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Biomedical subjects

S A Spencer

Publications and source records attributed to S A Spencer.

At least 19 recordsLinked to original sources
PubMed1992

GAP-43, a protein associated with axon growth, is phosphorylated at three sites in cultured neurons and rat brain.

GAP-43 is a neuronal calmodulin-binding phosphoprotein that is concentrated in growth cones and presynaptic terminals. By sequencing tryptic and endoproteinase Asp-N phosphopeptides and directly determining the release of radioactive phosphate, we have identified three sites (serines 41 and 96 and threonine 172) that are phosphorylated, both in cultured neurons and in neonatal rat brain. These three sites account for most of the 32PO4 that was incorporated into GAP-43 in cultured neurons; 8-15% of each site was occupied with phosphate in GAP-43 isolated from neonatal rat brain. Phosphorylation of serine 41 in cultured neurons was stimulated by phorbol ester, indicating that it is the only site phosphorylated by protein kinase C. The resemblance of the sequence surrounding the other two sites suggests that they may be substrates for the same protein kinase. None of the sites phosphorylated by casein kinase II in vitro was phosphorylated in living cells or in neonatal rat brain. These results show that GAP-43 is a substrate for at least one protein kinase in addition to protein kinase C in living cells and brain.

Amino Acid Sequence↗
PubMed1992

Treatment of recurrent head and neck cancer with 5-fluorouracil, hydroxyurea, and reirradiation.

Head and neck cancer locally recurrent after previous irradiation and surgery presents a difficult management problem. Conventional treatment alternatives include chemotherapy, reirradiation with interstitial implant, and hyperthermia. Reirradiation with external beam is generally not considered because of previous high radiation dose and limited tissue tolerance. In this study, 21 patients with recurrent and previously irradiated head and neck cancer were treated in a Phase I-II fashion. Patients received 5 days of 5-fluorouracil, 300 mg/m2/day IV bolus, Hydroxyurea 1.5 or 2 g/day by mouth and external beam radiation therapy every 2 weeks for up to four courses. Of 20 evaluable patients, 9 have attained a complete response (CR) and 6 a partial response (PR). Fifteen patients completed all planned therapy, eight on time, seven patients with delays. With a median follow-up of 7 months, 13 patients are alive, 7 disease-free (3 after salvage surgery) and 6 with recurrence. Eight patients have died. The 1-year survival is 56%. Treatment toxicity was mainly neutropenia. No major early or late radiation related side effects have been observed at a median follow-up of 7 months. Neither previous radiation dose, time since first radiation, prior chemotherapy, or site of recurrence was predictive of response or treatment tolerance. Patients with a performance status of at least 80 had a significant higher CR rate, with 7/10 patients in this group, as compared to 2/10 patients in patients with a performance status less than 80, achieving a CR. Reirradiation with 5-fluorouracil and hydroxyurea is a well tolerated outpatient treatment program for patients with recurrent and previous irradiated head and neck cancer that produces a high response rate and can provide significant palliation of symptoms.

Adult↗
PubMed1992

Two different low birth weight formulae compared.

The performance of two different, commercially available, low birth weight formulae feeds was compared in preterm infants. The aim of the study was to determine the effect of compositional differences on tolerance, stool frequency and consistency, fat balance and weight gain. Inborn infants with birth weight less than 1500 g were randomised at birth to receive Prematil or Osterprem. Thirty infants received more than 900 ml/kg per week of designated formula alone during a total of 70 weeks of study. Three day fat balance was performed on 23 infants. Osterprem contains 40% more fat than Prematil. The composition of this fat is different in that Osterprem contains no medium chain triglycerides (MCT) compared to 30% in Prematil. Clinical evaluation demonstrated that Osterprem is associated with a significantly higher mean energy intake compared to Prematil (3442 and 3127 kJ/kg per week) but mean weight gain is not significantly different (123 and 112 g/kg per week). Mean stool frequency is higher on Osterprem (20.5 and 14.5 stool/week) and the consistency of stools firmer. This is attributable to a higher mean fat output (2.3 and 0.9 g/kg per day) secondary to the higher fat content of the feed and lower mean absorption (71.6 and 83.5%). Both feeds are well tolerated. The study also confirms that absorption of unsaturated fatty acids is inversely proportional to chain length.

Dietary Fats↗
PubMed1992

A phase I study of high-dose cisplatin, prolonged infusion 5-fluorouracil, and concomitant conventional fraction radiation therapy in patients with inoperable squamous cell carcinoma of the head and neck.

Cisplatin (CDDP) and 5-fluorouracil (5-FU) have been used alone, in combination, and in various doses and sequences with radiation therapy in attempts to improve local control and survival of patients with advanced head and neck cancer. This study was undertaken to determine the toxicity and maximum tolerated dose of high-dose CDDP plus prolonged infusion 5-FU with concomitant conventional radiation therapy. Twenty-two patients with inoperable Stage III and IV squamous cell cancer were treated with CDDP (30 or 35 mg/m2 for 5 days every 4 weeks for three courses) and 5-FU (200 or 300 mg/m2 per day continuous i.v. infusion for 12 weeks) with concomitant conventional radiation therapy. This aggressive treatment regimen is accompanied by severe mucositis, myelosuppression, and chronic neuropathy. CDDP, 35 mg/m2/day x 5, and 200 mg/m2/day of 5-FU infused over 12 weeks were identified as potential doses for future Phase II studies.

Adult↗
PubMed1992

Effect of post-delivery care on neonatal body temperature.

A prospective observational study of post-delivery care and neonatal body temperature, carried out at Kathmandu Maternity Hospital, was followed by a randomized controlled intervention study using three simple methods for maintaining body temperature. There were 500 infants in the initial observation study and 300 in the intervention study. In the observation study, 85% (420/495) of infants had temperatures < 36 degrees C at 2 h and nearly 50% (198/405) had temperatures < 36 degrees C at 24 h (14% were < 35 degrees C). Most of the infants who were cold at 24 h had initially become cold at the time of delivery (only seven infants had been both well dried and wrapped). In the intervention study, all infants were dried and wrapped before random assignment to one of the three methods: the "kangaroo" method, the traditional "oil massage" or a "plastic swaddler". All three were found to be equally effective. Overall, 38% (114/298) of the infants had temperatures < 36 degrees C at 2 h and 18% (41/231) at 24 h (when none was < 35 degrees C).

Body Temperature↗
PubMed1992

Cyclical fluctuations in cerebral blood volume.

Cyclical fluctuations of cerebral blood flow velocity have been reported previously using Doppler ultrasound. The same phenomena was detected during investigations of changes in cerebral blood volume using near infrared spectroscopy. Rhythmic fluctuations of cerebral blood volume at a frequency of 3.5 cycles/minute is reported here.

Blood Volume↗
PubMed1992

Plethysmographic validation of near infrared spectroscopic monitoring of cerebral blood volume.

The validation of measurement of cerebral blood volume (CBV) and cerebral blood flow (CBF) using near infrared spectroscopy (NIRS) against jugular venous occlusion plethysmography is described. Repeated measurements in six infants were made using both techniques simultaneously. A close relationship between the two measurements of change in CBV was obtained in five infants. There was also a close relationship for measurement of CBF in four infants. This study confirms the possibility of using NIRS to monitor CBV continuously in the premature infant. This parameter may prove to be of greater clinical value than the intermittent measurement of CBF.

Blood Flow Velocity↗
PubMed1991

Immunohistochemical localization of GAP-43 in rat and human sympathetic nervous system--effects of aging and diabetes.

The neuronal 43 kDa growth associated peptide (GAP-43) is expressed in conditions of embryonic growth, axonal regeneration, and, to a limited degree, within the central nervous system as an indicator of synaptic plasticity. Although much is known about the expression of GAP-43 in cultured sympathetic neurons, information concerning the existence, immunolocalization and response of GAP-43 to experimental injury is not available for intact sympathetic ganglia in vivo. In this study we have characterized the in situ distribution and identity of GAP-43 in adult rat and human prevertebral and paravertebral sympathetic ganglia using immunohistochemical and biochemical methods. Antisera to GAP-43 intensely labeled intraganglionic presynaptic axons and synapses terminating on neurons of normal adult rat and human sympathetic ganglia in situ. There was minimal GAP-43 immunoreactivity of principal sympathetic neuron perikarya, proximal dendrites and initial axonal segments. The immunohistologic appearance of GAP-43 was unchanged in the ganglia of aged and diabetic rats and elderly humans, conditions in which presynaptic terminal axons and synapses show evidence of chronic degeneration, regeneration and neuroaxonal dystrophy, an unusual ultrastructural alteration which may represent disordered synaptic plasticity. Radioimmunoassay of ganglionic GAP-43 is comparable in young adult, aged and diabetic rat prevertebral or paravertebral sympathetic ganglia. Double immunolocalization of NPY (which labeled markedly swollen dystrophic axons) and GAP-43 in human sympathetic ganglia using a sequential immunogold-silver/fluorescence technique demonstrated that typical dystrophic axons contain little GAP-43.

Aged↗
PubMed1991

Effect of light on endogenous ligands carried by interphotoreceptor retinoid-binding protein.

Interphotoreceptor retinoid-binding protein (IRBP) is a vitamin A carrier present only in the extracellular material lying between the neural retina and the retinal pigment epithelium of vertebrate eyes. The amount of retinol bound endogenously by IRBP in this interphotoreceptor space is known to increase upon illumination. This finding led to the hypothesis that IRBP may act as a shuttle for vitamin A during the visual cycle that regenerates rhodopsin. In the present work, we separated IRBP from other retinoid-binding proteins in bovine interphotoreceptor matrix preparations by means of size-exclusion chromatography. IRBP's endogenous ligands were retained during this procedure and were then extracted into hexane and analysed by normal-phase HPCL. We found that IRBP carries, in a light-dependent manner, all the retinoid isomers involved in the visual cycle. For dark-adapted eyes the amounts of bound ligands are (in nmol per eye) 0.09 all-trans retinol, 0.11 11-cis retinol, 0.04 all-trans retinal, 0.16 11-cis retinal, and 0.07 retinyl esters. For light-adapted eyes the amount of all-trans retinol was found to increase by a factor of five, and that of 11-cis retinal to decrease by a factor of four. (These eyes contain 3.1 nmol of IRBP, which does not change in amount with lighting conditions). Thus, the major endogenous ligand of IRBP is 11-cis retinaldehyde in the dark and all-trans retinol in the light. The data are consistent with a role for IRBP as a non-selective scavenger and stabilizer of retinoids released from photoreceptors and pigment epithelial cells. However, it cannot be concluded from these data that IRBP is involved in directed transport of retinoids across the interphotoreceptor matrix, since there is no evidence for the appropriate spatial gradients in the ligands bound to the protein.

Adaptation, Ocular↗
PubMed1991

A phase I study of prolonged infusion 5-fluorouracil and concomitant radiation therapy in patients with squamous cell cancer of the head and neck.

The radiosensitization properties of 5-FU are well documented, and clinical trials have suggested improved local control and survival in head and neck cancer. Clinical trials to date have used bolus injection or short term (less than or equal to 5 days) 5-FU infusions. To determine the maximum tolerated dose (MTD) of 5-FU given as continuous intravenous infusion for 12 weeks concomitant with conventional radiation therapy, 18 patients with advanced inoperable head and neck cancers were treated with conventional irradiation and 100, 200, 250, or 300 mg/m2/day of 5-FU. A dose of 250 mg/m2/day was determined to be the maximum tolerated dose and is recommended for Phase II studies.

Adult↗
PubMed1991

Critical appraisal and further development of the methodology for open circuit calorimetry in neonates.

A non-invasive technique for open circuit calorimetry based on a Vickers 79 incubator as the gas collection chamber was developed and evaluated. The technique, which involved drawing air from the incubator hood at 11 1/min for gas analysis, did not have a significant cooling effect on the infant and the noise levels within the incubator did not exceed current safety standards. A new technique for checking the calibration of the whole system was developed as the traditional alcohol burn method proved unsatisfactory. Either pure oxygen or carbon dioxide were fed into the incubator hood at controlled physiological rates using a calibrated throttling valve. Over a number of calibration checks the mean error of the system proved to be +/- 4.3% for oxygen and +/- 4.45% for carbon dioxide. Less than a fifth of this error was attributable to the pump and flow meter. When oxygen is introduced to the system at a constant physiological rate it takes 30 min for a plateau to be reached. Therefore it is recommended that this system is used when readings are to be taken in a steady state situation or data is to be cumulated over a long period of time such as in an energy balance study. A run in period of 30 min before collecting data is essential. It is recommended that a calibration check is performed before each study.

Acoustics↗
PubMed1991

Effects of hypoxaemia and bradycardia on neonatal cerebral haemodynamics.

Near infrared spectroscopy has been used to assess the effects of bradycardia and hypoxia on the cerebral circulation in the premature neonate. The technique is well tolerated and can be applied in almost any infant. Continuous monitoring of changes in cerebral oxygenated, deoxygenated, and total haemoglobin is possible. Total haemoglobin is analogous to cerebral blood volume; thus information on circulatory changes as well as oxygenation state can be obtained. Twenty five babies had cerebral monitoring carried out using this technique. During episodes of hypoxia, both spontaneous and induced, impairment of haemoglobin oxygenation within the brain was detected together with an overall increase in the total mean haemoglobin concentration, which was 0.8 x 10(-2) mmol/l. Bradycardia with apnoea also led to impairment of cerebral oxygenation, and to a rapid fall in the concentration of total mean haemoglobin to 1.4 x 10(-2) mmol/l, which was followed in some cases by an increase to above the resting value on recovery of the heart rate to a mean of 0.7 x 10(-2) mmol/l. These disturbances to total haemoglobin concentration represent abnormalities of cerebral blood volume that may be implicated in the pathogenesis of neonatal cerebral injury.

Bradycardia↗
PubMed1991

Three-port perineal sparing technique.

The records were reviewed of 103 patients with low-lying pelvic malignancies irradiated with a skin-sparing technique involving use of a pair of anteroposterior-posteroanterior opposed ports and a direct perineal port. Patients had rectal, anal, cervical, vaginal, urethral, or vulvar cancer. Use of a special lead compensator allowed the three beams to be applied perpendicularly to the surface, while delivery of a homogeneous dose to the pelvis and perineum was maintained. Skin dose with this method was greatly reduced compared with that delivered with simple opposing or four-port techniques, in which irradiation is tangential to the surface at the perineum. Acute perineal skin irritation was assigned a grade between 0 and 3, with grade 0 representing the least amount of irritation. All patients were in the grade 0 or grade 1 category. Patients treated for low-lying rectal carcinoma showed no increase in perineal recurrences when compared with historic control subjects. Use of this approach allowed delivery of adequate doses to the pelvis and perineum and a definite decrease in local toxic effects, and local control was not compromised.

Adenocarcinoma↗
PubMed1991

Pharmacokinetics, immune response, and biodistribution of iodine-131-labeled chimeric mouse/human IgG1,k 17-1A monoclonal antibody.

Pharmacokinetics, immunogenicity, and biodistribution of a 131I-labeled mouse/human chimeric monoclonal antibody (C-17-1A) was studied in six metastatic colon cancer patients. Pharmacokinetics obtained from serum radioactivity or chimera concentration were identical after 5 mCi of 131I-C-17-1A with mean alpha half-lives of 17.6 +/- 2.3 and 19.7 +/- 2.9 and mean beta half-lives of 100.9 +/- 16.1 and 106.4 +/- 14.1 hr, respectively. HPLC analysis documented the monomeric chimeric 17-1A without evidence of immune complexes or free 131I. None of the patients developed antibody after 131I-chimeric 17-1A exposure. Radiolocalization occurred in known areas of disease greater than 4 cm in all patients. The half-life of total-body radioactivity was 58 +/- 7 hr by whole-body counts and 64 +/- 13 hr by urine measurements. Whole-body and bone marrow dose estimates ranged from 0.75-1.03 and 0.76-1.05 rad/mCi, respectively. These studies confirm the prolonged circulation and reduced immunogenicity of chimeric 17-1A versus murine 17-1A. Marrow radiation exposure using antibodies with prolonged circulation is a critical factor in planning for radioimmunotherapeutic applications.

Adenocarcinoma↗
PubMed1990

The non-invasive monitoring of cerebral tissue oxygenation.

The instrument drift was found to be less than 0.004 OD/hour and from measurements on glass filters of 8 optical density units, a coefficient of variation of 0.01 over the 30 second averaging time was observed. The instrument is sufficiently sensitive to enable monitoring of changes in the cerebral oxygen saturation level of haemoglobin and to enable changes in the concentration of cyt aa3 (oxidised form), to be measured with reasonable confidence. It is of the utmost importance in NIRS investigations to be certain of the specificity of the technique, and it is vital that reliable determinations of the amount of cytochrome aa3 in brain are made in addition to measurements of the extinction coefficients. This is still a matter of considerable debate, not only in the isolation and properties of the multisubunit structured membrane bound protein, which many enzymologists have been investigating for the last 50 years, (Keilin and Hartree, 1939; Brunori et al, 1981) but also in relating to in-vivo versus in vitro comparisons. An additional point for consideration is the validity of employing multiplier coefficients derived from the rat brain, as several groups have done (Wyatt et al 1986, Ferrari et al 1985,) and applying them to the human brain and to the infant brain. There may be significant differences in the activity of the enzyme, and the profound physiological effects which will arise during the end point fluorocarbon studies: the presence of fetal haemoglobin must also be considered (Carta et al., 1987). The clinical determination of the optical path length is a considerable problem (Cope etal., 1988,) and once again estimates of the pathlength correction factor made in animals and dead fetuses may not be valid for living human tissue. Results from our animal studies indicate that NIRS can be used to monitor changes in the oxygenation level of Hb and, in extreme hypoxia, changes in the level of the redox state of cyt aa3 can be reliably measured and are well within the sensitivity of the instrument. The results indicate that under small change in saturation the redox state of cyt aa3 appears to be unaltered. It may be that under normal physiological conditions the redox state of aa3 appears to be apparently unchanged under episodes of mild hypoxia of short duration.

Algorithms↗
PubMed1990

Purification and partial sequence of the rabbit mammary gland prolactin receptor.

1. The prolactin receptor from rabbit mammary gland was purified to near homogeneity using a novel hydrophobic interaction chromatographic procedure. 2. Part sequencing (101 residues) revealed 34% identity with the rabbit liver growth hormone receptor, providing support for the existence of a new class of transmembrane receptors regulating growth and lactation.

Amino Acid Sequence↗