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Biomedical subjects

C J Jones

Publications and source records attributed to C J Jones.

At least 73 records · Page 4Linked to original sources

Perosomus elumbis (vertebral agenesis and arthrogryposis) in a stillborn Holstein calf.

Perosomus elumbis, an infrequently encountered congenital anomaly of unknown etiology, was studied in a female Holstein calf. This error of morphogenesis represents a set of multiorgan malformations that produce a deformity of the caudal one third of the fetus. In this case, the spinal and pelvic malformations were radiographed and then dissected. Intra-abdominal abnormalities of the soft tissues are also described. The normal sequential embryologic development of the vertebrate skeleton, anterior-posterior fetal positioning, and neural tube migration are discussed. An extensive literature of this birth defect in cattle (and sheep) is reveiwed. The reports from a period covering 165 years are compared with the pathologic features in this case. Chromosomal aberrations within the homeobox gene family are postulated to be contributory factors in the development of this type of dysorganogenesis.

Abnormalities, Multiple↗

Zonal rotor purification and characterization of "mannosomes": a tubular membrane system in gastropod mollusc digestive gland.

Mannitol oxidase (manox) is an H2O2-generating oxidase apparently unique to molluscs and especially abundant in alimentary tissues. In the digestive gland it is localized to an organelle ("mannosome") that forms an unusual tubular membrane system. We have developed a novel centrifugation procedure for >100-fold purification of these membranes in 20% yield from approximately 30 g of digestive gland of the slug Arion ater. Mannosomes from several other gastropod species are also substantially purified by the procedure. Four successive density gradient separations are employed which minimize structural damage by exploiting near isosmotic conditions early on and by completely avoiding traumatic pelleting and resuspension. Plasma membrane contamination is reduced by digitonin-induced density perturbation. The purified preparation is characterized by a predominant 68-kDa integral membrane protein and retains the in situ appearance of hexagonally arranged tubules with an enveloping outer membrane.

Animals↗

Interactions of the transcription/DNA repair factor TFIIH and XP repair proteins with DNA lesions in a cell-free repair assay.

We have studied the interactions between DNA damage and human proteins involved in the early steps of nucleotide excision repair (NER) reaction under in vitro conditions with human protein extracts. By using a new assay, we have detected a long-lived DNA/protein complex involving XPA and TFIIH in the course of the NER process. The formation of this complex is exclusively limited to DNA lesions that are substrates of the human excinuclease. We show that, while XPA binding to damaged DNA is ATP-independent, stable association of TFIIH with DNA lesions is promoted by ATP hydrolysis and is dependent on the integrity of XPA and XPC proteins in the cell extract. In addition, XPC is necessary to promote a stable binding of XPA to UV-irradiated DNA. Finally, the co-binding of XPA and TFIIH to DNA damage is correlated to a dose-dependent titration of TFIIH and not XPA from the free protein fraction.

Adenosine Triphosphate↗

Dissociation of telomere dynamics from telomerase activity in human thyroid cancer cells.

Prevention of telomere erosion through acquisition of telomerase activity is thought to be an essential mechanism in most human cancer cells for avoidance of cellular senescence and crisis. It has been generally assumed that once telomerase has been activated, no further telomere shortening should ensue. We show here, however, that a much more complex pattern of telomere dynamics can exist in telomerase-positive immortal cancer cells. Using a panel of subclones derived from a human thyroid cancer cell line, K1E7, we found that some clones show persistent decline in mean telomere restriction fragment (TRF) length by up to 2 kb over 450 population doublings (pd), despite sustained high telomerase activity (as assessed by the in vitro "TRAP" assay). TRF length subsequently stabilized at around 5 kb, but with no corresponding increase in telomerase activity. One clone showed an even more unexpected biphasic time course, with the mean TRF length initially increasing by 1.5 kb over 90 pd, before "plateauing" and then returning over a similar period to its original value, again without any correlation to TRAP activity. Such dissociations between telomere dynamics and telomerase activity support the existence of additional controls on telomere length in the intact cell. Our observations are consistent with current negative-feedback models of telomere length regulation by telomere binding proteins and these cell lines should prove useful experimental tools for their further evaluation.

Humans↗

Purification of guinea pig small intestinal peroxisomes and the subcellular localization of glucose-6-phosphate dehydrogenase.

A method for the isolation of highly purified peroxisomes from guinea pig small intestine was developed. This two-stage process involved a rate-dependent banding of a light-mitochondria lambda-fraction followed by a density-dependent banding of the catalase enriched fractions obtained from the first step, using a horizontal rotor. Furthermore, the subcellular localization of glucose-6-phosphate dehydrogenase (NADP+-dependent) activity in guinea pig small intestine was examined. Analysis of density-gradient fractions indicated that approximately 3-4% of the cellular NADP+-dependent glucose-6-phosphate dehydrogenase activity is associated with peroxisomal fractions and that it is localized to the matrix of peroxisomes. It is therefore suggested that a peroxisomal source of NADPH may be utilized by enzyme systems that use NADPH specifically as a reductant.

Animals↗

Fibrillin microfibrils are reduced in skin exhibiting striae distensae.

Striae distensae (striae: stretch marks) are a common disfiguring condition associated with continuous and progressive stretching of the skin--as occurs during pregnancy. The pathogenesis of striae is unknown but probably relates to changes in those structures that provide skin with its tensile strength and elasticity. Such structures are components of the extracellular matrix, including fibrillin, elastin and collagens. Using a variety of histological techniques, we assessed the distribution of these extracellular matrix components in skin affected by striae. Pregnant women were assessed for the presence of striae, and punch biopsies were obtained from lesional striae and adjacent normal skin. Biopsies were processed for electron microscopy, light microscopy and immunohistochemistry. For histological examination, 7 microns frozen sections were stained so as to identify the elastic fibre network and glycosaminoglycans. Biopsies were also examined with a panel of polyclonal antibodies against collagens I and III, and fibrillin and elastin. Ultrastructural analysis revealed alterations in the appearance of skin affected by striae compared with that of normal skin in that the dermal matrix of striae was looser and more floccular. Light microscopy revealed an increase in glycosaminoglycan content in striae. Furthermore, the number of vertical fibrillin fibres subjacent to the dermal-epidermal junction (DEJ) and elastin fibres in the papillary dermis was significantly reduced in striae compared with normal skin. The orientation of elastin and fibrillin fibres in the deep dermis showed realignment in that the fibres ran parallel to the DEJ. However, no significant alterations were observed in any other extracellular matrix components. This study identifies a reorganization and diminution of the elastic fibre network of skin affected by striae. Continuous strain on the dermal extracellular matrix, as occurs during pregnancy, may remodel the elastic fibre network in susceptible individuals and manifest clinically as striae distensae.

Actin Cytoskeleton↗

The reliability and validity of a chair sit-and-reach test as a measure of hamstring flexibility in older adults.

The purpose of this study was to examine the test-retest reliability and the criterion validity of a newly developed chair sit-and-reach (CSR) test as a measure of hamstring flexibility in older adults CSR performance was also compared to sit-and-reach (SR) and back-saver sit-and-reach (BSR) measures of hamstring flexibility. To estimate reliability, 76 men and women (M age = 70.5 years) performed the CSR on 2 different days, 2-5 days apart. In the validity phase of the study, scores of 80 men and women (M age = 74.2 years) were obtained on three field test measures of hamstring flexibility (CSR, SR, and BSR) and on a criterion test (goniometer measurement of a passive straight-leg raise). Results indicate that the CSR has good intraclass test-retest reliability (R = .92 for men; r = .96 for women), and has a moderate-to-good relationship with the criterion measure (r = .76 for men; r = .81 for women). The criterion validity of the CSR for the male and female participants is comparable to that of the SR (r = .74 and r = .71, respectively) and BSR (r = .70 and r = .71, respectively). Results indicate that the CSR test produces reasonably accurate and stable measures of hamstring flexibility. In addition, it appears that the CSR is a safe and socially acceptable alternative to traditional floor sit-and-reach tests as a measure of hamstring flexibility in older adults.

Aged↗

An elastin gene mutation producing abnormal tropoelastin and abnormal elastic fibres in a patient with autosomal dominant cutis laxa.

Elastin is the protein responsible for the characteristic elastic properties of many tissues including the skin, lungs and large blood vessels. Loss-of-function mutations in the elastin gene are known to cause the heart defect supravalvular aortic stenosis (SVAS). We and others have identified deletions, nonsense mutations and splice site mutations in SVAS patients that abolish the function of one elastin gene. We have now identified an elastin mutation in a patient with a completely different phenotype, the rare autosomal dominant condition cutis laxa. A frameshift mutation in exon 32 of the elastin gene is predicted to replace 37 amino acids at the C-terminus of elastin by a novel sequence of 62 amino acids. mRNA and immunoprecipitation studies show that the mutant allele is expressed. Electron microscopy of skin sections shows abnormal branching and fragmentation in the amorphous elastin component, and immunocytochemistry shows reduced elastin deposition in the elastic fibres and fewer microfibrils in the dermis. These findings suggest that the mutant tropoelastin protein is synthesized, secreted and incorporated into the elastic matrix, where it alters the architecture of elastic fibres. Interference with cross-linking would reduce elastic recoil in affected tissues and explain the cutis laxa phenotype.

Adult↗

Releases of Spalangia nigroaenea and Muscidifurax zaraptor (Hymenoptera: Pteromalidae) increase rates of parasitism and total mortality of stable fly and house fly (Diptera: Muscidae) pupae in Illinois cattle feedlots.

Weekly releases of Spalangia nigroaenea Curtis and Muscidifurax zaraptor Kogan & Legner from May through August of 1991-1993 at small, owner-operated cattle feedlots in Illinois provided weekly emergence of 100-300 parasitoids of each species per feedlot animal. In assessments based on fly and parasitoid emergence from > 47,000 stable fly and house fly puparia collected during the 3-yr period, total stable fly mortality was greater in lots where releases were made (60.7%) than in paired, untreated control lots (51.7%) (P = 0.04; paired t-test); parasitism of stable fly pupae by S. nigroaenea averaged 11.6% where releases were made and 6.4% in paired control lots (P = 0.0016). In lots where releases were made, total mortality of house fly pupae was greater (68.7 versus 56.1%; P = 0.0001); unexplained mortality was greater (55.5 versus 46.1%; P = 0.0018); and parasitism by Muscidifurax spp. was greater (2.4 versus 1.4%; P = 0.07) than in paired control lots. Parasitism, unexplained mortality, and total mortality of both fly species varied significantly from 1991 to 1992 in lots that received the same treatment each year, presumably due primarily to weather. Over the 3-yr period, releasing these species, particularly S. nigroaenea, significantly reduced production of stable fly and house fly adults in cattle feedlots. The potential value of such reductions is likely to vary as a result of feedlot conditions and weather.

Animals↗

Cyclic modulation of epithelial glycosylation in human and baboon (Papio anubis) endometrium demonstrated by the binding of the agglutinin from Dolichos biflorus.

Glycoconjugate expression in endometrial epithelium varies in a cycle-dependent manner in many species and is probably fundamental to the establishment of a receptive uterine environment for the implanting embryo. We have examined the distribution of N-acetyl galactosamine (GalNAc)-containing sequences bound by Dolichos biflorus agglutinin (DBA) in the cycling endometrium of the human and baboon (Papio anubis). In the human, DBA binding was absent in the proliferative and early secretory phases of the cycle, increasing thereafter both in glands and on the surface epithelium. In contrast, DBA binding in the baboon was maximal in the proliferative phase, diminishing to almost indistinguishable levels in the late secretory phase. Treatment of early to mid-secretory-phase baboons with the antiprogestin Onapristone caused staining to revert to the proliferative-phase pattern, confirming the importance of progesterone in the decrease in DBA staining. Investigations with other GalNAc-binding lectins indicated that epithelial GalNAc residues were present throughout the cycle. Variation in steroidally dependent 1,2 fucosyl transferase activity may therefore be responsible for the appearance of the new, DBA-binding, nonreducing terminal structure GalNAcalpha1,3(Fucalpha1,2)-Galbeta1,4GlcNAcbeta1++ + in the human during the mid-secretory phase and in the baboon during the late proliferative phase.

Acetylgalactosamine↗

Polychlorinated biphenyl (PCB) exposure produces placental vascular and trophoblastic lesions in the mink (Mustela vison): a light and electron microscopic study.

Polychlorinated biphenyls (PCBs) cross the placenta and cause fetal death in mink. No indications of impaired implantation have been reported. To study the effects of PCB on mink placental morphology, 2 groups each of 10 animals were orally exposed to Clophen A50 at 0.65 mg (low dose) and 1.3 mg (high dose) per day for 54 days, starting before mating, with 10 control animals. Placentae from mid to late gestation were examined by light and electron microscopy. In the controls, 11% of placentae were degenerate compared to 31% (low dose) and 64% (high dose) in PCB-exposed mink. All control animals exhibited implantation sites, while one animal in the low dose and four in the high-dose group exhibited none. However, there was no difference between PCB-exposed and control animals in the number of placentation sites in implanted animals. Fetal death was markedly increased in PCB-exposed mink, with only four animals (low dose) having all viable fetuses and eight (low and high dose) having a mixture of viable and dead fetuses. Nine exposed animals displayed maternal vascular lesions in the placental labyrinthine zones of viable fetuses, comprising loss and degeneration of endothelial cells, thrombi and haemorrhages. Extracellular fluid was present between the interstitial layer of maternal vessels and the syncytiotrophoblast, and there was focal degeneration of the trophoblast and fetal vasculature. It appears, therefore, that exposure of the mink placenta to PCBs affects maternal vasculature and produces degenerative changes in the trophoblast and fetal vessels, leading to fetal growth retardation or death.

Animals↗

Aortic blood momentum--the more the better for the ejecting heart in vivo?

OBJECTIVES: The aim of the present study was to test two hypotheses: (1) the momentum of the blood flowing out of the left ventricle toward the aorta (inertia force) plays an important role in the initiation of decay and the maximum rate of decay (peak (-dP/dt)) of left ventricular pressure (P); (2) a normal heart itself generates the inertia force which enhances its function. METHODS: The contribution of the inertia force to (-dP/dt) was theoretically given as rho c alpha, where rho is the blood density, c the pulse wave velocity, and alpha the deceleration rate of aortic blood flow. The correlations of peak (-dP/dt) with rho c alpha and with the time constant (tau) of the pressure decay during isovolumic relaxation, which was considered to represent myocardial relaxation characteristics, were compared in seven dogs. We developed a method of grading the strength of the inertia force, using the phase loop of left ventricular pressure (dP/dt vs. P relation). The method was applied to the records of 25 patients with ischemic heart disease, from which high fidelity left ventricular pressure recordings were available. RESULTS: The correlation of peak (-dP/dt) with rho c alpha was much higher than with tau (0.75 vs. -0.46). 16 of the 25 patients showed evidence of the inertia force. However, other patients showed no inertia force. The strength of the inertia force showed a significant (P < 0.05) correlation with left ventricular end-diastolic pressure (r = -0.46), cardiac index (r = 0.62), stroke volume index (r = 0.69), ejection fraction (r = 0.46), and peak (-dP/dt) (r = 0.56). CONCLUSION: The inertia force of late systolic aortic flow contributed to ventricular relaxation in the normal heart.

Aged↗

Environmental pollutants as aetiological agents in female reproductive pathology: placental glycan expression in normal and polychlorinated biphenyl (PCB)-exposed mink (Mustela vison).

Polychlorinated biphenyls (PCB) may cause growth retardation or fetal death in mink. Pathological changes in endotheliochorial mink placentae were examined following exposure to PCB during gestation. Placentae from six animals with average fetal crown-rump (C-R) lengths between 16 and 53 mm given 0.65 mg/day Clophen A50 (low dose), and one from five animals with an average fetal C-R length of 14 mm given 1.3 mg/day (high dose), were examined. Mink were treated from 9 to 24 days before mating until killed at day 53. Placentae were formalin-fixed with four size-matched controls and embedded in resin. Sections were stained with five biotinylated lectins to detect specific glycans. Both control and treated (low dose) mink showed degenerative changes in maternal endothelium from 13-16 mm, revealed by increased lectin binding, caused probably by high cell turnover during tissue remodelling. Controls of 47 and 50 mm exhibited fewer degenerate maternal endothelial cells. The 31-mm PCB-treated tissue showed separation of the trophoblast from the interstitial layer and, at 53 mm, loss of its normal architecture, increased damage to maternal endothelium and infarction. High-dose PCB was extremely toxic, producing fetal death or extensive placental infarction by 14 mm C-R length. Lectin staining thus revealed the effects of PCB toxicity, shown by increased injury to maternal endothelium and severe trophoblastic damage.

Animals↗

South Asians with ulcerative colitis exhibit altered lectin binding compared with matched European cases.

Ulcerative colitis is associated with abnormalities of mucin synthesis and secretion, features that may also be associated with malignant change. It has been shown that South Asians in Britain have a high incidence of ulcerative colitis but a low incidence of colorectal carcinoma compared with their European counterparts. Previous studies have demonstrated changes in colonic mucin sialylation and sulphation in both South Asian and European cases with ulcerative colitis. This was related to disease severity, but changes were also found in quiescent disease. The aim of the present study was to determine glycoconjugate expression in the colon from South Asian cases and to compare results with those from a group of affected Europeans. Glycans were identified in formalin-fixed, paraffin-embedded tissue from 17 South Asian patients with ulcerative colitis and from 11 European patients with a similar degree of colitis, by the application of 10 biotinylated lectins. These were directed against a range of sialyl, fucosyl and 2-deoxy, 2-acetamido-galactosyl sequences, using an avidin-peroxidase revealing system and semiquantitative assessment. The South Asian group showed a reduction in the binding of agglutinins from Sambucus nigra in the apical-membranous region of enterocytes, and a decrease in apical Maackia amurensis agglutinin binding. These results suggest that South Asians with ulcerative colitis show a different distribution of terminal N-acetyl neuraminyl residues, either in their alpha-2,6 or alpha-2,3 linkage, compared with their European counterparts. The changes in sialylation observed in European cases compared with normal disease-free control subjects were present in quiescent disease, but were also related to disease activity. Their absence in Asians with ulcerative colitis may imply an inherent, genetically determined variation in this group, which may also play a part in their reduced risk of subsequent malignancy.

Asia, Southeastern↗

Role of the eastern chipmunk (Tamias striatus) in the epizootiology of Lyme borreliosis in northwestern Illinois, USA.

The role of the eastern chipmunk (Tamias striatus) in the epizootiology of Lyme borreliosis was evaluated in Castle Rock State Park, Illinois (USA), an enzootic region, from June to August 1993. Prevalence, intensity, and molting rate of immature Ixodes scapularis were determined for chipmunks, white footed mice (Peromyscus leucopus), and raccoons (Procyon lotor). Chipmunks were the primary host for I. scapularis nymphs and an important secondary host for I. scapularis larvae. Based upon ear punch biopsy analysis, B. burgdorferi prevalence in chipmunks was similar to that of mice in August and greater than that of mice in June and July. Thus we propose that chipmunks are the primary source of B. burgdorferi infection for I. scapularis nymphs and an important secondary source of infection for larvae.

Animals↗