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Biomedical subjects

R L Zimmerman

Publications and source records attributed to R L Zimmerman.

At least 37 records · Page 2Linked to original sources

A fast non-fluorescent staining method for the detection of primed in situ synthesis products.

For the assessment of chromosomal numeral aberrations in cells, the method of choice is fluorescent in situ hybridisation (FISH) or, a newly introduced technique, oligonucleotide primed in situ hybridisation (PRINS). In the PRINS method labeled nucleotides are incorporated into newly synthesized DNA mediated through the Taq polymerase. Both PRINS and FISH reactions are visualized with a fluorescent light detection system. We present a method whereby PRINS products can be reliably and rapidly visualized by a streptavidin DAB detection system.

3,3'-Diaminobenzidine↗

Pulmonary thrombosis in a 10-year-old child with minimal change disease and nephrotic syndrome. A clinical, radiologic, and pathologic correlation with literature review.

The nephrotic syndrome has long been recognized as a hypercoagulable state. Arterial thrombosis is a rare complication of the syndrome. Diuretics and steroids, standard treatment for exacerbations, have been implicated as contributing to the development of arterial thrombosis. The authors present the pathologic, clinical, and radiologic findings of a patient with nephrotic syndrome and minimal change disease. The patient died of pulmonary thrombosis while on high-dose steroid therapy for an acute exacerbation of proteinuria following a recent hospital admission for chest pain and dyspnea.

Biopsy↗

Prognostic value of flow cytophotometric DNA content analysis in single treatment stage IB-IIA squamous cell carcinoma of the cervix.

DNA content was measured flow cytometrically in archival tissue from 65 single-treatment stage IB and IIA squamous cell carcinomas of the cervix with at least 5 years of clinical follow-up. Thirty-five cases were treated exclusively by hysterectomy and thirty exclusively by radiation therapy. Tumors were categorized into four groups on the basis of DNA content and cell cycle distribution. DNA content was measured relative to the position of the first resolvable cell peak. G2/M and S-phase fractions were estimated as percentage of cells with DNA contents greater than or equal to relative position 1.70 and percentage of cells with relative positions between 1.20 and 1.70, respectively. The 40 tumors characterized as either aneuploid or nondemonstrably aneuploid with high S-phase fraction estimate had a 5-year recurrence rate significantly higher than that of the 25 tumors categorized as tetraploid or nondemonstrably aneuploid with low S-phase fraction estimate (52 and 4%, respectively; chi 2 = 15.8, P less than 0.001). Similar results were found when radiation and surgically treated tumors were considered independently (chi 2 = 7.95, P less than 0.005 and chi 2 = 5.7, P less than 0.025, respectively). These data suggest that an increased 5-year recurrence rate is associated with both abnormal DNA content and elevated S-phase fraction in stage IB-IIA squamous cell carcinoma of the cervix, and that this relationship is largely independent of treatment method.

Adult↗

Rapid separation of gram quantities of phospholipids from biological membranes by preparative high performance liquid chromatography.

We present a detailed description of a rapid preparative high performance liquid chromatography (HPLC) procedure for isolation of large scale quantities (a minimum of 200 mg) of rat liver microsomal and mitochondrial phospholipid classes in 40 min on a 25 X 2.5 cm preparative HPLC column of 7-mu silica gel particles using a linear gradient of hexane-isopropanol-water mixtures. A minimum of 1.5 g of phospholipids can be quantitatively separated per day into diphosphatidylglycerol (cardiolipin), phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine, sphingomyelin, and a phosphatidylcholine-sphingomyelin fraction. The procedure uses no salts, buffers, acids, or bases, and the isolated phospholipids are suitable for preparing model membranes.

Animals↗

Role of connective tissue proteases in the pathogenesis of chronic inflammatory lung disease.

The normal structure and function of the human lung is dependent on the maintenance of the connective tissue matrix. These structural macromolecules provide the template for normal parenchymal cell architecture on which efficient gas exchange depends. In addition, the organization and amount of this extracellular matrix accounts for much of the mechanical behavior of the lung parenchyma during the respiratory cycle. The preservation of this intricate connective tissue scaffold depends on the lung's capacity to prevent enzymatic disruption of the component matrix proteins. Specifically, the integrity of the normal connective tissue skeleton of the lung is determined by the maintenance of a balance between proteases capable of cleaving these structural elements and the specific protease inhibitors. The normal extracellular matrix is preserved when the local concentrations of protease inhibitors prohibits expression of active connective tissue proteases within the lung parenchyma. Conversely, the disruption of lung structure during the course of acute and chronic inflammatory diseases of the lung is often associated with an imbalance of protease-antiprotease activity. The consequence is the expression of unimpeded proteolytic attack on the connective tissue matrix of the lung. In this context, the nature of the pulmonary lesion and its physiologic consequences, reflect the specificity of the expressed proteases for the individual connective tissue components. Experimental evidence suggests that the differential expression of collagenase and elastase, prototypes of connective tissue proteases, may determine whether the pathologic outcome is fibrosis (e.g., idiopathic pulmonary fibrosis) or destruction (e.g., emphysema) of the alveolar structures.

Animals↗

Psychopharmacological correlates of post-psychotic depression: a double-blind investigation of haloperidol vs thiothixene in outpatient schizophrenia.

A 24-week double-blind study was conducted to compare haloperidol and thiothixene for efficacy and safety in 46 schizophrenic outpatients. In addition to the standard psychiatric rating scales, Brief Psychiatric Rating Scale (BPRS), Nurses' Observation Scale for Inpatient Evaluation (NOSIE), and Evaluation of Social Functioning Rating (ESFR), two scales more sensitive to the incidence of treatment emergent depression were utilized. They were the Hamilton Depression Scale (HPRSD) and the Zung Self-rating Depression Scale (ZUNG). On the BPRS factors, haloperidol was significantly superior to thiothixene in Thought Disturbance and Hostility-Suspiciousness, and in Total symptomatology. Haloperidol was also significantly superior to thiothixene in Cognitive Disturbance on the HPRSD. Results of global evaluations suggested haloperidol produced slightly more rapid relief of symptoms than did thiothixene. The inclusion of the depression scales was useful in following patients who exhibited depressive symptoms; clinically significant depression was seen in 5 patients receiving haloperidol and 3 receiving thiothixene. A high incidence of akathisia in the thiothixene group was responsible for a statistically significant difference between groups in the number of central nervous system symptoms. Mean doses of test drugs were 17.5 mg/day for haloperidol an 31.8 mg/day for thiothixene. The study showed that haloperidol was equal to and in some parameters superior to thiothixene in producing improvement in the symptoms of psychosis.

Adolescent↗

Antielastases of the human alveolar structures. Implications for the protease-antiprotease theory of emphysema.

The current concepts of the pathogenesis of emphysema hold that progressive, chronic destruction of the alveolar structures occurs because there was in imbalance between the proteases and antiproteases in the lower respiratory tract. In this context, proteases, particularly neutrophil elastase, work unimpeded to destroy the alveolar structures. This concept has evolved from consideration of patients with alpha 1-antitrypsin deficiency, who have decreased levels of serum alpha 1-antitrypsin and who have progressive panacinar emphysema. To directly assess the antiprotease side of this equation, the lower respiratory tract of non-smoking individuals with normal serum antiproteases and individuals with PiZ homozygous alpha 1-antitrypsin deficiency underwent bronchoalveolar lavage to evaluate the antiprotease screen of their lower respiratory tract. These studies demonstrated that: (a) alpha 1-antitrypsin is the major antielastase of the normal human lower respiratory tract; (b) alpha 2-macroglobulin, a large serum antielastase, and the bronchial mucous inhibitor, an antielastase of the central airways, do not contribute to the antielastase protection of the human alveolar structures; (c) individuals with PiZ alpha 1-antitrypsin deficiency have little or no alpha 1-antitrypsin in their lower respiratory tract and have no alternative antiprotease protection against neutrophil elastase; and (d) the lack of antiprotease protection of the lower respiratory tract of PiZ individuals is a chronic process, suggesting their vulnerability to neutrophil elastase is always present.

Bronchi↗

In vivo measurements of the viscoelasticity of the human vitreous humor.

A point of source of light against a dark background is perceived by the human retina as a point image enhanced by off-axis points (rays if the source is polychromatic) of light scattered from objects along the optic axis. As a consequence of movement of the vitreous humor, scattering centers imbedded there impart of this scattering pattern a corresponding movement. A method has been devised to give the vitreous humor reproducible initial conditions and to record the observed relaxation of the scattering pattern to its new rest position. The vitreous humor is found to be overdamped, and the heretofore unreported shear elastic modulus has been determined. A striking gravitational effect is revealed by comparing observations along a horizontal optic axis with ones along a vertical optic axis. For the former, gravitational torque is found to dominate the elastic torque. The reason nature has developed a slow-responding gravitational sensor in the vitreous humor is not clear.

Elasticity↗

Regulation of the release of alveolar macrophage-derived neutrophil chemotactic factor.

In order to further clarify the physiologic role of the neutrophil-directed chemotactic factor derived from alveolar macrophages, we evaluated those stimuli that possess the potential to regulate the quantity and kinetics of its release in vitro. In short-term culture, particulate stimuli (Staphylococcus albus, Micropolyspora faeni, zymosan, and Sepharose 4B) as well as IgG-immune complexes induced normal guinea pig alveolar macrophages to release significant quantities of this chemotactic factor. In addition, serum opsonization of particulate stimuli resulted in significant augmentation of release of the chemotactic factor from alveolar macrophages responding to these particles. This serum augmentation was associated with the fixation of C3b to the particle surface via the alternative complement pathway. Purified C3b, by itself, was also capable of inducing release of this macrophage-derived mediator. Partial characterization of this chemotactic factor revealed that it was a material of low molecular weight (400 to 600 daltons), and that it was antigenically and physically distinct from C5a. These studies suggested that the induction of chemotactic factor release from alveolar macrophages responding to microorganisms, noninfectious particulates, antigen-complexed IgG, and C3b may contribute to the pathophysiologic events observed in those lung diseases characterized by an influx of neutrophils into the pulmonary parenchyma.

Animals↗

The treatment of anxiety with a polyfluorinated benzodiazepine derivative.

Following 4 weeks of treatment with ORF-8063 a polyfluorinated benzodiazepine derivative, 8 hospitalized patients manifesting a primary pathology of anxiety showed marked general improvement. 2 other persons were treated, but for shorter periods: 9 and 14 days. Both are included in the pre-post analysis. Mean optimal dosage was 66.5 mg. The five instruments used to measure therapeutic effect showed pre- to posttreatment change with high level of statistical significance in serveral of the pathological factors. When measures of change are considered, patients showed more improvement related to psychic than somatic components of anxiety. Change data also indicates more patients improvement in anxiety than depression. Side effects reported more were dizziness, faintness and insomnia; these were reported in 8 patients. 6 patients noted drowsiness, and 4 noted excitement. 5 persons tolerated optimum dosages with no extreme reactions; 5 others (including the 2 subjects who terminated treatment early) were unable to maintain optimum dosages because of side effects.

Adult↗

Aluminum levels in brain in Alzheimer's disease.

In both human Alzheimer's disease and aluminum encephalopathy of animals, changes are observed in neurofibrillary structures. We have found that brains from Alzheimer patients contain approximately 1.4 times the aluminum level found in a control series. Some possible methodological problems are discussed. We have proposed a plausible chemical mechanism for the changes of aluminum encephalopathy.

Aged↗

Induced piezoelectricity in isotropic biomaterial.

Isotropic material can be made to exhibit piezoelectric effects by the application of a constant electric field. For insulators, the piezoelectric strain constant is proportional to the applied electric field and for semiconductors, an additional out-of-phase component of piezoelectricity is proportional to the electric current density in the sample. The two induced coefficients are proportional to the strain-dependent dielectric constant (depsilon/dS + epsilon) and resistivity (drho/dS - rho), respectively. The latter is more important at frequencies such that rhoepsilonomega less than 1, often the case in biopolymers. Signals from induced piezoelectricity in nature may be larger than those from true piezoelectricity.

Electricity↗