Task-relevant late positive component in rats: is it related to hippocampal theta rhythm?

In the last 2 years (1994-95), two symposium volumes and three reviews have been published that were fully devoted to peptide antibiotics (antibacterial peptides or antimicrobial peptides). Since the field has been growing rapidly, this review is largely a follow-up of new results published in the last 2 years. Sequencing of the 16S RNA of the small ribosomal subunit indicate that the microbial world is much larger than generally appreciated. The importance of the natural flora is stressed and its effect on the evolution of peptide antibiotics and immunity in general is discussed.     

Identification of glycoprotein 330 as an endocytic receptor for apolipoprotein J/clusterin

Glycoprotein 330 (gp330) is a member of a family of endocytic receptors related to the low density lipoprotein receptor. gp330 has previously been shown to bind a number of ligands in common with its family member, the low density lipoprotein receptor-related protein (LRP). To identify ligands specific for gp330 and relevant to its localization on epithelia such as in the mammary gland, gp330-Sepharose affinity chromatography was performed. As a result, a 70-kDa protein was selected from human milk and identified by protein sequencing to be apolipoprotein J/clusterin (apoJ). Solid-phase binding assays confirmed that gp330 bound to apoJ with high affinity (Kd = 14.2 nM). Similarly, gp330 bound to apoJ transferred to nitrocellulose after SDS-polyacrylamide gel electrophoresis. LRP, however, showed no binding to apoJ in either type of assay. The binding of gp330 to apoJ could be competitively inhibited with excess apoJ as well as with the gp330 ligands apolipoprotein E, lipoprotein lipase, and the receptor-associated protein, a 39-kDa protein that acts to antagonize binding of all known ligands for gp330 and LRP. Several cultured cell lines that express gp330 and ones that do not express the receptor were examined for their ability to bind and internalize 125I-apoJ. Only cells that expressed gp330 endocytosed and degraded radiolabeled apoJ. Furthermore, F9 cells treated with retinoic acid and dibutyryl cyclic AMP to increase expression levels of gp330 displayed an increased capacity to internalize and degrade apoJ. Cellular internalization and degradation of radiolabeled apoJ could be inhibited with unlabeled apoJ, receptor-associated protein, and gp330 antibodies. The results indicate that gp330 but not LRP can bind to apoJ in vitro and that gp330 expressed by cells can mediate apoJ endocytosis leading to lysosomal degradation.     

Laboratory studies in cross-species lung transplantation

The lack of sufficient suitable human donor lungs for the many patients requiring pulmonary transplantation as life-saving therapy for end-stage lung diseases has generated extensive interest in cross-species lung transplantation. Ethical concerns and those of animal rights advocates have prompted studies of nonprimate species as potential solid organ donors for humans. This paper provides an overview of some of the laboratory studies of cross-species pulmonary transplantation performed over the past 20 years and focuses, in particular, on more recent work (from our laboratory and others) in the area of porcine-to-primate pulmonary xenotransplantation.     

Successful pregnancies in the presence of spinal muscular atrophy: two case reports

We report two cases of successful pregnancy in women with chronic, infantile onset, or type II spinal muscular atrophy, both of whom delivered healthy, unaffected babies. The patients required concurrent management by a physiatrist, pulmonologist, and perinatologist throughout the pregnancy. Complications included recurrent urinary tract infections, dyspnea and worsening of pulmonary function, wheelchair seating and positioning problems, and musculoskeletal and low back pain. These problems resolved postpartum. One woman had vaginal delivery, the other had caesarean section, both of which were well-tolerated. Because of severe musculoskeletal deformity, pelvic assessment is necessary to determine the mode of delivery. The uterus has normal contractility and effective labor patterns can be established. Spinal/epidural anesthesia may be contraindicated because of spine deformity. The pregnancies had no deleterious effect on the progression of the disease in our patients, both of whom reported a positive experience with great personal fulfillment.     

Anti-inflammatory activity of myricetin-3-O-beta-D-glucuronide and related compounds

OBJECTIVE AND DESIGN: The anti-inflammatory effect of myricetinglucuronide (MGL) was investigated and structurally-related compounds were compared to examine the structure/activity-relationship in carrageenan-induced rat paw edema. MATERIALS AND SUBJECTS: In vitro studies were performed using rat basophilic leukemia (RBL-1) cells, human polymorphonuclear leukocytes (PMNL), COX-1 from ram seminal vesicle, COX-2 from sheep placenta and human venous blood. For the in vivo tests male Wistar rats were used, for the ex vivo test perfused rabbit ears. TREATMENT: 1-300 microg/kg MGL or myricetinmethylglucuronate and 0.1-5 mg/kg other related compounds administered p.o. (carrageenan edema). 5, 50 and 150 microg/kg MGL p.o. for 14 days (Freund's adjuvant arthritis), 5 and 50 microg/kg p.o. for 6 days (ulceration). METHODS: Anti-inflammatory effects were measured in carrageenan edema and in adjuvant arthritis. Incidence of gastric lesions was tested in an ulcerogenicity model in vivo. Influence on COX was determined in the perfused rabbit ear, in PMNL and in a test assay using COX-1 and COX-2. 5-LOX activity was studied using PMNL and RBL-1. The influence on platelet aggregation was evaluated measuring light transmission. RESULTS: MGL exerted a marked and dose-dependent anti-inflammatory effect in acute (carrageenan edema, ED50 15 microg/kg, indomethacin ED50 10 mg/kg) and chronic (adjuvant arthritis, inhibition at 150 microg/kg 18.1 % left paw, 20.6% right paw, indomethacin 3 mg/kg 18.0% and 19.4%)) models of inflammation. In the perfused rabbit ear 1 microg MGL inhibited the release of PGI2, PGD2 and PGE2 to the same extent as 1 microg indomethacin. The inhibition of COX-1 in the intact cell system was IC50 = 0.5 microM, that of indomethacin 0.0038 microM. In the isolated enzyme preparations of COX-1 and COX-2 the IC50 was 10 microM and 8 microM, that of indomethacin 9.2 mM and 2.4 microM. In the RBL-1 and PMNL test assay the inhibition of 5-LOX was 0.1 microM and 2.2 microM. An orally administered dose of 50 microg/kg/day induced no gastric ulcers in rats treated for 6 days. The investigations on carrageenan edema showed a close relationship between the structure of MGL and the anti-inflammatory effect. CONCLUSIONS: MGL is a COX-1, COX-2 and 5-LOX inhibitor. In view of the moderate in vitro activity and the very potent in vivo activity an additive mechanism must be involved. Small changes in the molecular structure lead to the loss or reduction of the anti-inflammatory activity.     

Ultrastructural studies of the ileum neobladder

Of 101 women, 15-50 years of age, presenting with vaginal discharge, 34 had bacterial vaginosis and were randomly assigned to a seven-day course of oral treatment with either erythromycin (0.5 g b.i.d.) or metronidazole (0.4 g b.i.d.) in a single-blind, cross-over study. Treatment failure (> or = three clinical signs of bacterial vaginosis) occurred in 13 (81%) of 16 patients given erythromycin, as compared with three (17%) of 18 women treated with metronidazole (p < 0.001). Persistence of Gardnerella vaginalis, Mobiluncus species and/or Mycoplasma hominis was found in 14 of 16 patients treated with erythromycin, and in four of 16 patients treated with metronidazole. Treatment with metronidazole was successful (< or = two clinical signs of bacterial vaginosis) in eight of 10 cases of erythromycin treatment failure. Neither of two cases of metronidazole treatment failure was cured with erythromycin. At three-month follow-up of 31 women, persistence or recurrence of bacterial vaginosis was diagnosed in 11 cases (36%).     

Resistance to care

Resisting care is defined as any patient behavior which prevents or interferes with the care provider performing or assisting with ADLs for the patient, including bathing, eating, toileting, dressing and grooming. Significant consequences of resisting care include malnutrition, skin breakdown, dehydration, constipation and weight loss. Creativity, flexibility and patience are key components of any intervention. Due to the lability of the person with cognitive impairment, a plan that works perfectly one day may never work again.