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Biomedical subjects

J Bernstein

Publications and source records attributed to J Bernstein.

At least 19 recordsLinked to original sources

The influence of inhibitory afferents on the development of postsynaptic dendritic arbors.

The growth and maintenance of dendritic form is dependent on normally functioning excitatory afferents. We have now examined the development of dendritic arbors in the gerbil lateral superior olive (LSO), following contralateral cochlear removal at postnatal day 7, a manipulation that substantially eliminates driven inhibitory transmission. Previous studies have demonstrated that the morphology of LSO dendritic arbors varies with tonotopic position and becomes more restricted with age. The presumed decrease of inhibitory transmission in the contralateral LSO resulted in a hypertrophic response. Quantification of Golgi-impregnated neurons revealed that dendrites had a significantly greater number of branch points, and their arbors were more spread out along the frequency axis compared to normal. This was especially apparent in the high frequency projection region where the glycine receptor density is known to be 4-fold higher than in the low frequency projection region. A measure of LSO nucleus size, cross-sectional area, was identical to control values, indicating no overt signs of degenerative phenomena. Cochlear ablation resulted in a significant atrophy of the ipsilateral LSO, with significant effects on dendritic structure. We conclude that decreased inhibitory transmission during development does not lead to a net degenerative response. Rather, the postsynaptic neurons exhibit a hypertrophic phenotype that may be due to the persistence of an immature state. These results indicate that activity-dependent morphogenetic events are a consequence of both excitatory and inhibitory synaptic transmission.

Afferent Pathways

A defective splice site at the phenylalanine hydroxylase gene in phenylketonuria and benign hyperphenylalaninemia among Palestinian Arabs.

Phenylketonuria (PKU) and benign hyperphenylalaninemia (HPA) result from different combinations of mutations at the locus for phenylalanine hydroxylase (PAH). While some of these mutations show widespread ethnic distribution, others are unique to specific communities. We report here the first point mutation common among Palestinian Arabs. The mutation (IVS2nt1) involves a dinucleotide substitution (Gg-->Aa) at the donor splice site of intron 2 of the PAH gene and abolishes a recognition site of the restriction enzyme MnlI. IVS2nt1 is associated with two PAH polymorphic haplotypes, 7 and 42. Homozygotes for this mutation are affected with severe, classical PKU. Compound heterozygotes carrying the IVS2nt1 allele and one of several other yet unknown mutations show different degrees of benign HPA.

Base Sequence

Heat-resistant variants of the Chinese hamster ovary cell: alteration of cellular structure and expression of vimentin.

Three heat-resistant mutant cell lines (78-1, 78-2, 78-3) were previously selected from Chinese hamster ovary cells. In this study, we investigated whether the differences in intrinsic thermal sensitivity result from alteration of stress protein levels or cellular structural changes. Although there was no significant difference in the levels of stress proteins, i.e., constitutive HSP70 in wild type and three heat-resistant mutant strains, there were marked differences in the amounts of vimentin among the cell lines. Two-dimensional gel electrophoresis and Western blot showed a 2.3-2.9-fold increase in the level of vimentin in the mutant cells under normal growth conditions. Northern blot also revealed higher amounts of vimentin mRNA in the mutant cells. Electron microscopy and immunofluorescence suggest that increased amounts of the vimentin-containing intermediate filaments are correlated with the heat-resistant phenotypes.

Animals

Treatment of mesangiocapillary glomerulonephritis with alternate-day prednisone--a report of the International Study of Kidney Disease in Children.

It has been claimed that long-term prednisone treatment ameliorates the course of children with mesangiocapillary glomerulonephritis (MCGN). The International Study of Kidney Disease in Children conducted a randomized, double-blinded, placebo-controlled clinical trial in 80 children with idiopathic MCGN, including 42 patients with type I disease, 14 with type II disease, 17 with type III disease, and 7 with nontypable disease. Criteria for admission included heavy proteinuria and a glomerular filtration rate of greater than or equal to 70 ml/min per 1.73 m2. Prednisone or lactose, 40 mg/m2, was given every other day as a single morning dose. The mean duration of treatment was 41 months, renal failure being the most common reason for termination of therapy. Treatment failure was defined as an increase from baseline of 30% or more in serum creatinine, or more than 35 mumol/l. Overall, treatment failure occurred in 55% of patients treated with lactose, compared with 40% in the prednisone group. Life-table analysis showed a renal survival rate (i.e., stable renal function) at 130 months of 61% among patients receiving prednisone and 12% among patients receiving lactose (P = 0.07). Of patients with type I or III MCGN, 33% treated with prednisone were treatment failures, compared with 58% in the lactose group. Long-term treatment with prednisone appears to improve the outcome of children with MCGN.

Adolescent

Renal cortical and renal medullary necrosis in the first 3 months of life.

Renal cortical necrosis, renal medullary necrosis, and combined renal cortical-medullary necrosis result from renal ischemia without vascular occlusion. Renal hypoperfusion and ischemic injury in infants have been ascribed to massive blood loss, hemolytic disease, septicemia, and severe hypoxemia. In a postmortem study we identified 82 cases among 1,638 autopsies during the 20 years between 1970 and 1989 in infants 3 months old or less at the time of death. The frequency of renal necrosis in autopsy cases increased significantly during the last 6 years of the study. The distribution of the renal lesion was cortical in 28, medullary in 23, and combined in 31. Forty infants carried diagnoses of congenital heart disease, 17 of asphyxial shock, 9 of sepsis, 3 of infectious myocarditis, 9 of major malformations, 4 of anemic shock, 1 of vascular malformation, and 1 of gastroenteritis and dehydration. A significantly higher proportion of babies with congenital heart disease had cortical involvement. Comparison of clinical characteristics revealed a significantly higher frequency of prematurity, respiratory distress syndrome, bleeding diathesis, and possibly sepsis in the children with congenital heart disease, suggesting that these factors are important in the pathogenesis of the renal lesion. Fourteen infants underwent cardiac catheterization; there was no demonstrable association between the renal lesions and the use of radiographic contrast medium. We conclude that severe congenital heart disease itself is a risk factor for life-threatening renal cortical and medullary necrosis.

Female

Morphological characteristics of segmental renal scarring in vesicoureteral reflux.

We examined 25 complete and partial nephrectomy specimens from 21 patients with advanced reflux nephropathy, all of which showed severe renal atrophy and loss of parenchyma. All specimens that included nonatrophic or partially atrophic renal tissue contained small medullary scars that involved only portions of the medullary pyramids. These sublobar medullary scars, which appeared linear and were typically discrete, extended from the inner medulla to the cortex. They obliterated collecting ducts, vasa recta and recurrent loops. The cortical portions of the scars contained remnants of nephrons and variable infiltrates of chronic inflammatory cells with lymphoid follicles. Seven of the specimens also contained acute disruptive ductal lesions with histopathological features characteristic of intrarenal reflux. We believe that the linear scars are the result of single duct medullary disruptions, mediated perhaps through obstruction of the several thousand nephrons subtended by each papillary duct and perhaps through localized disruption of the renal microvasculature. These sublobar scars accumulate as scarring progresses to end stage renal atrophy.

Adolescent

Role of pathology indices in the management of severe lupus glomerulonephritis. Lupus Nephritis Collaborative Study Group.

The principal value of the renal biopsy in patients with SLE is as a therapeutic guide. Although semiquantitative indices of nephron loss (chronicity = CI) and acute potentially reversible inflammation (activity = AI) are reported by some to have separate values from traditional classifications of glomerular pathology as predictors of outcome and therapeutic guides, this point remains controversial. We have tested the predictive value of the AI and CI in a large group of patients with severe lupus glomerulonephritis (SLE GN) and a mean follow-up of 281 weeks +/- 116 (mean +/- SD). A total of 86 patients entered into the study of plasmapheresis in severe SLE GN by the Lupus Nephritis Collaborative Study Group, and long-term follow-up was available in 83. The predictive value of the AI and the CI was described over the entire range of cut-off points by the method of receiver operator characteristics (ROC). ROC analysis demonstrated that there was no level of either AI or CI that predicted the outcome of death or renal failure with sufficient sensitivity and specificity to be useful in the individual patient. The CI signifies renal damage and nephron loss, whereas the AI describes potentially reversible pathology. Neither the CI nor the AI taken by itself predicts individual outcomes of renal failure or death in patients with aggressively treated SLE GN. Since the indices fail to identify the patient whose disease will progress to renal failure, they are both insufficient as therapeutic guides and add little to the management of the patient with severe SLE GN.

Adult

Intraglomerular pressure and mesangial stretching stimulate extracellular matrix formation in the rat.

To define the interplay of glomerular hypertension and hypertrophy with mesangial extracellular matrix (ECM) deposition, we examined the effects of glomerular capillary distention and mesangial cell stretching on ECM synthesis. The volume of microdissected rat glomeruli (Vg), perfused ex vivo at increasing flows, was quantified and related to the proximal intraglomerular pressure (PIP). Glomerular compliance, expressed as the slope of the positive linear relationship between PIP and Vg was 7.68 x 10(3) microns 3/mmHg. Total Vg increment (PIP 0-150 mmHg) was 1.162 x 10(6) microns 3 or 61% (n = 13). A 16% increase in Vg was obtained over the PIP range equivalent to the pathophysiological limits of mean transcapillary pressure difference. A similar effect of renal perfusion on Vg was also noted histologically in tissue from kidneys perfused/fixed in vivo. Cultured mesangial cells undergoing cyclic stretching increased their synthesis of protein, total collagen, and key components of ECM (collagen IV, collagen I, laminin, fibronectin). Synthetic rates were stimulated by cell growth and the degree of stretching. These results suggest that capillary expansion and stretching of mesangial cells by glomerular hypertension provokes increased ECM production which is accentuated by cell growth and glomerular hypertrophy. Mesangial expansion and glomerulosclerosis might result from this interplay of mechanical and metabolic forces.

Animals

Effect of prior antibiotic treatment on middle ear disease in children.

The effect of prior antibiotic treatment on the course of otitis media was assessed in a group of 62 children who experienced 83 episodes of ear infection during 3 years of observation. Bacterial quantitation in middle ear fluids demonstrated a significantly higher colony count in symptomatic children (3.9 x 10(4) +/- 12 bacteria per milliliter) compared to asymptomatic children (6.3 x 10(3) +/- 10 bacteria per milliliter; p = .05). Bacterial counts similarly tended to be higher in children with Streptococcus pneumoniae (4.0 x 10(6) +/- 16 bacteria per milliliter) and Hemophilus influenzae (2.0 x 10(6) +/- 16 bacteria per milliliter), who were more often symptomatic (73% and 55%, respectively, versus 38%) than children with Moraxella catarrhalis (7.9 x 10(3) +/- 2). Antibiotic therapy between 3 and 30 days prior to bacterial diagnosis was associated with a reduction in symptoms from 70% to 38% (p less than .025). However, prior treatment did not statistically reduce bacterial colony counts, although S pneumoniae decreased 90% in the previously treated group. Resistance to ampicillin occurred in 0% of S pneumoniae, 39% of nontypeable H influenzae, and 80% of M catarrhalis subjects without prior treatment and in 0%, 46%, and 100%, respectively, of subjects previously treated (p less than .025). These data suggest that prior treatment has a significant impact on the subsequent course of otitis media in children.

Anti-Bacterial Agents

Antibodies against a 30 kilodalton cochlear protein and type II and IX collagens in the serum of patients with inner ear diseases.

Collagen molecules are major extracellular matrix proteins involved in the development and support of delicate auditory sensory organs. Type II collagen is widely distributed within inner ear tissues, while type IX is found only within the labyrinthine membrane and dense fibers of the tectorial membrane. Antibody specific for type II collagen has been shown to be elevated in some patients with hearing loss due to several presumably autoimmune illnesses (including Meniere's disease, otosclerosis, chronic progressive sensorineural hearing loss, and relapsing polychondritis). Purified human type II and IX collagens and an extract of human cochlear tissue were subjected to isolation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and transferred to nitrocellulose. The sera of 21 patients with inner ear disease were examined for the presence of anticollagen and anticochlear antibodies; the sera were used to probe Western blots of purified human collagens II, IX, and XI, and cochlear protein extract with peroxidase-conjugated goat anti human polyvalent immunoglobulin as the second antibody. Anti-type II collagen antibodies were seen in 12 of 21 (57%) patients, while 13 of 21 (62%) had anti-type IX antibodies detectable by Western blot. A previously unreported 30 kd (probably noncollagen) protein was 21 (62%) had anti-type IX antibodies detectable by Western blot. A previously unreported 30 kd (probably noncollagen) protein was found by SDS-PAGE of human cochlear tissue extracts, with 3 patients, all with Meniere's disease, having antibody activity to this protein detected by Western blot.(ABSTRACT TRUNCATED AT 250 WORDS)

Blotting, Western

Coping with infertility: a new nursing perspective.

Infertility is a major life stressor, and reproductive failure is difficult to accept. Many couples become trapped in a cycle of repeated medical treatment, repeating painful patterns without developing insight or growth, feeling powerless to achieve their goal or move on. The causes of inappropriate coping behaviors are not well understood, and there is little direction for the nurse clinician's efforts to assist the couple with decision making. The use of superstition and ritual (magical thinking or magical ideation) by couples with infertility is discussed, and its role as a potential barrier to resolution is evaluated. A clinical tool for assessing the extent of magical ideation is described and its potential clinical utility explored. Women who have experienced a previous pregnancy may be more likely than nulliparas to substitute magical thinking for coping behaviors that might bring them closer to resolution. Problems with current research in this area are discussed, and directions for developing clinical nursing interventions are suggested.

Adaptation, Psychological

Effect of diet composition on renal morphology in diabetic rats.

Streptozotocin-induced diabetic rats were fed rodent diets with standard (4.5%) or high (10%) polyunsaturated fatty acid content for up to 12 months. Diabetic rats fed a standard diet developed thickening of glomerular basement membrane (GBM) when compared to similarly fed controls (285 +/- 21 vs. 243 +/- 18 nm, respectively; p = 0.0003). No differences in GBM thickening were observed between control and diabetic rats fed high-fat diets (188 +/- 23 vs. 195 +/- 21 nm, respectively; p = n.s.). Regardless of diabetes, all rats fed high polyunsaturated fat diets had decreased GBM thickness compared to standard-fed rats (p = 0.0001). Glomerular and mesangial volumes were similar in control and diabetic rats fed standard or high fat diets. Diets high in polyunsaturated fatty acids prevent GBM thickening in diabetes and reduce GBM thickness in control rats.

Animals

Monoclonal antibody to human cartilage cells and its reactivities to chondrocytic tumors.

A murine monoclonal antibody (E10) was made against cultured cartilage cells. The E10 antibody binding is localized to the surface of cultured cartilage cells in suspension and is present in the cytoplasm in paraffin embedded sections. There is no reactivity with cartilage matrix, or with the matrix of cartilaginous tumors. Reactivity is removed by treatment with trypsin and hyaluronidase, but not by treatment with heparinase, neuraminidase, and chondroitinase. Regeneration of E10 antigen after trypsinization takes 48 hours in chondrocytes in tissue culture. SDS-polyacrylamide gel electrophoresis of an E10 immune precipitate of cultured chondrocytes results in two peaks: one at a very high molecular weight and a small fragment at approximately 250 kd. Specificity has been demonstrated by cytofluorometry, immunofluorescence, and immunohistochemistry, in both frozen and paraffin-embedded tissues. Positive reactivity was seen in cultured cartilage cells, chondrocytes in fetal and adult cartilage, chondrosarcomas, and chordomas. Minimal reactivity was found in a chondromyxoid liposarcoma. Acinar cells of salivary and sweat glands and mast cells in various tissues and tumors were also positive. There was no reactivity with other tissues and tumors, including myxoid and mucinous tumors and epithelial tissues.

Antibodies, Monoclonal

Development of a model quality-of-care assessment program for adult preventive care in rural medical practices.

A four-year project of quality-of-care assessment for 37 practices in rural North Carolina used chart abstraction and formal feedback to practitioners to improve compliance standards for 13 adult health maintenance interventions. In 1987, performance of Papanicolaou (Pap) test within two years ranged from 20% to 100% (mean, 61%), mammogram 0% to 70% (mean, 20%), and influenza vaccination 0% to 90% (mean, 59%). Practices received individual results and remediation took place for those practices that performed poorly; a reaudit took place in 1989, with improvement in all measures for all practices, except the influenza vaccination. Compliance results for 1989 were 30% to 100% (mean, 67%) for the Pap test, 10% to 100% (mean, 40%) for the mammography screening, and 5% to 80% for the influenza vaccination. These results suggest that coordinated quality-of-care assessment for rural practices can be performed with a modest administrative burden and substantial benefit to the practices.

Feedback

Renal involvement in tuberous sclerosis.

TSC in the kidney is expressed principally as renal cysts and angiomyolipomas. Both abnormalities may occur separately or together, and both are commonly multiple and bilateral. Cystic disease is sometimes so severe as to be confused with polycystic kidney disease, although the histopathologic findings are practically diagnostic of TSC. Severe cystic disease causes renal insufficiency; large angiomyolipomas predispose to life-threatening hemorrhage. Renal malignancies have been reported in what appears to be a significant number of patients. We hypothesize that the renal abnormalities result from cell hyperplasia and hypertrophy, much like the other abnormalities of tuberous sclerosis, such as cerebral tubers and cardiac rhabdomyomas. The renal abnormalities can therefore be regarded as an expression of the TSC gene, and their recognition as such carries importance for treatment and counseling.

Carcinoma, Renal Cell

Arachidonic acid metabolites in middle ear effusions of children.

Middle ear effusions (MEEs) from 78 children (98 ears) with otitis media were examined for products of arachidonic acid (AA) metabolism, including leukotrienes B4, C4, D4, and E4 and prostaglandins D2 and E2, by high-performance liquid chromatography. Leukotrienes B4 and D4 were recovered most frequently: 59% and 54%, respectively. Leukotriene B4 was found in highest concentration, 1.29 +/- 3.46 ng/0.1 mL. The concentrations of leukotrienes B4 (p less than .03), (4 (p less than .01), and E4 (p less than .02) were significantly higher in culture-positive than in culture-negative MEEs. Neither the concentration nor the type of AA metabolite correlated with bacterial species isolated, chronicity of effusion, age of subject, or consistency of MEE. These data suggest that the AA metabolites are synthesized relatively frequently during otitis media of childhood. Leukotriene B4 is the most frequently detected AA metabolite in MEEs and is highly associated with the presence of viable bacteria.

Arachidonic Acid