Biomedical subjects

G A Johnson

Publications and source records attributed to G A Johnson.

At least 109 records · Page 6Linked to original sources

PubMed1995

MR imaging with hyperpolarized 3He gas.

Magnetic resonance images of the lungs of a guinea pig have been produced using hyperpolarized helium as the source of the MR signal. The resulting images are not yet sufficiently optimized to reveal fine structural detail within the lung, but the spectacular signal from this normally signal-deficient organ system offers great promise for eventual in vivo imaging experiments. Fast 2D and 3D GRASS sequences with very small flip angles were employed to conserve the norenewable longitudinal magnetization. We discuss various unique features associated with performing MRI with hyperpolarized gases, such as the selection of the noble gas species, polarization technique, and constraints on the MR pulse sequence.

Animals↗

PubMed1995

MR microscopy of the rat carotid artery after balloon injury by using an implanted imaging coil.

Neointimal hyperplasia after angioplasty was followed in vivo in rats by using MR microscopy and surgically implanted RF imaging coils. By using an inductively coupled pick-up coil, the arteries were imaged 4 days before and 3, 7, and 14 days after angioplasty with a 3DFT spin echo sequence. Eight of 10 angioplastied rats showed moderate to severe stensois based MR measures of lumen diameter reduction from baseline images. There was a good correlation between total wall thickness between MR and hematoxylin and eosin (H&E)-stained sections obtained on the last day. Arteries in the intact and sham groups remained unchanged from baseline measurements. Because this imaging technique examines the artery under in vivo conditions of arterial pressure and flow, it promises to be a useful tool for evaluating pharmacological and mechanical methods of reducing the incidence of vascular stenosis.

Angioplasty, Balloon↗

PubMed1995

Detection of bromobenzene-induced hepatocellular necrosis using magnetic resonance microscopy.

The authors used magnetic resonance (MR) microscopy to assess hepatic tissue damage induced by bromobenzene both in living rats and in fixed rat liver tissues. Experiments were conducted at 7 Tesla on three groups of Fisher rats treated with bromobenzene at a single dose of 68, 135, and 269 mg/kg, respectively. Optical microscopy of hematoxylin and eosin stained sections showed liver damage only at the highest dose, whereas with MR microscopy, tissue alterations were detected at all three doses both in vivo and ex vivo. The contrast mechanism of the superior sensitivity of MR microscopy is believed to be related to the changes in local diffusion coefficients that accompany cellular degeneration and death, although other contrast mechanisms may also be involved. The superior sensitivity of MR microscopy, as demonstrated in this study, has many implications for potential use of MR techniques to perform in vivo histology.

Animals↗

PubMed1995

Baculovirus-insect cell production of bioactive choriogonadotropin-immunoglobulin G heavy-chain fusion proteins in sheep.

A hybrid cDNA encoding a fusion protein between the beta subunit of hCG (beta hCG) and constant domains of a mouse IgG heavy chain (CH1-3) was inserted into a baculovirus expression vector. Insect cells transfected with foreign DNA synthesized multimeric forms of fusion protein that inhibited hCG-induced steroid hormone secretion by mouse Leydig tumor cells. Leydig cells were lysed by beta hCG-CH1-3 in the presence of complement. Intravenous injection of beta hCG-CH1-3 in rams was associated with testicular mononuclear leukocyte infiltration, interstitial tissue damage, and a transient depression in circulatory testosterone (levels returned to normal within 2 wk). It appears that targeted cell-killing can be mediated by recombinant proteins composed of the receptor-binding moiety of hormones and truncated effector (Fc) regions of lethal antibodies.

Animals↗

PubMed1995

Prevalence of depression after stroke: the Perth Community Stroke Study.

BACKGROUND: The Perth Community Stroke Study (PCSS) was a population-based study of the incidence, cause, and outcome of acute stroke. METHOD: Subjects from the study were assessed initially, by examination and interview, and at four- and 12-month follow-ups to determine differences in prevalence of depression between the sexes and between patients with first-ever and recurrent strokes. RESULTS: The prevalence of depressive illness four months after stroke in 294 patients from the PCSS was 23% (18-28%), 15% (11-19%) major depression and 8% (5-11%) minor depression. There were no significant differences between the sexes or between patients with first-ever and recurrent strokes. With a non-hierarchic approach to diagnosis of those with depression, 26% of men and 39% of women had an associated anxiety disorder, mainly agoraphobia. Nine per cent of male and 13% of female patients interviewed had evidence of depression at the time of the stroke. Twelve months after stroke 56% of the men were still depressed (40% major and 16% minor), as were 30% of the women (12% major and 18% minor). CONCLUSION: The prevalence of depression after stroke was comparable with that reported from other studies, and considerably less than that reported from in-patient and rehabilitation units.

Adaptation, Psychological↗

PubMed1995

Anxiety disorders after stroke: results from the Perth Community Stroke Study.

BACKGROUND: The prevalence of anxiety disorders in 294 patients who survived to four months in the Perth Community Stroke Study (Perth, Australia), and a follow-up of these patients at 12 months, are presented. METHOD: Diagnoses are described both in the usual DSM hierarchic format and by a non-hierarchic approach. Adoption of the hierarchic approach alone greatly underestimates the prevalence of anxiety disorders. RESULTS: Most cases were of agoraphobia, and the remainder were generalised anxiety disorder. The prevalence of anxiety disorders alone was 5% in men and 19% in women; in community controls, it was 5% in men and 8% in women. Adopting a non-hierarchic approach to diagnosis gave a prevalence of 12% in men and 28% in women. When those who showed evidence of anxiety disorder before stroke were subtracted, the latter prevalence was 9% in men and 20% in women. CONCLUSION: One-third of the men and half of the women with post-stroke anxiety disorders showed evidence of either depression or an anxiety disorder at the time of the stroke. At 12 month follow-up of 49 patients with agoraphobia by a non-hierarchic approach, 51% had recovered, and equal proportions of the remainder had died or still had agoraphobia. The only major difference in outcome between those with anxiety disorder alone and those with comorbid depression was the greater mortality in the latter.

Adaptation, Psychological↗

PubMed1995

Incidence and location of para-aortic lymph node metastases in gynecologic malignancies.

BACKGROUND: We sought to determine the location of metastases to para-aortic lymph nodes in patients with gynecologic malignancies. STUDY DESIGN: A retrospective chart review was performed for all cases of endometrial, ovarian, and cervical carcinoma in which right and left para-aortic lymph node dissection was done at our institution from 1985 to 1993. Records were assessed for tumor type as well as for presence and location of metastases to para-aortic lymph nodes. RESULTS: A total of 315 patients had bilateral para-aortic lymphadenectomy performed at the time of laparotomy as part of staging or therapy for their gynecologic malignancies. A total of 47 patients (15 percent) had metastasis to the para-aortic lymph nodes. Para-aortic metastasis were identified in 22 (30 percent) of 73 patients with ovarian carcinoma, 11 (8 percent) of 141 patients with cervical carcinoma, and 14 (14 percent) of 101 patients sampled. Unilateral left-sided para-aortic node involvement was observed in 13 patients, unilateral right-sided involvement was present in 14 patients, and bilateral involvement occurred in 20 patients. Regarding tumor type or origin, no significant difference was noted in right-sided compared with left-sided para-aortic metastases. CONCLUSIONS: Our data suggest no difference in the incidence of metastases to right-sided compared with left para-aortic lymph nodes in patients with gynecologic malignancies, emphasizing the need for bilateral evaluation of the para-aortic lymph nodes. This information is important in the clinical staging of gynecologic malignancies and in establishing protocols requiring para-aortic lymph node dissection.

Abdomen↗

PubMed1995

Human skin and platelet minoxidil sulfotransferase activities: biochemical properties, correlations and contribution of thermolabile phenol sulfotransferase.

Human scalp skin high speed supernatants were used to test whether minoxidil sulfotransferase (MNX-ST) and phenol sulfotransferase (PST) activities were present. Platelet homogenates from the same skin donors were used to test whether levels of sulfotransferase activities in the blood platelet would reflect levels of the enzyme activities in skin. Dopamine, p-nitrophenol and minoxidil were used as substrates for skin and platelet thermolabile (TL PST), thermostable (TS PST) and MNX-ST activities, respectively. Biochemical properties of each skin enzyme were the same as the platelet enzymes with respect to apparent Km values for substrates, pH optima, thermal stabilities and responses to inhibition by 2,6-dichloro-4-nitrophenol (DCNP). An unexpected finding was that skin and platelet MNX-ST thermal stabilities and responses to DCNP were more similar to TL PST than to TS PST, the enzyme reported to be responsible for MNX-ST activity. There were significant positive correlations of platelet sulfotransferases with the relative levels of activities of the same skin sulfotransferases. Unexpected findings were significant positive correlations of MNX-ST and TL PST activities. Partially purified platelet TS PST assayed with minoxidil as the substrate showed a response to DCNP and thermal stability that were the same as TS PST. Platelet TL PST assayed with minoxidil showed thermal stability and a response to DCNP that were essentially the same as TL PST. The results indicated that not only TS PST, but also TL PST activities in human skin and platelet contributed to MNX-ST activity. It will be feasible to test whether measures of platelet PST activities will predict physiologic responses to minoxidil.

Arylsulfotransferase↗

PubMed1994

Induction of apoptotic or lytic death in an ovarian adenocarcinoma cell line by antibodies generated against a synthetic N-terminal extracellular domain gonadotropin-releasing hormone receptor peptide.

A polyclonal antiserum was generated in ovariectomized sheep against a synthetic peptide corresponding to amino acids 5-17 of the deduced mouse pituitary gonadotropin-releasing hormone (GnRH) receptor. Antipeptide antibodies did not bind native cells, but did react strongly with a human ovarian cancer cell line (OVCAR-3) reportedly sensitive to GnRH. Growth of cultured OVCAR-3 cells was specifically suppressed by antipeptide serum. This was attributed in part to programmed death (chromatin condensation and DNA fragmentation) of cells by antibody-induced apoptosis. Antibodies also exhibited a cytolytic effect (lactate dehydrogenase release) toward OVCAR-3 cells in the presence of the complement. Endometria of passively immunized mice lacked development; thus, antipeptide antibodies evidently recognize Mullerian duct derivatives. Experiments are in progress to determine whether the putative antigen is a variant of the pituitary GnRH receptor or a largely dissimilar protein. Effector-functional antibodies could be useful in the management of ovarian or uterine neoplasia.

Adenocarcinoma↗

PubMed1994

Magnetic resonance microscopy of mouse embryos.

The increased use of the mouse as a model for various aspects of mammalian biology has caused a renewed interest in developing strategies for examining and comparing normal and abnormal mouse embryonic development and anatomy. In this study, we have explored the use of magnetic resonance microscopy as a tool for these purposes. Techniques for the fixation, embedding, perfusion, and image acquisition of mouse embryos are described. The perfusion of bovine serum albumin-diethylenetriamine pentaacetic anhydride-gadolinium as a contrast agent enhances images of the developing embryonic vasculature during critical stages of organogenesis and allows for comparisons when embryos have been treated with teratogens such as retinoic acid. The acquired three-dimensional data sets are available for archiving, distributing, and postacquisition manipulations such as computer segmentation of anatomical structures.

Age Factors↗

PubMed1994

Tensile and viscoelastic properties of human patellar tendon.

The tensile and viscoelastic properties of fresh-frozen, nonirradiated human patellar tendon were investigated in two groups of 15 specimens: one group was from individuals 29-50 years old and the other group was from individuals 64-93 years old. The central portion of each patella-patellar tendon-tibia complex was subjected to cyclic preconditioning, stress-relaxation, cyclic stress-relaxation, and load to failure tests. For each age group, stress-relaxation and stress-strain curves were obtained, from which percentage relaxation, ultimate tensile strength, strain at failure, modulus, and strain energy density were determined. Viscoelastic behavior was described with use of quasilinear viscoelasticity. The younger group showed a 46 +/- 9% (mean +/- SD) decrease in stress after 15 minutes, whereas the older group exhibited a 50 +/- 6% decrease. The values for ultimate tensile strength and strain at failure, respectively, were 64.7 +/- 15.0 MPa and 14 +/- 6% for the younger group and 53.6 +/- 10.0 MPa and 15 +/- 5% for the older group. Modulus values were 660 +/- 266 MPa for the younger group and 504 +/- 222 MPa for the older group. Except for ultimate tensile strength, which was 17% less for the older group than for the younger one, no statistically significant differences were found in tensile or viscoelastic properties. This study indicated that there were minimal differences in biomechanical properties of the substance of the patellar tendon between younger and older age groups.

Adult↗

PubMed1994

Studies on bromobenzene-induced hepatotoxicity using in vivo MR microscopy with surgically implanted RF coils.

Using surgically implanted RF coils at 300 MHz, three-dimensional microscopic MR images of rat liver were obtained in vivo to follow the development of pathology induced by bromobenzene exposure. Formalin fixed specimens of liver from these animals were also imaged using in vitro MR microscopy, followed by conventional optical microscopy. All MR images were acquired using a spin-warp pulse sequence with TR = 950 ms and TE = 23 ms. The in vivo images were reconstructed as 256(2) x 32 arrays with a voxel size of (50 microns)2 x 219 microns, while the in vitro images were reconstructed as 256(2) x 128 arrays, giving an isotropic resolution at (39 microns)3. Based on results from six animals, we have found in all animals exposed to bromobenzene, image intensity decreased in specific hepatic tissue regions. These regions were well correlated to low signal intensity areas observed in in vitro MR images at higher resolution. Conventional optical microscopy indicated that the low signal intensity regions corresponded to areas of necrosis. The decrease in signal intensity is consistent with increased local diffusion coefficients as a result of necrosis. This study demonstrates that MR microscopy with implanted RF coils can be successfully used to follow tissue pathological changes in living tissues.

Animals↗

PubMed1994

Three dimensional magnetic resonance microangiography of rat neurovasculature.

Techniques are described to perform three dimensional (3D) MR microangiography. We have combined the use of a blood pool agent (Gd-DTPA-complexed with bovine serum albumin), three dimensional Fourier encoding, careful animal stabilization, and volume rendering to permit imaging with voxels of 60 x 60 x 60 microns. 3DFT encoding has been performed at 7.1 T with very large arrays (256 x 512 x 512). Interactive volume rendering allows a number of unique display opportunities that effectively exploit these isotropic 3D arrays.

Animals↗

PubMed1994

Correlation of C-myc and HER-2/neu amplification and expression with histopathologic variables in uterine corpus cancer.

OBJECTIVE: Initial studies of protooncogenes in uterine corpus cancer have focused on a single aspect of the gene in question (deoxyribonucleic acid, ribonucleic acid, protein) or have studied a small number of patients. Therefore we evaluated c-myc and HER-2/neu gene amplification and ribonucleic acid overexpression in such malignancies and correlated these molecular changes with known pathologic risk factors. STUDY DESIGN: Quantitative Southern blot analysis for oncogene deoxyribonucleic acid was used to examine 37 tumors from patients with primary untreated uterine corpus cancer referred to the City of Hope National Medical Center. Six normal endometrial specimens were controls. Seventeen tumors were also examined by Northern blotting to assess increased ribonucleic expression. RESULTS: Histologic types included adenocarcinoma (n = 30), papillary serous adenocarcinoma (n = 2), adenosquamous carcinoma (n = 2), mixed mullerian sarcoma (n = 2), and leiomyosarcoma (n = 1). Carcinomas were stage I (n = 10), II (n = 18), or III (n = 6). Twenty-three had myometrial invasion of less than one third, six one third to two thirds, and eight deeper invasion (greater than two thirds). According to the criteria of the International Federation of Gynecology and Obstetrics stage was as follows: I (n = 22), II (n = 3), III (n = 7), and IV (n = 5). Ten (27%) and four (11%) tumors showed gene amplification of c-myc and HER-2/neu, respectively. Six demonstrated overexpression of either the c-myc or HER-2/neu gene. HER-2/neu gene amplification was associated more closely with overexpression. Stepwise logistic analysis demonstrated c-myc amplification to be associated with higher grade (p = 0.01). CONCLUSION: In this referral population, c-myc activation is more common than HER-2/neu activation in uterine corpus cancer and is associated with tumors of higher grade.

Adenocarcinoma↗

PubMed1994

Imaging the cochlea by magnetic resonance microscopy.

The isolated, fixed cochlea of the mustached bat was studied with three dimensional magnetic resonance (MR) microscopy. The cochlea of this animal is about 4 mm in diameter and its entire volume was imaged. With the field of view and matrix size used, the volume elements (voxels) making up the volume data set were isotropic 25 x 25 x 25 micron cubes. Three dimensional (3D) MR microscopy based on isotropic voxels has many advantages over commonly used light microscopy: 1) it is non destructive; 2) it is much less time consuming; 3) no dehydration is required and shrinkage is minimized; 4) the data set can be used to create sections in any desired plane; 5) the proper alignment of sections is inherent in the 3D acquisition so that no reference points are required; 6) the entire data set can be viewed from any point of view in a volume rendered image; 7) the data is digital and features can be enhanced by computer image processing; and 8) the isotropic dimensions of the voxels make the data well-suited for structural reconstructions and measurements. Good images of the osseous spiral lamina, spiral ligament, scala tympani, scala vestibuli, and nerve bundles were obtained. The vestibular (Reissner's) membrane was easily identified in the mustached bat and it appears to bulge into the scala vestibuli. The visibility of this structure suggests that MR microscopy would be well-suited for studies of endolymphatic hydrops.

Animals↗

PubMed1994

Magnetic resonance microscopy of the rat carotid artery at 300 megahertz.

RATIONALE AND OBJECTIVES: Magnetic resonance microscopy (MRM) has evolved from a technical curiosity to a tool with which researchers can study important disease models. But MRM is not simply an extension of clinical magnetic resonance imaging. In this article, the unique adaptations of MRM required in the study of carotid artery disease are outlined. The techniques of MRM are integrated into a specific model of carotid artery disease in the rat to allow in vivo studies of vascular wall thickening after removal of the vascular endothelium. METHODS: Imaging was performed at 300 MHz in 250-gm Sprague-Dawley rats using surgically implanted radiofrequency coils to localize the region of interest and to provide an increase in the signal-to-noise ratio over that of volume or surface coils. A three-dimensional Fourier encoding sequence was modified with flow-dephasing gradients to minimize signal and artifacts from moving blood. RESULTS: In vivo images were acquired with spatial resolution of 25 x 25 x 400 microns and signal-to-noise ratio more than sufficient to define the morphology of the vascular wall. Significant changes in the intensity and distribution of signal were visible in the area surrounding the vessel after angioplasty. CONCLUSIONS: Signal-to-noise improvements from surgically implanted coils coupled to a three-dimensional radiofrequency-refocused sequence with flow-dephasing gradients were sufficient to define the wall of the carotid artery. The diffusion-weighted pulse sequence detects signal changes in the area surrounding the vessel after angioplasty. The MRM techniques described and the contrast observed allow us, for the first time to follow in vivo the early stage of developing atherosclerosis in the vessel wall and closely surrounding tissue.

Angioplasty, Balloon↗

PubMed1994

Use of gamma-glutamyl transpeptidase activity as a marker of hair cycle and anagen induction in mouse hair follicles.

gamma-glutamyl transpeptidase activity was monitored in cycling mice by histologic localization and biochemical assay. Our objective for this study is to establish the relationship between gamma-glutamyl transpeptidase activity and hair growth and to determine whether its activity can be correlated to induced hair growth. In cycling mouse skin, gamma-glutamyl transpeptidase activity is pronounced during anagen and greatly diminished during telogen. In the skin, the enzyme is present exclusively in the outer and inner root sheaths of hair follicles. gamma-glutamyl transpeptidase is limited to the follicle below the level of the sebaceous gland and is completely absent in the follicle above the sebaceous gland level. During anagen, the outer root sheath in the hypodermis is intensely positive for gamma-glutamyl transpeptidase activity whereas the hair matrix cells and dermal papillar are negative. The inner root sheath above the bulb shows distinctive membrane staining for gamma-glutamyl transpeptidase. gamma-glutamyl transpeptidase activity can be seen to vary only in cycling follicles. Inducing anagen by plucking hair shafts results in an increase in gamma-glutamyl transpeptidase activity directly correlated to hair regrowth. In a similar manner, mice were plucked and treated with a daily dose of 2% minoxidil. A slight difference in cycle lengths was seen in animals treated with minoxidil when compared to vehicle control. Minoxidil treatment may cause an early initiation of anagen, but both the minoxidil-treated skin and the vehicle-treated skin entered telogen at the same time. Together, these studies indicate that gamma-glutamyl transpeptidase is a specific marker of anagen in growing hair.

Animals↗

PubMed1994

Immunization of mice against a synthetic N-terminal extracellular domain gonadotropin-releasing hormone receptor peptide: evidence for a direct uterine effect.

PROBLEM: Immature male and female mice were immunized with a synthetic peptide corresponding to amino acids 5-17 (ASLEQDPNHCSAI) of the mouse hypophyseal gonadotropin-releasing hormone (GnRH) receptor. METHOD: Effect of immunization (postpuberal) was restricted to the uterus. Pituitary-gonadal functions were not altered. RESULTS: The endometrial lining of immunized females was thin and lacked glandular development. These observations were corroborated in actively immunized and passively immunized adult females. CONCLUSIONS: Apparently endometrial cells express a unique surface antigen, though reactive with antipeptide antibodies, that differs from the prototype pituitary GnRH receptor. Antibodies that selectively inhibit endometrial maturation might be used to treat proliferative diseases of the uterus.

Amino Acid Sequence↗