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P Johnson

Publications and source records attributed to P Johnson.

At least 325 records · Page 18Linked to original sources
PubMed1992

Reactivity of P-glycoprotein monoclonal antibodies in childhood cancers.

P-Glycoprotein (P-gp), the product of the mdr-1 gene, is implicated in the development of chemoresistance in a variety of, mostly adult, cancers. Its role in paediatric tumours, most of which are non-epithelial in origin, has yet to be fully elucidated. A study was undertaken to investigate reactivity of two P-gp monoclonal antibodies (MAbs), JBS-1 and MRK16, recognising cytoplasmic and surface epitopes, respectively, of the P-gp molecule, in a variety of newly diagnosed and relapsed childhood cancers. P-gp was not expressed in any of 36 tumours examined (neuroblastoma 13, nephroblastoma 12, rhabdomyosarcoma 6, lymphoma 3, teratoma 1, Ewings 1), 14 of whom had chemoresistant disease. Reactivity to both MAbs was also investigated in patients with acute leukaemia. Out of 10 diagnostic acute lymphoblastic leukaemia (ALL) samples, a positive reaction with JSB-1 was observed in 1 patient who failed to remit on standard induction therapy and in 3 of 6 patients in ALL relapse, only 1 of whom showed low grade positivity with MRK16. Both MAbs reacted positively in 1 patient with acute non-lymphocytic leukaemia (ANLL) at diagnosis who achieved remission with teniposide and cytosine arabinoside, but relapsed 7 months later and was again positive with both Mabs. JSB-1 also showed varying degrees of positivity in 4 out of 4 other patients in ANLL relapse. It would therefore appear that P-gp is unlikely to mediate chemoresistance in most solid tumours of childhood, but may well play a major role in the development of chemoresistance in acute leukaemia.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

The relationship between environmental temperature, metabolic rate, sleep state, and evaporative water loss in infants from birth to three months.

We have investigated the effect of changing environmental temperature on metabolic rate, sleep state, and water loss in a longitudinal study of 22 lightly clothed babies from 2 d to 3 mo of age. Studies were performed in a modified barometric plethysmograph while recording sleep state, oxygen consumption, and skin and axillary temperatures. Oxygen consumption was higher in rapid eye movement sleep than in quiet sleep at all ages and varied widely between infants at each temperature. Within the first week, there was a 19% rise in oxygen consumption on cooling to 19-22 degrees C during rapid eye movement sleep and a 6% rise during quiet sleep. The median duration of quiet sleep periods was reduced from 17 to 12 min on cooling within the first week. No such change was seen at 1, 2, and 3 mo. Axillary temperature was reduced at 3 mo during cooling. This may be a part of normal patterns of change in temperature during sleep, unrelated to cooling. At each age, total evaporative water loss fell linearly with falling environmental temperature both within and below the temperature range at which metabolic rate was minimal. The evaporative water losses were greater than expected and suggested that sweating was occurring, both at temperatures at which metabolic rate was minimal and at those at which it was increased. The metabolic response to cooling and the process of sweating appear to be in dynamic equilibrium across this temperature range. Thus, it was not possible to define a temperature range over which both metabolic rate and evaporative water loss were at minimum values.

Body Temperature Regulation↗
PubMed1992

The Homefinder service.

This paper describes the establishment of a Homefinder service for elderly patients at Charing Cross Hospital in 1985. The contribution made by this service over a five-year period in reducing acute medical bed occupancy by long-stay patients is discussed.

Aged↗
PubMed1992

Comprehensive restaging laparotomy in women with apparent early ovarian carcinoma.

OBJECTIVE: To determine the yield and morbidity of comprehensive restaging laparotomy in women with presumed early ovarian carcinoma who have undergone incomplete initial staging procedures. METHODS: We conducted a retrospective review of 30 women with apparent early ovarian carcinoma who underwent a comprehensive restaging laparotomy including multiple random intraperitoneal biopsies and selective pelvic/para-aortic lymphadenectomy before receiving adjuvant therapy. Positive findings were compared with clinicopathologic features. RESULTS: Only 17% of patients had adequate skin incisions, 53% had pelvic washings, and 37% had omental biopsy at primary surgery. Complications of restaging laparotomy included 53% severe adhesions, 20% bowel complications, and 20% vascular complications requiring suture. Nine patients (30%) had disease upstaged and six (20%) had stage III disease established by comprehensive restaging laparotomy. Two-thirds of the upstaged patients had occult metastases identified only through cytology, random peritoneal biopsies, or selective lymphadenectomy. Women with poorly differentiated or papillary serous lesions were more likely to have disease upstaged than those with well- and moderately differentiated lesions or other histologic types (P < .05). Other clinicopathologic features did not predict upstaging. CONCLUSION: A comprehensive staging laparotomy is needed to detect occult metastatic disease in women with apparent early ovarian carcinoma.

Adult↗
PubMed1992

Wasting malnutrition and inadequate nutrient intakes identified in a multiethnic homeless population.

The few previous studies of the nutritional status and dietary intakes of the homeless have been limited by small sample sizes. We collected information from a multiethnic sample of 277 homeless men and women in Miami, Fla. Data collected included a brief personal history, anthropometric variables, and a detailed 24-hour dietary recall. An additional 24-hour dietary recall was collected from a subsample of 36 men. Socioeconomic characteristics of our sample were similar to that of other samples of the homeless. Using measurements of the upper arm muscle area, we identified wasting malnutrition in 20% of the men. Dietary intakes (percentage of the Recommended Dietary Allowances [RDAs] +/- standard error of the mean) for energy (82 +/- 2.88%), calcium (63 +/- 3.28%), zinc (56 +/- 2.61%), and vitamin B-6 (68 +/- 3.93%) were significantly below RDA guidelines for all ethnic groups. In addition, thiamin (75 +/- 6.34%) intakes for whites and vitamin A (61 +/- 12.53%) and riboflavin (74 +/- 7.72%) intakes for Hispanics were below RDA guidelines. Compared with men, women consumed significantly less energy, calcium, and zinc.

Adult↗
PubMed1992

Friend virus induced murine erythroleukaemia: the p53 locus.

The development of Friend virus induced murine erythroleukaemia is associated with specific genetic events. One of these events is loss of wild type p53 expression, which can occur by internal deletion or proviral insertion in the p53 gene and by single point mutations in the coding sequence. In all cases, the corresponding wild type allele is absent. The high frequency of observed p53 mutations strongly suggests that inactivation of p53 may be an obligatory step in the development of Friend disease. Further evidence that abrogation of normal p53 expression contributes to the development of malignant clones was provided by in vitro reconstitution experiments in Friend cell lines: whereas exogenous mutant p53 was stably expressed in p53 negative FCLs, long term wild type p53 expression was not detected. Friend erythroleukaemia arises as a late consequence of infection of susceptible mice with Friend virus. In addition to p53 gene mutations, proviral insertions occur frequently adjacent to one of two cellular genes, Spi-1/PU.1 or Fli-1. Aberrant expression of these genes may therefore be involved in virus induced erythroleukaemia. Interaction of SFFV env gp55 with the EPO-R also appears to be important in providing a mitogenic signal to infected cells. The order in which these events occur and whether the order is relevant to the progression of the disease are not known. Investigation of the stepwise appearance of these events could provide information on the possible interactions of the gene products involved. Abrogation of normal p53 expression is not restricted to Friend erythroleukaemia: the observation of p53 mutations and allele loss in human breast, lung, colon and hepatocellular carcinomas and in leukaemia suggests that mutation of p53 may be the most common genetic abnormality detected in human cancer (reviewed in this issue). Studies of p53 expression in FCLs provided an early indication that p53 was a tumour suppressor gene. Further studies of the mechanisms by which wild type and mutant p53 affect the growth of p53 negative FCLs may reveal important biochemical properties of p53 in relation to cell cycle control and differentiation of erythroid cells.

Alleles↗
PubMed1991

Differential tissue expression of the Lewis blood group antigens: enzymatic, immunohistologic, and immunochemical evidence for Lewis a and b antigen expression in Le(a-b-) individuals.

The Lewis blood group system comprises two main carbohydrate antigens, Le(a) and Le(b). Lewis typing has traditionally been based on serologic determinations using erythrocytes and saliva. Several recent studies have demonstrated that erythrocyte Lewis phenotype may change during pregnancy or disease, and inappropriate Lewis antigens have been found in both normal and neoplastic tissue. To evaluate whether these observations are in conflict with the presently proposed genetic and biosynthetic basis of the Lewis blood group system, we performed a combined enzymatic, immunohistologic, and immunochemical study of Lewis antigen expression in normal and neoplastic tissues, as well as erythrocytes, plasma, and saliva of Le(a-b-)-typed individuals. Of six cancer-bearing patients typed Le(a-b-), three were identified as nongenuine owing to the presence of alpha 1----4fucosyltransferase activity (alpha 1----4FT) and Lewis antigens in saliva and three were identified as genuine (lacking alpha 1----4FT and Lewis antigens in saliva). These genuine Le(a-b-) individuals were shown to express significant alpha 1----4FT in tissues, and Lewis antigens were detected in tissues by immunohistology as well as immunochemistry. We conclude that the Lewis phenotype obtained by serologic determination of erythrocytes and saliva does not apply to all tissues. We discuss biosynthetic and genetic consequences of this finding.

Colon↗
PubMed1991

The differential diagnosis of enlarged hyperechogenic kidneys with normal or increased liquor volume: report of five cases and review of the literature.

We report five cases of enlarged, hyperechogenic kidneys detected prenatally where the liquor volume was normal or increased. The etiology was different in all cases and included infantile and adult polycystic kidney disease, Perlman syndrome, trisomy 13 and cystic dysplasia. The differential diagnosis of such findings is discussed and other cases reported in the literature are reviewed.

Journal Article↗
PubMed1991

Differential expression of the alternatively spliced exons of murine CD45 in Th1 and Th2 cell clones.

Antigen-specific murine CD4+ T cell clones can be divided into functionally distinct subsets known as Th1 and Th2. To date these cells have been indistinguishable by surface phenotype. This report identifies two anti-CD45R monoclonal antibodies (14.8 and C363.16A) that bind preferentially to Th2 cells. Further analysis of the CD45-specific mRNA in Th1 and Th2 cells shows clear differences between these two cell types. Th1 cell clones express mRNA for the two smallest forms of CD45 containing none or only one of the alternatively splices exons. In contrast, Th2 cell clones express predominantly the high molecular weight isoforms of CD45 containing two or three of the alternatively spliced exons.

Animals↗
PubMed1991

MULTI: a shared memory approach to cooperative molecular modeling.

A general purpose molecular modeling system, MULTI, based on the UNIX shared memory and semaphore facilities for interprocess communication is described. In addition to the normal querying or monitoring of geometric data, MULTI also provides processes for manipulating conformations, and for displaying peptide or nucleic acid ribbons, Connolly surfaces, close nonbonded contacts, crystal-symmetry related images, least-squares superpositions, and so forth. This paper outlines the basic techniques used in MULTI to ensure cooperation among these specialized processes, and then describes how they can work together to provide a flexible modeling environment.

Computer Communication Networks↗
PubMed1991

Fetal blood sampling and pregnancy loss in relation to indication.

OBJECTIVE: To assess the relation between the indication for fetal blood sampling and pregnancy loss following the procedure. DESIGN: Retrospective study. SETTING: The tertiary referral Fetal Medicine Units at Guy's and University College Hospitals, London. SUBJECTS: Women undergoing diagnostic fetal blood sampling in four groups: (1) 94 having prenatal diagnosis with normal ultrasound findings; (2) 94 with a structural fetal abnormality; (3) 30 having fetal assessment and (4) 35 with non-immune hydrops. INTERVENTIONS: Freehand ultrasound guided fetal blood sampling from umbilical cord, intrahepatic vein or fetal heart. MAIN OUTCOME MEASURES: Pregnancy losses were divided into those within 2 weeks and those 2 weeks after the procedure, obstetric accidents and neonatal deaths. RESULTS: The 253 patients had fetal blood sampled on 268 occasions. Fifty-one pregnancies were terminated. Overall, 51 of the remaining 202 desired continuing pregnancies were lost, of which 19 (9%) were lost within 2 weeks of the procedure. After exclusion of the pregnancies that were terminated, the procedure-related losses within 2 weeks of sampling were 1 in 76 (1%), 5 in 76 (7%), 4 in 29 (14%) and 9 in 36 (25%) in groups 1, 2, 3 and 4 respectively. CONCLUSIONS: The risk of fetal blood sampling is increased in abnormal pregnancies, reflecting the underlying pathology and this must be taken into account when counselling patients before the procedure.

Abortion, Spontaneous↗
PubMed1991

The prevalence, aetiology and clinical significance of pseudo-sinusoidal fetal heart rate patterns in labour.

OBJECTIVE: To investigate the prevalence of sinusoidal and pseudo-sinusoidal fetal heart rate (FHR) patterns in labour and the relation between the characteristics of the FHR pattern and fetal outcome. DESIGN: A prospective observational study over a 6-month period in which all women who had continuous FHR monitoring in labour had their intrapartum cardiotocographs (CTGs) scrutinized for the presence of sinusoidal or pseudo-sinusoidal FHR patterns. SETTING: John Radcliffe Hospital, Oxford. SUBJECTS: 1520 women who had fetal monitoring during labour for various reasons. MAIN OUTCOME MEASURES: Both internal (electrocardiographic) and external (ultrasound) recordings of the FHR were analysed. Abnormal FHR patterns were related to obstetric characteristics and fetal outcome in terms of Apgar scores, umbilical artery pH and admission to the special care unit. RESULTS: No true sinusoidal FHR patterns were observed, but pseudo-sinusoidal FHR patterns were found in 230 of the 1520 CTGs examined (15%). Of these, 219 were classified as minor (amplitude 5-15 beats/min) and 11 as intermediate (amplitude 16-24 beats/min). Major pseudo-sinusoidal FHR patterns (amplitude greater than 24 beats/min) were not observed. Minor pseudo-sinusoidal FHR patterns had a mean duration of 21 (SD 13) min and typically occurred once or twice early in labour. Using logistic regression analysis a significant, independent relation was demonstrated between the presence of minor pseudo-sinusoidal FHR patterns and the use of pethidine (RR 1.84, 95% CI 1.3 to 2.59, P less than 0.0001) and epidural analgesia (RR 1.85, 95% CI 1.24 to 2.76, P less than 0.001). Intermediate pseudo-sinusoidal FHR patterns were found in association with both in utero fetal sucking and transient episodes of fetal hypoxia such as that caused by periodic umbilical cord compression. CONCLUSION: Pseudo-sinusoidal FHR patterns in labour will usually be associated with a normal fetal outcome but a careful fetal assessment is mandatory.

Blood Gas Monitoring, Transcutaneous↗
PubMed1991

Expression of wild-type p53 is not compatible with continued growth of p53-negative tumor cells.

Inactivation of the cellular p53 gene is a common feature of Friend virus-induced murine erythroleukemia cell lines and may represent a necessary step in the progression of this disease. As well, frequent loss or mutation of p53 alleles in diverse human tumors is consistent with the view of p53 as a tumor suppressor gene. To examine the significance of p53 gene inactivation in tumorigenesis, we have attempted to express transfected wild-type p53 in three p53-negative tumor cell lines: murine DP16-1 Friend erythroleukemia cells, human K562 cells, and SKOV-3 cells. We found that aberrant p53 proteins, which differ from wild-type p53 by a single amino acid substitution, were expressed stably in these cells, whereas wild-type p53 expression was not tolerated. The inability of p53-negative tumor cell lines to support long-term expression of wild-type p53 protein is consistent with the view that p53 is a tumor suppressor gene.

Animals↗