Search PubMed⌕ Search

Biomedical subjects

R B Winter

Publications and source records attributed to R B Winter.

At least 127 records · Page 7Linked to original sources
PubMed1982

Pathophysiological effects of paraquat intoxication in domestic ruminants: low dose studies.

Two studies, one in mixed breed feedlot calves and one in domestic goats, evaluated the effects of low doses of parentally administered paraquat dichloride on lung function and pulmonary structure. Calves were injected IV with 5 mg/kg paraquat and studied on days 3, 5, and 7 postinfusion. Goats were intoxicated IP with 10 mg paraquat/kg and studied on days 2, 4, 8, and 10. Each animal served as its own control. The two dosage regimes in calves and goats did not alter pulmonary function or blood gases (calf study only). Only goats intoxicated at the higher dose demonstrated histopathological paraquat-related structural changes.

Animals↗
PubMed1981

Diffusion-driven mechanisms of protein translocation on nucleic acids. 1. Models and theory.

Genome regulatory proteins (e.g., repressors or polymerases) that function by binding to specific chromosomal target base pair sequences (e.g., operators or promoters) can appear to arrive at their targets at faster than diffusion-controlled rates. These proteins also exhibit appreciable affinity for nonspecific DNA, and thus this apparently facilitated binding rate must be interpreted in terms of a two-step binding mechanism. The first step involves free diffusion to any nonspecific binding site on the DNA, and the second step comprises a series of protein translocation events that are also driven by thermal fluctuations. Because of nonspecific binding, the search process in the second step is of reduced dimensionality (or volume); this results in an accelerated apparent rate of target location. In this paper we define four types of processes that may be involved in these protein translocation events between DNA sites. These are (i) "macroscopic" dissociation--reassociation processes within the domain of the DNA molecule, (ii) "microscopic" dissociation--reassociation events between closely spaced sites in the DNA molecule, (iii) "intersegment transfer" (via "ring-closure") processes between different segments of the DNA molecule, and (iv) "sliding" along the DNA molecule. We present mathematical and physical descriptions of each of these processes, and the consequences of each for the overall rate of target location are worked out as a function of both the nonspecific binding affinity between protein and DNA and the length of the DNA molecule containing the target sequence. The theory is developed in terms of the Escherichia coli lac repressor--operator interaction since data for testing these approaches are available for this system [Barkley, M. (1981) Biochemistry 20, 3833; Winter, R. B., & von Hippel, P. H. (1981) Biochemistry (second paper of three in this issue); Winter, R. B., Berg, O. G., & von Hippel, P. H. (1981) Biochemistry (third paper of three in this issue)]. However, we emphasize that this approach is general for the analysis of mechanisms of biological target location involving facilitated transfer processes via nonspecific binding to the general system of which the target forms a small part.

Binding Sites↗
PubMed1981

Diffusion-driven mechanisms of protein translocation on nucleic acids. 3. The Escherichia coli lac repressor--operator interaction: kinetic measurements and conclusions.

The association and dissociation kinetics of the Escherichia coli lac repressor--operator (RO) complex have been examined as a function of monovalent ion concentration and operator-containing DNA fragment length in order to investigate the mechanisms used by repressor in locating (and dissociating from) the operator site. Association rate constants (ka) measured with an 80- or a 203-base-pair lac operator containing DNA fragment are 3--5-fold smaller than those determined with a 6700-base-pair operator fragment or with intact lambda plac5 DNA (50000 base pairs) at all salt concentrations tested. At salt concentrations less than approximately 0.1 M KCl, association rate constants to all operator-containing DNA fragments (except lambda plac5 DNA) are insensitive to variations in salt concentration, but the limiting low salt value of ka appears to depend upon operator-containing DNA length. The value of ka for lambda plac5 DNA decreases significantly from the approximately 0.1 M KCl maximum at low salt. Above approximately 0.1 M KCl, repressor--operator association rate constants for all operator-containing DNA substrates tested show a similar decrease with increasing salt concentration, which does not appear to depend upon the length of the DNA molecule (except for the very small DNA fragments). In contrast to the association reaction, kd, the dissociation rate constant, decreases linearly (on a log kd vs. log [KCl] plot) with decreasing salt concentration over virtually the entire salt concentration range studied (0.05--0.2 M KCl). These results are consistent with the explanation of the unusually fast association kinetics for this system in terms of a two-step model in which repressor initially diffuses to a nonoperator DNA binding site (forming an RD complex) and then rapidly "scans" (in a locally correlated fashion) adjacent sites until the operator is located or the repressor dissociates from the chain. Dissociation of the RO complex follows the same two-step process in reverse. Quantitative comparisons are made between these results and the theoretical predictions of the two facilitating translocation mechanisms (one-dimensional "sliding" along the DNA double helix and direct transfer between DNA segments) developed in the first paper of this series [Berg, O. G., Winter, R. B., & von Hippel, P. H. (1981) Biochemistry (first paper of three in this issue)]. We conclude that the experimental data for the "faster-than-diffusion-controlled" interaction of repressor and operator can be quantitatively modeled by a two-step process in which sliding is the dominant transfer mechanism. Molecular models of the initial nonspecific binding event (including "hopping") as well as sliding and interchain transfer are discussed, and the possible roles of facilitated translocation mechanisms of the diffusion-driven type in this and other in vitro and in vivo protein--nucleic acid interaction processes are considered.

DNA, Bacterial↗
PubMed1981

Convex anterior and posterior hemiarthrodesis and hemiepiphyseodesis in young children with progressive congenital scoliosis.

Ten children with progressive congenital scoliosis have been treated by convex anterior and posterior epiphyseodesis and arthrodesis. The average curve was 54 degrees, the average age at surgery 3 years, 10 months, and the average follow-up 2 years, 9 months. There were no complications. The curve progression was halted in all cases, no fusion mass bending has been observed to date, and two patients have shown evidence of spontaneous curve improvement. Follow-up for several more years will be necessary before definitive conclusions can be reached.

Arthrodesis↗
PubMed1981

Surgical treatment of adult scoliosis. A review of two hundred and twenty-two cases.

We evaluated the cases of 222 patients older than twenty years in whom scoliosis was the primary diagnosis. No patient had had prior surgical treatment. The diagnoses were idiopathic scoliosis in 160 patients, paralytic scoliosis in forty-four, and congenital scoliosis in eleven, and there were miscellaneous diagnoses in seven patients. The average age of the patients when first seen was 30.7 years. The indications for operation were pain, progression of the curve, magnitude of the curve, and cardiopulmonary symptoms. Preoperative traction, including halo-femoral traction, did not result in increased correction when compared with the initial supine side-bending roentgenogram. A one-stage fusion was performed in 174 patients and multiple-stage procedures, in forty-eight patients. At an average follow-up of 3.6 years the average loss of correction was 6.2 degrees, 68 per cent of the patients were free of pain, and a solid fusion had been obtained in all but six patients. Complications developed in 53 per cent of the patients, the most common problems being pseudarthrosis, urinary tract infection, wound infection, instrumentation problems, a pulmonary disorder, and loss of lumbar lordosis. Paraplegia occurred in one patient. The over-all mortality rate was 1.4 per cent. Complications increased with age, and the highest mortality rate was in patients with congenital scoliosis who had cor pulmonale.

Adult↗
PubMed1981

Post-traumatic kyphosis. A review of forty-eight surgically treated patients.

We reviewed the cases of forty-eight patients who were treated surgically for symptomatic post-traumatic kyphosis of the thoracic or lumbar spine six months or longer after the initial injury. Presenting signs and symptoms included pain in 94 per cent, progression of kyphosis in 46 per cent, instability in 36 per cent, and increasing neural deficit in 27 per cent. Twenty-four patients had had a prior laminectomy. Posterior fusion (sixteen patients) and combined anterior and posterior fusion (twenty patients) always resulted in primary fusion. Anterior fusion alone was attempted in twelve patients, but failed in six. The average final correction of the deformity was 26 per cent. Pain was reduced significantly in 31 per cent of the patients and was relieved completely in 67 per cent. Fourteen of the forty-eight patients also had an anterior decompression, of whom five were neurologically improved, four were unchanged or stabilized, and four were immediately worse after operation. One patient was neurologically stable for twenty-three months postoperatively and then deteriorated again. No patients were neurologically improved following posterolateral decompression or repeat exploratory laminectomy.

Adolescent↗
PubMed1981

Spine deformity subsequent to acquired childhood spinal cord injury.

The cases of forty children who had incurred a spinal cord injury between birth and the age of eighteen years were reviewed at two to 26.8 years (mean, ten years) after injury. In all of the twenty-five patients who were injured prior to the adolescent growth spurt paralytic spinal deformity developed; in twenty-four (96 per cent) of them it was progressive. Scoliosis developed in twenty-three (92 per cent); kyphosis, in sixteen (64 per cent); and excessive lumbar lordosis, in five (20 per cent). Management of the spinal deformities by bracing was difficult, and seventeen patients (68 per cent) required spine fusion, usually to the sacrum. Complications were frequent. All of the fifteen patients who were injured after the onset of the adolescent growth spurt had sustained a spinal fracture or fracture-dislocation. Nine (60 per cent) had an acute angular thoracic or thoracolumbar fracture kyphosis and seven (47 per cent) had progressive fracture kyphosis. A history of a thoracic and thoracolumbar laminectomy always was associated with increased kyphosis progression. Six (40 per cent) of these patients required spinal stabilization, usually for unstable injuries and progressive post-laminectomy deformity. Progressive paralytic spinal deformity was uncommon in the postadolescent patient.

Adolescent↗
PubMed1980

Frontometaphyseal dysplasia--evidence for X-linked inheritance.

Fewer than two dozen cases of frontometaphyseal dysplasia have been reported, some doubly or erroneously. In most reports, no information is available on possible variable manifestations in female relatives. Statements that the disorder is inherited as a dominant trait, and as an X-linked recessive have caused us to consider genetic heterogeneity. A recent large kindred prompted us to survey all published examples. We asked authors to reexamine the families they studied for any expression in relatives. In some cases, no further information could be elicited, but some additional information was gathered and pedigrees modified. This evidence was sufficient to indicate X-linked inheritance, with severe manifestations in males and extremely variable manifestations in females.

Bone Diseases, Developmental↗
PubMed1980

Long-term follow-up of scoliosis fusion.

One hundred and ten scoliotic patients underwent correction and spine fusion by one of us (J. H. M.) at Gillette Children's Hospital between 1947 and 1957. Sixty-one of these patients were evaluated in 1977 for this follow-up study. The evaluation consisted of physical and roentgenographic examination, photographs, and a detailed psychosocial analysis. The aims of the study were to evaluate: (1) the long-term stability of the fusion; (2) the incidence and severity of low-back pain; and (3) the degree of integration of the patient into society. The results showed that a solid fusion had no significant loss of correction with time. Eighty-four per cent of the patients lost only zero to 5 degrees of correction during an average follow-up of twenty-six years. Low-back pain was found to be no more frequent than in the normal population in this age group, and there was less low-back pain than in a comparable series of scoliotic patients without fusion. There was no correlation between the occurrence of low-back pain and the length or magnitude of the fused curve or the lowest extent of the fusion. An unexpected finding was the high incidence of neck pain, the cause of which is unknown. Psychosocial analysis revealed that the patients were productive, active, stable persons who were working and contributing members of society.

Adolescent↗
PubMed1980

Disorders of the spine in diastrophic dwarfism.

In this series of nine patients with diastrophic dwarfism, multiple problems with the spine were noted. Scoliosis was present in all patients and usually became rapidly progressive in the preadolescent years. The scoliosis had a strong tendency to become severe and rigid, with a large rotatory component. Early brace treatment appeared to have merit. Cervical kyphosis was noted in four patients; it resolved in three patients, but progressed in one to a 130-degree deformity, quadriplegia, and death. All patients in this series had spina bifida occulta in the cervical spine. Six of the nine patients demonstrated a narrowed interpedicular distance below the third lumbar vertebra, but none had spinal stenosis.

Adolescent↗
PubMed1980

The lumbosacral curve in idiopathic scoliosis. Its significance and management.

In 850 consecutive patients with idiopathic scoliosis, no primary lumbosacral curve with only secondary curves above it was found. Forty-four patients with double structural thoracic and lumbar, single structural thoracic, and single structural lumbar curves showed progressive loss of flexibility in the lumbosacral area. Of these, five patients had correction and fusion of the lumbosacral curve and seventeen had correction and fusion of the major curve above the third or fourth lumbar segment without surgical treatment of the lumbosacral area. The results were better in the latter group. Correction and fusion in the lumbosacral area was difficult to achieve. No patient had a permanent list when only curves above the lumbosacral curve were corrected and fused. Lumbosacral fusion should be reserved for primary lumbosacral curves associated with congenital anomalies or spondylolisthesis.

Adolescent↗
PubMed1980

Treatment of idiopathic scoliosis in the Milwaukee brace.

The results of treatment of idiopathic scoliosis with a Milwaukee brace were studied in 133 patients (127 girls and six boys) whose ages ranged from eight years and five months to sixteen years and two months at the beginning of treatment. These 133 patients had 192 separate curves (119 right thoracic, thirty-nine high lumbar, twelve thoracolumbar, and twenty-two high left thoracic). Of these patients, seventy-four with 109 curves were followed for five years or more after the brace was discontinued (average, eight years; range, five to thirteen years); twenty-nine patients were treated surgically because of a poor response to the brace or progression of the curve; and thirty patients were lost to follow-up. More than 80 per cent of the seventy-four patients followed for five years or more showed some increase of their curves after the brace was discontinued. The average correction at follow-up compared with the original curve was 2 degrees for thoracic curves (range, -18 to 24 degrees) and 4 degrees for the thoracolumbar and lumbar curves (range, -11 to 17 degrees). The brace was more effective for curves of less than 40 degrees. More than one-third of the patients with curves of 40 degrees or more eventually required surgical treatment. Age, curve pattern, and status of the iliac and ring epiphyses did not correlate withe response to brace treatment. The best guideline for prediction of the results of brace treatment was the response of the curve to the brace, especially during the first year of treatment. If the curve is reduced in the brace to less than 50 per cent of its initial measurement, there is a good chance of obtaining significant permanent correction.

Adolescent↗
PubMed1980

The surgical management of patients with Scheuermann's disease: a review of twenty-four cases managed by combined anterior and posterior spine fusion.

Twenty-four patients with Scheuermann's kyphosis underwent correction of the deformity through a combined anterior and posterior spine fusion. All patients had a solid arthrodesis and most were relieved of their preoperative pain. Deformity was improved in all patients. Significant loss of correction did not occur in the fusion area but it did occur below the posterior arthrodesis in five patients.

Adolescent↗
PubMed1980

Congenital kyphosis due to defects of anterior segmentation.

Twenty-seven patients with Type-II congenital kyphosis (failure of anterior vertebral segmentation) all had progression of the kyphosis which varied in magnitude. The average rate of progression was 5 degrees per year. Pain due to compensatory lumbar hyperlordosis (eight patients) and objectionable deformity (fifteen patients) were the most frequent complaints. Unlike patients with Type-I kyphosis (failure of vertebral formation), paraplegia did not occur and associated congenital anomalies were infrequent (three of the twenty-seven patients). Spontaneous ossification of the anterior part of seemingly normal intervertebral discs leading to bar formation and progression of deformity occurred in five patients. A Milwaukee brace had little effect on this fixed kyphotic deformity in the six patients in whom the brace was used. Early recognition and spine fusion are the recommended treatment. Posterior fusion is sufficient in young children with progressive deformity, whereas combined two-stage anterior and posterior fusion with osteotomy of the anterior bar is recommended in children with severe deformity.

Adolescent↗