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Biomedical subjects

S Harrison

Publications and source records attributed to S Harrison.

At least 19 recordsLinked to original sources

Predeposit autologous blood transfusion in patients with colorectal cancer: a feasibility study.

Over a 2-year period, a predeposit autologous blood transfusion service was provided for all patients undergoing elective surgery for left-sided colonic or rectal cancer in one hospital. Of 129 such patients, 28 were suitable for autologous donation. Eight of these received autologous blood only, 13 required no transfusion, and seven needed additional homologous blood. Thus, although predeposit autologous transfusion for patients with colorectal cancer is possible, only a very small proportion are likely to derive any benefit which it might confer.

Aged

Control of contamination of the operative team in total joint arthroplasty.

Reports of percutaneous transmission of blood-borne disease emphasize the need for control of intraoperative contamination. In a randomized prospective study, surgeons and surgical assistants involved in total hip and total knee arthroplasty adopted the following protocol: total body exhaust with hood, aspirator, knee-length impermeable gowns, foot covers, including knee-high covers and waterproof covers, and one of three combinations of gloving protocols: latex/latex changed hourly, latex/cloth, or latex/cloth/latex. All inner gloves were tested by a leak test. All needles and sharp instruments were passed on trays, and all contaminations and perforations were recorded. Each surgeon and assistant was inspected twice for contamination. There were no needle sticks, and only one of 267 personnel had head, neck, body, leg, or foot contamination. Perforation rates of inner gloves were 9.2% for latex/latex, 7.9% for latex/cloth, and 4.3% for latex/cloth/latex.

Blood

The career development internship program. Pathway to enhanced nursing practice.

Nurse administrators can enhance nursing practice and improve patient care by providing clinical nurses with ways to develop and share their expertise in areas such as education, management, quality assurance, advanced clinical practice, and research. The authors describe the Career Development Internship Program that grew out of the Management Internship Program. This creative program allows for professional growth in specific fields while also developing leadership capability.

Career Mobility

Sexual dimorphism and growth hormone regulation of a hybrid gene in transgenic mice.

The sexually dimorphic expression of the urinary protein genes of mice (Mup genes) in the liver is mediated by the different male and female temporal patterns of circulating GH. Normal females were induced to male levels when GH was administered by injection to mimic the male GH pattern, showing that expression at the male level does not require a male sex steroid status in addition to intermittent GH. Two Mup-alpha 2u-globulin hybrid transgenes with different Mup gene promoters showed sexually dimorphic expression, and their expression in females increased to male levels upon testosterone treatment. GH-deficient (lit/lit) mice did not express these transgenes, and GH-deficient females did not respond to testosterone treatment, showing that GH was required for induction. Both normal and GH-deficient females were induced to male levels when GH was administered by injection. This is the first report of a transgene responsive to GH. A transgene consisting of a Mup promoter fused to a Herpes simplex virus thymidine kinase reporter sequence also showed sexual dimorphism, although to a lesser degree. It was expressed at the same level in normal females and GH-deficient mice of both sexes and was induced when GH-deficient mice were treated with GH. We propose that this transgene has a basal constitutive expression, possibly due to the absence of any rodent DNA downstream of the promoter. Since expression of the transgene was significantly induced by GH, the GH response is due at least in part to sequences in the promoter region.

Alpha-Globulins

Auditory-visual associations, hemispheric specialization and temporal-frontal interaction in the rhesus monkey.

Monkeys (Macaca mulatta) learned preoperatively to associate each of 6 auditory stimuli with 1 of 6 visual stimuli. Ablation of the left prefrontal cortex in a group of 3 monkeys produced a substantial impairment in performance of the task, though performance was still above chance. Ablation of the right prefrontal cortex in a second group of 3 monkeys was without effect. Subsequently the superior temporal gyrus (auditory cortex) was removed in each animal unilaterally in the hemisphere contralateral to the existing prefrontal ablation. Ablation of the left auditory cortex produced a severe impairment, but ablation of the right auditory cortex was without effect. Finally, forebrain commissurotomy in the animals with left prefrontal and right temporal ablation reduced their performance virtually to chance level. These results are consistent with previous findings indicating a left hemisphere specialization for audition in the monkey, and they give strong support to the idea, derived from previous experiments on difficult associative learning in the monkey, that auditory-visual association depends on a convergence of auditory and visual information in the prefrontal cortex.

Animals

The herpes simplex virus type 1 thymidine kinase is expressed in the testes of transgenic mice under the control of a cryptic promoter.

We reported previously that the herpes simplex virus type 1 (HSV-1) thymidine kinase reporter gene (tk) was expressed in the testes of transgenic mice when coupled to the promoter of a liver-specific mouse major urinary protein (MUP) gene. Here we show that HSV-1 tk is also expressed in the testis when coupled to a MUP pseudogene promoter, to a truncated MUP promoter that is not active in the liver, and to the promoter of the bovine thyroglobulin gene. Furthermore, HSV-1 tk itself was expressed in the testis, although its normal expression had been disabled by removing an upstream regulator of transcription. In every case, the same multiple transcripts were observed, with their 5' ends located downstream of the normal HSV-1 tk translation initiation codon. We conclude that the transcription of HSV-1 tk in the testis is directed by a cryptic TATA box-independent promoter located in the coding region of the gene. The longest HSV-1 thymidine kinase (TK) polypeptides synthesized in the testis were shorter than full-length TK and probably result from translational initiation at Met46 and Met60, the second and third ATG codons of the tk reading frame. Male mice of most transgenic lines were sterile, and the severity of the lesion in spermatogenesis was directly related to the level of TK expression. In the most highly expressing lines, sperm counts were low and morphologically defective sperm were common. In other sterile lines, TK was expressed at a lower level and sperm counts were normal but sperm motility was greatly reduced. Lines with the lowest levels of HSV-1 TK expression were fertile. HSV-1 TK was expressed in germ line cells, mainly in the haploid spermatids. However, low-level HSV-1 TK activity was found in the testis before the first germ cells entered meiosis, showing that if expression is confined to the germ cells, it also occurs in spermatogonia.

Animals

Working the markets: purchaser/provider separation in English health care.

In 1991 the U.K. health system embarked upon a series of apparently radical changes in its organization, centering upon the notion of "purchaser/provider separation." After summarizing these changes, and their ostensible rationale, this article reports early experiences of the new system and outlines the alternative proposals of the main opposition Labour Party. Early experience suggests that the new system is unlikely to function as ostensibly intended. The Labour alternative, however, fails to address crucial organizational issues.

Economic Competition

Feasibility of cellular microencapsulation technology for evaluation of anti-human immunodeficiency virus drugs in vivo.

We investigated the feasibility of micro-encapsulation technology for the evaluation of anti-human immunodeficiency virus (HIV) drugs in vivo. The ability to place human cells in microcapsules with semipermeable membranes for implantation into test animals led to the development of this assay. The anti-HIV activity assay involves microencapsulating human T-lymphoblastoid cells sensitive to the cytopathic effects of HIV; the encapsulated cells are then implanted into athymic nude mice and recovered after drug treatment in vivo. A positive antiviral effect of the test substance is indicated by growth or survival of the virus-infected cells in the microcapsules. Several HIV-sensitive cell lines of T-lymphocyte, monocyte, and nonlymphocyte origin were examined for growth in microcapsules in vitro and in vivo. Light and electron microscopic analysis of the capsules and the human cells contained therein revealed the invasion of mouse immune cells and other adverse effects that could not be overcome by any of numerous technical modifications attempted. We conclude that cellular microencapsulation technology is not feasible for in vivo drug-testing protocols because of immunogenic reactions.

Animals

Rat monoclonal antibodies to the external domain of the product of the C-erbB-2 proto-oncogene.

With the breast carcinoma cell line BT 474 used as a source of antigen, four rat monoclonal antibodies (MAbs) (3 IgG2a and I IgA) have been prepared against the external domain of the product of the c-erbB-2 proto-oncogene. All 4 antibodies stain frozen sections of tissues that over-express the product of the c-erbB-2 proto-oncogene, and competitive binding assays showed that the antibodies recognized 2 non-overlapping epitopes. Representative antibodies from the two groups (ICR12 and 13) were shown to specifically immunoprecipitate a 190 kDa protein from 35S-methionine-labelled breast carcinoma cells where the c-erbB-2 is amplified (BT 474 and MDA-MB 361). Two of the antibodies (ICR12 and ICR17) bind to the denatured antigen in Western blots and ICR12 stains formolsaline-fixed sections of breast carcinoma tissue that over-expresses the product of the c-erbB-2 proto-oncogene. These antibodies should be useful not only for immunocytochemical diagnoses but also for radio-immunoscintigraphic and therapeutic applications.

Animals

Parathyroid hormone regulation of cytosolic Ca2+ in rat proximal tubules.

The effect of parathyroid hormone (PTH) on cytosolic Ca2+ was studied on suspensions of purified rat renal proximal tubules using the fluorescent indicator quin-2. Rat PTH-(1-34) produced a transient 40% increase in apparent cytosolic Ca2+ at 20 s, followed by a rapid return toward the basal level. The half-maximal dose for both the rate of rise and peak apparent Ca2+ was 3 X 10(-8) M for rat PTH-(1-34). Unlike PTH, forskolin and dibutyryl adenosine 3',5'-cyclic monophosphate had no immediate effect. Bovine PTH-(3-34) blocked the effect of PTH in a concentration-dependent manner. Acute reduction of medium Ca2+ to less than 10(-6) M had no effect on either PTH- or angiotensin II (ANG II)-induced transients, but prevented any sustained increases. Washing tubules in nominally Ca2(+)-free medium followed by ethylene glycol-bis (beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid reduced both transients by 50%. PTH at 2 X 10(-7) caused small (6-9%) increases in accumulation of [3H]inositol phosphates comparable with that produced by norepinephrine at 10(-7) M. At 10(-7) M, norepinephrine produced increases in Ca2+ and inositol phosphates similar to PTH; at 10(-5) M much larger increases in inositol phosphates occurred. Exposure to high levels of either norepinephrine or ANG II before PTH administration prevented any subsequent stimulation by PTH or other agonists. A submaximal dose of norepinephrine only slightly blunted the effect of PTH or ANG II.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II

Multiple cooperative interactions constrain BPV-1 E2 dependent activation of transcription.

Transcription directed by the BPV-1 long control region (LCR) is conditional upon activation by the virally encoded E2 protein. Within the 1.0 kb LCR there are five separate regions, A to E, that contain E2 responsive enhancers. The smallest functional region, A, is only 38 bp and contains two copies of the consensus sequence ACC(N)6GGT that is known to function as an E2 binding site in vitro. We show that a pair of these constitutes a minimal functional E2 responsive enhancer element but that the strength of enhancer activity is dramatically reduced both by increasing the spacing between them and by removing the dual elements from the proximity of other key promoter elements. Furthermore, pairs of dual elements activated transcription to varying levels depending upon their spatial arrangement and promoter proximity. We have also identified a low level constitutive enhancer in the D region which lacks an E2 consensus binding site but which can be activated by E2. We show that the activation potential of this constitutive enhancer is increased by association with a single E2 binding site suggesting some cooperation/interaction between viral and cellular enhancer proteins.

Base Sequence

A comparison of the effects of fornix transection and sulcus principalis ablation upon spatial learning by monkeys.

In each of three experiments with Cynomolgus monkeys (Macaca fascicularis), there was a group of normal control animals, a group with bilateral cortical ablations in the principal sulcus, and a group with fornix transection. In Expt. 1, half of each group learned problems in which the position of a pair of visual stimuli, to the monkey's left or right, indicated which of the visual stimuli was the correct (rewarded) one. The other animals learned problems in which visual stimuli indicated, irrespective of their own spatial position, whether reward was to be found on the monkey's left or on the right. The animals with fornix transection were impaired in both tasks. The animals with sulcus principalis ablation were also impaired in both tasks. The impairment caused by fornix transection was more severe than that caused by sulcus principalis ablation. Within each of the two operated groups, the degree of impairment in the two tasks was equal, when assessed in proportion to the difficulty of each task for control animals. Expt. 2 showed that neither of the operated groups was impaired in visual discrimination learning with spatial position irrelevant. Expt. 3 tested spatial discrimination learning (acquisition and reversal of a left-right discrimination) with irrelevant visual cues. Here the fornix-transected group was impaired but the group with sulcus principalis ablations was normal. It is suggested, on the basis of these findings and previous results, that fornix transection produces a general deficit in remembering the spatial arrangement of whole scenes, while sulcus principalis ablation produces a deficit in high-order integration involving spatial information.

Animals

Place memory and scene memory: effects of fornix transection in the monkey.

Five experiments examined the effects of fornix transection upon some spatial and visual learning tasks in monkeys (Macaca fascicularis). For each trial of each task, the monkey was brought to a test tray and allowed to choose between 2 objects on the tray. In different tasks, different cues were provided by the experimenter to guide the monkey's choices. In total 5 different tasks were run (Experiments 1 to 5) and the results showed that the effects of fornix transection varied markedly between tasks: the animals with fornix transection were severely impaired in experiments 1, 3 and 5 but learned normally in experiments 2 and 4. It is concluded that the results cannot be explained by the simple hypothesis of a deficit in place learning, since some forms of place learning are unimpaired by fornix transection. A better general hypothesis is that the memory disrupted by fornix transection is like a snapshot memory, which stores the spatial arrangement of items in a witnessed scene.

Animals