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Biomedical subjects

A Goldberg

Publications and source records attributed to A Goldberg.

At least 55 records · Page 3Linked to original sources

Angiotensin-converting enzyme and matrix metalloproteinase inhibition with developing heart failure: comparative effects on left ventricular function and geometry.

The progression of congestive heart failure (CHF) is left ventricular (LV) myocardial remodeling. The matrix metalloproteinases (MMPs) contribute to tissue remodeling and therefore MMP inhibition may serve as a useful therapeutic target in CHF. Angiotensin converting enzyme (ACE) inhibition favorably affects LV myocardial remodeling in CHF. This study examined the effects of specific MMP inhibition, ACE inhibition, and combined treatment on LV systolic and diastolic function in a model of CHF. Pigs were randomly assigned to five groups: 1) rapid atrial pacing (240 beats/min) for 3 weeks (n = 8); 2) ACE inhibition (fosinopril, 2.5 mg/kg b.i.d. orally) and rapid pacing (n = 8); 3) MMP inhibition (PD166793 2 mg/kg/day p.o.) and rapid pacing (n = 8); 4) combined ACE and MMP inhibition (2.5 mg/kg b.i.d. and 2 mg/kg/day, respectively) and rapid pacing (n = 8); and 5) controls (n = 9). LV peak wall stress increased by 2-fold with rapid pacing and was reduced in all treatment groups. LV fractional shortening fell by nearly 2-fold with rapid pacing and increased in all treatment groups. The circumferential fiber shortening-systolic stress relation was reduced with rapid pacing and increased in the ACE inhibition and combination groups. LV myocardial stiffness constant was unchanged in the rapid pacing group, increased nearly 2-fold in the MMP inhibition group, and was normalized in the ACE inhibition and combination treatment groups. Increased MMP activation contributes to the LV dilation and increased wall stress with pacing CHF and a contributory downstream mechanism of ACE inhibition is an effect on MMP activity.

Angiotensin-Converting Enzyme Inhibitors↗

Medics in the Israel Defense Forces and their experience in trauma care during peacetime.

BACKGROUND: In the military environment it is the medics who usually provide the initial care of mass casualties in the field. OBJECTIVES: To determine the number of incidents of trauma encountered by medics in the Israel Defense Forces during peacetime, and to ascertain the role of these medics in providing primary trauma care to the victims. METHODS: A retrospective questionnaire, reviewing the activities of medics in treating injured trauma victims, was distributed to medics who were in service for at least 2 years after their professional training. RESULTS: Of the 128 responding medics, 87 (68%) had actively participated in the treatment of trauma victims under various circumstances. The average number of trauma events was 1.2 events over a period of 2 years per combat medic, and 0.7 for medics stationed in rear units. Their activities included insertion of numerous intravenous fluid lines (57% of medics), assistance in intubations (37%), tube thoracostomies (23%), insertions of central catheters (14%) or orogastric tubes (28%), and manual ventilations (41%). CONCLUSION: Since it is difficult to increase the level of practical experience in dealing with trauma within the military framework, new techniques should be applied to improve the trauma training.

Adult↗

Allergic responses to pollen of ornamental plants: high incidence in the general atopic population and especially among flower growers.

BACKGROUND: The incidence of allergy to pollen of ornamental plants has not been deeply investigated, and its extent has remained obscure. Most of such studies have concentrated only on pollen of ornamental plants from the Asteraceae family (Compositae). In this study an attempt was made to clarify whether various other ornamental plants may also cause skin responses and allergic symptoms among allergic urban dwellers and among rural flower growers. METHODS: Two hundred ninety-two patients were referred for allergic evaluation by their primary physicians; 75 flower growers and 44 university students were evaluated. For all participants, a detailed health record was obtained, and skin prick tests (SPTs) were performed. Extracts for SPTs included commercial common airborne allergens and autochthonous pollen extracts of 11 species of plants belonging to the Asteraceae, Ranunculaceae, Liliaceae, Scrophulariaceae, and Genetianaceae families. RESULTS: Fifty-one of the 292 patients (17%) referred for allergic evaluation had positive SPT responses to pollen of various ornamental plants. A similar incidence was found among the students (23%). However, the incidence among flower growers was significantly higher, reaching 52%. Higher incidence (83%) of positive SPT responses to ornamental plants was found among flower growers also sensitive to the common allergens. All the tested plants, not only those belonging to the Asteraceae family, provoked positive SPT responses in all 3 groups of participants. None of the participants from the general population or the group of students reported exacerbation of allergic symptoms on exposure to the tested plants. In contrast, almost half of the flower growers (45%) described nasal, ocular, or respiratory symptoms associated with occupational exposure to the tested plants. Some 15% of the growers were eventually compelled to change their profession. CONCLUSIONS: The incidence of positive SPT responses to ornamental plants was 17% to 23% among the general public but 52% among flower growers. Thus the effects of ornamental plant pollen on atopic patients should be seriously contemplated.

Adolescent↗

Pediatric laparoscopic biliary tract surgery.

Laparoscopic cholecystectomy is being performed with increasing frequency in children. The authors discuss the presentation, surgical technique, overall results, and potential complications associated with pediatric laparoscopic biliary tract surgery, citing a large personal experience as well as that reported in the literature.

Child↗

13th Meeting of the Scientific Group on Methodologies for the Safety Evaluation of Chemicals (SGOMSEC): validation and acute toxicity testing.

Scientific principles demand that before newly developed alternative methods for safety testing are fully embraced by the industrial or regulatory community, they reliably and reproducibly predict the designated toxic end point. The process used to determine reliability and reproducibility is termed validation, and it generally culminates with a highly controlled, blinded study using multiple chemicals and laboratories. It is imperative that the validation study is designed to confirm the previously established reproducibility and predictive power of the assay. Much has been learned recently about the practical aspects of validation through investigation of alternative methods for acute toxicity testing, i.e., those methods that assess acute systemic toxicity, skin irritation, and eye irritation. Although considerable progress has been made--many alternative tests are now commonly used in various industrial settings--there have been few tests that have successfully passed a complete validation. Some of the barriers to successful validation have been a) lack of high-quality, reproducible animal data; b) insufficient knowledge of the fundamental biologic processes involved in acute toxicity; and c) the development of truly robust in vitro assays that can accurately respond to materials with a wide range of chemical and physical characteristics. It is recommended that to progress in the areas of eye and skin irritation we need to expand our knowledge of toxic markers in humans and the biochemical basis of irritation; progress in the area of acute systemic toxicity will require the development of in vitro models to determine gastrointestinal uptake, blood-brain barrier passage, and biotransformation.

Animal Testing Alternatives↗

Self psychology since Kohut.

The changes in psychoanalytic self psychology since its origination by Heinz Kohut are described as differences in three branches: the traditional, the intersubjective, and the relational. Each claims both a distinctiveness and a major influence within self psychology. These are described and contrasted. It is suggested that an effort to integrate all three is premature, and that they will continue to grow separately.

History, 20th Century↗

Deconstructing the dialectic.

The author examines some of the newly offered ideas and concepts about the interaction of the patient and the analyst. This interaction is termed a dialectic in the sense of interacting forces and this study is called a deconstruction, which is an effort to see how unstable and self-contradictory these new ideas may be. They are examined in terms of viewpoints of analysis as a developmental process, the location of the data of analysis, and the technical modifications that follow from this changed theoretical vision. A clinical example is offered to demonstrate the resultant problems. The suggested present status of the impact of these new ideas is that of a family of related concepts with no unifying theory.

Humans↗

Two distinct proteolytic processes in the generation of a major histocompatibility complex class I-presented peptide.

Although cellular proteins degraded by proteasomes are the source of most antigenic peptides presented on major histocompatibility complex class I molecules, it is unknown whether the eight- to nine-residue peptides that fit in the binding groove of class I molecules are directly produced by proteasomes alone in vivo. If the eight-residue peptide SIINFEKL from chicken ovalbumin is extended by one or several residues at its C terminus and microinjected into cells or expressed from a minigene, it is processed and presented on major histocompatibility complex class I. However, processing and presentation are inhibited by proteasome inhibitors, such as lactacystin. In contrast, when SIINFEKL is extended by 2 to 25 residues at its N terminus, its presentation is not blocked by proteasome inhibitors. N-terminal processing also can occur when the extended peptide is cotranslationally inserted into the endoplasmic reticulum. Thus, two different proteolytic steps in the generation of an chicken ovalbumin-presented peptide can be distinguished. Cleavage by the proteasome defines the proper C terminus, whereas distinct peptidase(s) in the cytosol or endoplasmic reticulum may generate the appropriate N terminus from extended peptides.

Animals↗

Combined surgery and postoperative radiotherapy for carcinoma of the base of radiotherapy for carcinoma of the base of tongue: analysis of treatment outcome and prognostic value of margin status.

BACKGROUND: Choice of treatment for base of tongue carcinoma is controversial, with options including surgery alone, radiotherapy alone, or multimodality treatment. Given the highly aggressive nature of these tumors, it has been our institutional policy to manage this disease with combined partial glossectomy (with attempt to avoid laryngectomy if possible) with planned postoperative radiotherapy (RT). We reported on our institutional experience with this approach. METHODS: A retrospective review of the charts of 17 patients with primary base of tongue squamous cell carcinoma treated with surgery and postoperative RT was performed. Patients treated with chemotherapy as part of their management were excluded. All patients underwent partial, hemi-, or subtotal glossectomy; 15/17 patients underwent ipsilateral radical or modified radical neck dissection. All patients received comprehensive postoperative RT (median dose 6000 cGy; range 5040-6920 cGy). Stage distribution was as follows: stage I, 2; stage II, 3; stage III, 2; stage IV, 10. Positive margins for invasive carcinoma were found in 9/17 patients. Median follow-up of surviving patients is 46 months; median follow-up for all patients is 31 months. RESULTS: For the entire group of patients, the actuarial 3-year local-regional control rate was 68%. The actuarial 3-year overall survival rate was 46%. The local-regional control rate was 83% for patients with stage I-III disease versus 50% for stage IV disease. There were no local failures among eight patients with negative margins (local control 100%) compared with an actuarial local control rate of 36% among patients with positive margins (p = .03). Survival, disease-specific survival, and locoregional control were also highly correlated with margin status (p = .003). Late major complications included 5/17 patients requiring permanent G-tubes and/or tracheostomy to prevent aspiration. CONCLUSIONS: Surgery plus postoperative RT is an intensive treatment for carcinoma of the base of tongue which offers high locoregional control in patients in whom negative margins are achieved. Positive margins indicate a high risk of locoregional and systemic failure, and these patients should be considered for innovative clinical trials after surgery.

Actuarial Analysis↗

Growth inhibition of B-cell precursor acute lymphoblastic leukemia cell lines by monocytes: a role for prostaglandin E2.

Leukemic cell lines have proven invaluable in the molecular analysis of recurring chromosomal translocations but the optimal methods for leukemia cell line establishment are unknown. During in vitro culture, most B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cells die within 1 week at least partially mediated by inhibitors elaborated by peripheral blood mononuclear cells (PB MNCs) present within the leukemia sample. In experiments reported here, cyclooxygenase inhibitors (indomethacin and meclofenamic acid) blocked the PB MNC-mediated inhibition of BCP-ALL proliferation. Also, prostaglandin E2 (PGE2) was detected in supernatants from PB MNC cultures. When PGE2 was mixed directly with BCP-ALL cells, proliferation decreased significantly. Under the culture conditions used, PB MNCs secreted PGE2 which appears to be one of the major inhibitors of BCP-ALL growth in vitro.

Adult↗

Continuous avoidance measures with or without acaricide in dust mite-allergic asthmatic children.

BACKGROUND: Improvement in the quality of life in the Western world and increased time spent indoors by children have enhanced the spread of house dust mites and increased the exposure time for sensitive children. Also, exposure to house dust mites in infancy and subsequent development of childhood asthma have been clinically linked. Recently, new acaricides have been developed. OBJECTIVE: To test the efficacy of the new acaricide (esdepallethin and piperonyl butoxide--"Acardust") combined with environmental control compared with continuous house dust mite avoidance measures. METHOD: Forty-six house dust mite-allergic, asthmatic children were evaluated for 6 months in a prospective, randomized, double-blind, and placebo-controlled study. Patients were randomly allocated to active and placebo acaricide treatment combined with avoidance measures, whereas only continuous avoidance measures were taken in the third group. Symptom score, medication usage, and peak flow measurements were recorded daily. The amount of house dust mite allergen in the dust vacuumed from the bedrooms was also measured. RESULTS: Morning and evening peak expiratory flow rates and forced expiratory volume in one second remained unchanged throughout the study period. In all groups, the symptom scores improved significantly, whereas the amount of house dust mite allergen decreased significantly at the end of the trial. CONCLUSIONS: Continuous house dust mite avoidance measures have a significant positive effect on the symptomology of children with mild or moderate asthma. "Acardust" combined with continuous house dust mite avoidance measures is not more effective than continuous house dust mite avoidance measures alone in the treatment of house dust mite-allergic, asthmatic children.

Aerosols↗

ATPase and ubiquitin-binding proteins of the yeast proteasome.

The 26S proteasome is a 2-Megadalton proteolytic complex with over 30 distinct subunits. The 19S particle, a subcomplex of the 26S proteasome, is thought to confer ATP-dependence and ubiquitin-dependence on the proteolytic core particle of the proteasome. Given the complexity of the 19S particle, genetic approaches are likely to play an important role in its analysis. We have initiated biochemical and genetic studies of the 19S particle in Saccharomyces cerevisiae. Here we describe the localization to the proteasome of several ATPases that were previously proposed to be involved in transcription. Independent studies indicate that the mammalian 26S proteasome contains closely related ATPases. We have also found that the multiubiquitin chain binding protein Mcb1, a homolog of the mammalian S5a protein, is a subunit of the yeast proteasome. However, contrary to expectation, MCB1 is not an essential gene in yeast. The mcb1 mutant grows at a nearly wild-type rate, and the breakdown of most ubiquitin-protein conjugates is unaffected in this strain. One substrate, Ub-Proline-beta gal, was found to require MCB1 for its breakdown, but it remains unclear whether Mcb1 serves as a ubiquitin receptor in this process. Our data suggest that the recognition of ubiquitin conjugates by the proteasome is a complex process which must involve proteins other than Mcb1.

Adenosine Triphosphatases↗