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Biomedical subjects

M B Johnson

Publications and source records attributed to M B Johnson.

At least 19 recordsLinked to original sources

Spin waves in nickel nanorings of large aspect ratio.

The spin dynamics of high-aspect-ratio nickel nanorings in a longitudinal magnetic field have been investigated by Brillouin spectroscopy and the results are compared with a macroscopic theory and three-dimensional micromagnetic simulations. Good agreement is found between the measured and calculated magnetic field dependence of the spin wave frequency. Simulations show that as the field decreases from saturation, the rings switch from a "bamboo" to a novel "twisted bamboo" state at a certain critical field, and predict a corresponding dip in the dependence of the spin wave frequency on the magnetic field.

Journal Article↗

Energy loss of fast quarks in nuclei.

We report an analysis of the nuclear dependence of the yield of Drell-Yan dimuons from the 800 GeV/c proton bombardment of 2H, C, Ca, Fe, and W targets. Employing a new formulation of the Drell-Yan process in the rest frame of the nucleus, this analysis examines the effect of initial-state energy loss and shadowing on the nuclear-dependence ratios versus the incident proton's momentum fraction and dimuon effective mass. The resulting energy loss per unit path length is -dE/dz = 2.32+/-0.52+/-0.5 GeV/fm. This is the first observation of a nonzero energy loss of partons traveling in a nuclear environment.

Journal Article↗

Inhibition of mammary epithelial apoptosis and sustained phosphorylation of Akt/PKB in MMTV-IGF-II transgenic mice.

IGF-II is a growth factor implicated in human cancers and animal tumor models. While the mitogenic properties of IGF-II are well documented, its ability to suppress apoptosis in vivo has never been proven. We generated independent MMTV-IGF-II transgenic mice to examine the control of epithelial apoptosis at the morphological, cellular and molecular levels during the physiological event of postlactation mammary involution. Transgenic IGF-II expression was achieved in mammary epithelium and increased IGF-II bioactivity was confirmed by phosphorylation of the insulin receptor substrate-1, a signaling molecule downstream of the type I IGF receptor. IGF-II overexpression induced a delay in mammary involution, as evident by increased mammary gland to body weight ratios and persistence of both functionally intact lobulo-alveoli and mammary epithelial cellularity. The delayed mammary involution resulted from a significant reduction in mammary epithelial apoptosis, and not from increased epithelial proliferation. Recombinant IGF-II pellets implanted into involuting mammary glands of wild-type mice provided further evidence that IGF-II protein inhibited local epithelial apoptosis. At the molecular level, phosphorylated Akt/PKB, but not Erk1 or Erk2, persisted in IGF-II overexpressors and temporally correlated with reduced epithelial apoptosis. Levels of the phosphatase PTEN were unaltered in the transgenic tissue suggesting that the maintenance of Akt/PKB phosphorylation resulted from sustained phosphorylation rather than altered dephosphorylation of PIP-3. Together, this data reveal that IGF-II inhibits apoptosis in vivo and this effect correlates with prolonged phosphorylation of Akt/PKB

Animals↗

Global ischemia induces expression of acid-sensing ion channel 2a in rat brain.

Acid-sensing ion channels (ASICs) are ligand-gated cation channels that respond to acidic stimuli. They are expressed throughout the mammalian nervous system. In the peripheral nervous system, ASICs act as nociceptors, responding to the tissue acidosis that accompanies ischemic and inflammatory conditions. The function of ASICs in the central nervous system is not known. In this article, the authors present evidence that transient global ischemia induces ASIC 2a protein expression in neurons that survive ischemia. Western blot analysis with an anti-ASIC 2a antibody revealed up-regulation of an 80 kD protein in ischemic rat brain. Immunohistochemical analysis showed that ASIC 2a protein expression increased in neurons of the hippocampus and cortex. Klenow fragment-mediated labeling of DNA strand breaks determined that ASIC 2a induction did not occur in cells with detectable DNA damage. The current results suggest a possible role for ASICs in mediating a cellular response to ischemia.

Acid Sensing Ion Channels↗

Mesenteric ischemia: an unusual presentation of traumatic intrahepatic arterioportal fistula.

Traumatic hepatic arterioportal fistulae (APF) are described infrequently as sequelae of hepatic trauma. These anomalies are usually associated with blunt hepatic trauma or iatrogenic injury. The majority of APF present within weeks to months of injury with gastrointestinal hemorrhage, hemobilia, abdominal pain, and diarrhea. When presenting remotely APFs are associated with portal hypertension, heart failure, gastrointestinal hemorrhage, ascites, and splenomegaly. We report an unusual case of mesenteric ischemia due to an APF that resulted from a penetrating liver injury 20 years before presentation. Successful treatment of the APF was achieved by intravascular catheter occlusion resulting in resolution of symptoms.

Adult↗

Comparison of Doppler ultrasound, magnetic resonance angiographic techniques and catheter angiography in evaluation of carotid stenosis.

AIM: To compare the accuracy of ultrasound and two magnetic resonance (MR) angiographic techniques with catheter angiography in assessing atherosclerosis at the carotid bifurcation. MATERIALS AND METHODS: Forty patients with symptomatic carotid stenosis were studied by Doppler ultrasound, time-of-flight MR angiography, contrast-enhanced MR angiography and conventional catheter angiography. The degree of stenosis found on ultrasound and MR angiography was compared with the results of catheter angiography. Four different assessment methods were conducted for the MR angiographic data. Kappa, sensitivity and specificity (with confidence intervals) values were calculated for the US and MR angiography results compared to catheter angiography. RESULTS: Catheter angiography showed 12 internal carotid artery occlusions (15%), 34 severe (44%), 12 moderate (15%) and 20 mild stenoses (26%), using NASCET criteria. Ultrasound showed 65% sensitivity and 95% specificity in detecting surgically amenable lesions, whilst the MR angiographic techniques had sensitivities varying from 82-100%, and specificities from 95-100%.A moderate kappa value was calculated for the US data, whilst all MR techniques were found to show very good agreement with catheter angiography. CONCLUSION: This data suggests that MR angiography is more accurate than Doppler ultrasound in defining surgical lesions and has comparable accuracy to catheter angiography. The use of contrast-enhanced MR angiography is useful in certain situations but is not essential in all cases.

Aged↗

Functional comparison of specifically cross-linked hemoglobins biased toward the R and T states.

Selected functional and spectroscopic properties of two human hemoglobin (HbA0) derivatives that were site-specifically cross-linked in the cleft between beta-chains where 2, 3-bisphosphoglycerate normally binds have been determined to assess the effects of the cross-linking on the behavior of the protein. Trimesoyl tris(3,5-dibromosalicylate) (TTDS) cross-links Hb between beta82Lys residues. The resulting TTDS-Hb exhibits a slower rate of oxygen dissociation and an increased rate of carbon monoxide association than observed for HbA0. The electron paramagnetic resonance (EPR) spectrum of TTDS-HbNO does not exhibit the hyperfine structure that is indicative of significant conformational change despite the fact that the 2,3-bisphosphoglycerate binding site is occupied by the cross-linking reagent. The reactivity of the beta93Cys residues of TTDS-Hb is only slightly decreased relative to that of HbA0. On the other hand, cross-linking Hb between Lys82 and the amino-terminal beta1Val group with trimesoyl tris(methyl phosphate) (TMMP) increases the rate of oxygen dissociation and reduces the rate of CO association relative to the rates observed for HbA0. In addition, the EPR spectrum of the TMMP-HbNO exhibits the three-line hyperfine structure that results from disruption of the proximal His-Fe bond of the alpha-chains, and the accessibility of the betaCys93 residues in this derivative is decreased fourfold. The present results are consistent with the conclusion that the quaternary structure of TTDS-Hb is shifted toward the R state whereas the quaternary structure of TMMP-Hb is shifted toward the T state and provides additional evidence that the identity of the residues involved in intramolecular cross-linking of hemoglobin within the 2,3-bisphosphoglycerate binding site between beta-chains can have a significant influence on the conformational and functional properties of the protein.

Binding Sites↗

Resolution of hormonal markers of ectopic gestation: a randomized trial comparing single-dose intramuscular methotrexate with salpingostomy.

OBJECTIVE: To evaluate resolution of serum hCG and progesterone in patients with ectopic pregnancy receiving single-dose intramuscular (IM) methotrexate as compared with those undergoing laparoscopic salpingostomy. METHODS: In this prospective randomized clinical trial, 75 hemodynamically stable women with a diagnosis of ectopic pregnancy were randomized to treatment with single-dose IM methotrexate (1 mg/kg) or laparoscopic salpingostomy. All women had initial, day 4, and weekly serum hCG and progesterone measurements taken until hCG levels were less than 15 mIU/mL. Methotrexate therapy was repeated if posttreatment day 7 hCG levels did not decrease by 15%, as compared with day 4 levels. Success rate was defined as ectopic resolution without the need for the alternate mode of therapy. RESULTS: Thirty-eight women were randomized to treatment with methotrexate and 37 to laparoscopic salpingostomy. The mean (+/-standard deviation) time required for serum progesterone concentrations to decrease to less than 1.5 ng/mL was significantly less for laparoscopic salpingostomy than for treatment with methotrexate: 7.8+/-1.7 and 17.6+/-2.2 days, respectively (P < .01). Within each treatment group, serum progesterone levels resolved (less than 1.5 ng/mL) more rapidly than did hCG levels (less than 15 mIU/mL) (P < .01). No further treatment was required once serum progesterone levels had decreased to less than 1.5 ng/mL. Success rates were similar in both groups: 94.7% (36 of 38) for methotrexate and 91.4% (33 of 36) for laparoscopic salpingostomy. Mean time required for hCG concentrations to decrease to less than 15 mIU/mL was significantly less for laparoscopic salpingostomy than for methotrexate therapy: 20.2+/-2.7 and 27.2+/-2.3 days, respectively (P < .05). Additional methotrexate injections were required in 15.8% (6 of 38) of women randomized to methotrexate therapy. Initial serum hCG levels for patients receiving additional methotrexate doses were 4830+/-1588 mIU/mL as compared with 2133+/-393 mIU/mL for women receiving only one dose (P = .07). CONCLUSION: Serum progesterone levels of less than 1.5 ng/mL are a good predictor of ectopic pregnancy resolution regardless of treatment, and because its return to normal values occurs more rapidly than that of hCG levels, serum progesterone may be a better marker for predicting successful treatment. Although laparoscopic salpingostomy leads to faster resolution of hormonal markers of ectopic gestation, methotrexate is equally successful for treating small unruptured ectopic pregnancies. Initial hCG levels may be a marker for women requiring additional doses of methotrexate.

Abortifacient Agents, Nonsteroidal↗

Short-term macrophage interleukin-1 response to injected silicone in a rat model.

The short-term effects of silicone particles on the ability of splenic and peritoneal macrophages to produce Interleukin-1 (IL-1) were assessed. Lewis rats were divided into three groups. Group 1 animals (n=12) were injected subcutaneously with 2.5 ml of sterile saline; Group 2 animals (n=12) received 2.5 ml of Freund's Complete Adjuvant (FCA); Group 3 animals (n=12) received subcutaneous injections (2.5 ml) of a sonicated slurry comprised of equal parts of FCA and silicone. At days 1, 4, and 7 single-cell suspensions of splenic (10(8) cells/ml) and peritoneal (10(6) cells/ml) macrophages of four animals from each group were prepared. The supernatants from macrophages cultured in the presence or absence of lipopolysaccharide (LPS) were added to IL-1 dependent mouse thymocytes for 72 hrs, and subsequently pulsed with 3H-thymidine. Radioactivity incorporation was determined after 18 hrs. Peritoneal macrophage culture supernatants had significantly higher activity than splenic macrophages and all macrophages stimulated with LPS had significantly higher activity. At days 1 and 7, there were no significant differences in 3H-thymidine uptake. At day 4 there was an elevation of 3H-thymidine uptake from supernatant of peritoneal macrophages treated with FCA/silicone suggesting subcutaneous silicone injection has short-term effects.

Animals↗

Comparison of two methods of bedside blood glucose screening in the NICU: evaluation of accuracy and reliability.

Bedside whole blood glucose screening in the NICU has been an accepted method of care for several years. Meters or visually read reagent strips are used in bedside screening, but the reliability and accuracy of these methods are not always established before they are implemented as routine practice in the NICU. A study was conducted to determine which method of bedside whole blood glucose screening was the more accurate: visually read Chemstrip bG reagent strips or the One Touch II meter method. The values obtained were compared with lab analysis of serum glucose, and a correlation study was performed to compare the accuracy and reliability of the values produced by the two methods. One hundred samples were obtained from 38 NICU infants; 63 percent of the 100 samples were compared with lab values. Results revealed that the One Touch II method was more reliable (r = .92) than the Chemstrip bG method (r = .87). Furthermore, the One Touch II results correlated better with lab values when the meter was not operated in the neonatal mode. This study revealed that the One Touch II method appears to provide safe and accurate screening of bedside blood glucose in a high-risk neonatal population.

Blood Glucose↗

Catfish stings in Mississippi.

We reviewed a series of 83 catfish sting cases from inland hospitals (Belzoni and Indianola) and a coastal hospital (Pascagoula) to identify the type and severity of injury, as well as the type of treatment and its effectiveness. Oral cephalosporin was adequate in treating early infections.

Animals↗

Differentiation of benign and malignant adnexal masses: relative value of gray-scale, color Doppler, and spectral Doppler sonography.

OBJECTIVE: The purpose of this study was to evaluate prospectively the relative usefulness of color Doppler, spectral Doppler, and gray-scale sonography in differentiating benign from malignant adnexal masses. SUBJECTS AND METHODS: A total of 170 adnexal masses in 161 patients were classified prospectively as suggestive of or not suggestive of malignant tumor on the basis of gray-scale morphology, internal flow versus peripheral or no flow, and spectral Doppler pulsatility, as measured by a pulsatility index (PI) threshold of 1.0 and a resistive index (RI) threshold of 0.4. RESULTS: Surgical pathology revealed 123 benign masses and 46 malignant masses. One malignant mass was confirmed by cytologic evaluation of ascitic fluid. On gray-scale analysis, 46 of the 47 malignant masses were classified as suggestive of tumor, and 76 of the 123 benign masses were classified as not suggestive of tumor (sensitivity, 98%; specificity, 62%; negative predictive value [NPV], 99%; and positive predictive value [PPV], 50%). The use of internal color flow as a predictor of malignant tumor yielded a sensitivity of 77%, a specificity of 69%, an NPV of 89%, and a PPV of 49%. The PI and RI values were significantly lower (p < .0001) in malignant masses than in benign masses, although the values overlapped considerably. For a PI of less than 1.0, sensitivity was 67%, specificity was 66%, NPV was 83%, and PPV was 46%. For an RI of less than 0.4, sensitivity was 24%, specificity was 90%, NPV was 73%, and PPV was 50%. CONCLUSION: In our series, a gray-scale prediction of benignity was reliable (NPV = 99%), and a prediction of malignancy was unreliable (PPV = 50%). Internal color flow was not useful as a predictor of malignancy (PPV = 49%). Although the absence of internal or peripheral color flow suggested benignity (NPV = 94%), only 17 (16 benign) of the masses (about 10%) had no flow. Spectral Doppler analysis with RI and PI was not useful, as no reliable discriminatory value with both high sensitivity and high specificity could be found for either parameter because of the overlap in values obtained for benign and malignant masses.

Adnexal Diseases↗

CNS-directed case management. Cost and quality in harmony.

Preserving the integrity of high quality care in a financially restricted environment is the primary challenge facing healthcare providers. The critical question is which delivery system will use limited resources most efficiently without jeopardizing quality of care? Case management has been identified as a solution that offers the most promise. The case management model at Sioux Valley Hospital was developed to deal proactively with resource-intensive patients with chronic illnesses who have frequent admissions and who create financial risk for the hospital. The authors describe the fiscal and clinical outcomes of these select patients.

Adolescent↗

Antioxidant MDL 29,311 prevents diabetes in nonobese diabetic and multiple low-dose STZ-injected mice.

Recent investigations suggest a role for antioxidants in preventing IDDM. MDL 29,311 (4,4'-[methylenebis(thio)]bis](1,1- dimethylethyl)]-phenol) is an analogue of the antioxidant probucol. Administered as a 1% dietary admixture to female nonobese diabetic mice from 4 to 24 wk of age, MDL reduced the prevalence of diabetes from 49 to 4% at 24 wk of age (n = 50-61/group). Discontinuation of treatment at 24 wk of age did not result in a rapid onset of diabetes. Probucol (1%) did not prevent diabetes. Initiating MDL treatment at 4 or 8 wk of age was more effective (19 and 17%, respectively, compared with 60% in control mice) than initiating treatment at 12 wk of age (30% diabetic; n = 28-35/group). A lower dose of MDL (0.1%), started at 4 wk of age, decreased the prevalence of diabetes to 36%. Histopathology indicated that MDL did not prevent insulitis. MDL (0.1%) also was evaluated in combination with immunosuppressants. Compared with control mice (65% diabetic), the combination of MDL and deflazacort was more effective (21% diabetic) than either agent alone (39% diabetic for MDL and 59% diabetic for deflazacort), whereas the effectiveness of MDL, cyclosporin, and MDL plus cyclosporin was similar (39, 38, and 34% diabetic, respectively). In another model of IDDM, the multiple-low-dose streptozocin-injected mouse, MDL (1%) also reduced the prevalence of diabetes when administered beginning 8 wk before streptozocin (55% diabetic vs. 100% of control mice; n = 20-25/group). Probucol (1%) was ineffective. MDL appears effective in preventing the onset of disease in two mouse models of IDDM.

Aging↗

MDL 29311. Antioxidant with marked lipid- and glucose-lowering activity in diabetic rats and mice.

MDL 29311, an analogue of probucol, administered to rats as a 1% dietary admixture for 2 wk before and 5 days after intravenous injection of 40 mg/kg of ALX significantly (P < 0.05) reduced plasma glucose (6.9 +/- 0.3 vs. 19.2 +/- 1.3 mM) and serum triglyceride (0.17 +/- 0.01 vs. 1.82 +/- 0.39 mM) levels in overnight-fasted ALX-plus-MDL 29311-administered rats vs. ALX-administered rats. A cross-over study indicated that MDL 29311 did not attenuate the diabetogenic action of ALX, but rather, directly lowered glucose and triglycerides. In rats injected intravenously with 45, 65, or 85 mg/kg of STZ and then administered control or MDL 29311 diet for 7 days, MDL 29311 decreased fasted plasma glucose to nondiabetic levels, decreased fasted and nonfasted plasma triglycerides by 49-79%, but did not affect plasma insulin levels. In STZ-induced (65 mg/kg) diabetic rats, MDL 29311 attenuated the increase in plasma nonesterified fatty acids during an 18-h fast; had little or no effect on glucagon, pyruvate, lactate, beta-hydroxybutyrate, acetoacetate, or cholesterol; and did not induce hypoglycemia in rats fasted up to 64 h. In nonfasted hyperinsulinemic db/db mice treated for 10 wk, MDL 29311 significantly lowered glucose levels by 14-40%, triglyceride levels by 31-63% and GHb from 8.0 to 5.4%, and had no consistent effect on plasma insulin levels. Because of its marked glucose- and lipid-lowering activity in both nonfasted hyperinsulinemic and fasted insulinopenic animals, MDL 29311 merits additional investigation as a potential antidiabetic agent.

Animals↗