PubMed Health⌕ Search

Biomedical subjects

S M Phillips

Publications and source records attributed to S M Phillips.

At least 73 records · Page 4Linked to original sources

Progressive effect of endurance training on VO2 kinetics at the onset of submaximal exercise.

The rates of increase in O2 uptake (VO2) after step changes in work rate from 25 W to 60% of pretraining peak VO2 (VO2 peak) were measured at various times during an endurance training program (2 h/day at 60% pretraining VO2 peak). Seven untrained males [23 +/- 1 (SE) yr] performed a series of repeated step changes in work rate before training (PRE) and after 4 days (4D), 9 days (9D), and 30 days (30D) of training. VO2 kinetic responses were determined from breath-by-breath data averaged across four repetitions and analyzed using a two-component exponential model. Mean response time (time taken to reach 63% of steady-state VO2) was faster (P < 0.01) than PRE (38.1 +/- 2.6 s) at both 4D (34.9 +/- 2.4 s) and 9D (32.5 +/- 1.8 s) and was faster (P < 0.01) at 30D than at all other times (28.3 +/- 1.0 s). Blood lactate concentrations (after 6 min of cycling) were also lower at 4D and 9D than PRE (P < 0.01) and were lower at 30D than at all other times (P < 0.01). VO2 peak was unchanged from PRE (3.52 +/- 0.20 l/min) at 8D (3.55 +/- 0.20 l/min) but was increased (P < 0.01) at 30D (3.89 +/- 0.18 l/min). Muscle oxidative capacity (maximal citrate synthase activity) was not significantly increased until 30D (P < 0.01). It is concluded that at least part of the acceleration of whole body VO2 kinetics with endurance training is a rapid phenomenon, occurring before changes in VO2 peak and/or muscle oxidative potential.

Adult↗

Loss of the retinoblastoma susceptibility gene (RB1) is a frequent and early event in prostatic tumorigenesis.

Loss of the RB1 gene is an important event in the initiation and progression of many tumours. Prostate tissue from 43 patients with prostate cancers and ten with benign prostatic hypertrophy (BPH) were studied for loss of heterozygosity of the RB1 gene. Four intragenic polymorphic loci were studied with two techniques. These were restriction fragment length polymorphism (RFLP). Southern blotting and hybridisation with the p123m1.8 and p68RS2.0 probes (to introns 1 and 17 respectively) and also the polymerase chain reaction (PCR) to amplify loci within introns 17 and 20. Protein product (pRB) expression was determined by immunohistochemistry using the NCL-RB antibody in nine patients with cancer and four patients with BPH. Loss of heterozygosity was found in 24 out of 40 (60%) informative patients with cancer. Loss of RB1 occurred with a similar frequency in early-stage and low-grade cancers as in more advanced cancers. Loss of RB1 was also found in one patient with BPH. Expression of pRB was completely absent from seven cancers and markedly reduced in the other two, while nuclear pRB staining was always present in areas of BPH, whether alongside cancer-containing tissue or with BPH alone. We conclude that loss of RB1 is an early event in prostatic tumorigenesis.

Base Sequence↗

Loss of heterozygosity of the retinoblastoma and adenomatous polyposis susceptibility gene loci and in chromosomes 10p, 10q and 16q in human prostate cancer.

OBJECTIVE: To examine prostate tumours for losses of known or suspected tumour suppressor genes to determine some of the important events in the genesis of this common cancer. MATERIALS AND METHODS: Paired tumour and blood samples were obtained from 21 patients who underwent transurethral resection of malignant prostate glands for urinary outflow obstruction. Paired tumour and normal tissue (leucocytes) DNA was extracted and examined for possible losses of several known or suspected tumour suppressor genes, using restriction fragment length polymorphism techniques to detect loss of heterozygosity. RESULTS: Deletions of the retinoblastoma susceptibility gene (RB1) locus were found in six of nine informative cases using two intragenic probes (p68RS2.0 and p123m1.8). The locus related to the familial adenomatous polyposis susceptibility (APC) gene demonstrated loss of heterozygosity in three of seven informative cases using the EF5.44 probe. Losses were also noted in loci on chromosome 10p in four of 19 informative cases (probe cTBQ7), chromosome 10q in eight out of 19 informative cases (probes EFD75 and D10S90) and in 16q in three of 17 informative cases (probe D16S7). CONCLUSION: These findings suggest that losses of the RB1 and APC tumour suppressor genes and suspected tumour suppressor genes on 10p, 10q and 16q may be important events in the genesis of prostatic tumours.

Aged↗

Isolated testicular vasculitis mimicking a testicular neoplasm.

A 19 year old man presented with unilateral testicular swelling and pain. An initial diagnosis of epididymo-orchitis was modified to a presumed testicular neoplasm following ultrasonography. The final diagnosis of isolated testicular vasculitis was established following histological examination of the orchidectomy specimen. Staining for antineutrophil cytoplasmic antibodies was negative. Despite immunosuppressive treatment, the patient developed further symptoms affecting the remaining testis one year later. He responded well to an increase in immunosuppressive therapy and has remained asymptomatic 18 months from diagnosis. Symptomatic vasculitis confined to the testis is extremely rare, but must be considered in the differential diagnosis of testicular swelling and may be the presenting feature of a systemic vasculitis such as polyarteritis nodosa. The risk of progression to systemic disease in such cases is unknown. Immunosuppressive therapy must be considered carefully and long term follow up is important.

Adult↗

The regulation of lymphoid function during schistosomiasis: influence of T-cell-derived suppressor molecules on antigen recognition, cellular activation and granuloma formation.

We have previously studied a T-cell derived soluble suppressor factor (TseF) which regulates immunopathology in schistosomiasis. The current studies address the mechanism whereby TseF suppresses the functional immune response in murine schistosomiasis. We assessed three stages of the immune response: (1) initial antigenic recognition using the criteria of antigen-mediated cell division or blast transformation (AMBT); (2) intracellular differentiation utilizing criteria of glutathione (GSH) and ornithine decarboxylase (ODC) production; and (3) efferent function utilizing criteria of in vitro granuloma formation (IVGF). We studied these three criteria of immune reactivity during the course of schistosomiasis. Lymphoid cells from acutely infected animals demonstrated high levels of antigen-mediated cell division and in vitro granuloma formation; ODC and GSH levels were low. Cells obtained from chronically infected animals demonstrated lower antigen-mediated cell division and granuloma formation; however, ODC and GHS levels were much higher, indicating that cells obtained from chronically infected animals are in a non-reactive state of increased activation. TseF strongly increased GSH and ODC levels in lymphocytes obtained from acutely infected animals, and this effect was augmented by the presence of antigen. However, TseF had minimal effects on initial antigenic recognition, and profoundly suppressed the effector function. The relationship between the effects of TseF on antigen recognition and function was regulated at the clonal level. TseF function required the generation of GSH. Since TseF is produced in chronic disease under conditions of decreased immunological reactivity, the alterations of GSH and ODC activity, induced by TseF, may be responsible for the regulation of immunopathology.

Animals↗

The regulation of resistance to Schistosoma mansoni by a soluble alpha/beta TCR analog, produced by a cloned T cell hybridoma.

Immunity to Schistosoma mansoni is regulated by an auto-anti-idiotypic network. The T cells in this network interact through soluble regulatory factors. These studies describe a soluble suppressor-inducer factor (TsiF) derived from TCR+ suppressor-inducer clone Q37. Q37 is the fusion product of CD4+ T cells derived from S. mansoni-infected mice and TCR-, BW1100 thymoma cells. [35S]Methionine biosynthetically labeled TsiF was immunoprecipitated with mAb H57-597 (anti-pan alpha/beta TCR) and adsorbed with protein G-agarose. The eluted 72-kDa TCR analog was reduced with dithiothreitol. Components of 32 and 44 kDa were found on SDS-PAGE. These components were analogous to the alpha and beta chains of the TCR, binding antigen, or expressing V beta determinants, respectively. TsiF suppressed delayed-type hypersensitivity to S. mansoni antigens in a genetically and antigenically restricted manner. TsiF totally abrogated protective immune response against S. mansoni. These soluble TCR analogs may idiotypically regulate the resistance to S. mansoni. Q37 is an appropriate source of a suppressor TCR analog for the molecular analyses of this idiotypic regulation.

Animals↗

The role of ultrasound to detect aortic aneurysms in "urological" patients.

The adoption of ultrasound as a means of imaging the urinary tract instead of the intravenous urogram (IVU) has resulted in an interesting observation. Men undergoing ultrasound examination of the urinary tract are often noted to have an incidental abdominal aortic aneurysm. Screening programmes for such aneurysms are being investigated around the country. We have looked at the prevalence of abdominal aortic aneurysm in male urological patients aged 65-80 years as they pass through the radiology department, in order to have an ultrasound scan of the urinary tract. When the IVU was the standard rate of imaging, few aneurysms were noted. On changing to ultrasound, 3.1% of patients were found to have an aneurysm. This rose to 9.5% when a deliberate policy of imaging the abdominal aorta was included. We suggest it is well worth the minimal extra time and effort to examine the aorta of "urological" patients, as more serious pathology may be detected than that for which the scan was originally ordered.

Aged↗

Solitary fibrous tumour: report of two new locations in the upper respiratory tract.

Solitary fibrous tumours are uncommon spindle cell neoplasms generally associated with serosal surfaces, especially the pleura ('localized fibrous mesothelioma'). Recently, these tumours have been documented in extraserosal sites. We report two solitary fibrous tumours, including one occurring in the paediatric age group, arising in two previously unreported locations, parapharyngeal space and epiglottis. These cases expand the range of sites where this tumour may originate and confirm the tendency of extrapleural cases to involve the upper respiratory tract and adjacent structures.

Adolescent↗

Gender differences in leucine kinetics and nitrogen balance in endurance athletes.

The current Canadian Recommended Nutrient Intake (RNI) for protein (0.86 g.kg-1.day-1) makes no allowance for an effect of habitual physical activity. In addition, Tarnopolsky et al. (J. Appl. Physiol. 68: 302-308, 1990) showed that males may catabolize more protein than females consequent to endurance exercise. We examined nitrogen (N) balance and leucine kinetics during submaximal endurance exercise to determine the adequacy of the current Canadian RNI for protein for male and female endurance athletes. Athletes were matched for equal training volume, competitive status, and conditioning and were fed diets isoenergetic with their habitual intake, containing protein at the Canadian RNI. Subjects were adapted to the diet for 10 days before completing a 3-day measurement of N balance. N balance showed that the RNI was inadequate for females (-15.9 +/- 6.0 mg.kg-1.day-1) and males (-26.3 +/- 11.0 mg.kg-1.day-1). Leucine kinetics during exercise were determined for each subject on day 3 of the N balance experiment by use of a primed continuous infusion of L-[1-13C]leucine and the reciprocal pool model. Exercise resulted in a significant (P < 0.01) increase in leucine oxidation for both groups. Males oxidized a greater amount of leucine during the infusion than females (P < 0.01). Leucine flux also increased significantly (P < 0.01) during exercise in both groups. We conclude that the current Canadian RNI for protein is inadequate for those who chronically engage in endurance exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Transcriptional and posttranscriptional activation of urokinase plasminogen activator gene expression in metastatic tumor cells.

Urokinase plasminogen activator (uPA) is a serine protease which has frequently been implicated in the process of tumor cell invasion and metastasis. The degree of expression and mode(s) of regulation of the uPA gene in metastatic compared with nonmetastatic tumor cells have not yet been addressed. We have cloned and sequenced a full-length rat uPA complementary DNA and utilized Northern blot analysis to report that the uPA gene is expressed at levels 3.5- to 70-fold higher in metastatic cell lines than in nonmetastatic cell lines derived from two independent rat mammary adenocarcinomas. Nuclear run-on assays and RNA half-life estimations indicated that metastatic MAT 13762 rat mammary adenocarcinoma cells expressed 3.5-fold higher levels of uPA RNA than a nonmetastatic derivative (J-clone), due to a combined increase in uPA gene transcription and cytoplasmic RNA stability. By contrast, uPA RNA (and enzyme) levels were elevated by up to 70-fold in metastatic clones of dimethylbenz(a)anthracene-induced rat mammary adenocarcinoma (DMBA-8) due to predominantly posttranscriptional mechanisms. Moreover, treatment of nonmetastatic DMBA-8 cell lines with protein synthesis inhibitors led to an increase in nuclear and cytoplasmic uPA RNA levels, without altering the rate of uPA gene transcription. These results suggest that in addition to gene transcription, posttranscriptional events localized in the nucleus and cytoplasm are key determinants of uPA gene activation in rat mammary adenocarcinomas.

9,10-Dimethyl-1,2-benzanthracene↗

Effects of estrogen on memory function in surgically menopausal women.

The effects of estrogen (E) on memory were assessed in 19 women who required a hysterectomy and bilateral oophorectomy for benign disease. Blood samples were drawn and memory tests were administered before surgery and again after 2 mo of postoperative treatment consisting of either monthly E or placebo (PL) injections. Scores on the immediate and delayed recall of paired-associates stayed at the same level in E-treated women, whereas they decreased significantly pre- to post-operatively in the PL-treated subjects. In the immediate recall of paragraphs, the scores of those given E improved postoperatively compared to baseline; scores remained unchanged in the PL group. No hormonal effects were apparent on the immediate or delayed recall of visual material, delayed recall of paragraphs, or digit span scores. These findings suggest that variations in specific aspects of memory function may occur in surgically menopausal women coincident with changes in plasma estrone and estradiol levels.

Climacteric↗

Variations in memory function and sex steroid hormones across the menstrual cycle.

Memory, mood, and hormone levels were measured in 25 women during the menstrual and luteal phases of their cycles. Significantly lower visual memory (delayed recall) scores were found during the menstrual phase compared to the luteal phase. No phase differences were found on mood measures or on other memory measures including digit span, paired-associate learning, immediate recall of visual material, and immediate or delayed paragraph recall. The visual memory decrease was most prominent in approximately one-half of the sample and was significantly correlated with plasma progesterone in the luteal phase. For all subjects, paragraph recall scores were negatively correlated with free testosterone levels, whereas paired-associate learning was positively correlated with estradiol levels in the luteal phase. These results suggest that changes in memory test performance may be associated with sex steroid levels, particularly in some subgroups of women.

Adolescent↗

Adolescents' knowledge of medical terminology and family health history.

Compared 309 youths ages 11 to 15 years and their parents with respect to their comprehension of terms for seven common medical disorders: heart attack, stroke, atherosclerosis, ulcer, hypertension, diabetes, and cancer. For two thirds of the adolescent sample, accuracy of reporting of these disorders among the parents and grandparents was assessed. Results indicated considerable variation among disorders with respect to both comprehension of terms and accuracy of family health history. Adolescents' age was a major predictor of knowledge of medical terms (r = .41). Age was not related to accuracy of family health information. Consonant with this finding, adolescents' level of accuracy regarding family health history was generally similar to that of previous adult samples, suggesting that family health information is acquired and retained at an early age. Adolescents were more accurate concerning parents' compared with grandparents' history of hypertension.

Adolescent↗

Effects of catecholamines and potassium on cardiovascular performance in the rabbit.

Resting subjects risk cardiac arrest if plasma potassium ([K+]p) is raised rapidly to 7-9 mM, but brief bouts of exhaustive exercise in healthy subjects can give similar [K+]p without causing cardiac problems. We investigated the effects of [K+]p and catecholamines on systolic blood pressure (SBP) and mean aortic flow (MAF) in anesthetized rabbits and on maximum output pressure (MOP) in isolated working rabbit hearts. In six rabbits, hyperkalemia (11.4 +/- 0.4 mM) caused a fall in SBP from 116 +/- 6 to 49 +/- 6 mmHg and in MAF from 373 +/- 30 to 181 +/- 53 ml/min (P < 0.01). Raising [K+]p (11.6 +/- 0.3 mM) with norepinephrine (NE) (1.3 micrograms.kg-1.min-1 iv), however, increased SBP from 108 +/- 7 to 150 +/- 6 mmHg (P < 0.01) and MAF from 347 +/- 42 to 434 +/- 35 ml/min (P < 0.01). In 19 isolated working hearts, perfusion with 8 mM K+ Tyrode and then 12 mM K+ Tyrode reduced MOP from 87 +/- 3 (control 4 mM K+) to 67 +/- 3 (8 mM K+) and 51 +/- 2 cmH2O (12 mM K+) (P < 0.01); 12 mM K+ Tyrode with 0.08 microM NE or epinephrine, however, increased MOP from 67 +/- 6 (in 8 mM K+) to 85 +/- 6 cmH2O (NE) and from 58 +/- 2 to 76 +/- 5 cmH2O (epinephrine) (P < 0.01). Catecholamines may therefore play a key role in protecting the heart from exercise-induced hyperkalemia.

Anesthesia↗

Measuring teaching intensity with the resident-to-average daily census ratio.

This article analyzes a change in the measure of teaching intensity when calculating Medicare's indirect medical education (IME) adjustment: It looks at the potential for replacing, in the denominator of the ratio, beds with the average daily census (ADC). Among the findings are: (1) Hospitals with small teaching programs would benefit from this switch more than hospitals with larger programs because of their generally lower occupancy rates, (2) The adjustment formula currently used for the capital prospective payment system (PPS) would alleviate this effect relative to the adjustment formula used for the operating PPS, (3) Although ADC appears to vary more on average, the weighted average rates of change in the resident-to-ADC ratios for a matched group of teaching hospitals are equal to the rates of change for the resident-to-bed ratios.

Bed Occupancy↗