecyl-2-[N,N-dimethyl-N-(m[125I]iodobenzyl)-ammonium] ethyl phosphate (NM-326) demonstrated the ability of such compounds to localize in and thereby visualize the Walker 256 tumor in rats. However, the tumor avidity of NM-324 was far superior to NM-326. In addition, NM-324 showed excellent tumor localization in athymic mice bearing subcutaneous human tumors.

Animals↗
PubMed1991

Isolation and characterization of a full-length cDNA encoding the 55-kDa rabbit zona pellucida protein.

A full-length cDNA (rc55) encoding the major rabbit zona pellucida (ZP) glycoprotein (55 kDa) has been cloned and sequenced. A lambda gt11 expression library was constructed using poly(A)+ mRNA isolated from sexually immature rabbit ovaries which contain large numbers of developing follicles. The rc55 cDNA was identified using affinity purified polyclonal antibodies specific to ZP antigens which are shared among mammalian species. The deduced amino acid sequence of the full-length rc55 clone was matched to the NH2-terminal 25-amino acid sequence obtained for this protein. The predicted amino acid sequence consists of 540 amino acids including a putative signal peptide of 18-24 residues and six potential N-glycosylation sites. The cDNA hybridizes to a 2000-base species of mRNA from rabbit ovary which is not detected in other rabbit tissues. The message is present early in ovarian follicular development and is approximately 600-fold greater in sexually immature as compared with sexually mature rabbit ovaries. This cDNA was expressed as a cro-beta-galactosidase fusion protein using the pEX expression vector. Antibodies against native rabbit ZP, affinity-purified on the recombinant 55-kDa ZP protein, were found to recognize the native rabbit ZP glycoprotein, indicating partial conservation of native epitopes in the expressed recombinant protein.

Amino Acid Sequence↗
PubMed1991

Phenotypic inhibition of the renin-angiotensin system, emergence of the Ren-2 gene, and adaptive radiation of mice.

The renin-angiotensin system in sub-genus Mus displays unique features including duplication of the renin gene in most strains, strong expression of the second gene in submandibular gland of males, and inhibited responses to injected renin. Our findings indicate that this inhibition results from a paucity of renin substrate and is consistent with first-order kinetics. We find substrate paucity to be a feature of both sexes and all sub-species and strains of Mus irrespective of gene duplication. Attempts to increase the level of substrate in blood by intravenous injection caused marked increases in blood pressure in Mus, suggesting that substrate paucity was a phenotypic prerequisite for successful emergence of enhanced renin expression in salivary gland. We propose that these phenomena are linked to salivary "lethal factor", possibly transferred by biting, in an evolutionary sequence that has provided a major selective advantage for Mus and influenced the ecology and evolution of rodents.

Angiotensinogen↗
PubMed1989

The effect of prostaglandins and indomethacin on cytotoxic T-lymphocytes and their precursors.

The effect of prostaglandins of the E and F series on the generation of cytotoxic T-lymphocytes (CTL) was investigated. High concentrations (10(-6)-10(-7) M) of prostaglandin E2(PGE2) inhibited the generation of both antigen-specific CTL and "activated" killers from precursor cells. Virtually no effect on the growth and cytotoxic activity of antigen-specific CTL clones was detectable. As with prostaglandins of the F series, lower concentrations of the E series (10(-8)-10(-9) M) enhanced the generation of antigen-specific CTL but inhibited the generation of lymphokine and spontaneously-activated CTL. When endogenous PG production was blocked with indomethacin, the generation of antigen-specific CTL was enhanced in bulk culture. Indomethacin also increased the frequency of allo-reactive CTL precursors and in anti-fluorescein responses it created conditions in which suppression was overridden. These results indicate that prostaglandins can exert both negative and positive regulatory effects on an antigen-specific cytotoxic response and can influence the apparent specificity of the cytotoxic cells that are generated.

Animals↗
PubMed1988

Mercury and tetracycline resistance genes and flanking repeats associated with methicillin resistance on the chromosome of Staphylococcus aureus.

Sections of a cloned 27 kb segment of chromosomal DNA, associated with resistance to four antimicrobial agents in a clinical isolate of methicillin-resistant Staphylococcus aureus (MRSA), were tested for their ability to determine resistance when transformed into a sensitive laboratory strain of S. aureus. This was achieved by inserting the sections into a newly constructed shuttle vector, amplifying the recombinant DNA in E. coli, and transforming protoplasts of the sensitive S. aureus strain. Two sections of the cloned DNA were found to determine resistance separately to mercuric ion and to tetracycline, in both S. aureus and Escherichia coli.

Chromosomes, Bacterial↗
PubMed1986

[Absorption, distribution and elimination of a labelled extract of Ginkgo biloba leaves in the rat].

The absorption, distribution and elimination of a radiolabelled 14C extract prepared from Ginkgo biloba leaves have been studied in rats. Following oral administration, expired 14C-CO2 represented 16% of the administered dose excreted within the first 3 hours post-dose out of a total of 38% after 72 hours. An additional 21% of the administered dose was eliminated in the urine. The absorption of the radiolabelled Ginkgo biloba extract was at least 60%. The pharmacokinetics of the drug, based on blood specific activity data versus time course, were characteristic of a two-compartment model with an apparent first order phase and a biological half-life of approximatively 4.5 h. During the first 3 hours, radioactivity was primarily associated with the plasma, but through a gradual uptake after 48 h. The specific activity in erythrocytes matched that of plasma. A site of absorption in the upper gastrointestinal tract is suspected since specific activity in blood peaked after 1.5 hours. Glandular and neuronal tissues and eyes showed a high affinity for the labelled substance. These results provide the first tentative link between the therapeutic effectiveness of Ginkgo biloba extract and the biological fate of some of its constituents.

Animals↗
PubMed1983

Chronic encephalomyelitis caused by canine distemper virus in a Bengal tiger.

A chronic progressive neurologic disease was observed and monitored for 18 months in a young, tamed Bengal tiger. Clinical, serologic, and neuropathologic evidence of canine distemper virus infection was seen. Clinical signs included convulsions, myoclonus, and slowly progressive ataxia. Marked increases in neutralizing antibodies against canine distemper virus were seen in the serum and cerebrospinal fluid. Neuropathologic findings were nonsuppurative meningoencephalomyelitis, with perivascular cuffing, demyelination, and inclusion bodies typical of canine distemper virus. It was concluded that, in light of this case and an earlier report of canine distemper in lion cubs, vaccination of this subgroup of carnivores with a killed vaccine may be beneficial if exposure to other animals susceptible to canine distemper is anticipated.

Animals↗
PubMedDate not supplied

Comparative physiological disposition of some anthraquinone glycosides and aglycones.

The in vitro microbial degradation and the urinary excretion and biliary secretion in rats of two anthraquinone glycosides (sennosides A and B) and four aglycones (sennidins A and B, rhein, and danthron) were studied using a high performance liquid chromatographic system with gradient elution and amperometric detection. Microbial degradation of sennosides A and B occurred almost exclusively in the presence of mice caecum inoculae and was associated with the release of sennidins A and B. Rhein and danthron were indiscriminately metabolized by bacteria sampled from all regions of mice intestine, whereas sennidins lacked stability in biological media. The fraction of the dose administered orally to rats and recovered as aglycones or as glucuronides in bile and urine after 48 hours was five times greater for rhein (15 per cent) and danthron (13.4 per cent) than for sennosides A (1.8 per cent) and B (2.8 per cent) excreted or secreted as sennidins. These results support the concept that anthraquinone glycosides are less likely to enter the systemic circulation and, thus, are able to exert their laxative effect at lower doses than aglycones.

Animals↗
PubMedDate not supplied

Xenotransplantation of neonatal porcine islets and Sertoli cells into nonimmunosuppressed streptozotocin-induced diabetic rats.

The testis has been shown to be a privileged site for transplantation of allogenic islets in rodents, and the testicular cell aggregates are thought to confer this immunologic privilege. Recently, a group in Mexico reported transplantation of cocultured neonatal porcine islets and Sertoli cells resulting in insulin independence in nonimmunosuppressed type 1 diabetes patients. We have transplanted similar islets alone (naked islets) or cocultured islets with Sertoli cells (islet/Sertoli cells) into an omental site and other locations of nonimmunosuppressed, streptozotocin-induced diabetic male Sprague Dawley (SD) rats. Histologic examination showed viable neonatal porcine islets survived in xenografted rodents for at least 2 days, and some glucagon and inhibin stained cells appear to have survived for 4 days posttransplantation. However, histological examination did not demonstrate any difference in xenograft survival in the islets/Sertoli cells mixture compared to naked islets when transplanted into these nonimmunosuppressed diabetic rats.

Animals↗
PubMedDate not supplied

Transplantation of neonatal porcine islets and sertoli cells into nonimmunosuppressed nonhuman primates.

A Mexican group reported transplantation of cocultured neonatal porcine islets and Sertoli cells resulting in insulin independence in nonimmunosuppressed type 1 diabetes patients. We have transplanted similar islets alone (naked islets) or cocultured islets with sertoli cells (islet/sertoli cells) into an omental site and other locations of seven nondiabetic, nonimmunosuppressed, nonhuman primates. Porcine endogenous retrovirus was not detected in recipient blood 8 weeks after porcine islet grafts, and porcine C-peptide was detected at a very low level in all animals. Histology examination failed to demonstrate obviously recognizable islets, but in the animals transplanted with islet/Sertoli cells at the omentum site, there were some surviving glucagons, pan-cytokeratin, and inhibin stained cells at 8 weeks.

Animals↗
PubMedDate not supplied

Three-dimensional CT and MR imaging in congenital dislocation of the hip: clinical and technical considerations.

Three-dimensional (3D) CT and 3D magnetic resonance (MR) imaging were performed in four patients with congenital dysplasia of the hip. Two patients were studied by 3D CT and two by 3D MR. Prior to volume segmentation, two-dimensional (2D) MR image preprocessing was used to correct for nonuniform signal intensity distribution from local variations in field strength and coil response. An unsharp mask of the original MR scan was computed by extreme blurring of the image to suppress the details of the object. The unsharp mask was divided into the image on a pixel-by-pixel basis. For improved object contrast first and second echo images were combined in a 1:2 ratio. To add an additional feature for volume segmentation, 2D MR image homogeneity was computed based on 3 X 3 pixel neighborhoods. Volume segmentation was performed using one feature for CT, i.e., attenuation range, and two features for MR, i.e., signal intensity and image homogeneity range. Three dimensional CT and 3D MR demonstrated the 3D relationships of femoral heads and acetabula. Three-dimensional CT was limited to patients who had ossified femoral heads, whereas 3D MR demonstrated the cartilaginous femoral head. The extent of acetabular coverage on which the mode of therapy is based was shown. Three-dimensional MR permitted imaging without gonadal irradiation. The 2D MR image preprocessing described here should provide even better results in objects with greater contrast, i.e., nonosseus structures, and those of larger size with relation to image degradation from partial volume effect.

Child↗
PubMedDate not supplied

Focal scleroderma in children: an orthopaedic perspective.

Focal scleroderma is a connective-tissue disorder manifested by fibrosis of the skin and subcutaneous tissues. Consequently, it may be associated with joint contractures, extremity deformity, and impairment of extremity function. It has a variable clinical course, with both remissions and recurrences. In resistant cases of extremity involvement, treatment considerations should include physical and occupational therapy, medical treatment, bracing, serial casting, and surgical intervention. We reviewed seven patients treated between 1960 and 1990 with significant joint contractures secondary to focal scleroderma. Serial casting was found to be useful for contractures about the wrist, knee, and ankle. Soft-tissue release was an effective treatment for contractures at the wrist, hip, and ankle. Knee disarticulation was performed on one patient with a severe knee-flexion contracture. Epiphysiodesis and femoral shortening osteotomy were effective treatments for leg-length equalization in a case of hemiatrophy.

Adolescent↗