Search PubMed⌕ Search

Biomedical subjects

R C Jones

Publications and source records attributed to R C Jones.

At least 37 records · Page 2Linked to original sources

Antiinflammatory properties of inducible nitric oxide synthase in acute hyperoxic lung injury.

The objective of this study was to determine whether endogenous nitric oxide (NO), specifically the inducible NO synthase isoform (iNOS: NOS II), reduces or amplifies lung injury in mice breathing at a high oxygen tension. Previous studies have shown that exogenous (inhaled) NO protects against hyperoxia-induced lung injury, and that endogenous NO derived from iNOS inhibits leukocyte recruitment and protects against lung injury induced by lipopolysaccharide. In the present study, hyperoxia (> 98% O(2) for 72 h) induced acute lung injury in both wild-type and iNOS-deficient mice as determined by elevated albumin and lactate dehydrogenase levels in bronchoalveolar lavage fluid (BALF) and by increased extravascular lung water. Lung injury was greater in iNOS-deficient mice than in wild-type mice and was associated with an increased number of polymorphonuclear leukocytes in BALF. iNOS messenger RNA expression levels increased in the lungs of wild-type hyperoxic mice. Nitrotyrosine, a marker of reactive NO species, was expressed in both wild-type and iNOS-deficient mice in hyperoxia, indicating an iNOS-independent pathway for protein nitration. We conclude that iNOS is capable of reducing pulmonary leukocyte accumulation and lung injury. The data indicate that iNOS induction serves as a protective mechanism to minimize the effects of acute exposure to hyperoxia.

Acute Disease↗

Peptide specificity of RT1-A1(c), an inhibitory rat major histocompatibility complex class I natural killer cell ligand.

The rat major histocompatibility complex class Ia allelomorph RT1-A1(c) is a potent ligand for the recently identified inhibitory rLy-49 receptor, STOK-2. With the ultimate objective of studying the interactions of these molecules using structural and functional methods, we undertook a detailed study of its peptide specificity. The study revealed that designing an "ideal peptide" by choosing the most abundant residues in the "binding motif" obtained by pool sequencing does not necessarily yield an optimal binding peptide. For RT1-A1(c), as many as four positions, P2, P4, P5, and P9, were detected as putative anchors. Since this molecule displays a preference for highly hydrophobic peptides, we tested binding of peptides derived from the known leader peptide sequences of other rat histocompatibility complex class I molecules. One such peptide, found to bind well, requiring 1.6 microm peptide to achieve 50% stabilization, was searched for in vivo. Natural RT1-A1(c) binding peptides were purified from rat splenocytes and characterized by mass spectrometry using a combined matrix-assisted laser desorption ionization/time-of-flight and quadrupole time-of-flight approach. Results showed that the signal sequence-derived peptide was not detectable in the purified peptide pool, which was composed of a complex spectrum of peptides. Seven of these self-peptides were successfully sequenced.

Animals↗

An imidazoline pseudodipeptide suitable for solid phase peptide synthesis.

This paper describes the synthesis of two diastereoisomers of an imidazoline dipeptide mimetic (a 4,5 dihydroimidazole-4-carboxylic acid), suitably protected for incorporation into solid phase peptide synthesis (SPPS) using the Fmoc protocol, from a phenylalanine-derived thioimidate and an alpha,beta-diaminopropanoic acid ester, followed by protecting group manipulation.

Dipeptides↗

Angiogenesis in the hypertensive lung: response to ambient oxygen tension.

The present study further analyzes the growth and reorganization of the vessels adjacent to capillaries in the hyperoxia-adapted lung in response to a lower ambient oxygen tension. The aim of the study was to determine the source of the new smooth muscle cells known to develop in these segments on return to breathing air. To accomplish this we determined the reorganization of vessel walls by quantitative light-microscopy techniques, and vascular cell phenotype(s) by high-resolution microscopy, in the lungs of rats that breathed a high oxygen tension (87% O2 for 4 weeks), followed by weaning to a lower oxygen tension (87-20% O2 over 1 week) and return to breathing air (for 1, 2 or 4 weeks). Return to breathing air initially triggered wall growth in a subset of vessels and wall thinning in others before wall thinning predominated throughout the vessel population. Interstitial fibroblasts were identified as the source of new perivascular cells. The recruitment of these cells was accompanied by loss of elastic laminae from vessel walls. Subsequently, most perivascular cells expressed a smooth muscle phenotype and elastic laminae were restored. Arteriography demonstrated an increase in the number of patent vessels on return to air, and light- and high-resolution microscopy restitution of the capillary network. We propose that in the hyperoxia-adapted lung return to breathing air represents a relative hypoxia that triggers differential patterns of vessel and capillary growth to meet new functional demands set by the lower ambient oxygen tension.

Angiography↗

pH and bicarbonate in the ductuli efferentes testis of the rat.

The pH and bicarbonate concentrations of luminal fluids in the efferent ducts of the rat were estimated from pH measurements of samples in vitro under conditions of controlled temperature and carbon dioxide tension. The pH of scrotal blood was estimated to be more acidic than systemic blood (mean pH=7.44) at either of the putative scrotal carbon dioxide tensions (5% and 7%, pH, respectively,=7.42 and 7.28). For PCO2 tensions of 5% and 7%, respectively, the data indicated that the pH in the efferent ducts was significantly higher (distal initial zone pH=7.55 or 7.41; coni vasculosi pH=7.66 or 7.51; p < 0.01) than in fluid entering (rete testis fluid, pH=7.34 or 7.20) or leaving the ducts (zone 1a of the epididymal duct 7.26 or 7.11). Bicarbonate concentrations were also significantly higher (p < 0.01) in the efferent ducts (35.4 +/- 4.7 mM, distal initial zone; 45.2 +/- 7.6 mM, coni vasculosi) than in fluids entering (22.9 +/- 3.6 mM) or leaving (20.4 +/- 4.9 mM) the ducts. Estimates of the reabsorption of bicarbonate and fluid indicated that 96% of the testicular output of bicarbonate was reabsorbed in the efferent ducts, but there was also some secretion of bicarbonate into the ducts. It is concluded that luminal pH and bicarbonate levels in the efferent ducts of the rat are high relative to those found in the epididymis where low pH and bicarbonate contributes to sperm quiescence during storage. Nevertheless, the high rate of bicarbonate reabsorption in the efferent ducts is a major contributor to the establishment of the low pH and bicarbonate milieu of the epididymis.

Animals↗

Spermiogenesis and spermiation in a monotreme mammal, the platypus, Ornithorhynchus anatinus.

Spermatogenesis in the platypus (Ornithorhynchus anatinus) is of considerable biological interest as the structure of its gametes more closely resemble that of reptiles and birds than marsupial or eutherian mammals. The ultrastructure of 16 steps of spermatid development is described and provides a basis for determining the kinetics of spermatogenesis. Steps 1-3 correspond to the Golgi phase of spermatid development, steps 4-8 correspond to the cap phase, steps 9-12 are the acrosomal phase, and steps 13-16 are the maturation phase. Acrosomal development follows the reptilian model and no acrosomal granule is formed. Most other features of spermiogenesis are similar to processes in reptiles and birds. However, some are unique to mammals. For example, a thin, lateral margin of the acrosome of platypus sperm expands over the nucleus as in other mammals, and more than in reptiles and birds. Also, a tubulobulbar complex develops around the spermatid head, a feature which appears to be unique to mammals. Further, during spermiation the residual body is released from the caudal end of the nucleus of platypus sperm leaving a cytoplasmic droplet located at the proximal end of the middle piece as in marsupial and eutherian mammals. Other features of spermiogenesis in platypus appear to be unique to monotremes. For example, nuclear condensation involves the formation of a layer of chromatin granules under the nucleolemma, and development of the fibrous sheath of the principal piece starts much later in the platypus than in birds or eutherian mammals.

Animals↗

Galactography in patients with nipple discharge.

Nipple discharge is a common presenting symptom of underlying breast pathology. This study examined the impact of galactography on the evaluation of abnormal nipple discharge. Thirty-five women with spontaneous, unilateral nipple discharge who underwent galactography from 1995 to 1997 were retrospectively studied. Their presenting signs as well as mammographic, galactographic, and pathology findings were evaluated. Nipple discharge was bloody (n = 24), clear (n = 7), or serous (n = 4). A palpable mass was found in 5 patients, and discharge was spontaneous in 29 patients (83%). Mammography was normal in 25 patients (71%). Thirty patients (86%) had an abnormal ductogram that was characterized as a filling defect (n = 20), cutoff sign (n = 5), or ductal dilatation (n = 5). The ductogram demonstrated the location and depth of the lesion in 29 patients (97%). Excision was performed in 27 of 30 patients with an abnormal ductogram: 14 received complete subareolar duct excisions; 12, focused excisions; and 1, excision with a vacuum-assisted biopsy device. Pathology included intraductal papilloma (n = 20) and ductal ectasia (n = 7). Follow-up was completed in 24 patients, including 2 postoperative patients who had persistent discharge on manipulation. In conclusion, galactography is accurate in identifying the location of the ductal abnormality. It allows a focused surgical approach to the pathologic lesion in these patients.

Journal Article↗

Laparoscopic cholecystectomy for acalculous gallbladder disease.

Use of laparoscopic cholecystectomy (LC) to treat patients with symptoms due to gallstone disease is well established. However, use of LC for patients with acalculous gallbladder disease remains controversial. In this study, we examined the use of hepatobiliary iminodiacetic acid (HIDA) scans with cholecystokinin (CCK) infusion to identify patients with acalculous gallbladder disease who would benefit from LC. From December 1991 to February 1997, 4480 patients underwent cholecystectomy at Baylor University Medical Center, including 72 patients who underwent LC for acalculous disease following preoperative HIDA scan. We retrospectively analyzed their preoperative symptoms and workup. Follow-up was obtained by telephone questionnaire in 59 of 72 patients (82%). Overall, 48 of 59 patients (82%) reported an excellent outcome following LC. We found no significant difference in outcome in patients who underwent HIDA scan with CCK infusion, regardless of gallbladder ejection fraction or exacerbation of symptoms caused by the infusion. Preoperative symptom complex was also not predictive of postoperative outcome. LC is an effective treatment for patients with acalculous gallbladder disease. A preoperative HIDA scan with CCK infusion does not accurately predict treatment success or failure. Patients with a normal ejection fraction and absence of symptoms from a HIDA scan can still have excellent relief of symptoms after LC.

Journal Article↗

Avian infectious laryngotracheitis.

Avian infectious laryngotracheitis (ILT) herpesvirus continues to cause sporadic cases of respiratory disease in chickens world-wide. Sources of transmission of ILT infection are three-fold, namely: chickens with acute upper respiratory tract disease, latently infected 'carrier' fowls which excrete infectious laryngotracheitis virus (ILTV) when stressed, and all fomites (inanimate articles as well as the personnel in contact with infected chickens). Infectious laryngotracheitis virus infectivity can persist for weeks to months in tracheal mucus or carcasses. Rigorous site biosecurity is therefore critical in ILT disease control. Furthermore, while current (modified live) ILT vaccines can offer good protection, the strains of ILTV used in vaccines can also produce latent infections, as well as ILT disease following bird-to-bird spread. The regional nature of reservoirs of ILTV-infected flocks will tend to interact unfavourably with widely varying ILT control practices in the poultry industry, so as to periodically result in sporadic and unexpected outbreaks of ILT in intensive poultry industry populations. Precautions for trade-related movements of chickens of all ages must therefore include an accurate knowledge of the ILT infection status, both of the donor and recipient flocks.

Animals↗

Avian reovirus infections.

Avian reoviruses are ubiquitous among poultry flocks. Although infection is usually present without disease, reoviruses may occasionally be involved in several disease syndromes of which viral arthritis/tenosynovitis in chickens is the most important, particularly in broiler breeds. While reoviruses have been isolated from turkeys and several other species of birds with various conditions, the presence of the virus has been conclusively linked with disease in relatively few instances. In chickens in particular, avian reoviruses with a wide spectrum of pathogenic capability have been isolated and several antigenic types exist. Diagnosis is dependent on the detection of the virus in clinical samples, although the presence of the virus does not necessarily confirm that this is the cause of the disease, except where reoviruses are detected in affected joints. Serological tests are usually difficult to interpret in view of widespread and frequently harmless reovirus infection. The principal approach to control of viral arthritis/tenosynovitis is by vaccination using attenuated vaccines in young birds, followed by inactivated preparations for breeders intended to protect chicks by maternal antibodies. Many vaccines are based on the S1133 strain isolated in the United States of America, but these may not be effective against antigenic variants.

Animals↗

The Middle Years Group: a holistic approach to the management of the menopause in primary care.

OBJECTIVES: The menopause is attaining greater significance as symptoms and long-term sequelae are amenable to hormone replacement treatment. However, hormone replacement treatment is no panacea and all women undergoing the menopause need to make informed decisions about its use. The aim of this study was to assess the effects of a series of group sessions for women aged 45-55 years, dealing with physical, social, emotional and medical aspects of the climacteric. METHODS: All women registered at the Roborough surgery were invited to join a group for four sessions, led by the health visitor and counsellor, with a doctor leading one session on hormone replacement treatment. Women's views on the group were obtained by questionnaire. Prescribing data on hormone replacement treatment and antidepressants were analysed for attenders and a matched group of those invited who did not attend. RESULTS: Twelve percent of invited women attended. All stated that sessions helped an understanding of the physical and emotional changes at this time. No significant differences were found in the use of hormone replacement treatment, antidepressants or in subsequent use of the counsellor's services between the attenders and a matched group of non-attenders. CONCLUSIONS: This group offered all women at risk the opportunity to discuss, share and learn about all aspects of the menopause. It was well received and made no major differences to the uptake of hormone replacement treatment.

Antidepressive Agents↗

Expression of nitric oxide synthase isoforms (NOS II and NOS III) in adult rat lung in hyperoxic pulmonary hypertension.

Breathing air with a high oxygen tension induces an inflammatory response and injures the microvessels of the lung. The resulting development of smooth muscle cells in these segments contributes to changes in vasoreactivity and increased pulmonary artery pressure. This in vivo study determines the temporal and spatial expression of endogenous endothelial nitric oxide synthase (NOS III) and inducible NOS (NOS II), important enzymes regulating vasoreactivity and inflammation, in the adult rat lung during the development of experimental pulmonary hypertension induced by oxidant injury. We analyzed the cellular distribution of these NOS isoforms, using specific antibodies, and assessed enzyme activity at baseline and after 1-28 days of hyperoxia (FIO2 0.87). The number of NOS III-immuno-positive endothelial cells increased early in hyperoxia and then remained high. By day 28, the relative number of these cells had increased from 40% in proximal vessels and 13-16% in distal alveolar vessels of the normal lung to 73-86% and 40-59%, respectively, in hyperoxia. Pulmonary alveolar macrophages (PAMs), normally few in number and only weakly immunopositive for NOS II or III in the normal lung, increased in number in hyperoxia and were strongly immunopositive for each isoform. These morphological data were supported by a temporal increase in total and calcium-independent NOS activity. Thus NOS expression and activity significantly increased in hyperoxia as pulmonary hypertension developed, and NOS III expression increased selectively in vascular endothelial cells, while both NOS isoforms were expressed by the PAM population. We conclude that this increase in expression of a potent vasodilator, an antiproliferative agent for smooth muscle cells, and an antioxidant molecule represents an adaptive response to protect the lung from oxidant-induced vascular and epithelial injury.

Animals↗

The role of computed tomography in the diagnosis of acute appendicitis.

BACKGROUND: Routine contrast-enhanced computed tomography (CECT) has been described as an accurate diagnostic imaging modality in patients with acute appendicitis. However, most patients with acute appendicitis can be diagnosed by clinical findings and physical exam alone. The role of CECT in patients suspected of having appendicitis but with equivocal clinical exams remains ill defined. METHODS: One hundred and seven consecutive patients who were thought to have appendicitis but with equivocal clinical findings and/or physical exams were imaged by CECT over a 12-month period. Oral and intravenous contrast-enhanced, spiral abdominal and pelvic images were obtained using 7-mm cuts. CECT images were interpreted by a board-certified radiologist. Main outcome measures included CECT sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy in the diagnosis of acute appendicitis, comparing CECT with ultrasound, and determining the impact of CECT on the clinical management of this patient population. RESULTS: A group of 107 patients consisting of 44 males (41%) and 63 females (59%) with a median age of 33 years (range 13 to 89 years) were imaged with CECT to evaluate suspected appendicitis. Of the 107 CECTs performed, 11 false-positive and 3 false-negative readings were identified, resulting in a sensitivity of 92%, specificity of 85%, PPV of 75%, NPV of 95%, and an overall accuracy of 90%. Forty-three patients were imaged with ultrasound and CECT, and CECT had significantly better sensitivity and accuracy (30% versus 92% and 69% versus 88%, P<0.01). With regard to clinical management, 100% (36/36) of patients with appendicitis, and 4.2% (3/71) of patients without appendicitis underwent appendectomy. Therefore, the overall negative appendectomy rate was 7.6% (3/39). CONCLUSIONS: CECT is a useful diagnostic imaging modality for patients suspected of having acute appendicitis but with equivocal clinical findings and/or physical exams. CECT is more sensitive and accurate than ultrasound and is particularly useful in excluding the diagnosis of appendicitis in those without disease.

Adult↗

Early house moves, indoor air, heating methods and asthma.

OBJECTIVES: To assess whether house moves or certain housing conditions are a risk factor for the development of childhood asthma. DESIGN: A case-control study of asthmatic and non-atopic children aged 4-16 years. SUBJECTS: One hundred children with confirmed asthma in a group general practice of 11000 patients in Plymouth, U.K. Each was matched by age and gender with a child with no history of wheeze, eczema or hay fever. MAIN OUTCOME MEASURES: House moves and main heating methods, prior to the age of onset of asthma in cases and controls. RESULTS: There was a non-significant association between early house moves and the subsequent development of asthma. No association was found with heating methods, except for ducted-air heating which, because of the small numbers involved could have occurred by chance. None of the other factors studied affecting indoor air showed an association. CONCLUSION: Moving house at an early age may increase the risk of developing asthma, or may be associated with other more important risk factors, such as increased general mobility and hence, exposure to viral infections. Heating methods or other factors likely to affect the indoor air quality in early life were not useful predictors of subsequent asthma in children.

Adolescent↗

A retrospective study of the relationship between childhood asthma and respiratory infection during gestation.

BACKGROUND: Wheeze in children has been found to be associated with prior antepartum haemorrhage and raised levels of IgE in cord blood, and acute wheezing episodes are intimately linked with respiratory viral infections. OBJECTIVE: To assess the relationship between maternal presentation with respiratory tract infections in pregnancy and childhood asthma, taking into account factors which could affect presentation. METHODS: This was a case-control study of 200 asthmatic children, 5-16-year-old, age-matched with one control, having no recorded history of wheeze. Data on respiratory tract infections, maternal wheeze, atopy and smoking was collected from primary care records. Deprivation score was assessed according to small residential areas and subjects were equally distributed between four general practices in Plymouth, UK. RESULTS: Presentation with respiratory tract infections during pregnancy was significantly associated with childhood asthma (OR 1.69, 95% confidence interval 1.05-2.77, P = 0.03). The association was marginally stronger for infections in the first trimester (OR 2.30, 95% CI 1.05-5.41, P = 0.04) and for those with cough during pregnancy (OR 2.24, 95% CI 1.23-4.22, P = 0.007). The associations remained significant after allowing for the effect of the independent variables (gender, maternal smoking, maternal wheeze, allergic rhinitis, eczema, asthma treatment in pregnancy and deprivation [Townsend] score), using multiple logistic regression analysis (ORs and 95% CIs 1.91, 1.14-3.22; 2.32, 1.01-5.34 and 2.29, 1.17-4.48, respectively). There was also an association between numbers of presentations with respiratory infections and childhood asthma (test for trend, P = 0.02). CONCLUSIONS: This study has shown an association between presentation with respiratory infection during gestation and childhood asthma. The results were not affected by the other independent variable factors studied and therefore provide some evidence to support the theory that respiratory viruses may be implicated in the aetiology of asthma.

Adolescent↗

To store or mature spermatozoa? The primary role of the epididymis.

The function of the epididymis is considered in the context that it is necessary to transport spermatozoa for internal fertilization, but is also an adaptation involved in the competition between males to achieve paternity. Post-testicular sperm maturation and storage occur in lower vertebrates, such as the chondrichthyes, in which sperm storage is essential due to the slow rate of spermatogenesis. These roles persist in higher vertebrates, including mammals. However, they are less important in certain birds, in which the rate of sperm production by the testes is sufficient to supply enough spermatozoa to cope with the demands of a competitive mating system. There is no evidence for mammals, other than humans, that spermatozoa can achieve the capacity to fertilize an ovum without passing through some of the proximal epididymis. Storage of spermatozoa in the epididymis is probably not essential for a male to achieve conception in a protected mating system, but is very important in a competitive mating system. There is some variation between species in the magnitude of the epididymal storage region. This is related to the descent of the epididymides (and testes) into a scrotal sac in some species and/or the demands of the mating system in other species. The claims that humans are not dependent on post-testicular sperm maturation and storage need to be qualified, as they are based on studies of abnormal tracts and tests of fertility which are not rigorous. Nevertheless, the claims are of considerable clinical significance and may indicate that humans are less dependent on post-testicular sperm maturation and storage than other mammals. This may be an adaptation of the testes and epididymides to the scrotal conditions of modern man or a response to changing environmental factors.

Animals↗

Investigation into avian pneumovirus persistence in poults and chicks using cyclosporin A immunosuppression.

One-day-old poults or two-week old chicks were infected oculonasally with avian pneumovirus. Cloacal swabs were collected for virus isolation as were selected tissues (Harderian gland, turbinates, trachea, lungs and kidneys) from birds killed at regular intervals up to 33 days post infection (p.i.) for poults, and up to 40 days p. i. for chicks. In an attempt to induce virus re-excretion, the T-cell-suppressor cyclosporin A (CSA) was given for 12 days starting from three weeks p.i. in poults and from four weeks p.i. in chicks. Birds were sampled for virus isolations up to day 12 post CSA treatment. Virus was recovered only up to day nine p.i. in poults, and day five p.i. in chicks during the acute phase of the infection. Despite T-cell suppression, there was no evidence of re-excretion of the virus, and hence no evidence for the persistence of virus in the tissues examined.

Aging↗