Biomedical subjects
C M Johnson
Publications and source records attributed to C M Johnson.
Transient femoral nerve palsy after ilioinguinal block--comment.
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Protein stability as a function of denaturant concentration: the thermal stability of barnase in the presence of urea.
The conventional procedure for analyzing urea denaturation curves assumes that the free energy of unfolding (delta GU-F) is linearly related to [urea] that is, delta GU-F = delta GH2O(U-F)--m[urea], where m is a constant, specific for each protein, and delta GH2O(U-F) is the free energy of unfolding in water. This relationship can be measured directly, however, over only a small concentration range of approximately +/- 0.8 M urea around the midpoint of the unfolding transition. A nagging discrepancy (1.6 kcal mol-1) between delta GH2O(U-F) at 298 K of barnase extrapolated from such an equation and the equivalent value obtained from thermal unfolding measurements has stimulated a re-evaluation of the equation. Differential scanning calorimetric measurements have been made of the thermal unfolding of barnase in the presence of concentrations of urea between 0 and 4.5 M, the midpoint of the unfolding transition at 298 K, to test the denaturation equation over a wide range of [urea]. Values for delta GU-F at 298 K (delta G298U-F) for each concentration of urea were extrapolated from the calorimetrically measured enthalpies and the denaturational heat capacity change (delta Cdp) measured for that concentration of urea. A plot of delta G298U-F against [urea] deviates systematically from linearity and fits better the equation: delta G298U-F = 10.5 +/- 0.08 - ((2.65 +/- 0.05) x [urea]) + ((0.08 +/- 0.01) x [urea]2) kcal mol-1. The curvature in the plot leads to apparent values of m that increase when measurements are made at lower concentrations of urea. This could account for increases in m at low values of pH or in destabilized mutants since the protein denatures at lower concentrations of urea. It has been shown previously that small curvature in the free energy of unfolding versus [urea] leads to negligible errors in measurements of delta delta GU-F, the change in free energy of unfolding on mutation, providing that the curvature is similar for all mutants. The calorimetrically measured enthalpies of unfolding are decreased in the presence of urea while delta Cdp is increased. Both of these observations are consistent with an overall exothermic interaction between urea and protein with a net increase on unfolding.
Analysis of murine soluble Fc epsilon RII sites of cleavage and requirements for dual-affinity interaction with IgE.
The low-affinity receptor for IgE (Fc epsilon RII/CD23) is a type II integral membrane protein with an extracellular C-terminal sequence homologous to C-type animal lectins. Between this region and the membrane is a repetitive sequence predicted to form an alpha-helical coiled-coil and is termed the stalk region. The Fc epsilon RII is proteolytically cleaved when at the cell surface in this stalk region. Both the 38 Kd and 28 Kd major released fragments were isolated from culture media and N-terminal sequencing demonstrated that the cleavage sites were in the third and fourth repeat domains, respectively. The identified sites show no apparent similarity with the cleavage sites previously identified in human Fc epsilon RII. Recent studies have demonstrated that the intact Fc epsilon RII interacts with IgE with a dual-affinity, resulting from a multivalent interaction with the IgE Fc region; mutant Fc epsilon RII that have a disruption of the alpha-helical coiled-coil have a single low-affinity interaction consistent with a monomeric interaction with IgE. The soluble Fc epsilon RII were shown to interact with IgE with an affinity similar to these mutant Fc epsilon RII. Preparation of a chimeric Fc epsilon RII in which the transmembrane and cytoplasmic regions were replaced with sequences from Ly-49 revealed that these regions played no role in the multimeric association of the Fc epsilon RII necessary for dual-affinity interaction with IgE. In addition, a full-sized soluble Fc epsilon RII construct was expressed, and this molecule demonstrated increased capacity to interact with IgE.
Increased rates of tRNA charging through modification of the enzyme-aminoacyl-adenylate complex of phenylalanyl-tRNA synthetase.
The transfer of amino acid to tRNA by Escherichia coli phenylalanyl-tRNA synthetase (PheRS) was studied using replacements of Ala294 in the alpha subunit previously shown to have modified amino acid specificity. Steady-state analysis of tRNA charging showed little difference between wild-type and mutants, whereas pre-steady-state analysis revealed higher rates of tRNA charging by both the A294S PheRS-phenylalanyl adenylate and the A294G PheRS-p-Cl-phenylalanyl adenylate. The decrease in energy required for the formation of the transition state of amino acid transfer in these mutants could be related to a weaker binding of the amino acid in the aminoacyl adenylate complex. Thus a compromise appears to exist between amino acid activation and tRNA charging, because slowing down the first step increases the rate of the second step, possibly as a result of decreased stability of the PheRS.amino acid-AMP complex.
The anterior extension face-lift.
OBJECTIVE: To describe a face-lift technique with emphasis on extension of the temporal incision into the lateral orbital area. This modification serves several beneficial ends but must be used only in carefully selected patients. Gathering of excess skin in the lateral orbital area is prevented, eliminating the typical disparity between relatively tight lower and middle facial skin and flaccid upper facial skin, which is commonly seen after rhytidectomy. The anterior extension also helps to support the lower eyelid, which is helpful when lid laxity exists or when concomitant blepharoplasty is performed. SETTING: A private cosmetic surgery center. PARTICIPANTS: Thirty-five patients undergoing rhytidectomy (15 primary and 20 revision procedures). OUTCOME MEASURE: Patient satisfaction at 3 months after surgery. RESULTS: Thirty-four (97%) of 35 patients were pleased with their results. CONCLUSIONS: The anterior extension face-lift can provide excellent results in carefully selected patients. We have found this procedure to be especially helpful in patients undergoing revision surgery and in older patients with facial skin laxity.
The use of expanded polytetrafluoroethylene (Gore-Tex) in rhinoplasty. A 6-year experience.
OBJECTIVE: To determine the safety and efficacy of expanded polytetrafluoroethylene (Gore-Tex soft-tissue patch, W. L. Gore & Assoc Inc, Flagstaff, Ariz) as an implant in rhinoplasty. DESIGN: A retrospective study of 137 patients who underwent rhinoplasty including augmentation with Gore-Tex over a 6-year period. A review of the medical literature concerning the use of Gore-Tex as an implant in the head and neck was also conducted. SETTING: Two major academic medical centers and two private office surgical centers. PARTICIPANTS: One hundred thirty-seven consecutive patients who received Gore-Tex implants in the course of rhinoplasty. INTERVENTION: Sixty-nine patients presented for primary rhinoplasty; the remaining 68 presented for revision surgery. All received Gore-Tex nasal implants to augment the nasal dorsum and/or base. The grafts ranged from 1 to 6 mm in thickness. Follow-up ranged from 6 to 80 months, with an average of 25 months. OUTCOME MEASURES: Clinically noted complications and patient satisfaction. RESULTS: Three (2.2%) of 137 grafts became infected and were removed. One graft was removed 5 months post-operatively because of excessive augmentation. None of the patients who underwent implant removal required subsequent augmentation. All 137 patients are pleased with their results. CONCLUSION: Gore-Tex is a safe and effective implant material to use in primary and revision rhinoplasty when augmentation is needed and autogenous material is not available or desirable.
Reduced provirus burden and enhanced humoral immune function in AZT-treated SCID-feline mice inoculated with feline immunodeficiency virus.
The lack of a safe, economical murine lentivirus model for human immunodeficiency virus type 1 (HIV-1) infection of humans has hampered the preclinical evaluation of potential antiviral compounds, vaccines, and biological response modifiers. A small animal model that does not employ HIV-1 is needed to minimize risk of accidental human exposure, enhance efficient use of scarce experimental compounds, and reduce laboratory space necessary to conduct statistically significant in vivo trials. Feline immunodeficiency virus (FIV), an immunosuppressive lentivirus of domestic cats, has been used extensively as an animal model for the pathogenesis and therapy of human HIV-1 infection. Cats, however, are not amenable to large-scale efficacy trials because of their relatively large size, high cost, and limited degree of physiologic characterization, particularly with regard to drug metabolism. To adapt the feline immune system to a small laboratory animal host, severe combined immunodeficient mice (SCID mice) were engrafted with feline lymphoid tissues (forming the SCID-fe mouse) and inoculated with FIV. Two quantitative parameters, the incidence of provirus detection in feline tissue grafts and the level of feline IgG in plasma, were used to demonstrate the antiviral efficacy of 3'-azido-3'-deoxythymidine (AZT, azidothymidine, Retrovir, zidovudine) in the SCID-fe system. Of 17 SCID-fe mice inoculated with 7 x 10(6) peripheral blood mononuclear cells (PBMC) from an FIV-infected cat, eight had detectable FIV provirus in both the feline thymus and feline lymph node implants, as measured by polymerase chain reaction (PCR)/Southern blot analysis. Treatment of these mice with AZT at a dose of 125 mg kg-1 day-1 in drinking water beginning 1 day prior to FIV inoculation and continuing throughout the study interval prevented the dual detection of provirus in feline lymph node and thymus grafts of all mice tested. In a separate experiment, the level of spontaneous feline IgG production was quantified by ELISA 2 weeks after FIV inoculation with and without AZT treatment. Mean plasma feline IgG level of five SCID-fe mice inoculated with 10(3) TCID50 cell-free FIV was 2.23 mg ml-1. Mean feline IgG level of five mice inoculated with the same quantity of FIV and treated with AZT beginning 1 day prior to virus inoculation and continuing for 2 weeks thereafter was 14.98 mg ml-1. AZT significantly (P < 0.05) enhanced feline humoral immune function at a virus inoculum titer of 10(3) TCID50.(ABSTRACT TRUNCATED AT 400 WORDS)
The tension nose: open structure rhinoplasty approach.
The term tension nose is known to many rhinoplastic surgeons, yet confusion exists as to its precise meaning. We define the tension deformity as excessive growth of the quadrilateral cartilage, resulting in a high nasal dorsum and anterior and sometimes inferior displacement of the nasal tip cartilages. A review of the surgical literature shows that little attention has been given to the evaluation and management of this problem. We reviewed 50 consecutive primary rhinoplasty candidates and found that 46 percent had some manifestation of tension deformity that required correction at the time of surgery. The techniques of open structure rhinoplasty are ideally suited to manage the tension nose. The essence of correction is a deprojection-reprojection process. First, excessive elements of the septal cartilage and anterior nasal spine, which comprise what we have termed the nasal pedestal, are reduced, resulting in tip deprojection. Open structure methods are then employed to achieve reprojection of the domes by using cartilage grafts and suturing techniques to build strength, support, and elegance into the nasal tip.
In vivo induction kinetics of the arabinose promoters in Escherichia coli.
In Escherichia coli, the AraC protein represses transcription from its own promoter, PC, and when associated with arabinose, activates transcription from three other promoters, PBAD, PE, and PFGH. Expression from all four of these promoters is also regulated by cyclic AMP-catabolite activator protein; however, the arrangement of the protein binding sites is not identical for each promoter. We are interested in determining how the AraC protein is able to activate PBAD, PE, and PFGH despite their differences. We have characterized the induction response of the wild-type arabinose operons from their native chromosomal locations by primer extension analysis. In this analysis, mRNA from the four arabinose operons plus an internal standard could all be assayed in the RNA obtained from a single sample of cells. We found that each of the operons shows a rapid, within 15 to 30 s, response to arabinose. We also found that the expression of araFGH is more sensitive to catabolite repression but not to arabinose concentration than are araE and araBAD. Finally, we have determined the relative levels of inducibility in wild-type cells of araBAD, araFGH, and araE to be 6.5, 5, and 1, respectively. These results provide a basis for subsequent studies to determine the mechanism(s) by which AraC protein activates transcription from the different arabinose promoters.
Pulmonary embolism: diagnosis with contrast-enhanced electron-beam CT and comparison with pulmonary angiography.
PURPOSE: To determine the sensitivity and specificity of contrast material-enhanced electron-beam computed tomography (CT) in the diagnosis of pulmonary embolism (PE). MATERIALS AND METHODS: Sixty patients suspected of having PE were prospectively evaluated with pulmonary angiography and contrast-enhanced electron-beam CT. Thirty-eight patients underwent ventilation-perfusion (V-P [also known as V/Q]) scanning. The pulmonary vasculature was divided into 12 anatomic zones. CT and angiographic findings were correlated on a patient-by-patient basis and for each vascular zone. RESULTS: Both studies were negative for PE in 36 patients. Both studies were positive in 15 patients, with the site of the emboli correlating well. Prospective sensitivity of CT was 65%; specificity, 97%; positive predictive value, 94%; and negative predictive value, 82%. After review of the nine discordant cases, sensitivity and specificity approached 100% for clinically important acute PE. CT depicted central and peripheral emboli equally well. CT was more sensitive and specific than V-P scanning. CONCLUSION: Electron-beam CT is a sensitive and specific noninvasive method for the diagnosis of PE. It has the potential to replace V-P scanning as the primary screening examination for PE.
Thermogenesis after a mixed meal: role of leg and splanchnic tissues in men and women.
To determine the relative contribution of splanchnic and leg tissues to postprandial thermogenesis, systemic and regional oxygen consumption rates were measured in nine women and eight men before and for 6 h after the consumption of a mixed meal that provided one-third of the daily energy needs. In women, the increase in splanchnic oxygen uptake accounted for 63 +/- 12% of the postprandial increase in oxygen consumption, whereas in men it accounted for 35 +/- 14% (P = not significant between women and men). Leg oxygen uptake accounted for 11 +/- 4 and 10 +/- 3% of the increase in postprandial oxygen consumption in women and men, respectively. The combined data suggest that approximately 48% of postprandial thermogenesis over 6 h occurs in splanchnic tissues, whereas 30-35% occurs in skeletal muscle. Thus the increase in oxygen consumption after a mixed meal is primarily localized to splanchnic tissues, and major reductions in postprandial thermogenesis are unlikely to be attributable solely to abnormalities of skeletal muscle metabolism.
Effect of Guglielmi detachable coils on experimental carotid artery aneurysms in primates.
BACKGROUND AND PURPOSE: Clinical experience has established that intravascularly placed metal coils can be a useful treatment for cerebral vascular aneurysms. However, the mechanism by which the coils induce occlusion of the aneurysm is unclear. Appropriate use of this promising treatment modality requires basic understanding of the occlusive process. We used an animal model system of experimentally induced carotid aneurysms to investigate the initial events induced by Guglielmi detachable coils (GDCs), as well as the subsequent vascular changes induced by the coils over time. METHODS: We induced 23 aneurysms in the carotid arteries of 16 Japanese monkeys. Nineteen aneurysms were then occluded with GDCs placed via endovascular surgery; 4 aneurysms served as controls. We then used gross and microscopic pathological examination, angiography, and scanning electron microscopy to assess the effects of the GDC. RESULTS: In the first few hours after placement of the GDC in the experimental aneurysms, we observed leukocyte attachment and deposition of fibrinlike materials and other proteins. By 4 days after coil placement, leukocytes and fibroblasts were observed in the thrombus. By 2 weeks after coil placement, there was evidence of an endothelial-like covering of the coils. At 3 months after coil placement, we observed development of an arterial media in the occluded aneurysms. CONCLUSIONS: The GDCs initiated a cellular response within several hours of aneurysm occlusion. By 2 weeks after coil placement, endothelialization was proceeding, and by 3 months after occlusion, remodeling of the aneurysm had progressed to produce a media-like structure in the former aneurysm.
Distinction between cavernous hemangiomas of the liver and hepatic metastases on CT: value of contrast enhancement patterns.
OBJECTIVE: Differentiating between cavernous hemangiomas of the liver and hepatic metastases on the basis of single-pass, contrast-enhanced CT is a significant and frequently encountered diagnostic challenge. Recognition of characteristic enhancement features of cavernous hemangiomas can aid in effectively distinguishing between these lesions. The purpose of this study was to determine sensitivity and specificity of dense, globular enhancement for differentiating cavernos hemangiomas and metastases during single-pass, contrast-enhanced CT. MATERIALS AND METHODS: CT appearance of 133 lesions in 91 patients with cavernous hemangiomas (44 patients) or metastases (47 patients) was retrospectively evaluated in a blinded review. CT examinations were performed with nonhelical technique following injection of 150 ml of contrast material. All patients with metastases had pathologic proof (n = 47). Patients with cavernous hemangiomas were clinically stable for at least 2 years after CT (n = 43) or had tissue proof (n = 1). All lesions were evaluated based on the following criteria: (1) Type of enhancement: globular, linear, diffuse and homogeneous, or diffuse and heterogeneous. (Globular enhancement was considered to be present when enhancing nodules less than 1 cm in diameter were seen within lesions.) (2) Continuity of enhancing tissue: continuous or noncontinuous. (Uninterrupted collections of contrast material within at least 50% of a lesion were considered continuous. Multiple, separate collections of contrast material were considered noncontinuous.) (3) Degree of enhancement: hypo-, iso-, or hyperdense relative to the aorta. (4) Distribution of enhancement: peripheral, central, or mixed. RESULTS: Seventy-six percent of cavernous hemangiomas had globular enhancement, compared to 10% of metastases (p < .001). Seventy-two percent of cavernous hemangiomas had enhancement isodense with the aorta, and 96% of metastases were hypodense (p < .001). Sixty-seven percent of cavernous hemangiomas had peripheral enhancement, compared to 38% of metastases (p < .001). The combined finding of globular, isodense enhancement was seen in 67% of cavernous hemangiomas and none of the metastases. Only 10% of cavernous hemangiomas had nonglobular, hypodense enhancement, compared with 90% of metastases. Combining all criteria, reviewers correctly classified 122 (92%) of the lesions. Presence of globular enhancement, isodense with the aorta, was 67% sensitive and 100% specific in differentiating cavernous hemangiomas from hepatic metastases. CONCLUSION: In most cases, differentiation of cavernous hemangiomas from hepatic metastases can confidently be made with single-pass, contrast-enhanced CT. Globular enhancement, isodense with the aorta, is 67% sensitive and 100% specific in differentiating cavernous hemangiomas and hepatic metastases.
Renal artery angioplasty: technical results and clinical outcome in 320 patients.
OBJECTIVE: To review the results of percutaneous transluminal renal artery angioplasty (PTRA), including technical success and clinical outcome, at Mayo Clinic Rochester. DESIGN: We retrospectively reviewed our experience with 320 patients who underwent PTRA for stenosis of 396 arteries during a 14-year period. MATERIAL AND METHODS: We reviewed medical records and angiograms of patients who underwent PTRA at Mayo Clinic Rochester between January 1980 and December 1993. The patients were divided into four groups, based on clinical history and angiographic appearance of the stenosing lesion: renal artery atherosclerosis (ASO group), fibromuscular dysplasia (FMD group), previous renal artery bypass or endarterectomy, and renal artery stenosis in a solitary kidney. Technical results of the PTRA were determined by evaluation of angiograms obtained before and after the procedure. Data on patient demographics, blood pressure, antihypertensive medications, and serum creatinine were recorded for the period preceding PTRA, after the procedure, and at last follow-up. RESULTS: All groups had statistically significant reductions in mean arterial pressure and antihypertensive medications after PTRA. The percentage of patients who benefited after renal artery angioplasty was 70% for patients with ASO (8.4% cured), 63% for patients with FMD (22% cured), 53.8% for patients with prior surgical revascularization (23.1% cured), and 91.7% for patients with a solitary kidney (0% cured). No significant overall change in serum creatinine level was noted after the procedure in any group. Complications were comparable to those reported in other studies. The 30-day all-cause mortality rate was 2.2% for the current study, all deaths occurring in the ASO group. CONCLUSION: PTRA rarely leads to a "cure" of renovascular hypertension but provides effective control of blood pressure and decreases the medication requirements in selected patients.
Rheumatoid vasculitis manifesting as intra-abdominal hemorrhage.
Rheumatoid vasculitis, an extra-articular component of rheumatoid arthritis, causes a wide spectrum of manifestations that range from clinically insignificant to life-threatening disease. As a systemic necrotizing arteritis, rheumatoid vasculitis is usually characterized by end-organ ischemia. Herein we describe a patient with abdominal pain and syncope due to intra-abdominal hemorrhage from a ruptured aneurysm of the inferior pancreaticoduodenal artery in the setting of rheumatoid vasculitis. Although the intra-abdominal hemorrhage was the unusual manifestation of rheumatoid vasculitis in this patient, he had a history of prior extra-articular rheumatoid disease, including pulmonary fibrosis and Sjögren's syndrome with associated parotid lymphoproliferative disease. In patients with rheumatoid arthritis who have abdominal pain and an unexplained rapidly decreasing hemoglobin concentration, the diagnosis of intra-abdominal hemorrhage from a ruptured visceral aneurysm due to rheumatoid vasculitis should be considered, even in the absence of other indications of systemic vasculitis.
Recurrent spontaneous abortion.
The patient with recurrent pregnancy loss is often frustrated and on the verge of despair. Evaluation can sometimes take several visits, allowing the physician the time and opportunity to provide emotional support to the couple. With proper evaluation and therapy, the majority of patients will become pregnant. For those who have exhausted diagnostic and treatment options, the physician should encourage consideration of assisted reproductive technologies or adoption.
[Clinical, electrocardiographic and angiographic evaluation of natural reservoirs of Chagas' disease in the Republic of Panama].
The authors studied two groups of natural animal reservoirs for Trypanosoma cruzi: a wild one, the common rat Rattus rattus and the house dog, Canis canis. Thirty one naturally infected rats were evaluated with a technique developed by the authors which allows the recording of the ECG and the performance of a ventricular angiogram without altering the functional capacity of the animal. Forty four dogs were followed clinically for a period of twenty years to study the development of the cardiac lesion seen in the chronic phase of the disease. The authors demonstrate the epidemiologic importance of the dog as a reservoir and the ease with which the infection can be acquired from rats, which live in the same habitat with human patients. The most common lesions in both groups were ventricular and atrial arrhythmias and second degree AV block; and, in the dogs, also death due to refractory cardiac failure, such as is seen in the human patient. Right bundle branch block and dilatation of the right cardiac chambers was the rule in both groups. The authors discuss the pathogenesis of the ECG in the rat and its anatomical basis. They propose the possibility of establishing and standardizing this techniques in the laboratories that study rats or other species.