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Biomedical subjects

C Lee

Publications and source records attributed to C Lee.

At least 775 records · Page 43Linked to original sources

Inhibition of prostatic tumor cell proliferation by suramin: alterations in TGF alpha-mediated autocrine growth regulation and cell cycle distribution.

Suramin is a trypanocidal drug that has generated recent interest as an antineoplastic agent because of its ability to inhibit the binding of growth factors to their cell surface receptors. Our studies, and others, suggest that the androgen-independent human prostatic carcinoma cell lines PC3 and DU145 proliferate via autocrine growth mechanisms mediated by transforming growth factor alpha (TGFa) and its receptor, the epidermal growth factor (EGF) receptor. The present studies were designed to evaluate the ability of suramin to inhibit PC3 and DU145 proliferation by interfering with TGFa-mediated autocrine growth. Suramin induced a dose-dependent reduction of prostatic tumor cell proliferation which was reversed by removal of suramin from the culture medium. 3H-thymidine release studies showed that suramin had little direct cytotoxicity to either cell line. These findings suggest that the effects of suramin are mediated by cytostatic, rather than cytotoxic, mechanisms. Suramin also interfered with TGFa-mediated growth mechanisms. Specifically, suramin reduced the specific binding of TGFa to PC3 and DU145 cells. Additionally, the inhibitory effect of suramin on DU145 was reversed by cultivation of cells in the presence of excess TGFa. Further investigations revealed that suramin increased the percentage of cells in the S phase of the cell cycle for both cell lines. These studies show that the inhibitory effect of suramin on PC3 and DU145 cell growth is mediated, in part, by alteration of TGFa-mediated autocrine growth mechanisms and cell cycle kinetics.

Antineoplastic Agents↗

Requirement of innervation for maintenance of structural and functional integrity in the rat prostate.

The rat prostate is innervated by pelvic and hypogastric nerves through a single pelvic ganglion, removal of which would result in complete denervation of the prostatic complex. The present study was conducted to investigate the effect of denervation on the rat prostate. Adult Sprague-Dawley rats of 300 g in body weight were divided into two groups. Bilateral pelvic ganglion denervation was performed in one group of animals; the other group received a sham operation. Three weeks later, animals were killed; and the ventral prostates were removed, weighed, and subjected to routine procedures for light and electron microscopy. The average weight, total protein content, and total content of acid phosphatase of the ventral prostates in the denervated group were significantly less than those in the control group. Total DNA content per prostate, however, was not significantly different between the two groups. Results of histological examination indicated that the prostates from control animals showed normal morphology, whereas those from the denervated animals showed reduced cell height and enlarged vacuoles surrounding the nuclei. Inspection of electron micrographs revealed that the prostates from denervated animals, compared with those of controls, showed a reduced ratio of cell height:cell width, which is associated with a reduced number of microvilli and secretory granules. These results indicate that denervation in the prostate is associated with a lower prostatic weight, decreased cell height, and reduced secretory activity.

Acid Phosphatase↗

Carotid and vertebral artery injury in survivors of atlanto-occipital dislocation: case reports and literature review.

Atlanto-occipital dislocation (AOD) usually results in immediate death from transection of the upper cervical spinal cord near the spinomedullary junction. However, over the last several decades increasing numbers of AOD survivors have been identified. Although many of these patients initially demonstrate profound neurologic deficits, a number who survive have regained most or all neurologic functions, indicating that they did not suffer mechanical disruption of the spinal cord at the time of AOD. In the survivors, a growing body of evidence indicates that many of the initial neurologic deficits are related to vascular injury to the carotid or vertebral arteries and their branches. We recently encountered three AOD survivors with no evidence of mechanical injury to the spinal cord in which angiography demonstrated vascular injury to the internal carotid artery in the form of vasospasm in one case and to the vertebral arteries in the forms of focal stenosis at the site of dural penetration, focal stenosis and distal vasospasm, and focal stenosis with distal intimal flap and dissection in one case each. Autopsy after one of the three died after cardiac arrest demonstrated diffuse infarction of the cerebrum, cerebellum, midbrain, brainstem, and upper cervical spinal cord without evidence of mechanical laceration or transection of the spinal cord. Recovery of neurologic function in two cases following prompt immobilization and angiography suggests that neurologic deficits secondary to vascular injury are potentially reversible.

Adolescent↗

Sagittally oriented fractures of the lateral masses of the cervical vertebrae.

Lateral flexion of the cervical spine may cause a sagittally oriented fracture of the lateral mass with shearing of all or part of the lateral mass away from the vertebral body. We report 22 patients with 24 sagittal fractures of the cervical lateral masses. Cross-table lateral roentgenograms suggested the presence of a sagittal lateral mass fracture in two thirds of the cases based upon malalignment or widening of the facet joints, displaced fracture fragments, subluxation of the spine, or rotation of the spine above the level of abnormality. However, the cross-table lateral roentgenogram was normal in one third of cases. Oblique roentgenograms were available in eight cases; these were positive in five, equivocal in one, and negative in two. Visible fracture lines, often associated with lateral displacement of part or all of the lateral mass, allowed all 24 fractures to be detected on the supine anteroposterior view films. Sagittal lateral mass fractures were unstable in 59% (13/22) of the cases; neurologic deficits, including quadriplegia, hemiplegia, and radiculopathy, were present in 45% (10/22). Computed tomography and complex-motion tomography were useful in confirming the sagittal lateral mass fracture and in detecting other associated fractures.

Adult↗

Prolactin reduction after combined therapy for prolactin macroadenomas.

The ability of surgery or bromocriptine to produce endocrine control of a prolactin macroadenoma decreases as the prolactin level increases. Guidelines for the use of multimodality therapy have not been developed for tumors associated with markedly elevated prolactin levels. We reviewed the records of 21 patients with prolactin levels greater than 200 ng/ml treated by transsphenoidal surgery and postoperative radiotherapy with or without a dopamine agonist. Values before and after treatment were available for 19 patients (13 men and 6 women). The mean basal prolactin level before treatment for the entire group was 2410 ng/ml. Surgery and radiotherapy resulted in a 90% reduction and serum prolactin levels within normal limits in 0 of 7 patients, versus the combination of surgery, radiotherapy, and dopamine agonist, which resulted in a 99.5% reduction and values within the normal range in 12 of 12 patients. Spontaneous physiological improvement was not often observed. One woman and two men were able subsequently to have children. A plan for these patients is discussed.

Adenoma↗

Spontaneous rupture of a normal bladder.

We have reported a case of spontaneous rupture of a normal urinary bladder. Patients with this rare condition characteristically have a recent history of heavy alcohol intake, sudden onset of abdominal pain coincidental with bloody urine, generalized peritonitis, and abnormal renal chemistry. A high index of suspicion will lead to early diagnosis and treatment, minimizing the mortality attributed to this condition.

Adult↗

Area 18 corticotectal cells: response properties and identification of sustaining geniculate inputs.

1. We examined the response properties and geniculate inputs of 35 antidromically identified corticotectal (CT) cells within area 18 of the paralyzed, anesthetized cat. Twenty-three were either standard complex or hypercomplex, 11 were special complex, and 1 was simple. 2. The response properties of CT cells in area 18 were in general quite similar to those examined in a previous study of area 17 CT cells, including similar proportions of standard and special complex CT cells, virtually identical length-response functions, and similar orientation and direction tuning. 3. Area 18 CT cells are rapidly conducting. They are considerably faster than area 17 CT cells. 4. We investigated the composition of thalamic inputs to CT cells by reversibly inactivating a portion of layer A and/or the C layers of the dorsal lateral geniculate nucleus with injections of cobaltous chloride. Blocking layer A strongly attenuated the visual responsiveness of about half of the cells tested. Blocking the C layers alone generally had only moderate effects, but simultaneous blockade of layer A and the C layers demonstrated a substantial C-layer input to many cells. Unlike area 17 in which there is a strong correlation between CT cell class and dependence on layer A, no single receptive-field parameter nor set of parameters was correlated with dependence on layer A. However, cells least affected by simultaneous blockade of layer A and the C layers were special complex, suggesting that, as in area 17, area 18 special complex CT cells integrate more geniculate inputs than standard complex CT cells. 5. We propose that the similarities of response properties of area 17 and area 18 CT cells results from their participation in similar interlaminar columnar circuits and that differences in the patterns of geniculate control reflect differences in the global patterns of geniculate inputs to these two areas.

Animals↗

Prostatic ductal system in rats: regional variation in localization of an androgen-repressed gene product, sulfated glycoprotein-2.

The rat prostate is a complex ductal system with branches and subbranches extending from one end to another. Owing to the relative distance of various regions from the urethra, the entire length of the ductal system can be divided into three segments, i.e. the proximal, intermediate, and distal segments. The present study was carried out to examine the pattern of localization of sulfated glycoprotein-2 (SGP-2), a marker protein associated with programmed cell death, in various regions of the prostatic ductal system under normal conditions and during castration-induced regression. SGP-2 has been considered an androgen-repressed gene product in the rat prostate and has previously been known as castration-induced protein or TRPM-2. In the normal rat prostate, immunoreactive SGP-2 was localized in epithelial cells lining the proximal segment in which signs of programmed cell death were apparent. Cells lining the distal and intermediate segments were, however, devoid of SGP-2. This observed regional variation in SGP-2 localization did not support an earlier hypothesis which stated that SGP-2 was constitutively expressed by all prostatic epithelial cells in the normal rat prostate. After castration in adult rats, there was a shift in the location of cells containing SGP-2 from the proximal segment toward the distal segment. Therefore, there is a regional variation in the distribution of SGP-2 in the rat prostate both before and after castration in the host. These findings are likely to be associated with a regional variation in cellular responsiveness to androgen stimulation and androgen depletion in the prostatic ductal system. Results also support the view that SGP-2 localization is associated with an early manifestation of programmed cell death in the rat prostate.

Androgens↗

Comparison of mononuclear cell proteins and plasma proteins before and during parturition by two dimensional electrophoresis.

Two dimensional electrophoresis is a technique whereby protein sources are organized by molecular weight and electrical charge on a polyacrylamide gel. To detect changes that may be associated with the onset of parturition, we compared electrophoresis patterns of mononuclear cell proteins and plasma proteins before and during active labor. Mononuclear cells and plasma were obtained from 5 pregnant volunteers. It appears that A-1 apolipoprotein, identified by Western Blot analysis, is increased in mononuclear cells during active labor. Conversely, a decrease in the concentration of A-1 apolipoprotein was seen in plasma during parturition. These "normal" protein patterns can now be compared with those observed in pathologic conditions including preterm labor and may allow early detection of disease by protein abnormalities before clinical signs and symptoms develop.

Blood Proteins↗

Intravenous double-dose contrast computed tomography in the diagnosis of spinal arteriovenous malformations: report of four cases.

Spinal IV double-dose computed tomography (DCT) followed by reformation imagings was performed on 4 patients. Three cases received double-dose contrast injections, one case received a conventional single dose contrast material. 'Dots' enhancement on axial CT scanning and 'vasculature-like' hyperdense enhancement on sagittal and coronal reformation imagings were found in four cases of spinal arteriovenous malformation (AVM). Two were at the cervical region and two at the thoracic level. Typical serpentine filling defects were noted in the myelogram of three cases of spinal AVM. One patient suffered from acute onset of paraplegia (case 2), requiring that she received immediate surgical intervention after DCT scanning without myelography. Time for the whole procedure lasted approximately 20 minutes. In addition DCT followed by reformation imaging may be used as a noninvasive preliminary screening procedure for spinal AVMs.

Adult↗

Treadmill gait retraining following fractured neck-of-femur.

The rehabilitation outcome of two methods of gait retraining, was studied in 40 elderly women who had fractured the neck-of-femur. Twenty control subjects received conventional gait retraining, and 20 experimental subjects participated in a treadmill gait retraining program. Rehabilitation outcome was determined by temporal-distance gait parameters and mobility level (house-bound, limited, or unlimited). Muscle strength and range of movement of the lower limb were measured. Previously reported predictors of poor outcome (age, prefracture mobility, admission from sites other than own home, availability of caring person, type of ambulatory aid, presence or absence of senile dementia, and number of concomitant medical diseases) were recorded. Subjects were assessed on admission to the gait retraining program and at discharge from hospital. A 3 x 2 chi-square analysis on discharge mobility level showed the mobility level of the treadmill group to be significantly (p less than .05) higher than the mobility level attained by the control group. Analysis of variance showed no significant differences between the two groups at either assessment time. However, a significant increase in within-group variance from admission to discharge (p less than .01) was noted, and this led to the analysis of a subgroup containing six pairs of subjects matched for number of predictors of poor outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Contrast-enhanced magnetic resonance imaging of the spine.

MRI of the spine and its contents is fast becoming the study of choice over CT myelography for the evaluation of spinal pathology. MRI is able to generate sagittal and coronal images in addition to axial images, to image the entire spine, and to produce a myelogramlike picture. These capabilities give MRI a distinct advantage over CT myelography not only because no intrathecal contrast injection is needed but also because intramedullary lesions, edema, and syrinx may be differentiated from each other by conventional, noncontrast, spin-echo MRI. This article reviews the current philosophies regarding contrast-enhanced MRI with gadopentate dimeglumine in the evaluation of the spine and its contents. It will provide an imaging strategy and approach to evaluation, briefly discuss spin-echo and gradient-echo pulse sequences, and give contrast indications focusing on disorders that benefit from the use of injected, intravenous gadopentate dimeglumine. Potential imaging artifacts related to spin-echo and gradient-echo imaging pertinent to imaging of the spine will also be discussed.

Contrast Media↗

Processing of the gastrin precursor. Modulation of phosphorylated, sulfated, and amidated products.

Post-translational processing of the precursor for rat gastrin yields products that include peptides phosphorylated at Ser96, amidated at Phe92, and sulfated at Tyr87 or Tyr103. The phosphorylation site is immediately adjacent to the processing point that gives rise to the biologically active amidated gastrins. We have examined changes in post-translational processing which occur in gastrin cells from rats that are physiologically stimulated (by feeding) or unstimulated (by fasting). Peptides were identified using site-directed radioimmunoassays and chromatographic systems that resolve phosphorylated, amidated, and sulfated progastrin products, including intermediates generated prior to amidation (i.e. C-terminal glycine-extended variants). Assays for Phe92-amidated peptides and for the C-terminal tryptic fragment of progastrin indicated decreases in the total tissue concentrations of immunoreactive peptide with fasting; in contrast, the tissue concentrations of glycine-extended biosynthetic intermediates were similar in fasted and fed rats. Taken together the data suggest a relative failure in amidation mechanisms in unstimulated cells. The endopeptidase cleavage of progastrin was not influenced significantly by fasting. However, the phosphorylation of peptide products containing Ser96 was depressed significantly in fasted rats. The proportions of amidated peptides sulfated at Tyr87 were generally lower than their corresponding glycine-extended biosynthetic precursors, but in both cases the proportion of peptide in the sulfated form was lower than for peptides sulfated at Tyr103. Feeding did not change the sulfation of amidated heptadecapeptide gastrin or its glycine-extended variant. The results suggest that the mechanisms determining phosphorylation and amidation of progastrin-related peptides depend on the patterns of stimulation of gastrin cells. The observation that decreased phosphorylation is associated with a failure to produce active amidated products is consistent with a regulatory function for phosphorylation in gastrin production.

Amides↗