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Biomedical subjects

L L Johnson

Publications and source records attributed to L L Johnson.

At least 91 records · Page 5Linked to original sources

Arthroscopic observations before and after manipulation of frozen shoulder.

The purpose of this article is to report the arthroscopic findings before and immediately after manipulation for frozen shoulder. Twenty patients were selected for manipulation under general anesthesia after failing to improve with conservative measures in 6 months. The findings showed the joint capsule was difficult to penetrate with the arthroscope cannula and obturator because of the thickness of the capsular tissue. The glenohumeral joint accepted less than the normal amount of fluid. The humeral head was tight against the glenoid even in the suspended position. The main intraarticular finding was vascular synovitis. There were no intraarticular adhesions or degenerative changes. An immediate postmanipulation second-look arthroscopy showed there was synovial and capsular hemorrhage indicative of tearing from the manipulation. After glenohumeral manipulation, the joint accepted more fluid, and the humerus was easily distracted away from the glenoid with intraarticular distention.

Arthroscopy↗

Effects of holmium:YAG laser on equine articular cartilage and subchondral bone adjacent to traumatic lesions: a histopathological assessment.

This study was performed to investigate the effects of holmium:yttrium-aluminum-garnet (Ho:YAG) laser energy on articular cartilage and subchondral bone adjacent to traumatically created cartilage lesions in a continuous weight-bearing model. The 2.1-microns wavelength was delivered efficiently and precisely in hand-controlled contact and near-contact hard tissue arthroscopic surgery in a saline medium. Bilateral arthroscopy was performed on normal antebrachiocarpal and intercarpal joints of four adult horses. One hundred twenty traumatic lesions were created on three weight-bearing articular surfaces with a knife, curet, or motorized burr. Depths of the lesions were partial and full thickness. Configurations of the lesions were lacerations, scrapes, and craters. Left limbs were used as controls. Right limb lesions were treated with various intensities of laser energy: 0.1. 0.16, and 0.2 J. Animals were killed at intervals of 1, 3, and 8 weeks. Gross microscopic anatomy was documented, and tissue sections were subjected to blind review by a pathologist. Mankin grading for cellularity and proteoglycan content was used to qualitatively evaluate cartilage response. Cartilage adjacent to all lesions exposed to laser energy had better cellularity and proteoglycan content (p < 0.05) than did corresponding controls by Mankin grading. Mankin grades for levels of 0.16 and 0.2 J were lower (p < 0.05) than were those of controls or lesions exposed to 0.1 J. There was loss of cellularity and necrosis in subchondral bone at higher energy levels (0.16 and 0.2 J). This study examined the effects of Ho:YAG laser on articular cartilage and subchondral bone in terms of depth of damage and healing response over time in a weight-bearing model. Additional research to define dose-response curves for Ho:YAG laser treatment of cartilage and subchondral bone are indicated.

Animals↗

Regulation of methylthioribose kinase by methionine in Klebsiella pneumoniae.

5-Methylthioribose (MTR) kinase catalyses a key step in the recycling of methionine from 5'-methylthioadenosine, a co-product of polyamine biosynthesis, in Klebsiella pneumoniae. In defined medium lacking methionine, K. pneumoniae exhibits abundant MTR kinase activity. When the bacterium is transferred to a medium containing 10 mM-methionine, the specific activity of MTR kinase decreases in a fashion consistent with repression of new enzyme synthesis and dilution of existing enzyme by cell division. The specific activity of methionine synthase decreases to a similar degree under the same conditions. In Escherichia coli and Salmonella typhimurium, the gene for methionine synthase is co-ordinately controlled as part of the methionine regulon. Taken together, our results indicate that a methionine regulon may function in K. pneumoniae and that expression of MTR kinase may be under its control.

Dose-Response Relationship, Drug↗

Gamma interferon-dependent temporary resistance to acute Toxoplasma gondii infection independent of CD4+ or CD8+ lymphocytes.

It is well established that resistance to acute primary Toxoplasma gondii infection is mediated by a gamma interferon (IFN-gamma)-dependent mechanism. The present in vivo experiments were undertaken to investigate the cellular basis for this resistance. We show here that immunocompetent T. gondii-infected C57BL/6 (B6) mice treated with anti-IFN-gamma or with anti-Thy-1 or anti-asialo-GM1 antibodies die sooner than infected mice treated with antibodies that deplete both CD4+ and CD8+ T lymphocytes. Thy-1+ CD4- CD8- cells accumulated in the peritoneal cavities of B6 mice during the early stages of an intraperitoneal infection but did not accumulate in sham-infected control mice, and substantial numbers of Thy-1+ CD4- CD8- cells were recovered from the peritoneal cavities of infected B6 mice treated with antibodies that depleted CD4+ and CD8+ lymphocytes. Depletion of Thy-1+ cells reduced IFN-gamma to undetectable levels, whereas depletion of CD4+ and CD8+ cells did not reduce IFN-gamma levels. Thus T. gondii infection in immunocompetent B6 mice elicits Thy-1+ CD4- CD8- cells which either produce protective IFN-gamma themselves or control its production by other cells. It is likely that the function of these Thy-1+ CD4- CD8- cells is to control T. gondii tachyzoites during the early stages of primary infection before specific CD4(+)- and/or CD8(+)-dependent immunity develops.

Animals↗

Arthroscopic shoulder capsulorrhaphy using metal staples.

Staple capsulorrhaphy on the shoulder using a metal staple for traumatic anterior instability has the advantages of increased diagnostic accuracy, microdebridement of the pathology, accurate assessment of the glenohumeral ligament pathology, and selective repair of the ligament pathology. Although the same advantages should apply to staple capsulorrhaphy for traumatic posterior instability, our experience remains very limited. Staple capsulorrhaphy on the shoulder has multiple disadvantages, including being technically difficult with a slow learning curve, not being applicable to all unstable shoulders, an average failure rate of 12% that may be related to inadequate postoperative immobilization, no extra-articular reinforcement, and the use of a metal implant that may need to be removed at a second operation. Staple capsulorrhaphy is currently performed for traumatic anterior instability in the shoulder, with a selected repair of the pathology using a single, well-placed staple and prolonged postoperative immobilization. The design of the staple affords a simpler insertion technique than rivets, screws, and intra-articular sutures. The advent of a biodegradable staple should eliminate inherent problems of metal implants while preserving the advantages of this method.

Adolescent↗

Purification and characterization of the human stromelysin catalytic domain expressed in Escherichia coli.

Human stromelysin is a member of the matrix metalloproteinase family involved in connective tissue degradation. The stromelysin catalytic domain (SCD) lacking both propeptide and C-terminal fragment was expressed in Escherichia coli in soluble and insoluble forms. The insoluble SCD was refolded to the active form in high yield. The protein showed remarkable thermal stability and was able to cleave a thiopeptolide substrate and its natural substrate proteoglycan. The stable and active 20-kDa protein provides an opportunity to elucidate the structure as well as the mechanism of catalysis and inhibition for matrix metalloproteinases.

Amino Acid Sequence↗

Diagnosis of right ventricular acute myocardial infarction by dual isotope thallium-201 and indium-111 antimyosin SPECT imaging.

To assess the diagnostic value of indium-111 antimyosin for detecting right ventricular (RV) wall acute infarction, 30 patients with electrocardiographic-documented left ventricular inferior (posterior) wall acute myocardial infarction underwent simultaneous dual isotope indium-111 antimyosin and thallium-201 single-photon emission computed tomography (SPECT) within 2 days of admission. RV necrosis was defined as uptake of indium-111 antimyosin anterior and to the right of septal thallium uptake. Twenty-nine of the 30 patients (97%) had indium-111 antimyosin uptake in the inferior, posterior or lateral walls of the left ventricle and 14 of 30 (47%) had additional RV antimyosin uptake. Three different patterns of RV uptake of indium-111 antimyosin were observed: crescent-shaped, focal and apical. Twenty-seven patients underwent gated blood pool scanning before hospital discharge. Twelve of the 14 patients with RV antimyosin uptake had gated blood pool scintigraphy and 7 of 12 had RV dysfunction; 5 had normal RV function. Except for 1 patient who had questionable RV antimyosin uptake and had RV dysfunction, no patient without RV antimyosin uptake had RV dysfunction. In summary, right and left ventricular necrosis can be detected on tomographic images of indium-111 antimyosin uptake in patients with inferior infarctions when simultaneous uptake of a perfusion tracer, thallium-201, is imaged and used as an aid to reconstruction and anatomic localization.

Adult↗

Gene synthesis and expression in E. coli for pump, a human matrix metalloproteinase.

The gene for PUMP (putative metalloproteinase), a human matrix metalloproteinase, was synthesized by a PCR-based method. The DNA fragment of 546 bases containing the PUMP gene was generated by overlap extension of six long oligonucleotides (length ranging from 101 to 116 bases) and subsequent amplification by two short terminal oligonucleotide primers (length from 20 to 48 bases) in one pot without using restriction and ligation enzymes. The synthetic gene was cloned into a T7 expression vector in two ways to express PUMP as a non-fusion protein. Both constructs showed high level expression in E. coli.

Amino Acid Sequence↗

Monoclonal Fab antimyosin in cardiac imaging.

Antimyosin is an Fab fragment of a murine monoclonal antibody directed against human heavy chain myosin. It is specific for myocyte necrosis. When linked via diethylenetriaminepentaacetic acid to indium-111, the agent has good imaging properties. With planar imaging, it has demonstrated high sensitivity and specificity for detecting and localizing acute myocardial infarction (MI). In addition, studies of dual isotope (indium-111 antimyosin/thallium-201) SPECT imaging at rest in the early in-hospital post-MI period appear to be predictive of further ischemic events. Antimyosin imaging also shows promise as a noninvasive tool to aid in the diagnosis and assessment of prognosis in cardiac transplant rejection and myocarditis. There is no evidence to date for allergic reactions to the murine protein.

Animals↗

A protective role for endogenous tumor necrosis factor in Toxoplasma gondii infection.

The involvement of tumor necrosis factor (TNF) in resistance to Toxoplasma gondii infection was examined by means of experiments in which mice were treated with anti-TNF antibodies prior to infection with ME49, a low-virulence Toxoplasma strain. In (BALB/cBy x C57BL/6J)F1 (CB6F1) mice, which are highly resistant to intraperitoneal (i.p.) infection with T. gondii ME49, 10(4) neutralizing units of anti-TNF caused a significant increase in trophozoite numbers in the peritoneal cavities of infected mice and transient signs of illness but no deaths. i.p. infection of anti-TNF-treated C57BL/6J (B6) mice, which are more susceptible to T. gondii and develop a chronic progressive toxoplasmosis, resulted in death for some of the mice. If the mice were infected perorally, however, and treated with anti-TNF, mortality was extensive in B6 mice but not in CB6F1 mice. Although it was not detected in their sera, TNF was found in the peritoneal fluids of i.p.-infected CB6F1 and B6 mice. Endogenously produced TNF thus appears to be an important mediator of resistance to T. gondii.

Animals↗

SCID mouse models of acute and relapsing chronic Toxoplasma gondii infections.

Lymphodeficient scid/scid (SCID) mice died from acute infection with a strain of Toxoplasma gondii that causes chronic infection with mild symptoms in immunocompetent non-SCID mice. However, most SCID mice reconstituted with spleen cells from immunocompetent mice 1 month prior to T. gondii infection survived in good health after a transient period during which they appeared ill. Unreconstituted SCID mice given sulfadiazine in their drinking water from day 10 of Toxoplasma infection onward survived the acute phase of infection and lived for many weeks without overt symptoms. Histological examination revealed Toxoplasma cysts in their brains. However, if sulfadiazine was withdrawn from the drinking water of these chronically infected SCID mice, the mice died within 1 week with large numbers of trophozoites throughout their brains. These findings establish SCID mice as a potentially useful resource with which to study various aspects of immunological control of T. gondii infection during either its acute or chronic phase. Furthermore, the ability to produce chronic infections with avirulent T. gondii in SCID mice and to cause acute relapsing infections at will suggests that SCID mice may be helpful in evaluating potential therapies for acute and chronic T. gondii infections in immunocompromised patients.

Acute Disease↗

Imaging of cardiac transplantation rejection in primates using two new antimyosin agents.

Indium-111-labeled monoclonal antimyosin Fab has been used to image myocardial infarction, myocarditis and cardiac transplant rejection with localization in myocytes that have suffered irreversible loss of cell membrane integrity. Technical factors potentially limiting clinical usefulness of 111In antimyosin include dosimetry (72 hr half-life of 111In), slow blood clearance of antibody proteins delaying optimal imaging to 24 to 48 hr postinjection and nontarget organ uptake. Therefore, two new antimyosin imaging agents experimentally shown to potentially improve dosimetry, shorten time from injection to imaging or decrease nonspecific cell binding were evaluated in a primate cardiac transplant model. The two agents evaluated were polylysine 111In-antimyosin (0.023 mg Fab modified with a 3.3 kd polymer of polylysine and labeled with 111In) and 99mTc-antimyosin (0.5 mg Fab' antimyosin labeled using the RP-1 ligand technique). A total of eight baboons were studied: three with heterotopic (cervical) xenographs, three with orthotopic allographs and two control animals. Each animal was injected first with 12-23 mCi of 99mTc-RP-1 antimyosin and 5-16 hr after completion of imaging, was injected with 0.72-1.88 mCi of 111In-polylysine antimyosin (PIs) and reimaged 12-48 hr later. The imaging results were compared to the histology of the animals. Biexponential curves were fit to the blood sample data and rate constants were determined and expressed as T1/2 values. There were no significant differences between the two agents in either the early fast components or the late slow components. On planar imaging, there was blood-pool activity at 10-12 hr postinjection of both agents, but by 16-24 hr postinjection, blood pool was negligible on the 111In-PIs scans. Both agents were concentrated in the rejected cardiac tissue. The slow blood-pool clearance combined with the 6 hr half-life of 99mTc-RP-1 AMA make this agent less promising for detection of diffuse myocardial uptake than 111In Fab modified with polylysine.

Animals↗

Left ventricular perfusion and performance from a single radiopharmaceutical and one camera.

To test the hypothesis that a small field of view portable multicrystal scintillation camera can perform stress/rest combined LV function by first-pass and perfusion studies using 99mTc-teboroxime, 26 patients with positive stress thallium studies within 2 wk and 8 healthy volunteers were studied. A 241Am point source marker over the sternum was used for motion correction. Dynamic dual-isotope (99mTc/241Am) acquisition was performed following injection of 15.6 +/- 2.3 mCi of 99mTc-teboroxime at peak treadmill exercise. Two minutes later (blood-pool clearance), while still standing on the flat treadmill, 3-4 40-sec planar images were acquired. One hour later patients were reinjected with 22.7 +/- 3.4 mCi of 99mTc-teboroxime while standing in front of the camera and the same dynamic/static acquisition protocol repeated. The planar images were interpolated from a 20 x 20 matrix to a 160 x 160 matrix, a sharpening filter and an interpolative background subtraction algorithm applied. The scans were divided into segments, each scored as normal, reversible and fixed. The agreement with thallium imaging for identifying an abnormal scan was 24/26 (92%) and for identifying abnormal vascular territories was 43/52, (83%). Fourteen patients had exercise LVEF less than 50% and all had either prior myocardial infarction, myocardial infarction plus ischemia or LAD ischemia. Diagnostic planar perfusion images and exercise LVEF can be acquired in less than 4 min using 99mTc-teboroxime and a portable multicrystal scintillation camera.

Adult↗

Effect of infarct size measured from antimyosin single-photon emission computed tomographic scans on left ventricular remodeling.

To evaluate the effect of infarct size on left ventricular volumes and geometric remodeling, 26 patients with a first acute Q wave myocardial infarction (anterior in 14, inferior in 12) had the infarct sized from single-photon emission computed tomographic (SPECT) imaging of indium-111 antimyosin. All patients underwent gated blood pool scintigraphy before hospital discharge for determination of ejection fraction and end-diastolic and end-systolic volume indexes. Infarct size was quantitated from indium-111 antimyosin uptake in coronal slices with use of a threshold technique for edge detection. Nineteen of 26 patients had additional simultaneous acquisitions of indium-111 and thallium-201 uptake and the infarct was expressed as a percent of the total left ventricle. Infarct size was larger (59 +/- 16 vs. 33 +/- 16 g), predischarge ejection fraction lower (35 +/- 5% vs. 60 +/- 9%) and end-systolic volume index higher (57 +/- 13 vs. 36 +/- 10 ml/m2) in the group with anterior infarction. Despite these differences, predischarge end-diastolic volume index was not significantly different between the group with anterior (88 +/- 17 ml/m2) versus inferior (89 +/- 14 ml/m2) infarction. There was a significant inverse correlation between percent infarct size and ejection fraction for patients with dual isotope imaging (r = -0.90) and a significant direct correlation between infarct size and end-systolic volume index (r = 0.79, p less than 0.01). Fourteen patients without subsequent myocardial infarction or coronary artery bypass grafting had a repeat gated blood pool study late (26 +/- 15 months) after infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Characteristics of the immediate postarthroscopic blood clot formation in the knee joint.

The immediate postoperative bleeding and blood clot formation was observed in 26 human knee joints following a variety of arthroscopic surgical procedures. Observations were made following lavage with lactated Ringer's and normal saline solutions. Bleeding occurred from all incised vascular tissue. Blood clot accumulated after each solution within 5 min following tourniquet release and decompression of the joint. Most of the blood clot remained unattached within the joint cavity. Blood clot did attach to all surgically incised or excised surfaces. The clinical relevance of these observations is related to the potential role of the blood clot in intraarticular tissue repair following arthroscopic surgery.

Adult↗

Clinical experience with technetium 99m teboroxime.

Technetium 99m teboroxime is a boronic acid adduct of technetium dioxime complex, a neutral lipophilic technetium-containing myocardial perfusion imaging agent with high myocardial extraction, rapid myocardial washout, and entero-hepatic excretion. Early "redistribution" occurs, and, based on preliminary animal data, appears to be due to differential washout alone since there is no reuptake of teboroxime into the heart; however, for practical purposes two injections of tracer, at stress and at rest, are used clinically. Due to the high photon flux of technetium, diagnostic images can be acquired in the narrow time window between the end of blood clearance and peak hepatic uptake. To begin an acquisition within 2 minutes of tracer injection, the patient must be moved rapidly from the treadmill to a camera that is set and ready to count. A complete set of planar images can be completed in less than 5 minutes. Optimal single photon emission computed tomography (SPECT) imaging requires a continuously counting single detector camera or a three-headed camera to complete acquisition in less than 10 minutes. The image quality is comparable to thallium 201 and the imaging time is a fraction of the time required to complete SPECT thallium scans. Both left ventricular function (ejection fraction) and planar imaging can be performed in less than 4 minutes, without moving the patient from the treadmill, using the Sim-400 (Scinticor, Milwaukee, WI), a portable high count-rate, multicrystal scintillation camera. Because teboroxime maintains high myocardial extraction at high myocardial flow, it may be uniquely suited to be used in combination with pharmacological stress, which does not require patient movement between stress and imaging. Work is in progress to further refine and optimize imaging protocols using teboroxime.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗