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Biomedical subjects

R Jones

Publications and source records attributed to R Jones.

At least 415 records · Page 23Linked to original sources
PubMed1996

Management of hydrocephalus by endoscopic third ventriculostomy in patients with myelomeningocele.

Endoscopic third ventriculostomy (ETV) was performed between July 1978 and July 1995 on 69 patients with hydrocephalus and myelomeningocele. Most of the patients had been previously shunted, although in 14 patients ETV was the initial treatment. Patient selection was based on preoperative imaging studies suggesting noncommunicating hydrocephalus. Only 2 patients exhibited transient hypothalamic dysfunction with complete resolution. Patients were assessed by their clinical status, imaging characteristics, and, in some cases, formal psychometric studies. The overall success rate was 72%, although selecting only patients who have been previously shunted or who were over 6 months of age at the time of endoscopy increases this to 80%. Our results indicate that ETV is a safe and effective means of treating hydrocephalus in the older spina bifida population and offers the hope of long-term, shunt-independent life for selected patients.

Adolescent↗
PubMed1996

TNF alpha gene and protein expression in alveolar macrophages in acute and chronic hyperoxia-induced lung injury.

Alveolar-capillary membrane remodeling, including microvessel wall thickening and interstitial fibrosis, is a well-known sequela of cell proliferation in the hyperoxia-injured lung. The array of growth molecules released locally that potentially mediate this response, and their cell(s) of origin, are currently being defined. To elucidate the role of tumor necrosis factor alpha (TNF alpha), an effector molecule of cell injury and proliferation, and the role of the alveolar macrophage (AM) as its source during the acute (1 to 24 h) and chronic stages (3 to 28 days) of hyperoxia-induced injury, we have analyzed gene and protein expression in cells recovered from rat lung by bronchoalveolar lavage. In the hyperoxic lung, cell number was similar to that in normal lung (1 x 10(6)) except on day 7, when it was higher (5 x 10(6)). Virtually all cells recovered from the normal and hyperoxic lung were AMs, with the exception that on days 3 and 7 of hyperoxia these cells represented 69% and 55% of the population, respectively, and polymorphonuclear leukocytes and lymphocytes the remainder. Probe specificity was confirmed by detection of TNF alpha RNA (1.6 kb) from lung cells recovered after lipopolysaccharide (LPS) treatment (positive control) and from the hyperoxic lung (at day 3), with an extremely low level of constitutive expression detected in cells from normal lung. In cytospin preparations, TNF alpha mRNA transcripts were detected in few AMs recovered from normal lung and in most AMs after LPS treatment. In the hyperoxic lung, a signal was detected at 3 h, when approximately 25% of the population was positive. The number of hybridizing cells then increased, being highest on day 7 (day 1 approximately 30%, day 3 approximately 58%, day 7 approximately 90%, day 28 approximately 65%). No expression of TNF alpha protein was detected in AMs from normal lung; positive cells were detected in the hyperoxic lung from day 1 and thereafter. We conclude from upregulation of the TNF alpha gene in a significant number of cells, and from the increase in the number expressing biologically active protein, that AMs are an important source of this molecule both in the acute and chronic stages of hyperoxic lung injury. It is anticipated that an increased understanding of the cellular sources of mediators effecting vascular and alveolar wall remodeling in vivo will contribute to the development of strategies to inhibit the response.

Animals↗
PubMed1996

Risk of dementia among relatives of Alzheimer's disease patients in the MIRAGE study: What is in store for the oldest old?

Despite recent advances in the molecular genetics of Alzheimer's disease (AD), several fundamental questions concerning risk of illness are unresolved, namely, if Mendelian factors account for the incidence of the disease, and if AD is an inevitable consequence of the aging process. This study was designed to address these issues and other aspects of familial aggregation of the disorder. A consecutive sample of 1,694 patients who met criteria for a diagnosis of probable or definite AD were ascertained in 13 centers participating in the Multi-Institutional Research in Alzheimer Genetic Epidemiology (MIRAGE) project. Lifetime risk and age at onset of AD among various strata of 12,971 first-degree relatives was estimated using survival analysis procedures. The lifetime risk of AD in first-degree relatives was 39.0% +/- 2.1% by age 96 years. Age-specific risk of AD declined after age 90 and the data set included 61 apparently unaffected persons who survived to age 96 without becoming demented. Female relatives had a higher risk of AD than male relatives at all ages. By age 80, children of conjugal AD couples had a cumulative risk of 54%, 1.5 times greater than the sum of the risks to children having affected mothers or fathers, and nearly 5 times greater than the risk to children having normal parents. Children of affected fathers had a cumulative risk that was 1.4 times the corresponding risk to children of affected mothers. Risk assessment in early-onset and late-onset families, using various strategies for determining the age cut-off, yielded contradictory results. These data suggest the following: (1) the lifetime risk among relatives does not support a simple autosomal dominant inheritance pattern of disease; (2) women are innately more susceptible to AD than men; (3) the proportion of hereditary cases may be higher in men than women; (4) distinction between early- onset and late-onset forms of AD has little meaning in the absence of a biological marker; (5) the risk of AD decreases after age 90; and (6) AD therefore may not be an inevitable concomitant of the aging process, a conclusion that has profound implications for basic and applied AD research. The age- and sex-specific lifetime risks derived from this study are sufficiently robust to be a reliable source of information for counseling relatives of AD patients.

Age Factors↗
PubMed1996

Testicular biosynthesis and epididymal endoproteolytic processing of rat sperm surface antigen 2B1.

Binding of mammalian spermatozoa to the zona pellucida of homologous eggs is mediated by specific molecules on their surface membranes. In the present investigation we describe the biogenesis, epididymal processing and cellular distribution of a plasma membrane antigen (2B1) on rat spermatozoa that has a potential role in mediating zona binding. 2B1 is expressed postmeiotically in the testis as a precursor glycoprotein (approximately 60 kDa) that first appears on the plasma membrane of stage 6 to 8 round spermatids. Northern and western blot analyses show that there is a close correlation between the timing of transcription and expression of the glycoprotein on the cell surface. During spermatid elongation 2B1 is excluded from the head domain and is sequestered onto the sperm tail. As spermatozoa pass through the caput epididymidis 2B1 is endoproteolytically cleaved at a specific arginine residue (Arg 312) to produce a heterodimeric glycoprotein (approximately 40 kDa and approximately 19 kDa) containing intramolecular disulphide bridges. Endoproteolysis at Arg 312 also takes place during culture of washed testicular or caput spermatozoa in vitro and can be prevented by serine proteinase inhibitors or enhanced by trypsinisation. However, neither processing in vivo or in vitro has any effect on the domain organisation of 2B1 antigen i.e. it remains localised to the tail. These results support the hypothesis that sperm antigens that are important for fertilization are synthesized as precursor molecules in the testis and are then "activated' during epididymal maturation and capacitation, thereby ensuring that they only become fully functional at the site of fertilization.

Animals↗
PubMed1996

Diagnostic probes targeting the major sperm protein gene that may be useful in the molecular identification of nematodes.

Discrimination of closely related nematode species is typically problematic when traditional identification characteristics are prone to intraspecific variation. In this study, a molecular approach that can distinguish Pratylenchus penetrans and P. scribneri is described. The approach uses universal primers in conjunction with polymerase chain reaction (PCR) to amplify equivalent fragments of the major sperm protein (msp) gene from any nematode. This gene fragment typically includes an intron of variable sequence. The presence of this highly variable segment in an otherwise conserved gene sequence allows P. penetrans and P. scribneri to be distinguished by either a species-specific amplification or by dot-blot hybridization. The approach is potentially of general utility in species-specific identification of nematodes.

Animals↗
PubMed1996

Laparoscopic fundoplication: a three-year review.

Laparoscopic treatment of gastroesophageal reflux disease provides decreased postoperative pain and shortens hospitalization. Experience with this procedure continues to grow. The charts of patients who had laparoscopic fundoplication for the treatment of symptomatic refractory gastroesophageal reflux over a three year period were reviewed. Age, sex, preoperative evaluation, surgical technique, length of procedure, length of hospitalization, time to regular diet, conversion to laparotomy, complications, and long-term outcome were analyzed. Eighty-eight patients, 39 females and 49 males, underwent laparoscopic gastric fundoplication. All patients has symptomatic gastroesophageal reflux. Preoperative evaluation including upper endoscopy demonstrated esophagitis in 71 patients (81%) with changes of Barrett's esophagitis in 12 patients (14%). Decreased lower esophageal sphincter pressures were found in 33 of 73 patients (45%) and none had abnormal motility identified. A 2-3 cm fundoplication with nonabsorbable suture was performed over a large dilator. Mean operative time was 109 minutes. The mean length of hospitalization was 1.9 days in patients completed laparoscopically and six days in the 3 patients that required conversion to celiotomy for completion of their fundoplication. A clear liquid diet was offered the evening of surgery and advanced to regular as tolerated. Mild dysphagia was found in most patients for the first week and full liquid or soft diet was prescribed. All but seven patients advanced to regular diet by two weeks. Operative complications occurred in four patients and included two pneumothoraces and two esophageal perforations. Follow-up to 40 months has identified one partial wrap disruption and one crural breakdown both repaired laparoscopically. Seventy-seven patients (88%) have remained asymptomatic and off all medication. Laparoscopic fundoplication is safe and effective, allowing the benefits of minimal access surgery, including decreased postoperative pain and disability.

Adolescent↗
PubMed1996

Incidence and causes of rectal bleeding in general practice as detected by colonoscopy.

BACKGROUND: Rectal bleeding is common, but it is still unclear which patients require investigation to exclude serious pathology, although it is known that colectoral cancer is very rare under the age of 40 years. Few studies have examined all patients presenting to their primary health physician rather than screening whole populations. AIM: The aim of this study was to investigate the view that all patients over the age of 40 who present to their general practitioner with rectal bleeding should undergo investigation by colonoscopy to rule out serious pathology, regardless of symptomatology. METHOD: A prospective study was carried out of 99 consecutive patients over 40 years presenting with rectal bleeding to 17 general practices in Newcastle upon Tyne. RESULTS: Serious pathology was detected by colonoscopy in 44.4% of patients. The diagnoses were: colorectal carcinoma, eight cases (two Dukes' grade A, two Dukes' grade B, four Dukes' grade C); one or more polyps, 25 cases (in 17 cases at least one polyp was 5 mm or greater in diameter); inflammatory bowel disease, 11 cases. In the remaining 55 patients, bleeding was associated with diverticular disease (16 cases) and haemorrhoids (28 cases). No cause was found in 11 patients. This high rate of pathology may be partly caused by selection of cases for referral by the general practitioner, despite efforts to minimize this. Three symptoms as elicited by the colonoscopist were found to be significantly associated with serious disease: blood mixed with stool (P < 0.001); change in bowel habit (P < 0.005); and the presence of abdominal pain (P < 0.025). However, symptoms elicited on primary presentation were less helpful and symptoms changed significantly between consultation with the general practitioner and colonoscopy. CONCLUSION: All patients over the age of 40 years presenting with rectal bleeding should be referred for flexible sigmoidoscopy or colonoscopy. Symptoms are unhelpful in deciding who requires investigation.

Adult↗
PubMed1996

Legionnaires' disease--a potential hazard of rationalisation.

The cases of two elderly patients who complained of general malaise after they had undergone ward transfer (due to rationalisation of the rehabilitation service) are discussed. Both were pyrexial and had signs of pneumonic consolidation. Subsequent investigation revealed that their symptoms were due to infection with Legionella pneumophila. Their cases highlight the problems associated with ward closures and the hazards of stagnant water.

Aged↗
PubMed1996

Information for patients with cancer. Does personalization make a difference? Pilot study results and randomised trial in progress.

Although there are a number of groups working on the provision of personalized patient information there has been little evaluation. We have developed and piloted a method of giving patients on-line access to their own medical records with associated explanations. We are comparing, in a randomised trial, personalized with general computer based information for patients undergoing radiotherapy for cancer. We present results from the pilot study and the evaluation methods to be employed.

Adult↗
PubMed1995

Structure of a new crystal form of a DNA dodecamer containing T.(O6Me)G base pairs.

The structure of the synthetic dodecamer (d[CGTGAATTC(O6Me)GCG])2 has been determined to a resolution of 2.25 A and refined to a final R factor of 16.7%. The volume of the unit cell is significantly smaller by 16% than the original Drew and Dickerson parent dodecamer [Drew, H. R., Wing, R. M., Takano, T., Broka, C., Tanaka, S., Itakura, K., & Dickerson, R. E. (1981) Proc. Natl. Acad. Sci. U.S.A. 78, 7318-7322]. The double helix is in a different position in the unit cell, rotated by -85.9 degrees, and translated by 9.9 A around the helical axis with respect to the parent structure. The intermolecular arrangement of helices, characterized by double hydrogen bonded guanine-guanine minor groove interactions, remains conserved. The molecular geometry exhibits several significant changes that are related to the changed position of the helix and the presence of two mismatched base pairs with O6-methylguanine. Both mispairs are found in a symmetrical T(anti).(O6Me)G(anti) conformation, and the methyl groups are in proximal orientation. The hydration pattern of the structure is different and can be related to changes in the minor groove geometry. An incorrect model that was isomorphous to the parent dodecamer could be refined to a low R factor. Characteristics of the refinement and of the geometry that are indicative of incorrect structures have been analyzed.

Base Composition↗
PubMed1995

Radioligand binding affinity and biological activity of the enantiomers of a chiral melatonin analogue.

Melatonin, a hormone secreted by the pineal gland, can act on the central circadian oscillator in the suprachiasmatic nucleus of the hypothalamus. It has been proposed that melatonin or its analogues may be useful in restoring disturbed circadian rhythms in jet-lag, shift-work and some blind subjects, and as sleep-promoting agents. In the present study, the (-)- and (+)-enantiomers of N-acetyl-4-aminomethyl-6-methoxy-9-methyl-1,2,3,4-tetrahydrocarbazole (AMMTC) were separated and tested. The affinity of the enantiomers at the specific 2-[125I]iodomelatonin binding site in chick brain membranes was compared in competition assays, and their biological activity in a specific melatonin receptor bioassay, aggregation of pigment granules in Xenopus laevis melanophores. The (-)-enantiomer of AMMTC was 130-fold and 230-fold more potent than the (+)-enantiomer in competition radioligand binding assays and melanophores, respectively. Both enantiomers are melatonin receptor agonists; (-)-AMMTC is slightly more potent than melatonin itself. As the tetrahydrocarbazole nucleus holds the C-3 amido side-chain of AMMTC in a restricted conformation, the analogues will be useful in modelling the melatonin receptor binding site.

Animals↗
PubMed1995

Crystal and molecular structure of a new Z-DNA crystal form: d[CGT(2-NH2-A)CG] and its platinated derivative.

The three-dimensional structure of d[CGTA'CG], where A' = [2-NH2-A], was determined to atomic (1.35 A) resolution by single isomorphous replacement. The d[CGTA'CG] hexamer crystallizes in space group P3221, and is not isomorphous with other DNA hexanucleotides. Despite completely different crystal packing, the essential characteristics of the Z-DNA conformation are maintained. The structure was determined by single isomorphous replacement using a triammine platinum fragment. Thus, this study also demonstrates, for the first time, the feasibility of the use of this reagent for the direct phasing of DNA crystal structures.

Base Sequence↗
PubMed1995

Analysis of transcripts encoding novel members of the mammalian metalloprotease-like, disintegrin-like, cysteine-rich (MDC) protein family and their expression in reproductive and non-reproductive monkey tissues.

A number of sequence-related, cysteine-rich proteins containing metalloprotease-like and disintegrin-like domains (the MDC protein family), at least one of which has been shown to play a role in egg recognition during fertilization, are abundantly expressed in the mammalian male reproductive tract. In this paper we report the cloning and sequence analysis of three closely related isoforms of a novel member of this family which are expressed not only in the testis, but also in the liver, albeit at a lower level. Using a PCR-based approach we also demonstrate the presence of transcripts encoding additional, novel, disintegrin-containing proteins, in the liver and epididymis. We conclude that while some members of the MDC family are specific to the reproductive tract, suggesting functions peculiar to those tissues, others have a broader tissue distribution and may therefore play a more general role in integrin-mediated cell-cell recognition, adhesion or signalling.

ADAM Proteins↗