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Biomedical subjects

R Brown

Publications and source records attributed to R Brown.

At least 685 records · Page 38Linked to original sources
PubMed1984

New cosmid vectors developed for eukaryotic DNA cloning.

A series of ColE1 and pSC101 cosmid vectors have been constructed suitable for cloning large stretches of DNA. All contain a single BamHI site allowing cloning of Sau3A, MboI, BglII, BclI , and BamHI-generated fragments. These vectors have the following characteristics: (i) they are relatively small (1.7-3.4 kb); (ii) the BamHI cloning site is flanked by restriction enzyme sites enabling direct cloning of unfractionated insert DNA without generating multiple insert or vector ligation products [ Ish - Horowitz and Burke, Nucl . Acids Res. 9 (1981) 2989-2998]; (iii) two vectors ( pHSG272 and pHSG274 ) contain a hybrid Tn5 KmR/ G418R gene which is selectable in both prokaryotic and eukaryotic cells, making them suitable for transferring DNA into eukaryotic cells, and (iv) the different prokaryotic selectable markers available in the other vectors described facilitate cosmid rescue of the transferred DNA sequences from the eukaryotic cell: CmR, ApR, KmR, ( pHSG429 ), CmR, ( pHSG439 ), colicin E1 immunity ( pHSG250 ), (v) the cosmid pHSG272 was used successfully to construct a shuttle vector based on the BPVI replicon [ Matthias et al., EMBO J. 2 (1983) 1487-1492].

Animals↗
PubMed1984

An alternative assay system for the detection of transforming genes.

We have developed an alternative assay system based on DNA mediated gene transfer (DMGT) for the detection of functional transforming genes which we find more sensitive and reliable than other assay systems. This approach involves selecting in tissue culture for cells which are expressing a drug-resistance marker co-transferred with the tumour DNA thus isolating the small number of cells which have taken up and are expressing exogenously added DNA. The ability of transformed cells present in this drug-resistant cell population to form tumours in athymic (nu/nu) nude mice was then used to assay for transforming genes. Using NIH3T3 and Rat 2 cells as recipients, tumours produced after DMGT with DNA from non-tumorgenic cells were only very rarely observed. Tumour induction was observed using DNA from a biopsy of a human ovary carcinoma and a spontaneous murine lung carcinoma. Two human retinoblastoma cell lines were negative for tumour induction. The transforming gene from the ovarian carcinoma was identified as c-K-ras2.

Animals↗
PubMed1984

Cause of death in rheumatoid arthritis.

A series of 489 consecutive patients with definite or classical rheumatoid arthritis was followed for a mean of 11.2 years. Cohort-analysis of the series showed a three-fold increase in mortality overall in comparison with age- and sex-specific rates in the general population. In patients first seen in hospital early in the course of the disease (less than 5 years from onset), the excess of deaths from circulatory, respiratory and musculoskeletal disorders was highly significant. Malignant disease and digestive system disorders accounted for a small excess of borderline significance. Patients who were referred later (greater than 5 years from onset) experienced, in addition, a highly significant excess of deaths from infections and disorders of the digestive and genito-urinary system but not from malignant neoplasms.

Adult↗
PubMed1984

An affinity technique for the isolation of Clostridium perfringens type C from man and pigs in Papua New Guinea.

Necrotising enteritis caused by Clostridium perfringens type C (CwC) is an important cause of morbidity and death in highland regions of Papua New Guinea (PNG) and the organism is readily isolated from clinical cases. Although detected in fluorescent antibody stains of faecal cultures, CwC has previously only once been isolated from normal people or from pigs in PNG. The difficulty results from the greater numbers of the much more common Cl. perfringens type A (CwA) which is morphologically and culturally indistinguishable from CwC. Separation of CwC from the more numerous CwA has been achieved by utilising their antigenic dissimilarity. Silicate beads covered with specific antibody to CwC added to a mixed culture bound CwC cells while most of the unbound cells were washed away. When the beads were plated out type C organisms were recovered. In laboratory tests CwC was isolated from mixtures with CwA where the type A organisms predominated by one million to one. With this system type C organisms have been isolated from human and pig faeces from PNG.

Animals↗
PubMed1984

Cancer morbidity in rheumatoid arthritis.

A consecutive series of 489 patients with rheumatoid arthritis seen at the centre was studied to determine their cancer morbidity. Overall the 36 cancers diagnosed in the series between 1964 and 1981 were not significantly in excess of the expected number, but there was a highly significant excess of tumours of the reticuloendothelial system. The excess was mainly due to 6 observed cases of lymphoma. We conclude that there is a highly significant association between rheumatoid arthritis and the subsequent development of lymphoproliferative malignancy in this series.

Adult↗
PubMed1984

Intra-airway gas mixing during high-frequency ventilation.

We examined the intra-airway gas transport mediated by high-frequency oscillations (HFO) in 10 nonintubated healthy volunteers using a method based on comparisons of single-breath N2-washout curves obtained after various durations of breath hold or high-frequency oscillations. With a mathematical analysis based on Fick's law of diffusion we computed the local transport parameter, effective diffusivity, during oscillations of frequency 2-24 Hz and tidal volume 10-120 ml and during breath hold alone. Local effective diffusivity increased with both oscillatory frequency and tidal volume at all levels in the tracheobronchial tree; the enhancing effect of tidal volume on local effective diffusivity was more pronounced than that of frequency so that effective diffusivity was greater with larger tidal volume at fixed frequency-tidal volume product (f . VT). The greatest enhancement of gas mixing within the lung during HFO (over breath hold) was seen in the central airways. In previous studies examining CO2 removal rate during HFO (J. Clin. Invest. 68: 1475, 1981), we found that CO2 output was also greater with larger tidal volume at fixed f . VT, and we attributed this to an end constraint imposed by a fresh gas bias flow. Results of the current study, performed without a bias flow, indicate that bias flow end constraint does not solely account for the observed dependence of CO2 output on frequency and tidal volume.

Adult↗
PubMed1984

Frequency dependence of plethysmographic measurement of thoracic gas volume.

With airways obstruction, panting frequency affects plethysmographically determined thoracic gas volume (Vtg) because the extrathoracic airway acts as a shunt capacitor. Stanescu et al. (19) suggested that in the calculation of Vtg, use of esophageal (delta Pes) rather than mouth pressure (delta Pm) swings might eliminate the problem. We measured total lung capacity (TLC) plethysmographically in 10 subjects with chronic airways obstruction (CAO) and in four normal subjects. TLC (using delta Pm) was derived from Vtg obtained from slow-(approximately 1 Hz) and fast- (approximately 4 Hz) panting frequencies. In the normal subjects and four subjects with CAO, TLC was also obtained using delta Pes. In these subjects abdominal gas compression and decompression did not contribute significantly to the frequency dependence of TLC. In CAO, TLC was frequency dependent in direct proportion to the severity of obstruction. Although the frequency dependence was greater using delta Pm to calculate Vtg, it also occurred using delta Pes. Thus it could not be explained entirely by the shunt capacitor effect of the extrathoracic airways. The residual and significant overestimations of TLC (reflected by frequency dependency of TLC derived from Vtg calculated from delta Pes) may be explained by interregional nonhomogeneities during the panting maneuver.

Adult↗
PubMed1984

Identification of patients with improved survival following coronary bypass surgery.

This study was designed to determine whether left ventricular performance measured noninvasively from the systolic time intervals could identify patients in whom coronary bypass surgery may improve survival. 71 patients with two- or three-vessel disease undergoing coronary bypass surgery were compared with 78 matched medically treated patients. All patients had recuperated from myocardial infarction by a mean of 17.6 months when systolic time intervals were performed. Surgical and medical patients were classified preoperatively into those with normal and those with abnormal left ventricular performance by preejection period/left ventricular ejection time (PEP/LVET less than or equal to 0.42 and greater than 0.42, respectively). Survival was analyzed by life table and log-rank test. Cumulative 5-year survival in patients with normal left ventricular performance was not statistically different in surgical and medical groups (96 vs. 93%, respectively). In contrast, cumulative survival in patients with abnormal left ventricular performance was significantly greater in the surgical group when compared to the medical group (84 vs. 62, p less than 0.01). Among the patients with abnormal left ventricular function, the mean PEP/LVET and the average vessel disease were not different in the medical and surgical groups. Multivariate analysis of 17 other clinical and laboratory risk variables were not different between these two groups. It is concluded that coronary bypass surgery my improve survival in patients with two- or three-vessel disease and left ventricular dysfunction.

Actuarial Analysis↗
PubMed1984

Antiallergic activity profiles in vitro of RHC 3164 and related compounds. I. A lack of correlation between inhibition of cyclic nucleotide phosphodiesterases and antigen-induced release of histamine from rat mast cells.

A series of 26 compounds belonging to the chemical class of (1,2,4)triazolo(4,3-a)-quinoxaline-1,4-diones have been investigated for their antiallergic activities in 3 in vitro models of anaphylaxis. Effects of these and other known antiallergic agents on cyclic nucleotide phosphodiesterases (cNUC-PDE) from purified rat mast cells have also been investigated. 18 compounds were potent (I50 less than or equal to 45 microM) inhibitors of antigen-induced release of histamine (AIR) from rat mast cells (RMC), 3 compounds inhibited anti-IgE-induced release of histamine from human basophils (I50 less than or equal to 25 microM) and none of the compounds significantly affected AIR from guinea pig lung slices. 13 of the compounds were more potent than theophylline as inhibitors of cyclic AMP-PDE and/or cyclic GMP-PDE from RMC. Parallel concentration-response curves for the inhibition of cyclic AMP-PDE and cyclic GMP-PDE indicated that these compounds probably interact with enzyme in the same manner. Paired regression analysis of the I50 values for inhibition of AIR and cNUC-PDE from RMC by these compounds revealed no statistically significant correlation between the inhibition of AIR and inhibition of cyclic AMP-PDE or cyclic GMP-PDE. We conclude: (1) some of these compounds are potent inhibitors of immunologic release of histamine from RMC with an in vitro activity profile similar to that of DSCG, and (2) inhibition of cyclic AMP or cyclic GMP hydrolysis by cNUD-PDE by these compounds, DSCG, and 6 known antiallergic agents is not the biochemical mechanism by which they inhibit AIR from RMC.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1984

Reliability of criteria for borderline personality disorder: a comparison of DSM-III and the Diagnostic Interview for Borderline Patients.

The authors compared the reliability of two methods of distinguishing borderline personality disorder--DSM-III and the Diagnostic Interview for Borderline Patients. The reference group, outpatients with other personality disorders and without major axis I pathology, was more difficult to distinguish from the patients with borderline personality disorder than such groups used in previous samples. The sensitivity and specificity of the Diagnostic Interview for Borderline Patients were calculated, with DSM-III used as a criterion. The findings confirm considerable overlap between borderline and schizotypal personality disorders, more impairment in functioning in borderline patients than in those with other personality disorders, and the high reliability with which borderline personality disorder can be diagnosed.

Adolescent↗
PubMed1984

The significance of changes in blood lymphocyte populations following surgical operations.

After surgery blood lymphocyte levels fell to one-third of the pre-operative value. Since this depression was transient, and followed the peak of serum cortisol closely, it was probably due to a redistribution of lymphocytes from the blood to the tissues. The proportion of activated lymphocytes, as measured by the incorporation of 3H-thymidine in vitro without added mitogen, was substantially increased about 5-8 days after operation. The greatest number of S-phase lymphocytes was found after operation combined with blood transfusion but surgery alone and blood transfusion alone each produced significant increases. The proportions of B lymphocytes, T helper cells and T suppressor cells remained nearly constant despite the fluctuations in total lymphocyte counts. The response of lymphocytes in vitro to phytohaemagglutin (PHA) was doubled on average 7 days after surgery provided the test was performed in the patient's own serum. In pooled serum there was no consistent change in the response to PHA. It is argued that none of the observed changes necessarily signify that a phase of immunosuppression follows surgical operations.

Blood Transfusion↗
PubMed1983

RHC 3288 [1-methyl-2(1,3,4-oxadiazol-2(3H)-one-5-yl) benzimidazole] and related compounds. Novel inhibitors of histamine release from rat mast cells and human basophils.

RHC 3288 [1-methyl-2(1,3,4-oxadiazol-2(3H)-one-5-yl) benzimidazole] and twenty-five related 5-substituted oxadiazolones have been investigated for their antiallergic activities in three in vitro models of anaphylaxis. Sixteen compounds were potent (I50 less than or equal to 50 microM) inhibitors of antigen-induced release of histamine (AIR) from rat mast cells (RMC), and seven compounds inhibited anti-IgE-induced release of histamine from human basophils (I50 less than or equal to 100 microM). The antiallergic activity profiles of RHC 3288 and three other compounds in these models have been compared with that of disodium cromoglycate (DSCG). As inhibitors of AIR from RMC, RHC 3288, 3334, 3354 and 3380 were 3 to 10 times more potent than DSCG. In the same model (AIR from RMC), activity profiles of all four RHC compounds were identical to that of DSCG in the following respects: loss of inhibitory activity with increasing preincubation time, tachyphylaxis and cross-tachyphylaxis to each other, and inability to inhibit histamine release stimulated by Ca2+ ionophore, dextran + phosphatidyl serine and compound 48/80. RHC 3288, 3334, 3354 and DSCG had no effect in the other two models, histamine release from guinea pig lung mediated predominantly by IgG1 class of antibodies and anti-IgE-induced histamine release from human basophils. We conclude that RHC 3288 is a potent inhibitor of mediator release with a mechanism of action similar to that of DSCG.

Animals↗
PubMed1983

Antepartum chronic fetal vesicoamniotic shunts for obstructive uropathy: A report of two cases.

Two fetuses with obstructive uropathy characterized by striking oligohydramnios and dilatation of the urinary collecting system were identified by ultrasound and treated by percutaneous insertion of a long-term vesicoamniotic silicone rubber shunt. Both fetuses were less than 16 weeks' gestation at diagnosis and less than 18 weeks at treatment. One fetus was delivered at 35 weeks and is alive and well; the other died early in the neonatal period at 31 weeks with pulmonary hypoplasia.

Adult↗
PubMed1983

Mutations in humans and animals which affect copper metabolism.

Various inherited disorders of copper metabolism in man and animals are reviewed. Emphasis is placed on the use of cultured cells from mutants to determine the primary molecular defects and to acquire basic knowledge of normal copper metabolism. This allows better diagnostic tests and possible treatment of the disorders. Menkes' disease in humans and mottled mouse mutants are discussed in detail, as they illustrate these approaches.

Animals↗
PubMed1983

The phase of hair growth in hypothyroidism in the dog.

The stage of hair growth which predominated in dogs not affected with hypothyroidism appeared to be breed-dependent. For example, in boxers, Labradors and collies, the resting stage (telogen) predominated, whereas in West Highland White terriers and cairn terriers the active stage (anagen) predominated. However, even in pet dogs kept mainly indoors, the proportion of hairs in anagen tended to increase during the winter months. In dogs affected with hypothyroidism, the proportion of hairs in anagen or telogen in members of a particular breed was the same as in the normal dogs of the breed. From this, it appeared that breed was more influential than hypothyroidism in determining the predominant phase of hair growth.

Animals↗