Showing papers by "Medical University of South Carolina published in 1987"
TL;DR: Results indicate that IL-3 and IL-6 act synergistically to support the proliferation of hemopoietic progenitors and that at least part of the effect results from a decrease in the G0 period of the individual stem cells.
Abstract: Interleukin-6 (IL-6, also known as B-cell stimulatory factor 2/interferon beta 2) was previously shown to support the proliferation of granulocyte/macrophage progenitors and indirectly support the formation of multilineage and blast cell colonies in cultures of spleen cells from normal mice. We report here that IL-3 and IL-6 act synergistically in support of the proliferation of murine multipotential progenitors in culture. The time course of total colony formation by spleen cells isolated from mice 4 days after injection of 5-fluorouracil (150 mg/kg) was significantly shortened in cultures containing both lymphokines relative to cultures supported by either of the two factors. Serial observations (mapping) of individual blast cell colonies in culture revealed that blast cell colonies emerged after random time intervals in the presence of IL-3. The average time of appearance in IL-6 alone was somewhat delayed, and in cultures containing both factors the appearance of multilineage blast cell colonies was significantly hastened relative to cultures grown in the presence of the individual lymphokines. In cultures of day-2 post-5-fluorouracil bone marrow cells, IL-6 failed to support colony formation; IL-3 alone supported the formation of a few granulocyte/macrophage colonies, but the combination of factors acted synergistically to yield multilineage and a variety of other types of colonies. In this system, IL-1 alpha also acted synergistically with IL-3, but the effect was smaller, and no multilineage colonies were seen. Together these results indicate that IL-3 and IL-6 act synergistically to support the proliferation of hemopoietic progenitors and that at least part of the effect results from a decrease in the G0 period of the individual stem cells.
824 citations
TL;DR: Examination of pure-tone acoustic damage in the chick cochlea revealed a significant amount of hair cell recovery over a 10 day period following the exposure, which included both a regeneration of stereociliary bundles to replace those that were lost and a reshuffle of the mosaic pattern of the hair cell surfaces that survived.
367 citations
TL;DR: Data suggest that growth inhibitors such as TGF-beta may act by altering the cell's response to growth-stimulatory factors.
325 citations
272 citations
TL;DR: Diagnostic thoracocentesis is a clinically valuable procedure if used in conjunction with the patient presentation with an understanding of its limitations for providing a specific etiologic diagnosis.
236 citations
TL;DR: Induction of ventricular AP (mRNA and peptide) may represent regression of the tissue to an earlier developmental form and provide a unique example of regulation of AP biosynthesis in nonatrial tissue.
Abstract: Left ventricular hypertrophy or treatment with dexamethasone caused a 2.5-fold to threefold increase in both immunoreactive atriopeptin (AP) and AP messenger RNA (mRNA), primarily in left ventricular tissue. The combined treatments increased immunoreactive AP and AP mRNA more than either treatment alone. In the animals in which cardiac hypertrophy had been produced by abdominal aortic constriction, there was a decrease in atrial levels of AP and an increase in plasma levels of immunoreactive AP. The increase in left ventricular immunoreactive AP was confirmed by immunohistochemical staining of tissue from hypertrophied and/or dexamethasone-treated rats. The mRNA accumulated in the left ventricle was identical to atrial AP mRNA, as judged by transcriptional start site and by size on Northern blots. Because the mass of ventricular tissue is substantially greater than that of atrial tissue, the induced mRNA levels may represent a total abundance approaching one third of the total AP mRNA in the atria. High performance liquid chromatographic purification of ventricular extracts primarily demonstrated the presence of the high molecular precursor and small amounts of C-terminal peptide AP. Induction of ventricular AP (mRNA and peptide) may represent regression of the tissue to an earlier developmental form. These data provide a unique example of regulation of AP biosynthesis in nonatrial tissue.
154 citations
TL;DR: The results suggest that human primitive progenitors are dormant in cell cycle and that they survive in the absence of colony-stimulating factors, and may provide a unique population of progenitor for studies of the early process of human hemopoiesis.
142 citations
TL;DR: The forced vital capacity, blood oxygen tension, and age are predictors of pulmonary complications in spinal cord injury patients and the use of a multidisciplinary approach and a rotating bed may minimize these problems.
Abstract: The records of 123 consecutive patients admitted with spinal cord injury were examined for the presence of pulmonary complications. Forty-nine had tetraplegia and 23 had paraplegia; the remainder suffered a variety of neurological deficits. Multiple injuries were encountered in 36 patients. Fifty-three pulmonary complications were noted in 44 (35.7%) patients. The most common problems were atelectasis and pneumonia. There were 22 (18%) deaths. Fourteen deaths were related to pulmonary complications. The mean age of patients who died was 52 +/- 13 (SE) compared to 28 +/- 12 for survivors. A mean forced vital capacity (FVC) of 1127 +/- 410 cc in patients suffering respiratory difficulties compared to a FVC of 1865 +/- 85 cc in patients without complications (P less than 0.001). Oxygenation (PaO2 90 +/- 19 torr) was normal in patients without respiratory problems and was abnormal in patients developing problems (PaO2 76 +/- 30 torr; P less than 0.05). Twenty patients were treated with a rotating bed. The complication rate of patients on the bed was only 10%. In conclusion, respiratory problems remain a significant cause of morbidity and mortality in spinal cord injury. The forced vital capacity, blood oxygen tension, and age are predictors of pulmonary complications. The use of a multidisciplinary approach and a rotating bed may minimize these problems.
129 citations
TL;DR: The results indicate that preoperative ventricular function is still an important determinant of outcome of aortic valve replacement for aorta regurgitation, however, current medical and surgical techniques permit a better prognosis in the presence of reduced ventricularfunction than was previously considered possible.
123 citations
TL;DR: The cochlear nuclear complex of the cat was immunostained with an antiserum to glutamate decarboxylase (GAD), the biosynthetic enzyme for the inhibitory neurotransmitter GABA, and studied with different procedures, including silver intensification, topical colchicine injections, semithin sections, und immunoelectron microscopy.
Abstract: The cochlear nuclear complex of the cat was immunostained with an antiserum to glutamate decarboxylase (GAD), the biosynthetic enzyme for the inhibitory neurotransmitter GABA, and studied with different procedures, including silver intensification, topical colchicine injections, semithin sections, und immunoelectron microscopy. Immunostaining was found in all portions of the nucleus. Relatively few immunostained cell bodies were observed: most of those were in the dorsal cochlear nucleus and included stellate cells, cartwheel cells, Golgi cells, and unidentified cells in the deep layers. An accumulation of immunoreactive cells was also found within the small cell cap and along the medial border of the ventral cochlear nucleus. Immunostained cells were sparse in magnocellular portions of the ventral nucleus. Most staining within the nucleus was of nerve terminals. These included small boutons that were prominent in the neuropil of the dorsal cochlear nucleus, the granule cell domain, in a region beneath the superfi-cial granule cell layer within the small cell cap region, and along the medial border of the ventral nucleus. Octopus cells showed small, GAD-positive terminals distributed at moderate density on both cell bodies and dendrites. Larger, more distinctive terminals were identified on the large cells in the ventral nucleus, in particular on spherical cells and globular cells. There was a striking positive correlation of the size, location, and complexity of GAD-positive terminals with the size, location, and complexity of primary fiber endings on the same cells. This correlation did not hold in the dorsal nucleus, where pyramidal cells receive many large GAD-positive somatic terminals despite the paucity of primary endings on their cell bodies. The GAD-positive terminals contained pleomorphic synaptic vesicles and formed symmetric synaptic junctions that occupied a substantial portion of the appositional surface to cell bodies, dendrites, axon hillocks, and the begin-ning portion of the initial axon segments. Thus, the cells provided with large terminals can be subjected to considerable inhibition that may be activated indirectly through primary fibers and interneurons or by descending inputs from the auditory brainstem.
112 citations
TL;DR: The results indicate that sucralfate used in conjunction with NSAIDs may allow patients to continue therapy by relieving gastrointestinal symptoms and mucosal damage associated with NSAID therapy.
TL;DR: Findings indicate that the tectorial membrane is regenerated in parallel with the hair cells during recovery from acoustic trauma but the full extent of this recovery and its effect on cochlear function are not yet clear.
TL;DR: The data show that a tissue kallikrein indistinguishable thus far from a urinary kallkrein is widely distributed in brain and pituitary and that levels of enzyme and mRNA are comparable in certain central sites.
Abstract: We have detected tissue kallikrein and kallikrein mRNA in various brain regions with a kallikrein direct RIA and with nucleic acid hybridization using a kallikrein cDNA probe. In the direct RIA, rat urinary kallikrein-like activity was found in the pituitary and pineal glands, hypothalamus, cerebral cortex, cerebellum, and brain stem. Pituitary and pineal gland kallikrein concentrations were significantly higher than those in other regions. Only in pituitary was there a significant difference in tissue kallikrein concentration according to sex, with glands from female rats showing levels 4-fold higher than those from male rats. Kallikrein mRNAs were detected in all of the regions and were about 4-fold higher in female than in male pituitary gland. Northern blot analyses show sex dimorphism of pituitary kallikrein mRNA, similar in size to submandibular gland and kidney mRNA. In castrated male rats, whole pituitary kallikrein content was reduced to 50% of the control value and increased 1.7-fold with testosterone replacement and 18-fold with 17 beta-estradiol treatment. Neither T4 nor cortisol affected whole pituitary kallikrein levels in the castrated male rat, but testosterone decreased pituitary kallikrein in normal female rats by 35%. When anterior pituitary or neurointermediate lobe extracts were separately examined, immunoreactive kallikrein was 10.2- and 1.3-fold higher respectively, in female than in male rat lobes. Estradiol benzoate (30 micrograms/kg) administration increased kallikrein levels 90- and 22-fold, respectively, in the anterior pituitary of gonadectomized male and female rats, while it increased by only 40-50% kallikrein levels in the male and female neurointermediate lobe. In dot blot analysis, kallikrein mRNA levels were increased 5-fold by 17 beta-estradiol in the whole pituitary of castrated male rats. In the cytoplasmic dot hybridization analysis, estradiol benzoate treatment increased kallikrein mRNA levels 54-fold in the anterior pituitary of ovariectomized rats. The data show that a tissue kallikrein indistinguishable thus far from a urinary kallikrein is widely distributed in brain and pituitary and that levels of enzyme and mRNA are comparable in certain central sites. Kallikrein levels in the anterior and neurointermediate pituitaries are differentially regulated by estrogen.
TL;DR: The acridine orange and propidium iodide assay enables the rapid estimation of the viability of a population of islet cells prior to time-consuming experiments rather than retrospectively.
Abstract: A rapid fluorometric method has been developed to evaluate the viability of isolated islet cells. The assay differentiates between viable and nonviable cells by the simultaneous use of the inclusion and exclusion dyes acridine orange and propidium iodide. When viewed by fluorescent microscopy, viable cells fluoresce green, while nonviable cells fluoresce bright red. Although the acridine orange and propidium iodide assay measures membrane integrity, the results of this assay correlate with other measures of cell viability. Compared to trypan blue exclusion, this assay is easier to read, more stable, and has fewer staining artifacts. The assay enables the rapid estimation of the viability of a population of islet cells prior to time-consuming experiments rather than retrospectively. This assay can also be used with intact islets. Stained islets can be divided into three distinct groups: green fluorescing islets contain insulin, red fluorescing islets contain little or no insulin and a third class of islets containing some non-viable cells fluoresce red, green, and yellow. The yellow colour is due to the superimposition of red and green fluorescing cells.
TL;DR: Results indicated that patients with either sarcoid or tuberculosis who developed an aspergilloma had a poor prognosis over the next decade and appeared to have a worse short-term prognosis.
Journal Article•
TL;DR: Time courses of methemoglobinemia in rat erythrocyte suspensions and in rats after treatment with 2- and 4-aminophenol, phenylhydroxylamine, and aniline are determined, consistent with phenyl Hydroxylamine being the sole mediator of anilines-induced methemoglobinemic response in these rats.
Abstract: Methemoglobinemia after aniline and certain aniline derivatives is thought to be mediated by toxic metabolites formed during the hepatic clearance of the parent compounds. However, three aniline metabolites--phenylhydroxylamine, 2-aminophenol, and 4-aminophenol--catalyze methemoglobin formation in erythrocyte suspensions and, hence, could contribute to methemoglobin formation in vivo after aniline. To determine the relative contributions of these aniline metabolites to aniline-induced methemoglobinemia in rats, we determined time courses of methemoglobinemia in rat erythrocyte suspensions and in rats after treatment with 2- and 4-aminophenol, phenylhydroxylamine, and aniline. The relative potencies for methemoglobin production in vitro after phenylhydroxylamine, 2-aminophenol, and 4-aminophenol were about 10:5:1, based on both peak and area of the methemoglobin versus time curve. Approximate minimum concentrations for observable methemoglobin formation in vitro from these compounds were 20, 50, and 200 microM, respectively. Compared with the in vitro data, the relative potencies of the aminophenols for methemoglobinemia in rats after intraperitoneal injections were reduced with respect to phenylhydroxylamine (to 100:4:1, respectively), apparently as a result of rapid in vivo clearance of the aminophenols. Subsequent experiments, in which the time courses of the aniline metabolites were determined in blood after toxic doses of aniline, demonstrated that only phenylhydroxylamine (measured as phenylhydroxylamine + nitrosobenzene) accumulated to blood levels exceeding the minimum concentration required for methemoglobin production in vitro. In addition, blood levels of phenylhydroxylamine remained in the toxic range throughout most of the methemoglobinemic response after aniline treatment. These data are consistent with phenylhydroxylamine being the sole mediator of aniline-induced methemoglobinemia in these rats.
TL;DR: Since all 16 children with renal disease exhibited significant growth delay, it is concluded that low serum IGF levels are unlikely to play a role in this growth failure and somatomedin carrier proteins should be evaluated for their role in the growth failure of children with chronic renal failure.
TL;DR: The results suggest that PRL, but not GH, cells from these pituitary regions are differentially responsive to at least two hypothalamic secretagogues, and raise the possibility that the release of PRL from mammotropes and mammosomatotropes is regulated differently and that the ratio of these two cell types may dictate, in part, the manner in which a specific region of the pituitsary responds to hypothalamic input.
Abstract: Reverse hemolytic plaque assays were used to compare the responsiveness of cells from different pituitary regions to the modulatory effects of human pancreatic GHreleasing factor (GRF), TRH, and dopamine (DA). Tissues from the peripheral rim (outer zone) and the central region (inner zone) of adenohypophyses from day 10 lactating rats were dispersed with trypsin, and the cells were placed into culture. On the following day, these cells were subjected to GH plaque assays (conducted in the presence or absence of GRF) and PRL plaque assays (performed with or without TRH and DA). Cells from both zones responded similarly to GRF with a rapid acceleration of GH plaque formation. However, the rate of PRL plaque formation in response to TRH and DA differed between cells from these regions. For outer zone cells, plaque development increased greatly with TRH treatment, but was only moderately affected by DA. Plaque formation from inner zone cells was influenced slightly by TRH, but markedly inhibited by DA. These r...
TL;DR: It is suggested that glycosylation of low density lipoproteins to the extent occurring in diabetes may alter their interaction with human monocyte-derived macrophages and may lead to increased intracellular cholesteryl ester accumulation.
Abstract: Diabetes mellitus is an independent risk factor in the development of atherosclerosis. In this study we aimed to demonstrate whether there is an abnormal interaction between low-density lipoproteins from diabetic patients and human macrophages. We measured cholesteryl ester synthesis and cholesteryl ester accumulation in human monocytederived macrophages (obtained from non-diabetic donors) incubated with low density lipoproteins from Type 1 (insulin-dependent) diabetic patients in good or fair glycaemic control. Low density lipoproteins from the diabetic patients stimulated more cholesteryl ester synthesis than low density lipoproteins from non-diabetic control subjects (7.19±1.19 vs 6.11±0.94 nmol/mg cell protein/20 h, mean±SEM, p<0.05). The stimulation of cholesteryl ester synthesis by low density lipoproteins isolated from diabetic patients was paralleled by a significant increase in intracellular cholesteryl ester accumulation (p<0.02). There were no significant differences in the lipid composition of low density lipoproteins between the diabetic and control groups. Non-enzymatic glycosylation of low density lipoproteins was higher in the diabetic group (p<0.01) and correlated significantly with cholesteryl ester synthesis (r=0.58). Similarly, low-density lipoproteins obtained from non-diabetic subjects and glycosylated in vitro stimulated more cholesteryl ester synthesis in macrophages than control low density lipoproteins. The increase in cholesteryl ester synthesis and accumulation by cells exposed to low density lipoproteins from diabetic patients seems to be mediated by an increased uptake of these lipoproteins by macrophages. This study suggests that glycosylation of low density lipoproteins to the extent occurring in diabetes may alter their interaction with human monocyte-derived macrophages and may lead to increased intracellular cholesteryl ester accumulation. The results suggest a possible mechanism by which hyperglycaemia may contribute to the acceleration of atherosclerosis in diabetes.
TL;DR: The presence of silent myocardial ischemia identified during exercise stress thallium testing is of prognostic value, independent of angiographic variables such as extent of CAD and left ventricular ejection fraction.
Abstract: Fifty-five patients with angiographically proved coronary artery disease (CAD) underwent Bruce protocol exercise stress testing with thallium-201 imaging. Twenty-seven patients (group I) showed myocardial hypoperfusion without angina pectoris during stress, which normalized at rest, and 28 patients (group II) had a similar pattern of reversible myocardial hypoperfusion but also had angina during stress. Patients were followed for at least 30 months. Six patients in group I had an acute myocardial infarction (AMI), 3 of whom died, and only 1 patient in group II had an AMI (p = 0.05), and did not die. Silent myocardial ischemia uncovered during exercise stress thallium testing may predispose to subsequent AMI. The presence of silent myocardial ischemia identified in this manner is of prognostic value, independent of angiographic variables such as extent of CAD and left ventricular ejection fraction.
TL;DR: Overall it appears that the CDI is a useful instrument to tap into depression from a self-perceived level although much more research needs to be done to determine the validity of the scale before it can be used with any degree of confidence with emotionally disturbed populations.
Abstract: This study presents data on the administration of the Children's Depression Inventory (CDI) to a psychiatrically hospitalized sample of children ranging from 6 to 17 years of age ( N = 535). The relationships between age, gender, and self-reported levels of depression are reported for the entire sample as well as for extremely depressed and nondepressed hospitalized children. The various properties of the CDI itself are examined in terms of the frequency of individually endorsed items. Interitem and interscale correlations as well as reliability data of the CDI are also computed. Overall it appears that the CDI is a useful instrument to tap into depression from a self-perceived level although much more research needs to be done to determine the validity of the scale before it can be used with any degree of confidence with emotionally disturbed populations.
TL;DR: It is reported that calcitonin gene-related peptide increases the discharge rate of afferent fibers innervating hair cells in the lateral line organ of Xenopus laevis, providing evidence for a neurotransmitter role for CGRP in a sensory system and helping explain the non-cholinergic excitatory effect seen with efferent stimulation in this and other hair cell organs such as the inner ear.
TL;DR: A survey of the literature on the use of antidepressants for treating patients with panic disorder and agoraphobia with panic attacks suggests that both tricyclic antidepressants and monoamine oxidase inhibitors have efficacy in blocking panic attacks.
TL;DR: The effects of an acute fast on acetaminophen metabolism and hepatotoxicity were investigated in male Long Evans Hooded rats and it was demonstrated that significant glucuronidation capacity was maintained in fasted rats, indicating that the glucuronidated capacity was not directly correlated with glycogen levels; and infasted rats the glucose required for UDP-glucuronic acid formation for acetaminphen glucuronisation was supplied from sources other than glycogen.
TL;DR: A lack of therapeutic efficacy of prostacyclin in a defined population of patients with nonhemorrhagic cerebral infarction is suggested.
Abstract: The therapeutic efficacy of prostacyclin in nonhemorrhagic cerebral infarction was assessed in a placebo-controlled double-blind trial. A total of 80 patients with stroke onset within 24 hours were randomized into placebo (37 patients) and prostacyclin (43 patients) groups. Demographic data and risk factors were comparable. Patients in the prostacyclin group received a continuous i.v. infusion of prostacyclin at an average rate of 8.5 ng/kg/min for an average of 64 hours. The placebo group received vehicle only in a similar fashion. During treatment hemodynamic changes were more prominent in the patients receiving prostacyclin and included reduction of systolic and diastolic blood pressure and increase in pulse rate. In contrast there was only a slight (but significant) reduction of diastolic blood pressure in the placebo group. Neurologic deficit scores were determined on admission, at Day 3, and at Weeks 1, 2, and 4. Mean neurologic deficit scores upon entry were comparable in the placebo and prostacyclin groups, and a significant improvement in the score for neurologic deficit was noted in both. The placebo group tended to fare better throughout the study, with a significant difference in neurologic deficit score favoring the placebo group at Week 2 (p = 0.0048). Two patients in the placebo and one in the prostacyclin group died. The only difference in adverse reactions was flushing (6 patients in prostacyclin vs. 0 in placebo group, p less than 0.05). The results of this study suggest a lack of therapeutic efficacy of prostacyclin in a defined population of patients with nonhemorrhagic cerebral infarction.
TL;DR: Although some clinical variables other than psychotic features differed between the two groups, these could not account for the UFC differences and the older patients in the MDPF group accounted for the high UFC excretion, suggesting an interaction between age and diagnosis.
Patent•
21 Aug 1987TL;DR: In this paper, a device for use in cryopreservation of blood vessels comprising a pair of stylets insertable into the ends of a dissected blood vessel segment is described.
Abstract: A device for use in cryopreservation of blood vessels comprising a pair of stylets insertable into the ends of a dissected blood vessel segment. The stylets are mountable on a support track whereby the blood vessel can be distended and supported during cryopreservation procedures. Also disclosed is a freezing and thawing profile capable of maximizing endothelial cell survival. The use of chondroitin sulfate or similar compound is discussed as a novel cryoprotectant.
TL;DR: Cytological studies of colonies derived from GM‐CSF and/or IL‐3 suggest that the eosinophilopoietic ability of murine GM‐ CSF is less than that of IL-3, and indicates that the progenitors for blast cell colonies that responded to GM‐csF are a subpopulation of multipotential progenitor that are supported by IL‐ 3.
Abstract: We studied the effects of murine recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) on murine hemopoiesis in methylcellulose culture. The GM-CSF was purified from cultures of Saccharomyces cerevisiae transfected with a cloned murine GM-CSF cDNA. In cultures of spleen cells from normal mice, only granulocyte-macrophage (GM) colonies were supported by GM-CSF. Blast cell colonies were the predominant type in cultures of spleen cells from 5-fluorouracil (5-FU)-treated mice. Dose-response studies revealed that maximal GM and blast cell colony formation is achieved with 100 U/ml GM-CSF. Blast cell colonies revealed variable but high replating efficiencies, and the secondary colonies included multilineage colonies. Serial replating of washed blast cell colonies in cultures with GM-CSF provided evidence for the direct effects of GM-CSF on the proliferation of multipotential blast cells. A combination of GM-CSF and interleukin-3 (IL-3) did not increase the number of blast cell colonies over the level supported by IL-3. This observation indicates that the progenitors for blast cell colonies that responded to GM-CSF are a subpopulation of multipotential progenitors that are supported by IL-3. Cytological studies of colonies derived from GM-CSF and/or IL-3 suggest that the eosinophilopoietic ability of murine GM-CSF is less than that of IL-3.
TL;DR: It is shown that STZ diabetes produces an impairment in renal kallikrein synthesis and suggested that this disease state also impairs renal prokallkrein activation and the findings suggest that insulin modulates renal k allikre in production, activation, and excretion.
Abstract: The effects of streptozotocin (STZ) diabetes and insulin on regulation of renal kallikrein were studied in the rat. 1 and 2 wk after STZ injection, diabetic rats had reduced renal levels and urinary excretion of active kallikrein. Tissue and urinary prokallikrein levels were unchanged, but the rate of renal prokallikrein synthesis relative to total protein synthesis was reduced 30-45% in diabetic rats. Treatment of diabetic rats with insulin prevented or reversed the fall in tissue level and excretion rate of active kallikrein and normalized prokallikrein synthesis rate. To further examine insulin's effects, nondiabetic rats were treated with escalating insulin doses to produce hyperinsulinemia. In these rats, renal active kallikrein increased. Although renal prokallikrein was not increased significantly by hyperinsulinemia, its synthesis was increased. As this was accompanied by proportionally increased total protein synthesis, relative kallikrein synthesis rate was not changed. Excretion of active kallikrein was unchanged, but prokallikrein excretion was markedly reduced. Therefore, increased tissue active kallikrein seen with hyperinsulinemia can be explained not only by increased synthesis but also by retention and increased activation of renal prokallikrein. These studies show that STZ diabetes produces an impairment in renal kallikrein synthesis and suggest that this disease state also impairs renal prokallikrein activation. The findings also suggest that insulin modulates renal kallikrein production, activation, and excretion.
TL;DR: Putative roles for calcium in proteolysis and lipolysis, inducing degradation of macromolecules and production of prostanoids which initiate edema, lysolecithin a myelinolytic factor and mitochondrial dysfunction in spinal cord injury are discussed.
Abstract: Experimental spinal cord injury in animals induced by weight drop produces neurological deficit and paralysis. Correlation of the progressive morphological changes in the lesion by both light and electron microscopy with the biochemical alterations revealed ischemia, edema, hemorrhage, tissue necrosis, granular changes in axons, vesicular degeneration of myelin and axonal calcification. The biochemical pathology was that of degradation of axonal (neurofilaments) and myelin proteins (MBP and PLP) with increased activities of proteolytic enzymes and particularly the neutral proteinase. The level of total calcium increased progressively in the lesion to a peak at 8 hrs. and subsequently remained constant thereafter. The capacity of calcium for activating proteinases and lipases and fostering the degradation of axon and myelin proteins as well as the liberation of arachidonic acid required for the synthesis oof prostanoids must be relevant. An increased production of prostanoids is indicated by elevation of thromboxane (TxB2), a stable metabolite of TXA2 at 1 hour after injury. The 6-keto-PG11a was also increased but to a lesser extent. We suspect that the activation of arachidonic acid metabolism contributes to post-traumatic vascular injury and the progressive ischemia. These putative roles for calcium in proteolysis and lipolysis, inducing degradation of macromolecules and production of prostapoids which initiate edema, lysolecithin a myelinolytic factor and mitochondrial dysfunction in spinal cord injury are discussed.