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Biomedical subjects

J Hahn

Publications and source records attributed to J Hahn.

At least 55 records · Page 3Linked to original sources
PubMed1998

Competence in Bacillus subtilis is controlled by regulated proteolysis of a transcription factor.

Competence is a physiological state, distinct from sporulation and vegetative growth, that enables cells to bind and internalize transforming DNA. The transcriptional regulator ComK drives the development of competence in Bacillus subtilis. ComK is directly required for its own transcription as well as for the transcription of the genes that encode DNA transport proteins. When ComK is sequestered by binding to a complex of the proteins MecA and ClpC, the positive feedback loop leading to ComK synthesis is interrupted. The small protein ComS, produced as a result of signaling by a quorum-sensing two-component regulatory pathway, triggers the release of ComK from the complex, enabling comK transcription to occur. We show here, based on in vivo and in vitro experiments, that ComK accumulation is also regulated by proteolysis and that binding to MecA targets ComK for degradation by the ClpP protease in association with ClpC. The release of ComK from binding by MecA and ClpC, which occurs when ComS is synthesized, protects ComK from proteolysis. Following this release, the rates of MecA and ComS degradation by ClpCP are increased in our in vitro system. In this novel system, MecA serves to recruit ComK to the ClpCP protease and connects ComK degradation to the quorum-sensing signal-transduction pathway, thereby regulating a key developmental process. This is the first regulated degradation system in which a specific targeting molecule serves such a function.

Bacillus subtilis↗
PubMed1998

Aesthetic enhancement of pontic sites for fixed partial dentures.

The ridge expansion technique using tapered osteotomes can be used anywhere in the maxilla when a change in external ridge morphology would be advantageous for both aesthetics and/or proper dental implant placement. Usually subsequent to tooth loss, the maxilla is generally somewhat undercut in form. This ridge expansion technique can be used to reduce the undercut by bulging out the base of the facial/buccal plate. This would recreate the illusion of root prominences (Figure 12) or permit implant fixtures to be inserted in a more upright position. The tapered osteotomes can therefore predictably be used to expand the buccal bone to simulate the presence of a root prominence for optimal aesthetics for placement of a fixed partial denture prosthesis (Figure 13).

Alveolar Ridge Augmentation↗
PubMed1997

Effects of diethylamine/nitric oxide on blood perfusion and oxygenation in the R3230Ac mammary carcinoma.

The effects of intravenous diethylamine/nitric oxide (DEA/NO), a short-acting nitric oxide (NO) donor, on systemic haemodynamics, muscle and tumour blood flow (MBF and TBF) and tumour oxygenation were examined in rats bearing subcutaneous R3230Ac carcinoma in the leg. The effects of DEA/NO on the diameters of tumour-feeding and normal arterioles were evaluated in window chambers with and without implanted tumours. DEA/NO reduced mean arterial pressure (MAP) when given at doses > or = 100 nmol kg(-1), with maximal suppression at 0.5-1 min followed by return to baseline within 20 min. DEA/NO did not affect MBF except at the highest doses (500 and 1000 nmol kg(-1)). In contrast, DEA/NO reduced TBF and constricted tumour arterioles at doses > or = 100 nmol kg(-1). Tumour arteriolar vasomotion occurred in more than half the animals during hypotension and with a significantly higher frequency than in normal granulating tissue at a dose of 500 nmol kg(-1). Normal arterioles rapidly and significantly vasodilated for about 3 min and then returned to baseline. The reductions in TBF and MAP were accompanied by synchronous reduction in tumour pO2. Our findings suggest that DEA/NO decreases TBF in two ways. In the window chamber model, vascular steal occurs as normal arterioles adjacent to tumour dilate more than tumour arterioles during the initial period of hypotension. In leg tumours, the predominant mechanism is attributable to reduced perfusion pressure induced by lowered MAP, which decreases flow to the tumour, probably because of relatively higher flow resistance. The vasoconstriction and vasomotion in tumour arterioles during DEA/NO-induced hypotension may reflect differences in regulatory metabolism of NO between neoplastic and normal arterioles. Thus, intravenous injection of a short-acting NO donor, DEA/NO, decreases MAP and heart rate, leading to subsequent decreases in tumour blood flow and oxygenation.

Animals↗
PubMed1997

Transnasal transseptal endoscopic approach to the sphenoid sinus.

A modified transseptal approach to the sphenoid sinus and pituitary gland utilizing rigid endoscopy has been developed by the Departments of Otolaryngology, Plastic Surgery, and Neurosurgery at The Cleveland Clinic Foundation. When compared with alternate approaches or the nonendoscopic transseptal procedure, the modified approach provides better visualization and increased illumination of the surgical sites. Other advantages include a decrease in operating time, dissection, bleeding, and postoperative morbidity without compromising nasal function in the postoperative period.

Adenoma↗
PubMed1997

Long-term efficacy of hydroxyapatite-coated cylindrical implants.

A two-site clinical study of hydroxyapatite-coated cylindrical titanium alloy implants was undertaken to evaluate their efficacy. Observations were recorded before surgery, at first-stage surgery, at second-stage surgery, at loading, and at quarterly postrestoration prophylactic examinations and annual comprehensive patient visits. Implant failure criteria included mobility, peri-implant radiolucency, fracture, exfoliation, removal for any reason, and patient reported pain on palpation. Soft tissue indices were monitored as part of the study. Postrestoration implant performance was analyzed using life table methodology. From the 316 implants restored in 154 patients, 11 implants in 8 patients failed before prosthetic attachment, for a surgical success rate of 96.4 percent. Four implants failed during an observation period extending up to 85 months after completion of prosthetic treatment. The Cutler-Ederer life table success rate after 6 years was 97.8 percent. No significant adverse events were reported during the observation period. Results of this investigation suggest that hydroxyapatite-coated cylindrical titanium alloy implants are an effective treatment modality.

Adolescent↗
PubMed1997

Cutaneous inflammation limited to the region of the ulcer in chronic venous insufficiency.

BACKGROUND: The role of inflammatory reactions in the pathogenesis of chronic venous insufficiency and the persistence of venous ulcerations is still not totally clear and remains a hotly debated topic. An investigation of the intensity and distribution of ICAM-1 expression and different inflammatory cells should help clarify whether inflammatory processes are limited locally to the area of the ulcer or if an upregulation can also be observed in clinically unaffected skin of CVI-III patients, as a sign of a primary inflammatory process. PATIENTS AND METHODS: We examined two skin areas in 10 patients with venous ulcerations. One area was at the border of the ulcer and another in clinically unaffected skin (distance from the ulcer: 12.6 +/- 5.1 cm). In addition skin specimens were obtained from the perimalleolar skin of 10 healthy controls. Our histological and immunohistochemical examinations were focused on inflammatory cells (B and T lymphocytes, macrophages, and mast cells) and on the adhesion molecule ICAM-1. RESULTS: A very strong expression of ICAM-1 could be seen at the border of the ulcer. This tissue also showed a dense infiltration, mainly by T lymphocytes and macrophages. In some cases the tissue was infiltrated by an increased number of mast cells. This is the typical picture of a chronic inflammatory reaction. Compared to healthy controls, the clinically unaffected skin of patients showed not an increased expression of ICAM-1 and only in some cases we could find a slight perivascular infiltrate of T lymphocytes. CONCLUSIONS: These data imply that the upregulation of endothelial adhesion molecules (ICAM-1) and dermal infiltration by T lymphocytes and macrophages in CVI-III patients is limited to the region of the ulcer, or at least to skin areas with a severe microangiopathy, and is part of a secondary elimination of necrotic issue (an 'injury and repair' process). These local chronic inflammatory reactions are certainly an important factor in the persistence and recurrence of venous ulcerations.

Adult↗
PubMed1996

[Multidisciplinary treatment program for chronic low back pain, part 2. Somatic aspects].

PROBLEM: There is a great need to expand current knowledge of the various functional capacity measurements used in the rehabilitation of chronic low back pain (CLBP) patients. The literature on these patients reports that mobility, endurance, trunk strength and lifting capacity decrease during the process of chronicity. Chronically disabled patients appear to have lower functional capacity than asymptomatic persons. METHODS: Our study group consisted of 90 disabled CLBP patients (44 female, 46 male; average age 42 years) who underwent a multidisciplinary 8-week daily treatment program of functional restoration with behavioral support (instruction, endurance training, strength exercises, behavioral and treatment to facilitate return to work therapy). Initially these patients where compared with 107 asymptomatic persons (44 female, 63 male, average age 41 years). The patients were investigated before and after treatment, and at intervals of 6 and 12 months. The reliability of the functional measurements was evaluated by interrater comparison. Physical assessment included a medical examination (mainly diagnosis of radicular or nonradicular pain), changes in the lumbar spine revealed by X-ray studies according to Herron and Turner, rating of physical impairment according to Waddell, flexibility, length of hamstrings muscles (SLR), test of power and endurance of trunk movement by standardized exercises according to the Swiss group of Spring and isokinetic measurements (LIDO Back), tests of lifting capacity (LIDO Lift), and (in part) of general endurance on a cycle ergometer (CASE 15 Marquette). RESULTS: Physical findings showed that mobility was reduced substantially in patients suffering from back pain due to reduced SLR (shortened hamstrings) and decreased spinal mobility. Patients also demonstrated significant reductions in their ability to perform lifting tasks in comparison to healthy individuals. The results of trunk flexion showed no significant differences between patients and the control group, whereas the ability to perform trunk extension was much better in the control group. In principle we found the same results with isokinetic measurements as in the exercises without machines. Cardiovascular endurance was also much better in the control group than it was in the back pain patients. At the end of the treatment program all physical deficits were improved significantly. In many cases performance was comparable with that of the control group. With time, however, training effects gradually decreased. The success of treatment (return to work, absence from work, pain reduction, use of medical care) was independent of the functional status of the patients before and after treatment. CONCLUSION: Study results showed that physical capacity in disabled patients with low back pain is substantially reduced in comparison to persons who do not suffer from back pain. The only exception was in trunk flexor strength and endurance, in which measurements did not differ between the patients and the control group. However, even CLBP- patients with long-term pain and severe physical illness can successfully improve their physical condition by participating in an active treatment program. Back extensor muscle training has to be included in physical therapy. Because of loss of condition during the time after treatment, regular monitoring of patients and their home training programs is necessary. Overall, treatment of CLBP has to include physical training and psychosocial treatment to achieve satisfactory results.

English Abstract↗
PubMed1996

Single axon IPSPs elicited in pyramidal cells by three classes of interneurones in slices of rat neocortex.

1. Using dual intracellular recordings in slices of adult rat neocortex, twenty-four IPSPs activated by single presynaptic interneurones were studied in simultaneously recorded pyramidal cells. Fast spiking interneurones inhibited one in four or five of their close pyramidal neighbours. No reciprocal connections were observed. After recordings neurones were filled with biocytin. 2. Interneurones that elicited IPSPs were classified as classical fast spiking (n = 10), as non-classical fast spiking (n = 3, including one burst-firing interneurone), as unclassified, or slow interneurones (n = 8), or as regular spiking interneurones (n = 3), i.e. interneurones whose electrophysiological characteristics were indistinguishable from those of pyramidal cells. 3. All of the seven classical fast spiking cells anatomically fully recovered had aspiny, beaded dendrites. Their partially myelinated axons ramified extensively, varying widely in shape and extent, but randomly selected labelled axon terminals typically innervated somata and large calibre dendrites on electron microscopic examination. One 'autapse' was demonstrated. One presumptive regular spiking interneurone axon made four somatic and five dendritic connections with unlabelled targets. 4. Full anatomical reconstructions of labelled classical fast spiking interneurones and their postsynaptic pyramids (n = 5) demonstrated one to five boutons per connection. The two recorded IPSPs that were fully reconstructed morphologically (3 and 5 terminals) were, however, amongst the smallest recorded (< 0.4 mV). Some connections may therefore involve larger numbers of contacts. 5. Single axon IPSPs were between 0.2 and 3.5 mV in average amplitude at -55 to -60 mV. Extrapolated reversal potentials were between -70 and -82 mV. IPSP time course correlated with the type of presynaptic interneurone, but not with IPSP latency, amplitude, reversal potential, or sensitivity to current injected at the soma. 6. Classical fast spiking interneurones elicited the fastest IPSPs (width at half-amplitude 14.72 +/- 3.83 ms, n = 10) and unclassified, or slow interneurones the slowest (56.29 +/- 23.44 ms, n = 8). Regular spiking interneurone IPSPs had intermediate half-widths (27.3 +/- 3.68 ms, n = 3). 7. Increasingly brief presynaptic interspike intervals increased the peak amplitude of, but not the area under, the summed IPSP. Only at interspike intervals between 10 and 20 ms did IPSP integrals exhibit paired pulse facilitation. Paired pulse depression was apparent at < 10 and 20-60 ms. During longer spike trains, summing IPSPs decayed to a plateau potential that was relatively independent of firing rate (100-250 Hz). Thereafter, the voltage response could increase again. 8. Summed IPSPs elicited by two to fifteen presynaptic spike trains decayed as, or more rapidly than, single-spike IPSPs. Summed IPSPs elicited by > 20 spikes (> 150 Hz), however, resulted in an additional, more slowly decaying component (latency > 50 ms, duration > 200 ms). The possible involvement of GABAB receptors in this component is discussed. 9. It is suggested that three broad classes of interneurones may activate GABAA receptors on relatively proximal portions of neocortical pyramidal neurones. The different time courses of the IPSPs elicited by the three classes may reflect different types of postsynaptic receptor rather than dendritic location. An additional class, burst firing, spiny interneurones appear to activate GABAA receptors on more distal sites.

Animals↗
PubMed1996

Regulatory inputs for the synthesis of ComK, the competence transcription factor of Bacillus subtilis.

Competence in Bacillus subtilis is expressed post-exponentially in response to signals which are interpreted by a complex network of regulatory proteins. This network culminates in the transcriptional activation of a set of late-competence proteins that mediate DNA binding and uptake during transformation. ComK, a protein that binds to competence promoters and appears to activate their transcription, is itself synthesized in response to the signal-transduction network. ComK is known to be required for the transcription of its own gene. We have placed comK under control of the xylose-inducible PxylA promoter and used this construct to show that ComK synthesis is sufficient as well as necessary to induce competence. We have also confirmed that the Mec proteins act post-transcriptionally to inactivate ComK, probably by protein-protein interaction. We have further demonstrated that ComS is required to generate an upstream signal that causes reversal of Mec-induced inactivation of ComK. In addition to ComK itself, DegU, AbrB, and SinR are required for comK transcription; mutations in their genes are bypassed by PxylA-comK induction, and therefore their products appear not to act via the Mec proteins. Overproduction of ComK, in a loss-of-function mec mutant, is also known to bypass the need for DegU, SinR and AbrB. We propose that these proteins enhance the activity of ComK as a positive autoregulatory transcription factor, acting as coactivator proteins when ComK is present at low concentrations. Finally, we demonstrate that when ComK is synthesized from the PxylA promoter and mecA is inactivated by mutation, no additional growth-stage-regulated control of competence can be detected.

Bacillus subtilis↗
PubMed1996

Polynucleotide phosphorylase is necessary for competence development in Bacillus subtilis.

comR (pnpA) is a newly identified gene in Bacillus subtilis that is necessary for the expression of late competence genes. Transformability of a comR (pnpA) mutant is 1-5% of that seen in comR+ strains. Cloning and sequencing identified ComR as polynucleotide phosphorylase (PNPase). The PNPase amino acid sequence has 50% identity and 67% similarity with the Escherichia coli enzyme. Enzymatic assays show that this is the only PNPase activity in B. subtilis. comR (pnpA) is necessary for comG-lacZ and comK-lacZ expression, but this requirement is bypassed by a mecA disruption. In B. subtilis, the loss of PNPase has little effect on expression from a fusion of the srfA promoter directly to lacZ, but is necessary for normal expression from certain srfA-lacZ fusions that include portions of the normal srfA transcript. When a srfA-lacZ translational fusion is tested in isogenic pnpA+ and pnpA derivatives of E. coli, lower expression is seen in the pnpA mutant. Since expression from lacZ fusions to comA, sinR, and mecA appeared similar in the B. subtilis pnpA and pnpA+ strains, the loss of PNPase does not have a strong general effect on gene expression. These results suggest that PNPase may be necessary for modification of the srfA transcript in order to activate translation or stabilize the transcript, and that this may be necessary for competence development. This is the first evidence of post-transcriptional effects on the development of competence in B. subtilis.

Amino Acid Sequence↗
PubMed1996

Histomorphological examination of endoluminal stent grafting in the descending aorta in a sheep model.

Experiments were designed to examine the wound healing characteristics at the aorta-endograft interface. Thoracic aneurysms were induced in sheep and excluded by endovascular placement of a selfexpanding stent graft (Corvita Endovascular Graft). After a follow-up of 1, 4, or 12 weeks sheep were sacrificed and the corresponding segments of the aorta were subjected to histological examinations. Histomorphological evaluation of all groups underlined sufficient exclusion of lesions of the aortic wall by endovascular grafting. There was no evidence of proximal or distal leakage, graft dislocation or migration. The results appeared to be evidence that the endoluminal stent graft may be incorporated by the host aortic tissue.

Animals↗
PubMed1996

Efficacy of threaded hydroxyapatite-coated implants in the anterior mandible supporting overdentures.

A data subset from an ongoing prospective multicenter clinical study of threaded hydroxyapatite-coated implants was evaluated to assess safety and efficacy of the implants when placed in the anterior mandible to support overdentures. Observations were recorded before surgery, at first-stage surgery, at second-stage surgery, at loading, and at quarterly postrestoration prophylactic exams and annual comprehensive patient visits. Implant failure criteria included mobility, radiographic evidence of bone loss greater than one-third the length of the implant or peri-implant radiolucency, fracture, exfoliation, removal for any reason, and patient reported pain upon palpation. Soft tissue indices were monitored as part of the study. Postrestoration implant performance was analyzed using life-table methodology. From the 2,062 implants restored in 720 patients in the parent study, a total of 660 implants in 174 patients were included in the anterior mandibular overdenture data subset. Twelve implants in 8 patients failed at or before second-stage surgery for a surgical success rate of 98.2 percent. Five implants failed during an observation period extending up to 72 months after completion of prosthodontic treatment. The Cutler-Ederer life table success rate after 5 years was 97.8 percent. No significant adverse events were reported during the observation period. Results of this investigation suggest that threaded hydroxyapatite-coated implants are effective when placed in anterior mandibular regions in support of overdentures.

Adult↗
PubMed1996

Efficacy of threaded hydroxyapatite-coated implants placed in the posterior mandible in support of fixed prostheses.

A data subset from an ongoing prospective multicenter clinical study of threaded hydroxyapatite-coated implants was evaluated to assess safety and efficacy of the implants when used to support fixed prostheses in the posterior mandible. Observations were recorded before surgery, at first-stage surgery, at second-stage surgery, at loading, and at quarterly postrestoration prophylactic exams and annual comprehensive patient visits. Implant failure criteria included mobility, radiographic evidence of bone loss greater than one-third the length of the implant or peri-implant radiolucency, fracture, exfoliation, removal for any reason, and patient reported pain upon palpation. Soft tissue indices were monitored as part of the study. Postrestoration implant performance was analyzed using life-table methodology. From the 2,062 implants restored in 720 patients in the parent study, a total of 423 implants in 195 patients were included in the posterior mandibular data subset. Thirteen implants failed at or before second-stage surgery for a surgical success rate of 96.9 percent. Prosthodontics was completed, and one or more postrestoration annual follow-up visits occurred for 314 implants as of the interim analysis cutoff date. Fourteen implants failed during an observation period extending up to 62 months after completion of prosthodontic treatment. One failed implant was removed, whereas the 13 remaining implants are functional despite having been identified as failures under the protocol criteria. The Cutler-Ederer life table success rate after 5 years was 92.2 percent. Results of this investigation suggest that threaded hydroxyapatite-coated implants are effective when placed in posterior mandibular regions in support of fixed prostheses.

Adult↗
PubMed1995

Influence of molecular characteristics on clinical outcome in human immunodeficiency virus-associated non-Hodgkin's lymphoma: identification of a subgroup with favorable clinical outcome.

The relationship between clinical and molecular characteristics of 45 treated individuals with histologically-documented human immunodeficiency virus (HIV)-associated B-cell non-Hodgkin's lymphoma was examined to determine whether differences in molecular features of lymphoma were associated with differences in clinical outcome. Tissue specimens from these tumors were evaluated for evidence of Ig heavy-chain gene rearrangements using both Southern blot analysis and reverse transcriptase polymerase chain reaction (RT-PCR). Lymphomas were also evaluated for the presence of Epstein-Barr virus (EBV) DNA sequences and c-myc gene rearrangements. Twenty-five lymphomas were characterized as polyclonal and 20 as monoclonal. PCR amplification of expressed Ig variable (V)-region genes confirmed polyclonality in three extensively studied polyclonal lymphomas. The median CD4 count was significantly higher in the group with polyclonal disease (277/microL) than in the group with monoclonal disease (123/microL), P = .04. The complete response rate to therapy was significantly higher in patients with polyclonal disease (78%) and CD4 greater than 200/microL (81%) than in those with monoclonal disease (31%) and CD4 less than 200/microL (33%). CD4 count, clonality, and presence of EBV DNA sequences were the most important predictors of survival. Both Kaplan-Meier and Cox proportional hazards analyses showed a markedly prolonged survival in those patients with both CD4 > or = 200/microL and polyclonal disease. Histologically the polyclonal lymphomas were high grade in appearance and contained prominent macrophages. All seven surviving patients were in this group. Median survival for those individuals whose tumors contained EBV sequences was only 3.2 months (range, 0.4 to 19.5), whereas those with EBV- tumors survived for a median of 9.0 months (range, 0.7 to 65.2), P = .0007. These data indicate that molecular features of HIV-associated lymphomas may be important predictors of clinical outcome. These characteristics define a distinct subset of patients with polyclonal EBV- tumors and CD4 counts greater than 200/microL that appear to have a less aggressive clinical course.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Two-year outcome following transjugular intrahepatic portosystemic shunt for variceal bleeding: results in 90 patients.

BACKGROUND/AIMS: Transjugular intrahepatic portosystemic shunt (TIPS) is a new therapy for variceal bleeding. Immediate technical and short-term clinical results have been reported. This study was undertaken to evaluate mid-term outcome after TIPS in patients who successfully underwent the procedure for variceal bleeding. METHODS: Ninety patients were followed up prospectively by clinical examination and radiological shunt evaluation including Doppler sonography and transjugular portal venography. RESULTS: The average follow-up in surviving patients was 2.2 years. The cumulative survival rate was 60% at 1 year and 51% at 2 years. The rate of cumulative rebleeding was 26% at 1 year and 32% at 2 years. A shunt abnormality was noted in all rebleeding patients. Rebleeding was successfully controlled in all but 1 of the patients who underwent shunt revision. Cumulative detection of stenosis or occlusion was 31% at 1 year and 47% at 2 years. Thirty-eight percent of shunt abnormalities were detected by routine surveillance. Percutaneous shunt revision was attempted in 22 patients and was successful in 21 (95%). CONCLUSIONS: Although mid-term primary patency is limited in many patients by the development of a shunt stenosis or occlusion, shunt function can be maintained in most patients by careful surveillance and periodic percutaneous intervention.

Adolescent↗