The use of polymerase chain reaction (PCR) gene amplification and synthetic oligonucleotide probes for HLA-DP typing in bone marrow transplantation.
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Bone Marrow Transplantation↗
Biomedical subjects
J L Smith
Publications and source records attributed to J L Smith.
Age-dependent differences in reorganization of primary somatosensory cortex following low thoracic (T12) spinal cord transection in cats.
The organization of primary somatosensory cortex was examined in chronic spinal cats that had sustained cord transection at T12 at 3 ages: 2 and 6 weeks of age, and as adults. Five months to 1 yr following transection, the deprived cortex was mapped electrophysiologically (multiunit recordings). The topographical organization found at each age was compared to that present in normal adults to study effects of developmental age on the ability of the somatosensory system to adjust to changes in afferent input. Cortical responses to deprivation of somatosensory input were age dependent. In animals cord transected at 2 weeks of age, the remaining somatic afferent input excited both its normal cortical area and the area normally reserved for the hindlimb. This resulted in 2 somatotopic maps of the rostral trunk and forelimb. In contrast, in cats spinalized at 6 weeks of age, there was only 1 map for the remaining somatosensory input that was distributed across the mediolateral axis of the primary somatosensory cortex. As a result, the remaining somatosensory input was shifted medially from its normal position and was narrower with respect to the rostrocaudal area driven by light tactile input. The amount of cortex that each body region could excite was essentially the same as in normal animals. In adults, a third response was observed; regions normally devoted to forelimb and trunk appeared to be unchanged, and the region previously serving the hindlimb responded only to a limited extent, and only to tactile stimulation of the trunk. In all cases, however, some sites in the cortex could be excited by parts of the body that in normal animals were served by cortical regions from 3 to 10 mm away, a distance much in excess of the maximum extent of reported thalamocortical overlap. We suggest that the various patterns of cortical organization observed at different ages reflect different developmental processes that are active at the time of transection. Further, we hypothesize that often, in major denervations such as spinal cord transection, a significant component of the reorganization occurs at synaptic levels below the cortex in young animals.
Afferent Pathways↗
Patterns of care of the elderly with cancer at a community hospital.
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Age Factors↗
Ocular Lyme borreliosis.
In six patients with ocular Lyme borreliosis, bilateral granulomatous iridocyclitis and vitritis were present in five. One of these five also had bilateral optic neuritis. Another patient developed combined trochlear and facial nerve palsies. A syndrome resembling pars planitis with atypical features such as granulomatous keratic precipitates and posterior synechiae should prompt a search for Lyme borreliosis. Topical corticosteroid therapy is necessary to prevent complications of anterior segment inflammation caused by Lyme uveitis, but the benefit of systemic and periocular corticosteroids is uncertain. Oral antibiotics may be effective in treating early stages of ocular Lyme borreliosis. In later stages, intravenous antibiotic therapy is indicated.
Adrenal Cortex Hormones↗
Molecular characterization of the Trypanosoma brucei RNA polymerase I and III largest subunit genes.
We have sequenced a 7.1-kilobase fragment of the Trypanosoma brucei RNA polymerase (pol) I largest subunit gene. The 6.9-kilobase transcript from this gene is of roughly equal abundance in bloodstream- and procyclic-form trypanosomes and has a 39-nucleotide trans-spliced leader 290 nucleotides upsteam of the putative initiation codon. The 1781-amino acid trypanosome pol I polypeptide is considerably less similar to its yeast homolog than the trypanosome pol II and pol III polypeptides are to their counterparts in yeast. The yeast and trypanosome pol I polypeptides are distinguished from pol II and pol III largest subunits by two inserts, 100-200 amino acids in length, which are found in the nonconserved portions of the polypeptides. We also report our sequence of the trypanosome pol III largest subunit gene, which agrees with that reported by Köck et al. (Köck, J., Evers, R., and Cornelissen, A.W.C.A. (1988) Nucleic Acids Res. 16, 8753-8772) except for 13 nucleotide differences. Four spliced leader addition sites between 60 and 99 nucleotides upstream of the AUG initiation codon were observed for the 5.4-kilobase transcript from this gene. Four short stretches of amino acid homology between the yeast and trypanosome pol III largest subunit polypeptides were identified which appear to be specific to this class of RNA polymerase; only one short pol I-specific sequence was identified in our comparison of the yeast and trypanosome pol I largest subunit polypeptides.
Amino Acid Sequence↗
Effect of ischaemia on the activities of human hepatic acyl-CoA:cholesterol acyltransferase and other microsomal enzymes.
The effect of ex vivo ischaemia at 37 degrees C on the activities of human hepatic acyl-CoA:cholesterol acyltransferase (ACAT), acyl-CoA hydrolase and carboxylesterase and on the microsomal cholesterol and total phospholipid concentrations was determined in liver tissue from two patients. ACAT activity decreased exponentially with ischaemia, corresponding to half-lives of 59 and 54 min in the two samples. Acyl-CoA hydrolase activity of microsomes was not affected by ischaemia, whereas carboxylesterase activity of microsomes decreased with a corresponding increase in cytosolic carboxylesterase activity. No changes in microsomal cholesterol and total phospholipid concentrations corresponding to the changes in ACAT or carboxylesterase activity were observed. ACAT activity was also determined in microsomes prepared from twenty human liver samples obtained at surgery with in vivo warm ischaemia times ranging from 5-120 min. The data obtained agree well with the ex vivo results, showing a half-life of 57 min for the loss of ACAT activity. Therefore, in comparing ACAT activities in liver samples with different ischaemia times, an appropriate correction must be made for warm ischaemia time.
Adult↗
In trypanosomes the homolog of the largest subunit of RNA polymerase II is encoded by two genes and has a highly unusual C-terminal domain structure.
We have isolated the genes encoding the largest subunit of all three classes of RNA polymerase from Trypanosoma brucei. While the pol II largest subunit is encoded by a single gene in all organisms examined to date, trypanosomes contain two copies of the gene. Both genes are expressed in the procyclic and bloodstream stages of the trypanosome life cycle. The two pol II genes differ from one another in their coding sequences by 21 silent substitutions and 4 amino acid substitutions. In the core part of the large subunit, the predicted polypeptides are similar to other eukaryotic RNA polymerases. Both trypanosome pol II polypeptides, like those of other eukaryotes, also have a unique C-terminal extension. However, this domain in the trypanosome polypeptides, unlike those of other eukaryotes, is not a tandemly repeated heptapeptide sequence.
Amino Acid Sequence↗
Chronic isolated sixth nerve palsies.
Twenty-seven cases of chronic isolated abduction deficit, seen in 25 years of neuro-ophthalmology consultation, were reviewed. "Isolated" was defined as the lack of any other neurologic or ophthalmologic findings for at least six months. Cases were further subdivided into the categories of true and pseudo-abducens paresis. The origin, diagnosis, and management of long-standing abducens palsies were determined. Cases of pontine glioma, chordoma, chondrosarcoma, and meningioma that presented as an isolated abducens palsy and remained undiagnosed for at least six months were reviewed.
Abducens Nerve↗
Desmoplastic melanoma. Histologic correlation with behavior and treatment.
Desmoplastic (neurotrophic) melanoma is a histologic variant of cutaneous melanoma that has a distinct clinical behavior. To better understand this behavior and to treat the disease more effectively, the medical records of 16 patients treated for this disease over a 12-year period were reviewed. Thirteen patients had head and neck lesions, the ear being a common site. The average thickness of the lesions was 5.75 mm. Six (46.2%) of 13 patients had local recurrence of disease. Only two patients (15.4%) developed regional node metastases. None of the patients with clinically NO desmoplastic melanoma were found to have positive nodes after elective neck dissection, regardless of the thickness of the primary lesion. Wide excision of the primary lesion with frozen section control of surgical margins and careful examination for the presence of perineural invasion is important in determining the extent of surgical resection.
Adult↗
Function of pancreas allografts more than 1 year following transplantation.
At the University of Iowa, Iowa City, 75 pancreas transplant procedures were performed for type I diabetes mellitus from March 1984 to September 1988. Forty-seven of these transplants were performed simultaneously with kidney transplants from the same donor; 23 followed previous kidney transplants, and 5 were preuremic pancreas-only transplants. The 1-year patient survival rate is 85% and pancreas graft survival rate is 54%. The simultaneous kidney and pancrease group had a 1-year patient survival rate of 82%, a pancreas graft survival rate of 59%, and a renal graft survival rate of 73%. Thirty-one of 70 kidney and pancreas recipients had a functioning pancreas 1 year post transplantation and 26 of 31 currently have a functioning pancreas and are insulin free. Patient symptoms of neuropathy and gastroenteropathy are improved with long-term graft function. Some patients may develop type II diabetes post transplantation with impaired glucose tolerance despite high insulin production by the graft. Pancreas transplantation is the only therapy that achieves a euglycemic state as indicated by glycosylated hemoglobin and glucose tolerance testing. Centers must continue to follow up patients on a long-term basis to determine the final effects on the secondary complications of diabetes.
Diabetes Mellitus, Type 1↗
Notochordal induction of cell wedging in the chick neural plate and its role in neural tube formation.
Cells in the median hinge point (MHP) of the bending chick neural plate are tightly apposed to the underlying notochord. These cells differ from those in adjacent lateral neuroepithelial areas (L) in that MHP cells are short and mainly wedge-shaped and line a furrow, whereas L cells are tall and mainly spindle-shaped and do not line a furrow. Cell generation time also differs in these regions. These consistent differences are detectable only after the notochord has formed and established contact with the neural plate; it is unclear whether they result from self-differentiation or induction. Two experiments were performed to evaluate the hypothesis that MHP characteristics develop owing to inductive interactions between the notochord and overlying neuroepithelial cells. First, notochordless chick embryos were generated to determine whether midline neuroepithelial cells still developed typical MHP characteristics. In the absence of the notochord, such characteristics did not develop. Second, isolated segments of quail notochord were transplanted subjacent to L of chick hosts to ascertain whether the notochord is capable of inducing MHP characteristics in L cells. When transplanted notochordal segments established apposition with host L cells, the apposing L cells usually developed typical MHP characteristics. Collectively, these results provide strong evidence that the notochord plays an inductive role in the formation of MHP characteristics. This investigation further revealed that bending can occur in the absence of MHP characteristics, forming a neural tube with an abnormal morphology. Thus, the formation of such characteristics, particularly cell wedging, is not required for bending but plays a major role in generating the normal cross-sectional morphology of the neural tube.
Animals↗
Multiwavelength anomalous diffraction as a direct phasing vehicle in macromolecular crystallography.
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Bacterial Proteins↗
Paw-shake responses with joint immobilization: EMG changes with atypical feedback.
To determine the effects of atypical motion-related feedback on motor patterns of the paw shake, EMG patterns of selected flexor and extensor muscles were recorded under four conditions of joint immobilization (hip and ankle alone, hip-knee, hip-knee-ankle) and compared to responses evoked in the freely-moving hindlimb of the chronic-spinal cat. With only the ankle joint casted, paw shaking was easily evoked by applying tape to the paw, and cyclic characteristics were not altered. However, under the three conditions with hip-joint immobilization (hip alone, hip-knee, hip-knee-ankle), responses were difficult to obtain, and if elicited, the number of cycles within a response decreased and cycle periods were prolonged. The temporal organization of consecutive cycles, however, was not altered by immobilization of any joint(s). Ankle (LG) and hip (GM) extensor activity was relatively unaffected by conditions of joint immobilization. In contrast, hip flexor (IP) and knee extensor (VL) bursts were often absent under all three conditions of hip-joint immobilization, and if present, VL burst durations decreased under the casted hip-knee-ankle condition, while the onset of IP activity occurred early in the cycle with prolonged bursts under casted ankle and casted hip-knee-ankle conditions. The coactivity of the knee extensor (VL) and ankle flexor (TA) was disrupted by conditions of hip-joint immobilization: VL onset was dissociated from TA onset and coincident with LG onset. These results suggest that motion-related feedback from the hip joint is particularly important in the initiation, cycle frequency, and the number of cycles of paw-shake responses. The presence of atypical motion-dependent feedback from the hip joint altered activity of knee and ankle anterior muscles, while motion-dependent feedback from the ankle joint changed activity of the anterior hip muscle. Moreover, the results suggest a differential control of posterior and anterior muscles of the hindlimb, consistent with paw-shake limb dynamics.
Animals↗
Psychological consequences of blunt head trauma and relation to other indices of severity of injury.
To investigate the relationship between APACHE II, Injury Severity Score (ISS), Glasgow Coma Score (GCS), and behavioral outcome, a group of 39 patients who had been admitted on an emergency basis with a traumatic head injury were selected from the Neuropsychology Registry for study. Except for subtle personality and cognitive changes, all of the patients were making good neurological recoveries. The Halstead-Reitan Neuropsychological Test Battery, which has been shown to be accurate in identifying brain-damaged patients, was used as the measure of outcome. The age of the patients ranged from 16 to 49 years (mean, 25.6; SD, 9.3). The patients' educational levels ranged from elementary school to college (mean, 11.6 years of education; SD, 1.5). Halstead Impairment Indexes (HII) ranged from 0.0 to 1.0 (mean, 0.6; SD, 0.26). APACHE II scores were calculated using the worst values, obtained during the first 24 hours. These scores ranged from 5 to 35 (mean, 16; SD, 7). APACHE II was found to not significantly correlate with HII (r = 0.21, P greater than .05). ISS was calculated for each patient and ranged from 5 to 70 (mean, 27; SD, 13). ISS was found to significantly correlate with HII (r = 0.38, P less than .01). GCS ranged from 3 to 15 (mean, 9.3; SD, 3.4). Of all the correlations, GCS was the most strongly correlated with outcome as measured by the HII (r = -0.44, P less than .01). Our data emphasize that head-injured patients have subtle cognitive dysfunction even when apparently recovering well and demonstrate the need for formal psychological evaluation in all patients with injury significant enough to warrant hospitalization.
Adolescent↗
Alignment of total knee arthroplasty.
A series of 65 total knee arthroplasties performed by the senior author was evaluated to determine the effect of alignment on outcome. Radiographs and results of clinical examination were reviewed. Sixty-one of the 65 knees were in varus on the mechanical axis (ie, the weight-bearing line passed through the medial compartment). At an average follow-up period of 48 months, alignment was not found to affect incidence or progression of radiolucent lines, changes in tibial metaphyseal density, or clinical outcome (pain or range of motion). The authors were unable to confirm the historical belief that alignment is critical to the durability of cemented total knee arthroplasty, nor that the mechanical axis must pass through the center of the knee joint.
Adult↗
Crystal structure of core streptavidin determined from multiwavelength anomalous diffraction of synchrotron radiation.
A three-dimensional crystal structure of the biotin-binding core of streptavidin has been determined at 3.1-A resolution. The structure was analyzed from diffraction data measured at three wavelengths from a single crystal of the selenobiotinyl complex with streptavidin. Streptavidin is a tetramer with subunits arrayed in D2 symmetry. Each protomer is an 8-stranded beta-barrel with simple up-down topology. Biotin molecules are bound at one end of each barrel. This study demonstrates the effectiveness of multiwavelength anomalous diffraction (MAD) procedures for macromolecular crystallography and provides a basis for detailed study of biotin-avidin interactions.
Bacterial Proteins↗
Dyspepsia in NSAID users: the size of the problem.
Gastroduodenal intolerance is one of the major factors limiting the use of aspirin and other nonsteroidal antiinflammatory drugs (NSAIDs) in patients with rheumatic diseases. We previously demonstrated that dyspepsia was not a marker for ulcer in NSAID users. We have now evaluated dyspeptic symptoms in 245 arthritic patients (receiving 13 different NSAIDs) from the practices of two rheumatologists. Fifty-seven patients (23%) gave a history of previous peptic ulcers. Heartburn, indigestion, or sour stomach at least once within the past year was present in 62.5%; 36.7% had experienced these symptoms within the previous 2 months and 28.6% within the previous week. Only 39 patients (15.9%) had experienced dyspepsia more than once daily within the previous month, and 8 (3.3%) had dyspepsia greater than 5 times/day. Thirty-four of the 39 patients with daily dyspepsia claimed to obtain relief with cimetidine or antacids (34 patients) or food (2 patients), whereas 3 had not discovered anything that provided relief. Women smokers were more likely than nonsmokers to experience dyspepsia (p less than 0.001). Neither men smokers nor those with a history of previous ulcer were more likely to have dyspepsia than nonsmokers or those without a history of ulcer (p greater than 0.5). We were not able to find a statistical association between any NSAID, or combination of NSAIDs, and the frequency of dyspepsia.
Adolescent↗
Increased frequency of posttransplant lymphomas in patients treated with cyclosporine, azathioprine, and prednisone.
We have documented seven B cell lymphomas over a six-month period in 132 (5.3%) kidney and heart allograft recipients immunosuppressed with cyclosporine, azathioprine, and prednisone (triple therapy). This is a significant increase (P less than 0.0001) over the number of such tumors seen by us previously. Only 2 lymphomas had occurred in 669 cadaver and 29 living-related kidney allografts treated with azathioprine and prednisone alone (0.3%). In 160 cadaver kidney recipients treated with cyclosporine and prednisone there have been no lymphomas. Similarly in 14 living-related kidney recipients who were transplanted since the introduction of triple therapy for cadaver grafts, but continued to receive only azathioprine and prednisone, no lymphomas occurred. There seemed to be a clear relationship between this increase and the use of triple therapy. This led us to examine other possible contributing factors. A case control study has not shown any other factor that differs in patients in whom lymphomas developed. We have only been able to demonstrate Epstein Barr virus nuclear antigen in the cells of one tumor. Four of these 7 tumors were monoclonal, one polyclonal, and two indeterminate. All patients had their immunosuppression withdrawn and six received intravenous acyclovir. Three patients have shown some response but four patients died. Triple therapy is being used by many centers to reduce the level of cyclosporine toxicity. We wish to sound a note of caution that this may result in an increased incidence of posttransplant lymphomas.
Adult↗