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History and current status of percutaneous arthroscopic disc surgery.

STUDY DESIGN: The relevant literature and the author's experience with the management of lumbar disc herniation is reviewed. OBJECTIVES: To describe the history of percutaneous arthroscopic discectomy, and to discuss the indications, the procedure's scientific validity, and its outcome. SUMMARY OF BACKGROUND DATA: In contrast to nuclear-debulking procedures, arthroscopic microdiscectomy is target-oriented and capable of retrieving the compressive elements in a carefully selected patient population. The insult to myoligamentous stabilizing structures and intracanalicular tissues is minimal. Extraction of herniated fragments not only can be demonstrated under arthroscopic visualization but also via postoperative imaging studies. METHODS: Search of the literature and the author's experience with arthroscopic disc surgery. RESULTS: Arthroscopic microdiscectomy has a learning curve. In properly selected patients, a successful outcome similar to macro- or microdiscectomy may be achieved. CONCLUSIONS: Proper patient selection is paramount to a successful outcome of arthroscopic disc surgery. Sequestered migrated herniations and large central herniations at L5-S1 in individuals with elevated iliac crests will require open surgery.

Arthroscopy↗

Changes in epidermal radiosensitivity with time associated with increased colony numbers.

Epidermal clonogenic cell survival and colony formation following irradiation were investigated and related to radiosensitivity. A rapid in vivo/in vitro assay was developed for the quantification of colonies arising from surviving clonogenic cells in pig epidermis after irradiation. Bromodeoxyuridine (BrdU)-labelled cells in full thickness epidermal sheets were visualized using standard immunohistochemistry. In unirradiated skin, approximately 900 BrdU-positive cells mm(-2) were counted. In a time sequence experiment, BrdU-positive cell numbers increased from an average of 900 cells mm(-2) to approximately 1400 cells mm(-2) after BrdU-labelling for 2-24 h. In irradiated skin, colonies containing >/=16 BrdU-positive cells were seen for the first time at days 14/15 after irradiation. The number of these colonies per cm(2) as a function of skin surface dose yielded a cell survival curve with a D(0)-value (+/-SE) of 3.9+/-0.6 Gy. This relatively high D(0)-value is possibly due to a rapid fall off in depth dose distribution for the iridium-192 source and consequently a substantial contribution of hair follicular epithelium to colony formation. At 14/15 days after irradiation, the ED(50) level of 33.6 Gy for the in vivo response of moist desquamation corresponded with 2.7 colonies cm(-2). Surprisingly, the number of colonies increased with time after irradiation with an estimated doubling time of approximately 4 days, while the D(0)-value remained virtually unchanged. This increase in colony numbers could be due to migration of clonogenic cells, to the recruitment of dormant clonogenic cell survivors by elevated levels of cytokines, or to both. Although frequent biopsying caused increased cytokine levels, which had a systemic effect on unirradiated skin, it had no influence on colony formation in irradiated skin. Smaller colonies, containing 4-8 cells or 9-15 cells, were abundant, particularly after higher doses, which resulted in higher D(0)-values. The majority of these small colonies were abortive and did not progress to larger colonies. There was no statistical evidence for significant variations in the interanimal responses.

Analysis of Variance↗

Symptomatic arterial luminal narrowing presenting months after subarachnoid hemorrhage and aneurysm clipping.

The authors describe three cases of clinical cerebral ischemia associated with angiographic evidence of cerebral arterial luminal narrowing presenting 7, 14, and 52 weeks after subarachnoid hemorrhage (SAH) and aneurysm clipping. Delayed vasospasm, in its usual time setting 1 or 2 weeks after hemorrhage, did not occur symptomatically in these patients. No evidence for aneurysm clip migration or rebleed was present. All patients responded favorably to volume expansion and elevation of blood pressure. This unusual occurrence of a very delayed vasospasm may further the understanding of the vasospastic process. The symptomatic onset of arterial luminal narrowing months after SAH may suggest that a proliferative vasculopathy more accurately explains the observed vessel narrowing, rather than conventional active constriction of vascular smooth muscle.

Adult↗

The alpha 3 beta 1 integrin is associated with mammary carcinoma cell metastasis, invasion, and gelatinase B (MMP-9) activity.

The alpha 3 beta 1 integrin is elevated in several types of metastatic tumor and has been associated with increased migration and invasion. Our analysis of a series of mammary carcinomas of different histotypes and their corresponding metastases demonstrated significantly increased expression of alpha 3 beta 1 in the tumor metastases. We therefore studied alpha 3 beta 1 expression of several human breast carcinoma cell lines and its association with the invasive phenotype. The MDA-MB-231 cell line expressed high levels of the beta1, alpha 2, alpha 3, alpha 5, and alpha 6 integrin subunits along with moderate levels of the alpha v beta 3 integrin. This line was highly migratory and the most invasive using a chemo-invasion assay. In contrast, the other lines tested, MDA-MB-145, MCF-7, and SK-BR-3, showed lower migratory and invasive activity and reduced alpha 3 integrin subunit expression. Metalloproteases capable of degrading collagen IV are necessary for the invasive process. RT-PCR showed that MDA-MB-231 cells expressed MMP-9, but not MMP-2, gelatinase/collagenase IV. Gelatin zymography demonstrated that invading MDA-MB-231 cells released high levels of MMP-9 gelatinase activity. A direct role for this gelatinase in MDA-MB-231 cell invasion was confirmed by inhibition of invasion using the metalloprotease inhibitor Batimastat. Treatment of MDA-MB-231 cells with a function-blocking anti-alpha 3 antibody strongly inhibited migration and invasion. This correlated with a marked reduction in MMP-9 activity produced by MDA-MB-231 cells, suggesting a role for alpha 3 beta 1 ligand binding in cell signaling and regulation of extracellular matrix degradation.

Adult↗

The Possible Immunological Mechanisms of Pathology in Mice with Congenitally Acquired Influenza Infection.

The fact that congenitally acquired viral infection often strongly influences specific and non-specific immunoreactivity is well documented. Viral infection of pregnant female may lead to serious of pathological consequences for the offspring, namely, to mortality, developmental disorders and in less severe cases to body growth retardation, wasting syndrome and immunodeficiency. In this connection, we have studied congenitally acquired influenza infection in CII mice. The progeny of C57BL/6 female mice, which were infected with influenza virus (A/WSN) by the 3rd week of pregnancy, exhibited a profound growth retardation and major morphological lesions of central nervous system, lymphoid and other organs. We have found out that mice with congenitally acquired influenza infection had autoreactive killer T cells in their lymphoid organs. CII mice exhibited some features of chronic immune activation, namely elevated spontaneous proliferation, spontaneous development of plaque forming cells, and spontaneous inhibition of migration activity. Lymphoid cells from mice with congenitally acquired influenza infection induced an enlargement of regional lymph nodes after they had been injected into syngeneic non-infected recipient in popleteal node assay. The level of this reaction depended on the level of virus-bearing cells in donor cell population and correlated with the increase of gammadelta and CD4(+) T cells. The role of these interactions in pathology is discussed herein.

Journal Article↗

[Expression of chemokine monokine induced by interferon-gama in patients with chronic hepatitis B].

OBJECTIVE: To study the expression levels of monokine induced by interferon-gama; (Mig) mRNA and its association with HBV DNA and alanine aminotransferase (ALT) in patients with chronic hepatitis B. METHODS: The level of Mig mRNA in peripheral blood mononuclear cells (PBMCs) was dynamically detected with real-time quantitative PCR, and the ratio of chemokine/GAPDH was considered to represent the final chemokine level. The plasma level of was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The mean level of Mig mRNA in PBMCs of the patients with chronic hepatitis B was 0.6883-/+0.0693, which was significantly higher than that in normal controls (P<0.001). The plasma Mig level in the patients was 609.6-/+73.8 pg/ml, also significantly higher than that in normal controls (P<0.05). In patients with chronic hepatitis B, the level of Mig mRNA in the PBMCs was significantly correlated with plasma Mig level (r=0.7157, P<0.001), and plasma Mig level was correlated with plasma ALT level (r=0.7220, P<0.001) and plasma HBV DNA level (r=0.7266, P<0.001). CONCLUSION: Both the expression of Mig mRNA in PBMCs and plasma Mig concentration are elevated in patients with chronic hepatitis B. Mig plays an important role in migration of the inflammatory cells to the liver and mediates the development of chronic hepatitis B.

Adolescent↗

[Diagnostic, prognostic and therapeutic value of Doppler echocardiography in pulmonary embolism. Apropos of 41 cases].

In 41 patients with acute or recent pulmonary embolus (PE), a prospective study was conducted with cardiac Doppler sonography (CDS). The test is performed first in all patients, then immediately following a treatment fibrinolytics in 10 of them. The PE is confirmed by pulmonary angiography in 39 patients and embolectomy for the 2 patients who presented a mobile thrombus in the right atrium. A tricuspid insufficiency (TI) is almost always recorded by continuous Doppler: the systolic pulmonary artery pressure (sPAP) is calculated from the maximum velocity of the regurgitating tricuspid flow, using Bernouilli's equation. The correlation between Doppler sPAP and sPAP obtained by catheterization is: r = 0.95 (n = 34; p less than 0.001). A severe pulmonary hypertension, corresponding to a TI exceeding 3.5 m/s is related to a pulmonary migration occurring on a pathological heart. There is a satisfactory relationship between the elevation of the Doppler sPAP and the degree of pulmonary obstruction in the "Pe on healthy heart" population: r = 0.6 (n = 29; p less than 0.001). The dilated right ventricle observed on the sonogram (RV) is proportional to the severity of the angiographic image: correlation between the RV/LV ratio and the percentage of vascular obstruction is r = 0.73 (n = 27; p less than 0.001). The drop in the sPAP and the regression of the symptoms of pulmonary heart noted on CDS after fibrinolysis, correspond to a significant improvement of the pulmonary perfusion. The CDS seems to be absolutely necessary in PE because of the major and reliable informations it provides.

Adult↗

Studies of humoral and cell-mediated immunity to peptides shared by HLA-27.1 and Klebsiella pneumoniae nitrogenase in ankylosing spondylitis.

One-hundred and twenty-four patients with spondylarthropathies were studied for antibodies to the peptides from HLA-B27.1 and Klebsiella pneumoniae nitrogenase which share a QTDRED hexamer sequence. Of 60 male Norwegian ankylosing spondylitis (AS) patients 23.3% showed positive ELISA reactivity for B27.1 peptide compared with 4% of Norwegian male controls (P less than 0.10). This difference was not observed among patients and controls from New Mexico. All patients with anti-B27.1 antibody were HLA-B27+. Antibody to B27.1 peptide was present in 20% of normal female controls with at least one previous pregnancy. No female control without previous pregnancy showed positive anti-B27.1 peptide reactivity. Anti-Klebsiella peptide antibody was neither significantly elevated in AS nor correlated with anti-B27.1 peptide antibody. Significant migration inhibition by these peptides was not observed in AS or normal controls. The possible influence of epitope conformation, rather than sequence homology, in potentially cross-reacting determinants shared by bacterial antigens and human Class I molecules requires further study.

Adult↗

Immune response against P815X2 mastocytoma growing in syngeneic DBA/2 mice. III. Morphometric assessment of the dynamic changes in post-capillary venules as regulatory elements of lymphocyte recirculation in tumor-draining lymph nodes.

To evaluate the dynamics of lymphocyte recirculation in tumor-bearing mice, the post-capillary venules (PCV) were subjected to quantitative measurements in the regional (RLN) and nonregional (NRLN) lymph nodes during the progression of P815X2 mastocytoma in syngeneic DBA/2 mice. Mice were sacrificed at two-day intervals, and RLNs and NRLNs were analysed for their content of B- and T-lymphocytes and their subsets, demonstrated by immunoperoxidase technique using monoclonal antibodies; Anti-Thy 1.2 (T cells), Anti-Lyt 1 (T-helper cells), Anti-Lyt 2 (T-suppressor cells), and Anti-I-Ad (B cell) antigens, separately in the B- and T-cell compartments. In the PCVs, migration index (MI) and endothelial height (Hend) were measured. There was a biphasic elevation of MI in the RLNs, as compared with only a late rise in the NRLNs, reaching the peak (1.54) on day 14. In RLNs, there was a sharp reduction in Hend starting from the values (6.37 microns) on day 2, down to 4.79 microns on day 8. This is followed by rapid elevation close to the second-day values, e.g. 6.07 on day 10. The changes in MI paralleled the early influx of B cells, as evidenced by the decrease of Thy 1.2+/I-Ad+ cell ratio and a late recruitment of T cells as indicated by the elevation of that ratio as well as the Hend values in both the RLNs and NRLNs. The present experiment shows that morphology of PCVs in the RLNs and in NRLNs of P815X2-bearing mice is subjected to alterations reflecting the dynamics of lymphocyte recruitment into these organs. When combined with lymphocyte subset enumeration using monoclonal antibodies, the quantitative analysis of the PCVs permits predictions to be made on the recirculatory activity of these cell populations during the tumor progression.

Animals↗

Hypothesis: in vitro evidence for the invasive and tumor-like properties of the rheumatoid pannus.

It is often considered that the inflammatory processes in the rheumatoid synovium are due to an immune response to an as yet unknown antigen; the resultant pannus has been referred to as "aggressive, invasive, proliferative and tumor-like." Data are presented which show that arthritogenic group A streptococcal cell walls stimulate human monocyte-macrophages to elevate the plasminogen activator (PA) activity of human synoviocytes. By analogy with other cellular systems, it is suggested that the monocyte-macrophage mediated elevation of synoviocyte PA activity can contribute to the tissue remodelling and cell migration found in the rheumatoid pannus. It is also proposed that the active moiety from the stimulated monocyte-macrophages is able to mimic, to some extent, the effects of transforming viruses and tumor promoters on cell function. This concept of a "tumor-like" synoviocyte transformation is suggested as being consistent with the descriptions of the rheumatoid pannus as "aggressive, invasive and tumor-like." Perhaps similar cellular interactions occur in other inflammatory diseases involving connective tissue turnover and cellular hyperplasia.

Animals↗

Recovery of hemopoiesis in lethally irradiated mice after treatment with propionibacteria.

Three investigated strains of propionibacteria (P. acnes, P. granulosum and P. avidum) injected intraperitoneally in doses of 1.5 mg per mouse, significantly prolonged survival of lethally (8.50 R) irradiated mice. P. granulosum, being the most effective in increasing survival of irradiated mice was chosen for the studies on the activity of bone-marrow pluripotent stem cells. The number of endogenous spleen colonies was significantly increased in mice injected with P. granulosum 3 days prior to or 4 hours after irradiation with 650 R. However, injection of P. granulosum to donors prior to bone-marrow transplantation significantly decreased the number of exogenous spleen colonies in recipients irradiated with 850 R. These results, together with the observed increase in number of CFU-S in peripheral blood and elevated relative spleen weight after injection of P. granulosum, suggest that propionibacteria stimulate migration of CFU-S from bone-marrow via peripheral blood into spleen. Stimulation of CFU-S proliferation and differentiation is also taken into account.

Animals↗

[The clinical and serological manifestations of Lyme disease in Russia].

Out of 86 Lyme's disease patients with a history of migrating erythema nervous system, cardiovascular and articular involvement was observed in 27, 6 and 43% of cases. Acrodermatitis was diagnosed in 2% of patients. Affection of locomotor system manifested with acute arthritis episodes or pains in major joints. 11 patients of 12 examined at arthritis onset showed elevated titer of anti-Borrelia IgG antibodies. Serologically, of 80 patients with arthritis or arthralgia without prior migrating erythema 6 demonstrated antibodies to 5 and more Borrelia polypeptides.

Adolescent↗

Synergistic effects of PDGF-BB and cAMP-elevating agents on expression of connexin43 in mesangial cells.

The gap junction plays an important role in the regulation of cell growth, migration, and differentiation. Platelet-derived growth factor (PDGF) is reported to be a potent inhibitor of gap junctional intercellular communication (GJIC). Short-term exposure of cells to PDGF causes rapid and transient disruption of GJIC without altering connexin43 (Cx43) protein level. In this study, we investigated long-term effects of PDGF-BB on Cx43 expression in mesangial cells (MCs). Exposure of MCs to PDGF-BB affected neither the Cx43 protein level nor GJIC. However, in the presence of cAMP-elevating agents, PDGF-BB dramatically increased the expression of Cx43, which was accompanied by obviously augmented membrane distribution of Cx43 and functional GJIC. The increased expression of Cx43 was closely correlated with reduction in alpha-actin, a dedifferentiation marker of MCs. The effect of PDGF on Cx43 was largely prevented by inhibitors of phosphatidylinositol 3'-kinase or mitogen-activated protein kinase, but not by inhibition of protein kinase C. Exposure of MCs to PDGF-BB caused elevation in intracellular cAMP, and it was abolished by indomethacin, a cyclooxygenase inhibitor. However, indomethacin did not affect the synergistic effect. In addition, PDGF-BB also did not affect the degradation of Cx43. With the use of MCs transfected with a Cx43 promoter-luciferase vector, cooperative activation of Cx43 promoter by PDGF and cAMP was found. Together, our data reveal, for the first time, unexpected synergy between PDGF-BB and cAMP-elevating agents in the induction of Cx43 and MC differentiation. Regulation of GJIC could be an important mechanism via which PDGF modulates MC phenotypes.

Animals↗

Autocrine/paracrine regulation of keratinocyte urokinase plasminogen activator through the TGF-alpha/EGF receptor.

Transforming growth factor-alpha (TGF-alpha) appears to be an important autocrine/paracrine regulator of keratinocyte function. Not only does TGF-alpha induce keratinocyte proliferation and migration in vitro, but it also has been detected in normal human epidermis and at elevated levels in hyperproliferative epidermis. In the present study we report that exogenous TGF-alpha increases urokinase-type plasminogen activator (uPA) in cultured human keratinocytes. Furthermore, in the absence of exogenous growth factors, the "basal" levels of uPA are decreased by an antagonist monoclonal antibody to the receptor shared by TGF-alpha and epidermal growth factor (EGF). These results suggest that an endogenous factor serves as an autocrine/paracrine regulator of keratinocyte uPA. We hypothesize that activation of the TGF-alpha/EGF receptor may coordinately regulate the keratinocyte response to cutaneous wounding, which includes enhanced uPA expression, migration, and proliferation.

Antibodies, Monoclonal↗

An evaluation of new attachment formation using a microfibrillar collagen barrier.

The objective of this study was to evaluate the effectiveness of microfibrillar collagen as a barrier to prevent epithelial migration and allow for guided tissue regeneration. Fourteen study teeth were selected. Mucoperiosteal flaps were elevated and roots were debrided and planed. Avitene was placed over teeth and alveolar bone. Flaps were then sutured over it. At control sites no Avitene was placed. At 90 days, block sections were obtained and processed for histologic and histometric evaluation. Results revealed that all specimens had a long junctional epithelial attachment. New attachment was present within the area of the root notch at the original level of the alveolar bone, and there was no significant difference in mean connective tissue attachment between the control and experimental specimens (P = 0.614). Avitene did not form an effective barrier to epithelial migration nor did it allow for guided tissue regeneration and significant new attachment formation in humans.

Alveolar Process↗

Leukocyte matrix metalloproteinase-9 is elevated and contributes to lymphocyte activation in type I diabetes.

Degradation of extracellular matrix proteins by matrix metalloproteinases (MMPs) is integral to cell migration and tissue remodeling in diabetes mellitus and its complications. MMPs also regulate the function of leukocytes via proteolytic processing of cytokines/chemokines. In this study, we measured the production of MMP-9 and its natural tissue inhibitor (TIMP)-1 by leukocytes isolated from human type I diabetic patients. MMP-9 was also detected in serum and splenocytes from non-obese diabetic (NOD) and BALB/c mice. MMP-9 was markedly elevated in leukocytes from diabetics compared to non-diabetic controls. TIMP-1 production was also enhanced in leukocytes from diabetics, but substantially less than MMP-9, with the MMP-9/TIMP-1 ratio being 1.6-fold higher in neutrophils and 3-fold higher in monocytes than controls. Interleukin (IL)-2 or lipopolysaccharide (LPS) treatment increased MMP-9 production in leukocytes from both diabetics and normal controls, whereas insulin decreased MMP-9 expression. Recombinant MMP-9 stimulated the proliferation of mouse splenocytes from NOD or BALB/c and a MMP-9 inhibitor dose-dependently inhibited splenocyte proliferation. In conclusion, our results demonstrate firstly that MMP-9 expression is elevated in leukocytes from type I diabetic patients and NOD mice and secondly, that MMP-9 elevates proliferation of mouse splenocytes. These data suggest that elevated leukocyte MMP-9 may contribute to the pathogenesis of type I diabetes and its associated complications.

Animals↗

Enhanced branching morphogenesis in mammary glands of mice lacking cell surface beta1,4-galactosyltransferase.

Development of the mammary gland is influenced both by the systemic hormonal environment and locally through cell-cell and cell-extracellular matrix (ECM) interactions. We have previously demonstrated aberrant mammary gland morphogenesis in transgenic mice with elevated levels of the long isoform of beta1,4-galactosyltransferase 1 (GalT), a proportion of which is targeted to the plasma membrane, where it plays a role in cell-ECM interactions. Here, we show that mammary glands of mice lacking the long GalT isoform exhibit a complementary phenotype. Cell-surface GalT activity was reduced by over 60%, but because the short GalT isoform is intact, total GalT activity was reduced only slightly relative to wild type. Mammary glands from long GalT-null mice were characterized by excess branching, and this phenotype was accompanied by altered expression of laminin chains. Laminin alpha1 and alpha3 were reduced 2.4- and 3.0-fold, respectively, while expression of laminin gamma2 was elevated 2.3-fold. The expression and cleavage of laminin gamma2 have been correlated with branching and cell migration, and Western blotting revealed an altered pattern in gamma2 cleavage products in long GalT-null mammary glands. We then examined the expression of metalloproteases that cleave laminins or that have been shown to play a role in mammary gland morphogenesis. Expression of MT1-MMP, a membrane-bound protease that can cleave laminin gamma2, was elevated 5.5-fold in the long GalT-nulls. MMP 7 was also elevated 5.1-fold. Our results suggest that expression of surface GalT is important for the proper regulation of matrix expression and deposition, which in turn regulates the proper branching morphogenesis of the mammary epithelial ductal system.

Animals↗

Stress-induced gastroduodenal motor disturbances in humans: possible humoral mechanisms.

The objectives of this study were threefold. First, we investigated the effects of acute stressful stimuli on gastroduodenal feeding activity after a physiologic meal. Second, we explored the possible role of humoral mediators of these effects by measuring concurrently plasma levels of beta-endorphin, catecholamines, and several gut peptides. Third, we wished to determine whether or not the gut responded selectively to different types of central stimuli. Thus, in 12 healthy volunteers we studied the effects of vertigo and cold pain on the gastrointestinal motor response to a solid meal. Pressure activity was recorded by a low-compliance perfusion system. Plasma concentrations of beta-endorphin and gut peptides were measured by radioimmunoassay, whereas catecholamine levels were measured by high-pressure liquid chromatography. Blood pressure, pulse rate, and skin conductance were also monitored. Labyrinthine vertigo (by otic stimulation with 10 degrees C water; control, 37 degrees C water) and cold pain (immersing hand in 4 degrees C water; control, 37 degrees C water) were simultaneously induced after the meal in each subject according to a 2 X 2 factorial experimental design. Cold pain and labyrinthine stimulation alone or in combination significantly reduced the antral phasic pressure response to solids while elevating plasma levels of beta-endorphin and norepinephrine. These effects occurred within the first 20 min poststimulus and were associated with changes in blood pressure, pulse rate, and skin conductance. Further, in 2 of 6 individuals in whom vertigo was induced by labyrinthine stimulation, a phase 3-like burst of motor activity appeared in the duodenum and migrated aborally. We conclude that centrally acting external stimuli may severely disrupt antral feeding activity. Furthermore, concurrent elevations in plasma levels of beta-endorphin and norepinephrine raise the possibility that these substances may be involved as mediators of the central effects on the gut.

Adult↗