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Biomedical subjects

L Gerber

Publications and source records attributed to L Gerber.

At least 19 recordsLinked to original sources

A new treatment for severe pulmonary embolism: percutaneous rheolytic thrombectomy.

BACKGROUND: The rheolytic thrombectomy catheter has been specially designed to remove intravascular thrombus from coronary and peripheral arteries. It demonstrates a practical application of Bernoulli's principle relating to a low-pressure zone in the region of a high-velocity jet. In this device, this effect is created by direct high-pressure saline jets located at the tip. Thrombus is drawn into this region and, because of the large pressure difference, undergoes mechanical thrombolysis due to the powerful mixing forces. The resulting microparticles are aspirated through the same catheter and removed from the body. METHODS AND RESULTS: We report the use of this device in two patients presenting with severe pulmonary embolism and contraindications to thrombolytic therapy. The two procedures were successfully performed with an excellent immediate angiographic result at the site of the rheolytic thrombectomy. In both cases, the clinical improvement was maintained at follow-up with the same good angiographic result and a decrease to a normal level of the systolic pulmonary pressure. CONCLUSIONS: This preliminary results suggest that this easy technical method may be useful in the treatment of life-threatening pulmonary embolism in patients with absolute contraindications to thrombolytic therapy. A larger cohort of patients is necessary to determine whether this treatment should be proposed as an alternative to the use of fibrinolytics in selected patients.

Aged↗

Compartmentalization of inflammatory cell phenotypes in normal gingiva and peri-implant keratinized mucosa.

The interpretation of studies aimed at understanding the pathophysiology of periodontal breakdown has been hampered by an insufficient understanding of the physiology of host responses in clinically healthy gingiva. This investigation was aimed at the evaluation of the in situ phenotype and topographic distribution of the inflammatory cells in clinically normal gingiva and peri-implant keratinized mucosa (PIKM). Soft tissue biopsies were obtained from clinically healthy gingiva or PIKM in 14 patients. Acetone fixed, cryostat sections were stained with a panel of monoclonal antibodies with a three stage avidin-biotin immunoperoxidase technique. Numbers of positive cells/mm2 were determined with a calibrated image analysis system. The major findings of the study were: (i) the presence of significantly higher densities of phenotypically characterized mononuclear cells in the ICT than in the JE in both gingiva and PIKM; (ii) the absence of a significant difference in PMN densities between JE and ICT in both gingiva and PIKM; (iii) the absence of statistically significant differences in densities of phenotypically characterized leukocytes associated with gingiva and PIKM; (iv) the presence of regional differences in the relative proportions of immunocompetent cells in both the gingiva and PIKM. It is concluded that inflammatory cells are selectively distributed in gingiva and PIKM. Unique functional compartments could be identified. The observed compartmentalization requires selective regulatory mechanisms.

B-Lymphocytes↗

Ethics and caring: cornerstones of nursing geriatric case management.

1. Paternalism, the most frequent ethical concern voiced by both elders and their caregivers, is unilateral decision-making not in accord with the client's stated wishes or value system. 2. It is common that older people are intimidated by professionals and lack the sophistication and vocabulary to express their desires in a rational and assertive manner. 3. Often the family's decisions regarding client care do not correlate with the patient's choices in the sense that clients want to avoid needless pain and suffering and are more accepting than the families of the potential outcome of death. 4. Detailing the nursing care plan in writing and allowing several days for client/family review and approval lessen misunderstanding and dissatisfaction.

Aged↗

Vascular adhesion molecules and initial development of inflammation in clinically healthy human keratinized mucosa around teeth and osseointegrated implants.

Expression of vascular cell adhesion molecules (HEV-CAMs) by capillary loops represents an early step necessary for leukocyte extravasation and subsequent migration to sites of inflammation. The purpose of this investigation was to compare, the presence and distribution of ICAM-1, ELAM-1, VCAM-1 and PECAM-1 expression in the microvasculature of healthy gingiva and peri-implant keratinized mucosa. The selected HEV-CAMs were detected by a three stage immunoperoxidase technique in serial sections from clinically characterized sites. Biopsies were qualitatively and quantitatively analyzed. All biopsies displayed a small inflammatory infiltrate subjacent to the most coronal extension of the junctional epithelium. HEV-CAMs were expressed both in the sulcular and oral aspects of biopsies. Intensity of ICAM-1, ELAM-1 and VCAM-1 staining, however, was consistently higher in the region of the infiltrated connective tissue subjacent to the most coronal extension of the junctional epithelium. Only a fraction of microvascular loops were positive for ICAM-1, ELAM-1 or VCAM-1 when compared to the constitutively expressed PECAM-1. No significant differences were observed between gingiva and keratinized peri-implant mucosa. It was concluded that in healthy gingiva or peri-implant mucosa 1. HEV-CAM expressing capillary loops were in close topographic association with the inflammatory infiltrate; 2. only a fraction of capillary loops are activated to express ICAM-1, ELAM-1 and VCAM-1 at any given time; and 3. HEV-CAM expression in the periodontium may be influenced by local factors.

Antigens, Differentiation, Myelomonocytic↗

Localized expression of mRNA for phagocyte-specific chemotactic cytokines in human periodontal infections.

In bacterial infections, mononuclear and polymorphonuclear phagocytes are key components of host defenses. Recent investigations have indicated that chemokines are able to recruit and activate phagocytes. In particular, interleukin-8 (IL-8) attracts polymorphonuclear leukocytes (PMNs), while monocyte chemoattractant protein-1 (MCP-1) is selective for cells of the monocyte/macrophage lineage. In this investigation, we analyzed the in situ expression of IL-8 and MCP-1 mRNAs in human periodontal infections. Specific mRNA was detected by in situ hybridization using 35S-labeled riboprobes in frozen tissue sections. Phagocytes (PMNs and macrophages) were specifically detected as elastase-positive or CD68+ cells by a three-stage immunoperoxidase technique. Results indicated that expression of phagocyte-specific cytokines was confined to selected tissue locations and, in general, paralleled phagocyte infiltration. In particular, IL-8 expression was maximal in the junctional epithelium adjacent to the infecting microorganisms; PMN infiltration was more prominent in the same area. MCP-1 was expressed in the chronic inflammatory infiltrate and along the basal layer of the oral epithelium. Cells of the monocyte/macrophage lineage were demonstrated to be present in the same areas. The observed expression pattern may be the most economic way to establish a cell-type-selective chemotactic gradient within the tissue that is able to effectively direct polymorphonuclear phagocyte migration toward the infecting microorganisms and modulate mononuclear phagocyte infiltration in the surrounding tissues. This process may optimize host defenses and contribute to containing leukocyte infiltration to the infected and inflamed area, thus limiting tissue damage.

Antigens, CD↗

Psychotherapy with Southeast Asian refugees: implications for treatment of Western patients.

Working with Southeast Asian refugees in psychotherapy can teach Western psychotherapists how our culture-impacted notions of health, psychopathology, and psychotherapy influence the way we hear, understand, and respond to our patients. Western conceptions of individual boundaries, family ties, the relationship of mind and body, and ways of knowing are among the issues that arise for the Western psychotherapist who works with Southeast Asian refugees. While we in the West have seen rapid technological advances, we also have suffered dislocations, change, and the loss of traditional bases of meaning. Yet despite the differences, there are also elements within Western culture that resonate with what are usually considered "Asian" ways. These include the self-in-relation concepts described by feminist writers and the attitude of therapist as learner described by some contemporary psychoanalysts as well as by a contemporary Western philosopher. Refugees and Western patients alike want their unique faces "seen" and hope to birth new and expanded meanings in their psychotherapeutic dialogues.

Adult↗

Evidence that the putative COOH-terminal signal transamidase involved in glycosylphosphatidylinositol protein synthesis is present in the endoplasmic reticulum.

Nascent proteins destined to be processed to a glycosylphosphatidylinositol (GPI)-anchored membrane form contain NH2-terminal and COOH-terminal signal peptides. The first directs a nascent protein into the endoplasmic reticulum; the second peptide targets the protein to a putative COOH-terminal signal transamidase where cleavage of the peptide and addition of the GPI anchor occur. We recently showed that ATP hydrolysis is required for maturation of GPI proteins at a stage prior to transamidation. Here we show that one of the ATP-requiring proteins involved in processing of GPI-anchored proteins in the endoplasmic reticulum is the immunoglobulin heavy chain binding protein (BiP; GRP 78). This and related findings indicate that GPI transamidase is localized in the endoplasmic reticulum.

Acyltransferases↗

Isometric exercise increases strength and does not produce sustained creatinine phosphokinase increases in a patient with polymyositis.

A patient with active stable idiopathic polymyositis received a 4-week supervised right quadriceps and biceps isometric strengthening program. He demonstrated a significant increase in isometric peak torque without a sustained rise in creatinine phosphokinase (CPK). A significant decrease in postexercise CPK occurred at the end of the exercise program. We conclude a randomized clinical trial using a nonexercised patient group vs an exercised patient group may be useful.

Creatine Kinase↗

Biosynthesis of phosphatidylinositol-glycan (PI-G)-anchored membrane proteins in cell-free systems: cleavage of the nascent protein and addition of the PI-G moiety depend on the size of the COOH-terminal signal peptide.

Nascent translation products of PI-G-anchored membrane proteins contain both NH2- and COOH-terminal signal sequences of approximately 15-30 residues that are removed during processing. Removal of the latter occurs concomitant with the addition of the PI-G moiety to the newly formed COOH terminus. In human placental alkaline phosphatase (PLAP) the COOH-terminal signal peptide contains 29 residues. An engineered form of PLAP, miniPLAP 208, containing the same NH2- and COOH-terminal signal peptides as PLAP, was used as a substrate for cell-free processing. A comparison was made with mutants (delta 202, delta 197, delta 184, and delta 179) truncated at the COOH terminus. Intact preprominiPLAP 208 and truncated delta 202 were processed to yield the same mature product which, by size and distribution between Triton X-114 and water before and after treatment with inositol-specific phospholipases, indicates that it contained the PI-G moiety. Mutants that were further truncated at the COOH terminus, miniPLAPs delta 197, delta 184, and delta 179, were processed only at their NH2 termini. Those portions of the COOH-terminal sequence in miniPLAPs delta 197 and delta 1984 that extended beyond residue 179 were not removed during processing.

Alkaline Phosphatase↗

Comparison of pain, motion, and edema after modified radical mastectomy vs. local excision with axillary dissection and radiation.

Recent data suggest that prognosis is similar for women with primary breast cancer whether they receive modified radical mastectomy (MRM) or local excision and axillary dissection with radiation (XRT). The effects of either of these treatments on arm mobility, pain, or edema have not been compared. To assess the impact of MRM or XRT on mobility, pain, or edema, we evaluated patients treated in a prospective randomized trial designed to assess prognosis following MRM or XRT. All were provided a standardized physical therapy program including arm mobilization, shoulder strengthening, prevention and treatment of upper extremity edema, and education about arm function. Patients were evaluated for chest wall pain, arm motion, muscle strength, and edema as determined by circumferential measurements at the wrist, forearm, and arm. Evaluations were performed preoperatively and at yearly anniversaries of their surgery. Women receiving XRT had more chest wall tenderness at 1 and 2 years after surgery than those receiving MRM (p2 less than 0.0001 and p2 = 0.0007 respectively). Those receiving MRM were slower to reach their preoperative range of motion (ROM) (p2 = 0.043). Incidence of muscle weakness was similar in both groups. The few patients with local recurrence of tumor had more upper extremity edema than those who did not recur (p2 = 0.085) at 1 year and (p2 = 0.02) at 2 years. In patients who did not develop local recurrence, those who had received XRT had greater but nonsignificant increases in upper extremity circumferential measures compared with those receiving MRM at any anniversary evaluation. Patients receiving MRM and XRT are likely to have some differences in functional outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

Breast Neoplasms↗

Biosynthesis of phosphatidylinositol glycan-anchored membrane proteins. Design of a simple protein substrate to characterize the enzyme that cleaves the COOH-terminal signal peptide.

Many nascent proteins that are destined to be anchored to plasma membranes by a phosphatidylinositol glycan (PI-G) are in the range of 50-70 kDa so that changes of 2-3 kDa between precursors and products during processing are not easily detected. Furthermore, PI-G-anchored proteins are generally glycosylated so that changes between the nascent (prepro) proteins and the mature products are not due simply to the loss of signal peptides. These problems have made it difficult to monitor the processing of the prepro form of wild type human placental alkaline phosphatase (PLAP) in a cell-free system. We have designed a smaller and simpler substrate of PI-G "transamidase" derived by deletion of approximately 60% of the internal sequence of preproPLAP 513. This engineered protein, preprominiPLAP 208, retains the NH2- and COOH-terminal signal peptides of PLAP as well as all the epitopes for site-directed antibodies of the latter, but is devoid of glycosylation sites, the active site, and most of the cysteine residues. With preprominiPLAP, it has been possible to demonstrate, in a cell-free system, step by step conversion to the pro form and then to the mature form, with the concomitant loss of the appropriate signal peptides. These changes were shown to be time- and enzyme concentration-dependent. Studies with Asp-179 site-directed mutants of preprominiPLAP showed the same specificity for amino acids with a monosubstituted beta carbon at the cleavage/attachment site that were found previously with wild type PLAP.

Acyltransferases↗

Level of axillary involvement by lymph node metastases from breast cancer is not an independent predictor of survival.

We examined the relationship of axillary level of lymph node metastases from clinical stage I and II breast cancer to overall survival and disease-free survival rates in 135 patients who underwent complete axillary lymph node dissection to determine if anatomic level of axillary involvement (I vs II vs III) is an independent prognostic factor. All patients underwent either modified radical mastectomy or lumpectomy with axillary dissection and whole breast radiotherapy for breast cancer. Median follow-up was 6.9 years. We found no difference in overall survival or disease-free survival between patients whose highest or only level of axillary involvement was level I compared with patients whose highest or only level was II. Although patients whose highest level of nodal involvement was III had significantly worse overall survival and disease-free survival rates than patients whose highest nodal involvement was I or II, when patients were stratified by the total number of positive nodes (one to three vs four or more), there was no difference in overall survival or disease-free survival rates between levels I, II, and III. These findings indicate that the level of axillary involvement for stage II breast cancer is not of independent prognostic significance.

Antineoplastic Combined Chemotherapy Protocols↗

Secreted alkaline phosphatase: an internal standard for expression of injected mRNAs in the Xenopus oocyte.

The Xenopus oocyte is widely used to study the various aspects of eukaryotic cell structure and function. It is also being used increasingly in expression cloning of cDNAs encoding proteins for which there are no structural data. One of the drawbacks of the Xenopus oocyte system is that individual oocytes taken at the same time from the same frog vary considerably in the amount of protein synthesized from the same amount of injected mRNA. In this report we describe the preparation and use of the mRNA for a secreted mutant form of human placental alkaline phosphatase as an internal, coinjected standard to monitor translation in oocytes. Secreted alkaline phosphatase can be readily determined in the medium of cultured oocytes by using a standard colorimetric assay. The amounts of alkaline phosphatase secreted into the medium were shown to parallel the level of expression of two membrane proteins. This permits rapid identification and selection of those oocytes that efficiently express injected mRNAs. The procedure yields more precise data and results in an enormous saving of time and expense, especially in investigations that involve complex measurements on individual oocytes.

Alkaline Phosphatase↗