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Biomedical subjects

I Morris

Publications and source records attributed to I Morris.

At least 19 recordsLinked to original sources
PubMed2000

Transcriptional targeting to anterior pituitary lactotrophic cells using recombinant adenovirus vectors in vitro and in vivo in normal and estrogen/sulpiride-induced hyperplastic anterior pituitaries.

The use of pituitary cell type-specific promoters is a powerful molecular tool to achieve pituitary cell type-specific transcriptional targeting of transgenes encoded by viral vectors. It has recently been proposed that transcriptional targeting of therapeutic genes could be harnessed as a gene therapy strategy for the treatment of pituitary disease. We describe the successful use of the human PRL promoter (hPrl) encoded within recombinant adenovirus vectors to target transgene expression of Herpes Simplex Virus Type 1-Thymidine Kinase (HSV1-TK) or beta-galactosidase to lactotrophic cells in vitro and in vivo. Functionally, the restriction of expression of HSV1-TK to lactotrophic tumor cells, using the hPrl promoter, resulted in the cell type-specific induction of apoptosis in the lactotrophic GH3 tumor cell line, in the presence of ganciclovir (GCV). In the corticotrophic AtT20 cell line, we detected neither HSV1-TK expression, nor apoptosis in the presence of GCV. The hPrl promoter encoded within a recombinant adenoviral vector also restricted transgene expression to lactotrophic cells in primary anterior pituitary (AP) cultures, and importantly, within the anterior pituitary gland in vivo. When the HSV1-TK driven by hPrl promoter was used in an in vivo model ofestrogen/sulpiride lactotroph induced hyperplasia within the AP in situ, the treatment was not effective in either reducing the weight of the gland, the number of lactotrophic cells within the transduced area in vivo, or the circulating PRL levels. This is in contrast to the human cytomegalovirus promoter (hCMV) driving expression of HSV1-TK in the same experimental paradigm, which was effective in reducing pituitary weight and circulating PRL levels. Our results have important implications in the design of gene therapy strategies for pituitary tumors. We demonstrate that both the choice of the in vivo animal model, i.e. adenoma in the AP gland in situ, and the particular gene therapy strategy chosen, i.e. use of strong ubiquitous promoters vs. weaker but cell type-specific promoters, determine the experimental therapeutic outcome.

Adenoviridae↗
PubMed1999

Differences in functional magnetic resonance imaging of sensorimotor cortex during static and dynamic finger flexion.

Functional magnetic resonance imaging (fMRI) studies of the human motor system have commonly used movement paradigms which contain a dynamic component; however, the relationship between the fMRI signal for motor tasks with and without a dynamic component is not known. We have investigated the relationship between the fMRI signal during a static finger flexion task and during dynamic finger flexion at 1-3 Hz, each at two levels of force (5% and 10% of maximum voluntary contraction). A small fMRI response could be recorded from only a few subjects during the static tasks. In contrast, a substantial fMRI response occurred during dynamic tasks in all subjects at both levels of force. The fMRI response was not significantly correlated with force or movement rate during the dynamic tasks. It is concluded that the factors responsible for generating an fMRI response are fundamentally different during steady contractions compared to those involving a dynamic component, and that the fMRI signal may be more sensitive to changes in the pattern of neural activation rather than the ongoing firing rate or extent of activation.

Adult↗
PubMed1999

Communications between staff and adults with intellectual disabilities in naturally occurring settings.

Videotapes were made of 43 staff-client dyads in small-scale residential and day service settings. Frequency counts were made of carers' communicative acts, and two experienced speech and language therapists rated these for appropriateness. Recommendations for enhancing communication were also noted. The results showed that clients were presented with few opportunities to engage as equal partners in the conversational interchanges: staff overly relied on verbal acts, even when they were communicating with predominantly non-verbal clients; they tended to favour the use of directives and questions, and the majority of staff failed to adjust their language to the client's level of understanding. The most commonly recommended changes for staff were to use simpler sentences and words, to increase their use of non-verbal signals and open questions, to provide more opportunities for clients to initiate topics, and to increase their responsiveness to client's non-verbal signals. The explanations for staff behaviour are reviewed and the implications for changing practice are discussed.

Adolescent↗
PubMed1998

DNA damage in human and mouse spermatozoa after in vitro-irradiation assessed by the comet assay.

The comet assay is widely employed as a method to measure DNA damage in a wide variety of cell types following genotoxic insult. We have used this method in order to characterise DNA damage in spermatozoa following in vitro irradiation with 137Cs gamma rays. In contrast to somatic cells, the DNA of mammalian spermatozoa is bound by protamine molecules allowing a sixfold more highly compact structure and thus rendering conventional cell lysis protocols ineffective. Therefore, this new method uses an extensive lysis step to ensure effective removal of DNA-associated proteins allowing DNA damage to be scored reproducibly in both murine and human spermatozoa. Mouse spermatozoa collected from the vas deferens at post-mortem or human spermatozoa provided by donors were irradiated with doses of gamma-rays from 0-100 Gy using a 137Cs source and then processed for both alkaline and neutral comet assays. Under neutral electrophoresis conditions, which permits the measurement of double-stranded DNA breaks, a linear increase in the amount of DNA damage measured was observed with increasing radiation dose for both murine and human spermatozoa. Similarly, using alkaline electrophoresis conditions to examine DNA single-strand breaks and alkali-labile sites, a linear relationship was also observed for murine sperm but in contrast no such relationship was apparent for human spermatozoa subjected to the same radiation treatments. Interestingly, unirradiated sperm (both human and mouse) showed extensive DNA migration from the nucleus after alkaline assay. Since it is unlikely that the DNA of normal spermatozoa contains high numbers of single-strand breaks and damage was not detected for unirradiated sperm in the neutral assay, it is more likely that this DNA migration is due to the presence of high numbers of alkali labile sites within sperm DNA and that these may be related to the highly condensed structure of spermatozoal DNA. The large radiation doses used in these experiments to produce measurable amounts of DNA damage reflects the high radioresistance of spermatozoa compared to somatic cells and this may also be related to the differences in DNA packaging and conformation. In conclusion, this work shows that the comet assay represents a new method for examining DNA damage in spermatozoa and should be evaluated for use in reproductive toxicity testing.

Animals↗
PubMed1998

Isometric force-related activity in sensorimotor cortex measured with functional MRI.

Isometric force-related functional magnetic resonance imaging (fMRI) signals from primary sensorimotor cortex were investigated by imaging during a sustained finger flexion task at a number of force levels related to maximum voluntary contraction. With increasing levels of force, there was an increase in the extent along the central sulcus from which a fMRI signal could be detected and an increase in the summed signal across voxels, but these parameters were related in such a way that the signal from each voxel was similar for each level of force. The results suggest that increased neuronal firing and recruitment of corticomotor cells associated with increased voluntary isometric effort are reflected in an expansion of a relatively constant fMRI signal over a greater volume of cortex, rather than an increase in the magnitude of the response in a particular circumscribed region, possibly due to perfusion of an increase in oxygen-enriched blood over a wider region of the cortex.

Adult↗
PubMed1997

Physical and sexual abuse of children in the West Midlands.

OBJECTIVE: To describe the convicted and cautioned abusers and the nature of the physical and sexual abuse of children using a legal classification in an attempt to formulate operational criteria for future comparative studies. DESIGN: A retrospective sequential survey of all cautioned and convicted physical and sexual abusers between the January 1, 1988 and June 30, 1994. SETTING: The West Midlands police jurisdiction. SUBJECTS: 1,113 abused children and 964 abusers. RESULTS: The majority of all abuse involved a single child. Many abusers lived in the same household and were in a position of trust or quasi-trust. When strangers committed abuse, the majority of abuse was sexual. A third of the abusers were unemployed. Multiple abuse tended to be sexual and was perpetrated by men. The physical abuse of young children tended to be committed by younger women. No women over the age of 40 had sexually abused a child. Of the children under 12 months, 1.5% had been sexually abused and 8.5% had been physically abused. The greater proportion of physical abuse had occurred in children under 9 years of age whereas sexual abuse was perpetrated more often in girls aged 9 to 11 years. No girls were murdered in this survey. Significantly more boys had been buggered. CONCLUSION: This preliminary study is representative of all the cautioned and convicted cases within the selected 5-year period and obtained from a source of material hitherto unavailable. Many of the findings of this preliminary study are in line with previous studies. Substantial descriptive information has been obtained on a selected population of cautioned or convicted abusers. Further studies may indicate that the cautioned and convicted are more representative of abusers generally than previously thought. Expanded studies may eventually produce particularized profiles of both abusers and the abused, but even the limited guidance provided by this preliminary study will give some assistance to law enforcement agencies in detection and child protection agencies in identifying children at risk and targeting resources more efficiently.

Adolescent↗
PubMed1996

The moderating influence of physical fitness on age gradients in vigilance and serial choice responding tasks.

The moderating influence of physical fitness on age gradients in measures obtained from vigilance and serial choice responding tasks is examined in a sample of 90 postal workers. Physiological data relating to aerobic fitness determined fitness level within 2 age groups: younger participants ages 18 to 30 years (M = 25.19; 24 men, 24 women) and older participants ages 43 to 62 years (M = 49.19; 20 men, 22 women). A performance decrement across time was found in several measures, and some variation as a function of age was apparent. However, post hoc statistical analyses did not indicate this was due to older adults underperforming younger adults. According to predictions, significant Age x Fitness interactions showed older less fit workers to consistently underperform other participants. The findings suggest that older less fit individuals have lower signal sensitivity and processing speed than older fitter people and younger individuals. Results are discussed in relation to underlying physiological mechanisms.

Adult↗
PubMed1996

Hepatic kinetics and magnetic resonance imaging of gadolinium-EOB-DTPA in dogs.

RATIONALE AND OBJECTIVES: To measure the hepatic uptake and biliary elimination kinetics of gadolinium (Gd)-EOB-DTPA in dogs. METHOD: Two groups of four beagles each were anesthetized and given an intravenous bolus of 25 mumol/kg or 250 mumol/kg of Gd-EOB-DTPA. Blood, hepatic bile, and urine were collected over 140 minutes, and liver samples were obtained immediately after the dogs were killed. Conventional T1-weighted spin echo sequences of the liver were performed on a 1.5-Tesla (T) magnetic resonance imager during sampling. A ninth beagle received a bolus of 25 mumol/kg followed 140 minutes later with a bolus of 250 mumol/kg of Gd-EOB-DTPA. Wedge liver biopsies were obtained for Gd estimation at various times after dosing, and Gd concentration was measured by inductively coupled plasma atomic emission spectroscopy. RESULTS: The plasma concentration of Gd-EOB-DTPA decreased in a biexponential manner with half-lives of approximately 4 minutes and 60 minutes for the distribution and elimination phase independent of the dose given. Gadolinium bile concentration reached peak values between 80 and 140 minutes: 6.3 +/- 1.6 mmol/L for the low dose (LD) and 11.6 +/- mmol/L for the high dose (HD). Bile Gd output was 62.0 +/- 8.8 (LD) and 78.3 +/- 30.2 (HD) nmol/minute-kg 50 to 80 minutes after injection. Gadolinium-EOB-DTPA was excreted by the biliary route to 24.8 +/- 2.6 (LD) and 3.6 +/- 1.2 (HD) percent of the dose within 140 minutes. Liver Gd concentration was 0.43 +/- 0.14 (LD) and 4.3 +/- 0.5 (HD) mmol/kg liver tissue at the conclusion of the studies. Calculated concentrations in the hepatocyte were 60 (LD) and 15 (HD) times higher than in plasma at 25 minutes after dosing. Whereas the low dose exhibited excellent contrast enhancement for the whole period, the high dose displayed a biphasic signal enhancement with a decreasing signal caused by the too-high hepatic gadolinium accumulation. CONCLUSIONS: Transport of the Gd-EOB-DTPA into the hepatocyte exceeded elimination from hepatocyte to bile. The high dose defined a biliary transport maximum for Gd-EOB-DTPA of 78.3 +/- 30.2 nmol/minute-kg. The liver accumulation results from fast transport into the hepatocyte and rate-limited slower transport from hepatocyte to bile. The accumulation occurs against a strong concentration gradient, suggesting energy-dependent active transport into the hepatocyte.

Animals↗
PubMed1995

Lightwand intubation: II--Clinical trial of a new lightwand for tracheal intubation in patients with difficult airways.

Lightwands have been used to assist in the tracheal intubation of patients with difficult airways for many years. A new lightwand (Trachlight) with a brighter light source and a flexible stylet permits both oral and nasal intubation under ambient light. This study reports the effectiveness of the Trachlight in tracheal intubation in patients with difficult airways. Two groups of patients were studied: Group 1--patients with a documented history of difficult intubation or anticipated difficult airways; Group 2--anaesthetized patients with an unanticipated failed laryngoscopic intubation. In Group 1, the tracheas were intubated using the Trachlight with patients either awake or under general anaesthesia. In Group 2, tracheas were intubated under general anaesthesia using the Trachlight. The time-to-intubation, number of attempts, failures, and complications during intubation for all patients were recorded. Two hundred and sixty-five patients were studied with 206 patients in Group 1, and 59 in Group 2. In most patients, the tracheas were intubated orally (183 versus 23 nasal) during general anaesthesia (202 versus 4 awake) in Group 1. Intubation was successful in all but two of the patients with a mean (+/- SD) time-to-intubation of 25.7 +/- 20.1 sec (range 4 to 120 sec). The tracheas of these two patients were intubated successfully using a fibreoptic bronchoscope. Orotracheal intubation was successful in all patients in Group 2 using the Trachlight with a mean (+/- SD) time-to-intubation of 19.7 +/- 13.5 sec. Apart from minor mucosal bleeding (mostly from nasal intubation), no serious complications were observed in any of the study patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Clinical trial of a new lightwand device (Trachlight) to intubate the trachea.

BACKGROUND: Transillumination of the soft tissue of the neck using a lighted stylet (lightwand) is an effective and safe intubating technique. A newly designed lightwand (Trachlight) incorporates modifications to improve the brightness of the light source as well as flexibility. The goal of this study was to determine the effectiveness and safety of this device in intubating the trachea of elective surgical patients. METHODS: Healthy surgical patients were studied. Patients with known or potential problems with intubation were excluded. During general anesthesia, the tracheas were intubated randomly using either the Trachlight or the laryngoscope. Failure to intubate was defined as lack of successful intubation after three attempts. The duration of each attempt was recorded as the time from insertion of the device into the oropharynx to the time of its removal. The total time to intubation (TTI), an overall measure of the ease of intubation, was defined as the sum of the durations of all (as many as three) intubation attempts. Complications, such as mucosal bleeding, lacerations, dental injury, and sore throat, were recorded. RESULTS: Nine hundred fifty patients (479 in the Trachlight group and 471 in the laryngoscope group) were studied. There was a 1% failure rate with the Trachlight, and 92% of intubations were successful on the first attempt, compared with a 3% failure rate and an 89% success rate on the first attempt with the laryngoscope (P not significant). All failures were followed by successful intubation using the alternate device. The TTI was significantly less with the Trachlight compared with the laryngoscope (15.7 +/- 10.8 vs. 19.6 +/- 23.7 s). For laryngoscopic intubation, the TTI was longer for patients with limited mandibular protrusion and mentohyoid distance, with a larger circumference of the neck, and with a high classification according to Mallampatti et al. However, there was no relation between the TTI and any of the airway parameters for Trachlight. There were significantly fewer traumatic events in the Trachlight group than in the laryngoscope group (10 vs. 37). More patients complained of sore throat in the laryngoscope group than in the Trachlight group (25.3% vs. 17.1%). CONCLUSIONS: In contrast to laryngoscopy, the ease of intubation using the Trachlight does not appear to be influenced by anatomic variations of the upper airway. Intubation occasionally failed with the Trachlight but in all cases was resolved with direct laryngoscopy. The failures of direct laryngoscopy were resolved with Trachlight. Thus the combined technique was 100% successful in intubating the tracheas of all patients.

Adult↗
PubMed1994

How does neurophysiological assessment influence the management and outcome of patients with carpal tunnel syndrome?

The objective of this study was to determine how neurophysiological assessment influenced the management and outcome of 100 consecutive patients referred to a department of clinical neurophysiology in a district general hospital with a provisional clinical diagnosis of carpal tunnel syndrome. Nerve conduction studies excluded the diagnosis in 36 patients who may have otherwise received inappropriate treatment. The decision whether to perform a carpal tunnel decompression was greatly influenced by a positive study. Symptoms subsequently resolved in 72-86% of patients treated on this basis, depending on the mode of treatment and the nerve conduction study findings, with similar outcomes for surgical and conservative measures. The clinical and estimated resource implications of this diagnostic service were found to be substantial.

Adult↗
PubMed1994

Assessment of upper airway anatomy in awake, sedated and anaesthetised patients using magnetic resonance imaging.

Magnetic Resonance Imaging was used to quantify the effects of 1. sedation and 2. general anaesthesia with a laryngeal mask airway (LMA) in place on the minimum antero-posterior (A-P) diameters of the naso-, oro- and hypopharynx and on the angle of the epiglottis relative to the adjacent posterior pharyngeal wall. Median sagittal T1-weighted images of the pharynx were obtained in 46 patients (16 awake, 14 sedated, 16 under general anaesthesia). In sedated patients, the A-P diameters of the pharynx were less than in awake patients, in particular at the levels of the epiglottis and soft palate. General anaesthesia and placement of a LMA was also associated with a reduced A-P diameter at the level of the soft palate, but with increased diameters at the levels of the tongue and epiglottis. Placement of a LMA caused abnormal downfolding of the epiglottis in most cases but this did not cause clinically significant airway obstruction.

Adult↗
PubMed1993

Testins are structurally related to the mouse cysteine proteinase precursor but devoid of any protease/anti-protease activity.

Testin I (M(r) 35,000) and testin II (M(r) 37,000) (testins) are two structurally and immunologically related testicular proteins that are actively synthesized and secreted by Sertoli cells. Treatment of adult rats with busulfan to destroy germ cells selectively in the testis could lead to a significant increase in the testicular testins level; as the germ cells reappeared in the testis, the testicular testins level declined and returned to the normal level. These observations indicated that the testicular content of testins in the rat is inversely correlated to the number of germ cells. When the partial N-terminal amino acid sequences for testin I and testin II were compared with the existing protein data base at Protein Identification Resource, it was noted that they displayed remarkable identity with CTLA-2 alpha and CTLA-2 beta, two novel molecules expressed in mouse activated T lymphocytes and mast cells, and the mouse cysteine proteinase proregion. When purified testins were assayed for the proteolytic and anti-protease activity using [14C]-casein, it was noted that it possessed neither proteolytic nor anti-protease activity, suggesting that it is not functioning as a protease and/or protease inhibitor in the testis.

Amino Acid Sequence↗