Search PubMed⌕ Search

Biomedical subjects

J Norman

Publications and source records attributed to J Norman.

At least 145 records · Page 8Linked to original sources

Epidermal growth factor accelerates functional recovery from ischaemic acute tubular necrosis in the rat: role of the epidermal growth factor receptor.

1. Severe, ischaemic, acute tubular necrosis was induced in rats by bilateral occlusion of the renal arteries. The experimental group received exogenous epidermal growth factor infused directly into the renal arterial circulation. Serum creatinine concentration was measured daily for 1 week. Epidermal growth factor receptor binding was measured by autoradiography of whole kidney sections. Renal cell proliferation was measured by incorporation of [3H]thymidine into DNA. 2. Serum creatinine concentration increased after acute tubular necrosis with a peak at 48 h and remained elevated above control levels after 7 days. Binding of radiolabelled epidermal growth factor occurred in all regions of the kidney 48 h after ischaemia. Treatment with exogenous epidermal growth factor attenuated the rise in serum creatinine by 4 days after acute tubular necrosis and after 7 days serum creatinine was lower than in animals that did not receive epidermal growth factor. Infusion of epidermal growth factor also increased renal DNA synthesis. 3. The increase in epidermal growth factor binding in the kidney after acute tubular necrosis and the attenuation of the increase in serum creatinine concentration by administration of exogenous epidermal growth factor, suggest a role for epidermal growth factor in recovery from ischaemic damage. The increase in DNA synthesis in response to epidermal growth factor indicates that its effect may be due, at least in part, to accelerated tubular cell proliferation.

Acute Kidney Injury↗

The effects of the antiprogestin mifepristone, in vivo, and progesterone in vitro on prolactin production by the human decidua in early pregnancy.

This study investigated the regulatory effect of progesterone on decidual prolactin (dPRL) production during early human pregnancy (6-7 weeks). Patients (n = 7) were treated with the antiprogestin-mifepristone (RU 486; 600 mg single oral dose) for 24-36 h before termination of pregnancy by curettage. Tissue was also obtained from patients without pretreatment in vivo (n = 8) and acted as controls. Decidual tissue was incubated in vitro with and without progesterone and mifepristone for 5 days and the medium changed daily. Prolactin production by decidua parietalis decreased over the period of incubation and was unaffected by addition of progesterone or mifepristone. However, in the group pretreated in vivo with mifepristone, the production of dPRL was markedly lower than in the control group. In contrast, the production of dPRL by decidua capsularis to which trophoblast was attached, was maintained at a constant level over 5 days of culture and was unaffected by pretreatment with mifepristone in vivo or its addition in vitro, or by progesterone. Prolactin was immunolocalized using avidin-biotin immunoperoxidase staining to decidualized cells within the decidua and the intensity of staining was reduced or absent in the decidua parietalis from the mifepristone group compared to controls, but was similar in decidua capsularis in both control and mifepristone groups, in good agreement with the in-vitro production of dPRL. Our findings suggest that the effect of progesterone may be only facilitative, maintaining decidual differentiation, and dPRL production might only be associated with the presence of progesterone-dependent differentiated decidual cells. Apart from progesterone, factors from trophoblast cells can maintain dPRL production during pregnancy.

Abortion, Induced↗

Why is word recognition impaired by disorientation while the identification of single letters is not?

Past research has shown that speed of identifying single letters or digits is largely indifferent to orientation, whereas the recognition of single words or connected text is markedly disrupted by disorientation. In a series of four experiments, we attempted to reconcile these findings. The results suggest that disorientation does not impair the identification of the characters but disrupts the perception of their spatial arrangement. When spatial order information is critical for distinguishing between different stimuli, disorientation is disruptive because some rectification process is required to restore order information. Utilizing the similarity between the letter B and the number 13, we found strong effects of orientation when a stimulus was interpreted as the two-digit number 13 but not when interpreted as the single letter B. This, however, occurred only when the set of numbers to be classified included permutations of the same digits (Experiments 1 and 2). Odd-even decisions on single-digit and two-digit numbers (Experiment 3) yielded strong effects of stimulus orientation for order-dependent numbers (e.g., 32), weaker effects for order-independent numbers (e.g., 24), and none for repeated-digit (e.g., 22) or single-digit numbers. Classification time for two-letter Hebrew words evidenced strong effects of orientation for words that differed only in letter order but much weaker effects for words that had no letters in common, even when these were embedded within some words that did (Experiment 4).

Adult↗

Establishing global and local correspondence between successive stimuli: the holistic nature of backward alignment.

Reflection decisions on alphanumeric characters display systemic effects of disorientation, suggesting that subjects mentally rotate the stimulus to the upright (the uprighting process). However, response time also increases with increasing angular disparity between the current and preceding orientations. This occurs only when the current stimulus is brought into congruence with the preceding one (the backward alignment process). In the present study, we examined the hypothesis that the transformation that occurs in backward alignment in holistic even in tasks in which the uprighting process is likely to be piecemeal. Evidence supporting this hypothesis is presented on the basis of tasks requiring either classification of numbers (Experiments 1 and 3) and words (Experiment 2), or mirror image discrimination on letter pairs (Experiment 4). The results indicated that backward alignment establishes global correspondence between successive stimuli and is indifferent to local correspondence at the level of the constituent elements. The establishment of this global correspondence decreases with the number of elements in the stimulus (Experiment 5), but its effects are still observed for four-letter strings (Experiment 6).

Adult↗

The analyst's visual images and the child analyst's trap.

The analyst's experience is different with an adult and a child. One element that constitutes the difference is that the analyst while listening to the adult can become aware of visual images which are created as a continuous commentary to the analysand's material, while the corresponding phenomenon in the child analyst is an emotional commentary. The child can break through the analyst's defenses and catch him in a trap consisting of his own unintegrated, phase-specific emotions and at the same time inhibited ability to introspect. Case material from adult and child analysis is presented to describe these phenomena and to demonstrate how the analyst's visual images in adult analysis and emotional states in child analysis can constitute a central element in the analyst's concept of the analysand.

Child↗

Doxacurium chloride: a preliminary clinical trial.

The onset, duration of action and reversibility of doxacurium were studied in 27 anaesthetized patients, using doses of 37.5 micrograms kg-1 (1.5 x ED95) and 62.5 micrograms kg-1 (2.5 x ED95). Onset was slow and, whilst tracheal intubation was always possible 3 or 4 min after injection, the conditions were not ideal. With the higher dose a mean 97.6 (SD 5.2)% block of the response of adductor pollicis to ulnar nerve stimulation was obtained in 9.85 (6.17) min and recovery of the integrated EMG response to 20% of control took 102 min (42 min). After these initial doses, when incremental doses were given there was no sign of cumulation of effect. Antagonism of block with edrophonium 1 mg kg-1, whilst fast in onset, was rarely complete; with neostigmine 50 micrograms kg-1 antagonism was satisfactory. No adverse haemodynamic effect was seen, although a gradual onset of bradycardia, which responded to atropine or glycopyrrolate, was noted in 12 of the patients. No histamine release or other adverse effects were noted.

Adult↗

Induction of hypertrophy in cultured proximal tubule cells by extracellular NH4Cl.

Ammonia production increases in several models of renal hypertrophy in vivo. The present study was designed to determine whether ammonia can directly modulate the growth of renal cells in the absence of a change in extracellular acidity. In serum-free media NH4Cl (0-20 mM) caused JTC cells and a primary culture of rabbit proximal tubule cells to hypertrophy (increase in cell protein content) in a dose-dependent fashion without a change in DNA synthesis. Studies in JTC cells revealed that the cell protein content increased as a result of both an increase in protein synthesis and a decrease in protein degradation. Total cell RNA content and ribosome number increased after NH4Cl exposure and the cell content of the lysosomal enzymes cathepsin B and L decreased. Inhibition of the Na+/H+ antiporter with amiloride did not prevent the hypertrophic response induced by NH4Cl. The results indicate that ammonia is an important modulator of renal cell growth and that hypertrophy can occur in the absence of functioning Na+/H+ antiport activity.

Amiloride↗

The expanding role of lymphoscintigraphy in the management of cutaneous melanoma. First Place Winner: Conrad Jobst award.

Accepted therapy for intermediate-thickness melanomas is wide local excision and regional lymphadenectomy for nodes known to be in the lymph drainage basin. Lymphoscintigraphy has been shown to be of great help in predicting the drainage pattern of truncal, shoulder, proximal extremity, and head and neck melanomas. Lymphoscintigraphy using Technetium-99 antimony sulfur colloid was performed on 17 patients with cutaneous melanomas at H. Lee Moffitt Cancer Center at the University of South Florida. Of 13 patients with primary truncal and shoulder lesions, drainage patterns were discordant 54 per cent of the time and resulted in dissection of nodal groups different than would otherwise have been planned. This resulted in several lymph nodes positive for metastatic disease removed from operative sites not expected to show metastatic spread by clinical experience alone. The discordant rate for head and neck drainage was also high with 2 of 3 forehead studies showing drainage to both anterior and posterior cervical chains when only anterior chain drainage was expected, while only one of these drained to the preauricular nodes. Again, this led to elective lymph-node dissections of nodal basins not anticipated on clinical grounds alone. After a mean follow-up of 2 years, in which 60 to 75 per cent of all recurrences from melanoma are expected to occur, there has been no lymph-node metastasis development in basins that were not predicted by the scan. It is clear from our data that well-known historical patterns of lymph drainage in addition to the clinical impression of experienced surgeons cannot reliably predict the lymphatic drainage of many truncal, shoulder, and head and neck melanomas.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Activation of a low specific activity form of DNA polymerase alpha by inositol-1,4-bisphosphate.

A low activity form of DNA polymerase alpha immunoaffinity-purified from adult-derived human fibroblasts was activated by interaction with phosphatidylinositol-4-monophosphate, while a high activity form of the enzyme did not interact with phosphatidylinositol-4-monophosphate or its derivatives. Phosphatidylinositol-4-monophosphate was apparently hydrolyzed in the presence of a highly purified low activity form of DNA polymerase alpha, effecting the release of diacylglycerol and the retention of inositol-1,4-bisphosphate by the enzyme complex. The resulting inositol-1,4-bisphosphate/protein complex exhibited increased affinity of binding to DNA template/primer and increased deoxynucleotidyltransferase activity. These data indicate that inositol-1,4-bisphosphate may function as an effector molecule in the activation of a low activity form of human DNA polymerase alpha and suggest that it may function as a second messenger during the initiation of mitosis in stimulated cells.

1-Phosphatidylinositol 4-Kinase↗