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Biomedical subjects

P Johnson

Publications and source records attributed to P Johnson.

At least 253 records · Page 14Linked to original sources
PubMed1995

The validation of a new vascular damage assay for photodynamic therapy agents.

The therapeutic effect of photodynamic therapy (PDT: photodynamic sensitizer + light) is partly due to vascular damage. This report describes a new vascular photodamage assay for PDT agents and a validation of the assay. The method described here quantitates changes in tissue blood perfusion based on the relative amount of injected fluorescein dye in treated and untreated tissues. A specially designed fluorometer uses chopped monochromatic light from an argon laser as a source for exciting fluorescein fluorescence. The fluorescent light emitted from the tissue is collected by a six element fiberoptic array, filtered and delivered to a photodiode detector coupled to a phase-locked amplifier for conversion to a voltage signal for recording. This arrangement permits a rather simple, inexpensive construction and allows for the simultaneous use of the argon laser by other investigators. The routine assay for characterizing a specific photosensitizer at a standard dose consists of the sequential allocation of eight mice to a set of different light doses designed to span the dose-response range of fluorescein fluorescence exclusion (measured 8-10 min after fluorescein injection). The assay validation experiment used an anionic photosensitizer, 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a at a dose of 0.4 mumol/kg. The parameter estimates (n = 34 mice) from fitting the standard Hill dose-response model to the data were: median fluorescence exclusion light dose FE50 = 275 +/- 8.3 J/cm2 and Hill sigmoidicity parameter m = -3.66 +/- 0.28. Subsets of the full data set randomly selected to simulate a standard eight mice experiment yielded similar parameter estimates. The new assay provides reliable estimates of PDT vascular damage with a frugal sequential experimental design.

Animals↗
PubMed1995

Environmental effects on thermoregulation and breathing patterns during early postnatal development in hand-reared lambs.

This study examines the effect of hand-rearing developing lambs in a warm (WR; 25 degrees C) or cool (CR; 10-15 degrees C) ambient temperature on the control of thermoregulation and breathing patterns, when maintained at a fixed level of nutrition over the first month of postnatal life. Measurements were made during non-rapid eye movement sleep whilst lambs were maintained for at least 1 h at warm (28-19 degrees C) and cold (14-5 degrees C) ambient temperatures at 1, 7, 14 and 30 days of age. All lambs were able to maintain normal body temperature, but oxygen consumption was higher in CR lambs at 14 and 30 days of age. At 1 day of age shivering was rarely observed in any lambs, but at 7 and 14 days of age more WR than CR lambs responded to cold exposure via shivering. Plasma concentrations of triiodothyronine were higher at 7 and 14 days of age in CR lambs. Breathing frequencies were similar in WR and CR lambs, and from 7 days of age the incidence of expiratory laryngeal braking was higher in warm compared with cold study temperatures. By 30 days of age the recruitment of this mechanism was greater in CR lambs. Mean growth rate was slower over the first week of postnatal life in CR compared with WR lambs. This difference decreased over the first month of life, as growth rate increased from 83 to 130 g day-1 in the CR group but remained constant at approximately 150 g day-1 in the WR lambs. Total weight of the lungs and heart, but not the liver, were lower at 1 month but not at 1 week of postnatal life in CR lambs. It is concluded that a modest decrease in the ambient temperature in which postnatal lambs are reared, when on a fixed feed intake, alters lung size, the recruitment of laryngeal braking and the control of body temperature.

Animals↗
PubMed1995

Complications after radiotherapy and radical hysterectomy in early-stage cervical carcinoma.

OBJECTIVE: To evaluate the overall complications, major as well as minor, in patients treated for early-stage cervical carcinoma as related to treatment parameters. METHODS: In this retrospective study, 167 consecutive patients with early-stage cervical carcinoma treated with preoperative radiotherapy and radical hysterectomy were investigated. Clinical data were collected from the medical files. RESULTS: Transient or permanent complications appeared in up to half of all patients. Seven percent exhibited intraoperative complications and 35% suffered from early postoperative urinary tract problems; most frequently urinary tract infection. After one year, the urinary tract complications dominated; voidance difficulties and incontinence being most common. Gastrointestinal complications occurred in 15% of patients. Lymphedema appeared during the first year in 21% of the patients but several of the mild or moderate cases improved after the first year. The relative risk of lymphedema was increased with shorter duration of surgery, extensive preoperative irradiation to the bladder and after external postoperative irradiation. Some form of late sequelae remained in every fifth patient, and every fourth patient, aged 24-44 years, periodically suffered from vasomotor symptoms despite estrogen replacement therapy. CONCLUSION: The complications after radiotherapy and radical hysterectomy in early stage cervical carcinoma suggest that attempts should be made to evaluate effective treatments designed to minimize risk to the patients.

Adult↗
PubMed1995

Expression of the alternatively spliced EIIIB segment of fibronectin.

Previous descriptions of the expression and distribution of the alternatively spliced EIIIB segment of fibronectin (FN) relied upon an antibody which, on subsequent testing, was shown not to recognize this segment directly. This raises concerns regarding the reliability of all such previous descriptions. In order to prepare reagents directly reactive with this segment, we raised polyclonal antibodies to two different bacterial fusion proteins containing intact EIIIB segments, and to a synthetic 36 amino acid peptide from the center of the EIIIB segment. Antibodies raised to each of these three immunogens recognized fusion proteins containing the EIIIB segment, but failed to recognize full length EIIIB+ FNs produced by mammalian cells, suggesting that oligosaccharide linked to Asn1359 within the EIIIB segment, or potentially to other residues in FN, might interfere with antibody recognition of this segment. Consistent with this hypothesis, N-deglycosylation of recombinant full and partial length EIIIB+ FNs permitted their specific recognition by the anti-fusion protein (but not anti-peptide) antibodies. Using anti-fusion protein antibodies coupled with deglycosylation procedures, we provide a series of new results relevant to the functions of the EIIIB segment: 1) Endogenously synthesized EIIIB+ FN is incorporated into the extracellular matrix of cultured fibroblasts, where it appears by immunofluorescence microscopy and radioimmunoprecipitation analyses to have a distribution very similar to both EIIIA+ forms and the total pool of FNs. 2) No reproducible changes can be shown to occur in the extent of synthesis or matrix incorporation of EIIIB+ FNs upon cellular transformation. 3) Low levels of EIIIB+ FN are normally present in blood plasma and consequently also in purified preparations of plasma FN. 4) EIIIB+ FN is present in blood platelets, where it constitutes a minor fraction of total platelet FN, yet is greater than 4-fold enriched relative to plasma FN. 5) EIIIB+ FN is synthesized by first passage cultured endothelial cells, suggesting that the endothelium could constitute a source for this FN isoform in the circulating blood. The antibodies and methods used in this study constitute the first direct assays of EIIIB+ FN protein expression and are applicable to a variety of species.

Adult↗
PubMed1995

Performance characteristics for the quantitation of plasma HIV-1 RNA using branched DNA signal amplification technology.

Highly sensitive assays that quantitate human immunodeficiency virus type 1 (HIV-1) RNA may be valuable for clinical research and the treatment of HIV-1-infected patients. In this study we evaluated the reproducibility and accuracy of the first-generation branched DNA (bDNA-1.0) signal amplification assay under conditions that are relevant to routine use in a clinical context. We show that the bDNA-1.0 assay was able to discern two- to three-fold changes in plasma HIV-1 RNA levels as significant. Reverse transcription coupled to polymerase chain reaction (RT-PCR) was less reproducible and required a 3.7- to 5.8-fold change in plasma HIV-1 RNA levels to be statistically significant. The accuracy of the bDNA-1.0 assay in RNA quantitation was not affected by HIV-1 genotypic variation or by the presence of hemoglobin, bilirubin, lipemia, or any of a dozen therapeutic drugs. Using the bDNA-1.0 assay, we show that HIV-1 RNA levels in plasma specimens were stable when stored at -80 degrees C and were able to withstand at least three freeze-thaw cycles without significant loss. We also examined the performance of an ultrasensitive bDNA assay with improvements to the signal amplification technology. The ultrasensitive bDNA assay displayed a quantitation limit of approximately 500 RNA Eq/ml, yet maintained a dynamic quantitation range up to 1.6 x 10(6) RNA Eq/ml. Like the bDNA-1.0 assay, the ultrasensitive bDNA assay was not affected by HIV-1 genotype variability.

Anticoagulants↗
PubMed1994

Protein tyrosine phosphorylation in Mycobacterium tuberculosis.

Crude cell extracts from three strains of Mycobacterium tuberculosis were analyzed for the presence of proteins possessing phosphorylated tyrosine residues. A protein migrating at approximately 55 kDa was detected using an antiphosphotyrosine monoclonal antibody. In addition, less predominant bands were observed between 50 kDa and 60 kDa. That M. tuberculosis contains specific tyrosine phosphorylated proteins implies that M. tuberculosis has tyrosine kinase activity. Examination of other, non-pathogenic mycobacterium species yielded no major antiphosphotyrosine reactive proteins. This suggests that the antiphosphotyrosine reactive protein is specific to M. tuberculosis strains. These results provide evidence that M. tuberculosis contains an antiphosphotyrosine reactive protein.

Antibodies, Monoclonal↗
PubMed1994

A method for filtering respiratory oscillations.

We present a method based on dynamical systems theory which can be used to filter time series in a way which is superior to classical Fourier decomposition. This method is applied to three data-sets, taken from respiratory measurements of two children in quiet and REM sleep. Our purpose is to filter the several different oscillatory mechanisms which operate, in order to provide clearer signals on which further analysis and diagnosis can be based.

Humans↗
PubMed1994

Infant care practices and the investigation of physiological mechanisms.

It is strange that some aspects of infant care have been strongly promoted by modern medicine while others have been neglected. Thus prone sleeping which has been strongly promoted is now related to an increase in SIDS, whereas the promotion of breast feeding in developed countries has been less successful. Unfortunately there has not been sufficient physiological investigation of many infant care practices and some of the proposed mechanisms for SIDS and prone sleeping have not been substantiated. Thus further work is needed on hypercapnia, hypothermia and periodic breathing and respiratory control. Studying infants alone may leave out important physiological mechanisms such as the effect on body warmth when the infant is close to the mother. More investigation is needed of antenatal factors related to SIDS and it is critically important that physiological investigation should not look for single mechanisms but be concerned with the interaction of many physiological factors.

Growth↗
PubMed1994

Spying on mothers.

Explore the source record for details and available documents.

Airway Obstruction↗
PubMed1994

Specific CD45 isoforms differentially regulate T cell receptor signaling.

Multiple isoforms of T cell CD45 tyrosine phosphatase are expressed as a result of alternative RNA splicing among extracellular exons. To discern the presence and identity of distinct functions among CD45 isoforms, we compared thymic T cell activation responses by elevating expression of two CD45 isoforms normally found on quiescent T cells. We report that CD45RABC significantly increased CD4+ thymic T cell proliferation in both a mixed lymphocyte reaction and following anti-T cell receptor (TCR) antibody stimulation. Additionally, CD45RABC enhanced Ca2+ mobilization and phosphotyrosine accumulation, and suppressed the inhibitory effect of anti-CD4 antibodies. By contrast, CD45R0 did not enhance TCR signaling or phosphotyrosine levels in CD4+ thymic T cells and required a TCR co-stimulus to augment cellular proliferation. These studies provide genetic evidence that alternative CD45 isoforms are functionally distinct and disclose a unique mechanism by which T cell immunologic responsiveness can be modified.

Animals↗
PubMed1994

Human exposure to magnetic fields: a comparative assessment of two dosimeters.

Two types of dosimeters for measuring human exposure to 60 Hz magnetic fields were compared. Fifty adults wore the single-axis, wrist model AMEX (average magnetic field exposure system) and the triple axis, hip-pocket or pouch model AMEX-3D meters for 2 days. Ninety-six percent of the tests were accomplished without apparent dosimeter failure. The average root mean square magnetic flux density measurements with the AMEX-3D (mean = 0.10 microT, S.D. = 0.07, range = 0.03-0.31) were significantly higher than with the AMEX meter (mean = 0.07 microT, S.D. 0.05, range = 0.02-0.27 microT) (t test, P < 0.01). There was substantial correlation between the AMEX and the AMEX-3D measurements (Pearson's correlation coefficient = 0.65, P < 0.01) but poor concordance (Intraclass correlation coefficient = -0.25). These results suggest that there is a wide variation in exposure to extremely low frequency magnetic fields in the population. Magnetic field measurements with the AMEX-3D are nearly always higher than with the AMEX dosimeters. Caution is advised when comparing magnetic field measurements made with different types of dosimeters.

Adult↗
PubMed1994

Community prevalence of hepatitis C viraemia: a polymerase chain reaction study.

In order to estimate the prevalence of HCV carriage in an inner city health district, we undertook a polymerase chain reaction (PCR) based survey of sera collected from 1,0002 patients attending general practitioners for reasons unrelated to liver disease. The series comprised 305 sample selected sera patients sample from sera 995 patients previously screened by C100 antigen-based anti-HCV tests. Overall, 7 patients were positive for HCV RNA. Four cases had anti-C100 antibodies to HCV, 2 were strictly negative but had high-normal/borderline optical densities by ELISA assay, while one was completely anti-HCV negative. All but one had normal liver function tests. Only 3/7 PCR positive cases had any serum marker for hepatitis B (HBV) exposure (2 HBsAg positive, 1 IgM anti-HBc positive). The minimum point prevalence of HCV carriage in this community is 0.7%, approximating the HBsAg carriage in the same population (1%). HCV carriage in this inner city population is considerably higher than would be predicted by blood donor surveys. A positive anti-HCV anti-body (anti-C100) test is poorly predictive (approximately 10%) of HCV RNA carriage in a general practice based population in which measurement of "surrogate" (HBV related) HCV markers would have detected only 3/7 cases of presumed chronic HCV carriage.

Adult↗
PubMed1994

Prognostic factors and relapse patterns in early-stage cervical carcinoma after brachytherapy and radical hysterectomy.

Patients with cervical carcinoma FIGO stage IB and IIA (n = 167) treated with brachytherapy, radical hysterectomy, and pelvic lymphadenectomy at the University Hospital of Uppsala were evaluated, and a multivariate analysis was performed to reveal clinical and histopathological variables of predictive value of recurrence. The 5-year survival rate was 90%. Nineteen patients developed recurrent disease (11%), 15 of whom died. Patient age, clinical stage, type, and histologic grade of tumor did not indicate an increased risk of recurrence. However, multiparity (3 children or more; relative risk, RR = 4.6), lymph node metastases (RR = 6.4), tumor size (RR = 5.1), and residual carcinoma in the hysterectomy specimen (RR = 3.4) were important predictive indicators of recurrence. The median interval from initial treatment to the diagnosis of recurrence was 15 months. The majority of recurrences occurred during the first 2 years after treatment (74%) and most of them had symptoms (84%). Only three patients with recurrence were diagnosed within our surveillance program. The data suggest that surveillance for recurrence can be made more cost efficient with a more individualized follow-up during the first 2 years after treatment, concentrating on the patients with high-risk factors such as large tumors, residual carcinoma after irradiation therapy, and/or lymph node metastases.

Adult↗