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Biomedical subjects

R Jacobs

Publications and source records attributed to R Jacobs.

At least 55 records · Page 3Linked to original sources

Masseter muscle fatigue before and after rehabilitation with implant-supported prostheses.

To establish whether different implant-supported prosthetic reconstructions influence jaw muscle resistance to clenching efforts, sustained submaximal (50%) clenching was performed in two groups of patients who were edentulous in one or both jaws. One group consisted of patients who were rehabilitated by means of an overdenture on two to four implants connected by a bar; the other group consisted of patients who were rehabilitated with an implant-supported fixed prosthesis on four to seven implants in either the maxilla or the mandible. Results indicated that after rehabilitation with implant-supported fixed reconstructions, the myoelectric output level increased over time, which was parallel to a higher bite force level. For the other group, such a time-dependent change in electromyographic amplitude did not occur. On the other hand, power spectrum analysis revealed a significant downward shift of the mean power frequency during sustained clenching after rehabilitation with implant-supported overdentures but not with implant-supported fixed prostheses. The absence of a spectral shift in the latter group probably expressed a fear of biting too hard and fracturing the prosthesis.

Adult

Reconstitution of vesiculated Golgi membranes into stacks of cisternae: requirement of NSF in stack formation.

We have developed an in vitro system to study the biochemical events in the fusion of ilimaquinone (IQ) induced vesiculated Golgi membranes (VGMs) into stacks of cisternae. The Golgi complex in intact normal rat kidney cells (NRK) is vesiculated by treatment with IQ. The cells are washed to remove the drug and then permeabilized by a rapid freeze-thaw procedure. VGMs of 60 nm average diameter assemble into stacks of Golgi cisternae by a process that is temperature dependent, requires ATP and a high speed supernatant from cell extract (cytosol), as revealed by immunofluorescence and electron microscopy. The newly assembled stacks are functionally active in vesicular protein transport and contain processing enzymes that carry out Golgi specific modifications of glycoproteins. The fusion of VGMs requires NSF, a protein known to promote fusion of transport vesicles with the target membrane in the exocytic and endocytic pathways. Immunoelectron microscopy using Golgi specific anti-mannosidase II antibody reveals that VGMs undergo sequential changes in their morphology, whereby they first fuse to form larger vesicles of 200-300-nm average diameter which subsequently extend into tubular elements and finally assemble into stacks of cisternae.

Adenosine Triphosphate

Biological activity of adrenocorticotropic hormone precursors on ovine adrenal cells.

Adrenocorticotropic hormone (ACTH) is synthesized in the corticotrophs as a precursor, pro-opiomelanocortin (POMC), which is processed via proACTH to ACTH. Both precursors and ACTH are secreted. Although the steroidogenic activity of ACTH is well characterized, that of the precursors is not. This study assessed the capacity of POMC and proACTH to alter cortisol synthesis. POMC and proACTH were prepared by subjecting medium, conditioned by exposure to DMS-79 cells, to Sephadex chromatography, and the bioactivity was assessed in cultured-dissociated ovine adrenal cells. Alone neither POMC (< or = 2.6 nM) nor proACTH (< or = 0.7 nM) showed any consistent acute (6 h) stimulatory or inhibitory action on cortisol in either fetal or adult cells. In contrast, in fetal cells the precursors inhibited steroidogenic response to ACTH-(1-24). POMC at 2.6 nM, but not lower concentrations, decreased the cortisol responses to 0.01, 0.1, and 1 nM ACTH by at least 50%. ProACTH (0.70 and 0.23 nM) decreased the responses to ACTH at 0.01 nM by 89 and 67%, respectively, and at 0.1 nM by 49 and 34%, respectively. At 1 nM ACTH only 0.7 nM proACTH decreased the response to ACTH (by 69%). In contrast, in adult adrenal cells, the precursors did not significantly reduce the response to ACTH (range 0.01-1 nM). Therefore, these data indicate that POMC and proACTH can inhibit the cortisol response to ACTH in fetal adrenal cells, an effect that is concentration dependent. The data suggest that precursors may play a physiological role, possibly regulating fetal plasma cortisol concentrations.

Adrenal Glands

Hepatitis C virus-polymerase chain reaction of routinely processed liver biopsies.

The aim of the study was to evaluate the specificity and sensitivity of detection of hepatitis C virus (HCV)-RNA in formalin-fixed paraffin-embedded (FFPE) liver biopsies by polymerase chain reaction (PCR). Routinely processed FFPE diagnostic needle liver biopsies as well as stored serum samples from 43 patients with liver disease were tested for HCV-RNA by reverse transcription-nested PCR using the same sets of primers and following strict anticontamination measures. Twenty-nine cases were positive and 14 were negative for serum HCV-RNA. Tissue HCV-RNA was detected in 17 out of the 29 serum HCV-RNA-positive cases but not in any of the 14 serum HCV-RNA-negative cases. Compared to serum-PCR, tissue-PCR was 100% specific, 58.6% sensitive, and 72% efficient. HCV-RNA was detected more frequently in biopsies stored for less than 1 year, than in those stored for more than 1 year (P = 0.046). In biopsies stored for up to 1 year detection of HCV-RNA by PCR was 81.8% sensitive and 90.9% efficient. Short (< 0.5 cm) liver biopsies were as sufficient for nucleic acid extraction and amplification as long (> 0.5 cm) ones. It is concluded that following strict anticontamination measures, HCV-RNA detection by PCR in routinely fixed, processed, and stored diagnostic liver biopsies provides a valuable adjunct to diagnosis of HCV infection. In this study, this option was free from contamination problems, even though routine batch histological processing schedules were used.

Base Sequence

TCR1+ large granular lymphocyte proliferation in rheumatoid arthritis.

The T gamma-lymphoproliferative syndrome is characterized by a proliferation of large granular lymphocytes (LGL). It is often associated with neutropenia, and in 30% of cases with rheumatoid arthritis (RA). Phenotypic analysis has demonstrated that in most cases of RA with T gamma-proliferative disease, the LGL represent T cells with a clonal rearrangement of the alpha/beta T cell receptor (TCR2). Here, three patients with gamma/delta TCR1+ LGL proliferation suffering from long-standing arthritis and neutropenia are described. The first patient with RA showed an expansion of a heterogeneous CD2+ CD16+ CD56- LGL population, of which 30% coexpressed TCR1 with V delta 1 rearrangement. The second patient with ankylosing spondylitis and RA was suffering from proliferation of TCR1+ (V gamma 9-, V delta 1-), CD2+ CD16- CD56- LGL with low coexpression of CD8. The third patient with RA was suffering from a proliferation of TCR1+ (V delta 1+, V gamma 9-) CD4- CD8- CD16- CD56- lymphocytes. On the basis of these unusual findings, the pathogenetic role of TCR1+ T cells in RA is discussed.

Aged

Idiopathic focal segmental glomerulosclerosis in a patient with systemic lupus erythematosus: an unusual combination.

Renal involvement is a major cause of morbidity in patients with systemic lupus erythematosus (SLE). Histologic examination of renal tissue using light microscopy, immunofluorescent staining, and electron microscopy permit identification of glomerular immune complex deposits in virtually all patients with SLE. We report a patient who fulfilled four American College of Rheumatology criteria for the classification of SLE whose clinical course was consistent with SLE, yet whose renal failure resulted from focal glomerulosclerosis that was not mediated by immune complexes. The characteristics of this case of focal glomerulosclerosis that differentiate it from healed focal proliferative glomerulonephritis are discussed.

Biopsy

The effect of electronic dental analgesia during sonic scaling.

The aim of the present study was to investigate the effects of electronic dental analgesia (EDA) during sonic scaling. The clinical trial included 30 healthy adult subjects and was conducted as a randomised single-blind split-mouth design. The applied procedure consisted of periodontal scaling by means of a sonic scaler, while using the EDA device either in an active or placebo state. Rather similar results were obtained for the subjective pain rating in both the active and the placebo trials. When patients rated their discomfort on a scale 0-4 from no pain to very severe pain, the mean (s.d.) score for both the EDA and the placebo was 1.2 (0.6). The subjective pain estimate was positively correlated to the electrical current intensity provided. This implied that with a stronger pain experience, patients tried to administer more anaesthesia by turning the dial of the control box to an increased intensity of the electrical current. This remained insufficient to eliminate pain sensation. It was concluded that application of electronic dental anaesthesia in periodontal treatment remains questionable.

Adult

Role of periodontal ligament receptors in the tactile function of teeth: a review.

The tactile function of the human periodontal mechanoreceptors has mostly been studied by psychophysical approaches. It was concluded that periodontal mechanoreceptors play a major role in the tactile function of teeth. It must be noted however that the interocclusal tactile threshold is not solely determined by periodontal mechanoreceptors but also by pulpal, muscular or articular receptors. While temporomandibular joint receptors play a minor role, muscular receptors are important in the discriminatory ability for a mouth opening of 5 mm and more. To discriminate between the contribution of periodontal and other receptors in the oral tactile function, future studies should use appropriate psychophysical methodologies and well-defined stimulus parameters.

Dental Pulp

Clinical, cerebrospinal fluid, and histological data from thirty-four cats with primary noninflammatory disease of the central nervous system.

The purpose of this study was to report the clinical, cerebrospinal fluid (CSF), and histological data derived from a study of 34 cats with noninflammatory central nervous system (CNS) disease, and to report the activities of the enzymes lactate-dehydrogenase (LDH), aspartate transferase (AST), and creatine kinase (CK) in the CSF from 15 cats with a variety of CNS diseases. The cats were part of a study of 61 cats that were admitted to two university clinics because of signs of CNS disease. The most frequent noninflammatory diseases were neoplasia (n = 12) and ischemic encephalopathy (n = 4). The majority of cats with CNS neoplasia had a mild increase in CSF protein concentration (less than 1 g/L [100 mg/dL]), an increased percentage of neutrophils or lymphocytes, and a normal total white cell count. Cats with ischemic encephalopathy (IE) had a mild to moderate increase in CSF protein concentration (< or = 2 g/L [200 mg/dL]) and a mild increase in white cell count (< or = 10 cells/microL) with an increased percentage of lymphocytes. The enzymes LDH, AST, and CK in the CSF were not sensitive indicators of chronic CNS disease. The CSF differential cell count was frequently abnormal when the total white cell count was normal, and blood contamination in the CSF samples was a frequent problem that had to be considered in the interpretation of the results. The history, signalment, and clinical signs, when combined with the CSF findings, were valuable in the diagnosis of noninflammatory CNS disease.

Animals

Effect of a lactoperoxidase containing toothpaste in radiation-induced xerostomia.

Fractioned irradiation of the oral region may cause xerostomia and an increased infection risk. The aim of this study was to evaluate, in a single blind, cross-over trial, the effectiveness of a test toothpaste containing the lactoperoxidase system, compared to a normal fluoridated toothpaste. Twelve patients with pronounced xerostomia were examined during a 52-day period. The following parameters were observed: plaque and gingivitis index, bleeding on probing, probing pocket depth, attachment level, and quality of subgingival plaque (phase contrast microscopy). The test toothpaste reduced the rate of supragingival plaque formation over a longer period. Furthermore, gingival inflammation was lower in the test group. For the other parameters, time-dependent changes were not significant. This pilot-study demonstrates the efficacy of the lactoperoxidase system administered by a toothpaste, on supragingival plaque control in xerostomic patients.

Adult

Clinical, cerebrospinal fluid, and histological data from twenty-seven cats with primary inflammatory disease of the central nervous system.

The purpose of this report is to present the clinical, cerebrospinal fluid (CSF) and histological data from 27 cats with inflammatory disease of the central nervous system (CNS). The cats were part of a study of 61 cats admitted to two university clinics over an eight-year period because of signs of CNS disease. The most frequent diseases were feline infectious peritonitis (FIP) (12/27) and suspected viral disease other than FIP (10/27). Typical CSF findings in cats with FIP were a protein concentration of greater than 2 g/L (200 mg/dL) and a white cell count of over 100 cells/microL, which consisted predominantly of neutrophils. In contrast, the CSF of cats with suspected viral disease had a protein concentration of less than 1 g/L (100 mg/dL) and a total white cell count of less than 50 cells/microL. In general, cats with FIP or suspected viral disease were less than four years of age. Neurological signs were usually multifocal in cats with FIP, but focal in cats with suspected viral disease. The CSF findings were variable in five other inflammatory diseases represented. Two cats with protozoan infection had normal CSF total cell counts but abnormal differential counts. The CSF findings were invaluable in differentiating FIP from other causes of inflammatory CNS disease.

Animals

Effects of scalaradial, a type II phospholipase A2 inhibitor, on human neutrophil arachidonic acid mobilization and lipid mediator formation.

The role of scalaradial (SLD) (or its 12-epi analog), a marine natural product purified from sponge (Cacospongia mollior) in human neutrophil (polymorphonuclear leukocyte, PMN) arachidonic acid metabolism was studied. SLD potently inhibited human recombinant (rh) type II-14 kDa-phospholipase A2 (PLA2) (IC50 = 0.07 microM) but displayed weak inhibition of U937 cell, 85 kDa-PLA2 (IC50 = 20 microM). Sn-2 acylhydrolytic activity expressed in human PMN acid extract, that was completely neutralized by anti-rh type II-14 kDa-PLA2 monoclonal antibody, was inhibited by SLD in a concentration-dependent manner (IC50 = 35 microM). Exposure of human PMN to SLD resulted in a concentration-dependent inhibition of calcium ionophore (A23187)-induced leukotriene B4 release (IC50 = 0.1-0.6 microM). In contrast to the action of selective 5-lipoxygenase inhibitors (WY 50295 or zileuton), SLD decreased A23187-induced PMN liberation of arachidonic acid mass and platelet-activating factor biosynthesis (IC50 = 1-2 microM). PMN acetyltransferase activity was not significantly affected by SLD suggesting that platelet-activating factor inhibition was due, predominantly, to inactivation of PLA2 activity. In vivo, topical application of SLD on mouse ear treated with phorbol ester, not only inhibited edema formation but also the increase in myeloperoxidase activity (an index of cellular infiltration). SLD had little or no effect on arachidonic acid-induced ear edema or myeloperoxidase which is consistent with an action on PLA2. Take together these data suggest that the predominant mechanism of SLD is via inhibition of 14 kDa-like-PLA2 and suggests that this enzyme may participate in PMN arachidonic acid liberation and lipid mediator formation.

Animals

Changes of natural killer cells during acute psychological stress.

Emotional stress is often followed by increased susceptibility to infections. One major role in the immediate immune response to infection is played by natural killer (NK) cells. This study was designed to establish whether acute psychological stress influences cellular immune functions and to elucidate the role of endocrine parameters as potent mediators of stress induced alterations of the immune system. Forty-five first-time tandem parachutists were examined continuously for their plasma concentrations of cortisol and catecholamines from 120 min before to 60 min after jumping. Lymphocyte subsets, NK activity, and ADCC were determined 2 hr before, immediately after, and 1 hr after jumping. There was a significant increase in sympathetic-adrenal hormones during (adrenaline, noradrenaline) and shortly after jumping (cortisol). Lymphocyte subsets and the functional capacity of NK cells revealed an increase immediately after jumping followed by a decrease significantly below starting values 1 hr later. These changes were significantly correlated to plasma concentrations of noradrenaline. Thus, quick mobilization of NK cells is suggested as one major mechanism for this effective adaptation of the immune system to stress situations.

Acute Disease

Catecholamines induce alterations of distribution and activity of human natural killer (NK) cells.

Catecholamines have been suggested to be responsible for altered cellular immunity after stress. This study was performed to determine the effects of adrenaline and noradrenaline on lymphocyte subpopulations and NK cell functions. Subjects were given a subcutaneous injection of either NaCl, adrenaline (5 micrograms/kg), or noradrenaline (10 micrograms/kg). Catecholamine concentrations, subsets of peripheral blood lymphocytes, NK activity, and antibody-dependent cellular cytotoxicity (ADCC) were analyzed before (baseline) and 5, 15, 30, 60, and 120 min after injection. There were no differences between groups in the distribution of CD2+ and CD8+ lymphocytes over time. However, CD3+ and CD4+ T cells decreased significantly 5 to 60 min after injection of adrenaline. In contrast, NK cell numbers (CD16+, CD56+) increased significantly 5 min after injection of adrenaline and noradrenaline, reached the highest values 15 to 30 min postinjection, and subsequently declined to baseline values 60 (noradrenaline) and 120 (adrenaline) min, respectively, after injection. Similar alterations for NK activity and ADCC were observed after administration of both catecholamines. These data suggest that both sympathetic-adrenal hormones are similarly potent modulators of natural immunity and provide further evidence that catecholamines might be responsible for the observed alterations in immune functions after phases of acute stress.

Adult

Maxillary bone resorption in patients with mandibular implant-supported overdentures or fixed prostheses.

For several years, implant-supported overdentures have been used with excellent results in rehabilitation of the edentulous mandible. The effect on the antagonistic jaw bone resorption however, has not yet been evaluated. The aim of this study was to examine on orthopantomograms the anterior and posterior maxillary ridge resorption in three groups of patients with different mandibular prosthetic reconstructions: (1) overdentures supported by two implants, (2) fixed prostheses supported by four to six implants, and (3) complete dentures. The results indicated a more pronounced annual bone resorption in complete denture wearers compared to patients with implant-supported overdentures. A limited but continuing bone resorption was observed for the patients with implant-supported overdentures, and a slightly higher annual bone resorption occurred in the implant-supported fixed prosthesis group.

Adult

Masseter muscle fatigue during sustained clenching in subjects with complete dentures, implant-supported prostheses, and natural teeth.

A sustained submaximal (50%) clenching effort was performed in four patient groups to establish whether implant-supported prosthetic reconstructions influence myoelectrical signal parameters. The first group consisted of patients with natural teeth in both jaws. The other three groups consisted of patients who were edentulous in both jaws: one group had complete dentures; one had an overdenture in the mandible on two implants connected by a bar; and the third had an implant-supported fixed prosthesis in either the maxilla or the mandible. Surface electromyography indicated an increased myoelectrical output level that paralleled a higher bite force level for implant-supported reconstructions compared with complete dentures. Power spectrum analysis revealed a downward shift of the mean power frequency during sustained clenching in all groups except the implant-supported fixed prosthesis. The absence of a spectral shift in the latter group probably reflected a fear of biting too hard and fracturing the prosthesis.

Adult

Linear single-dose pharmacokinetics of ganciclovir in newborns with congenital cytomegalovirus infections. NIAID Collaborative Antiviral Study Group.

The pharmacokinetic characteristics of ganciclovir were determined in neonates (age range, 2 to 49 days) after an 1-hour intravenous infusion of a single dose of either 4 mg/kg (n = 14) or 6 mg/kg (n = 13). Twenty-seven newborns with symptomatic cytomegalovirus inclusion disease were enrolled in this open phase I-II pharmacokinetics, safety, and tolerance trial of ganciclovir at one of two doses. Ganciclovir disposition was best described by a one-compartment open model with zero-order input and first-order elimination. The mean elimination half-life (t1/2) for both dose groups was 2.4 hours. The mean apparent volume of distribution (Vd) was 669 +/- 70 ml/kg for the 4 mg/kg group and 749 +/- 59 ml/kg for the 6 mg/kg group. The mean total body clearance (CL) for the 4 mg/kg and 6 mg/kg groups was 189 +/- 28 ml/hr/kg and 213 +/- 21 ml/hr/kg, respectively. No significant differences were observed in Vd or CL between the two groups. The Vd, expressed in milliliters, increased with increasing patient weight (r = 0.689; p = 0.0001). The CL, expressed in milliliters per hour per kilogram, increased with increasing age (r = 0.413; p = 0.032). No significant differences were observed between the two dose groups for the area under the curve normalized for dose (AUC/Dose) or the maximum plasma concentration normalized for dose (Cmax/Dose), indicating that ganciclovir exhibited linear pharmacokinetics in these neonates.

Creatinine