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Biomedical subjects

T Kaufman

Publications and source records attributed to T Kaufman.

At least 19 recordsLinked to original sources
PubMed2001

BLyS BINDS TO B CELLS WITH HIGH AFFINITY AND INDUCES ACTIVATION OF THE TRANSCRIPTION FACTORS NF-kappaB AND ELF-1.

B lymphocyte stimulator (BLyS) is a novel member of the TNF family of proteins expressed by myeloid cells as membrane-bound and soluble forms. BLyS was shown to act specifically on B cells, inducing proliferation and immunoglobulin production both in vitro and in vivo. The present study was undertaken to characterize binding of radiolabeled BLyS to its cognate receptor on human B lymphocytes and examine intracellular events initiated by BLyS binding. Similar to other TNF family members, BLyS is present in solution as a homotrimer as determined by gel filtration chromatography and light scattering analysis. BLyS binding to B cells is specific as other TNF family members tested did not compete for(125)I-BLyS binding. Analysis of equilibrium binding of(125)I-labeled BLyS to purified human tonsillar B cells demonstrated saturable binding. Scatchard analysis of the binding data revealed a single class of high-affinity binding on human B cells with approximately 2600 binding sites per cell and an apparent dissociation constant (K(D)) of about 0.1 nM. In addition we report that BLyS binding to B cells results in the activation of NF-kappaB and the Ets family transcription factor, ELF-1, and in the induction of mRNA for Polo-like kinase (PLK).

B-Cell Activating Factor↗
PubMed2001

Exercise-induced neuromuscular dysfunction under reflex conditions.

The purpose of this research was to describe further the effects of exercise-induced muscle damage on reflex sensitivity. The subjects were eight physically active, but untrained males, between the ages of 18 and 29 years. The effects of eccentric and concentric exercise on patellar tendon reflex responses were determined. The 8 week experiment consisted of two, 5 day, test protocols with a 6 week wash-out period between test protocols. Each 5 day test protocol consisted of the following six test sessions: (1) day 1--baseline, (2) day 2 baseline, (3) day 2--immediate post-exercise, and (4-6) days 3-5: 24, 48, and 72 h post-exercise. On day 2, the subjects made either 100 fatiguing concentric or eccentric isotonic contractions using the right leg at 75% of the corresponding repetition maximum values. During each test session, the electromyogram (EMG) and force-time characteristics of basic and conditioned patellar tendon reflex responses were measured. The reflex amplitudes of basic and conditioned patellar tendon reflex responses were decreased following fatiguing concentric exercise. There were no immediate effects of fatiguing eccentric exercise on the basic and conditioned patellar tendon reflex responses, but the EMG amplitudes of these reflex responses were reduced on the days following eccentric exercise. The amount of conditioned patellar tendon reflex facilitation was decreased following the concentric exercise protocol and at 48 h post-eccentric exercise. Our conditioned reflex data suggest that post-exercise changes to the physiological mechanisms that modulate the recruitment gain of the alpha-motoneuron pool may depend upon the type of fatiguing exercise.

Adolescent↗
PubMed2001

Cross-regulation of Hox genes in the Drosophila melanogaster embryo.

Cross-regulation of Homeotic Complex (Hox) genes by ectopic Hox proteins during the embryonic development of Drosophila melanogaster was examined using Gal4 directed transcriptional regulation. The expression patterns of the endogenous Hox genes were analyzed to identify cross-regulation while ectopic expression patterns and timing were altered using different Gal4 drivers. We provide evidence for tissue specific interactions between various Hox genes and demonstrate the induction of endodermal labial (lab) by ectopically expressed Ultrabithorax outside the visceral mesoderm (VMS). Similarly, activation and repression of Hox genes in the VMS from outside tissues seems to be mediated by decapentaplegic (dpp) gene activation. Additionally, we find that proboscipedia (pb) is activated in the epidermis by ectopically driven Sex combs reduced (Scr) and Deformed (Dfd); however, mesodermal pb expression is repressed by ectopic Scr in this tissue. Mutant analyses demonstrate that Scr and Dfd regulate pb in their normal domains of expression during embryogenesis. Ectopic Ultrabithorax and Abdominal-A repress only lab and Scr in the central nervous system (CNS) in a timing dependent manner; otherwise, overlapping expression in the CNS in tolerated. A summary of Hox gene cross-regulation by ectopically driven Hox proteins is tabulated for embryogenesis.

Animals↗
PubMed2000

Tumor necrosis factor (TNF) receptor superfamily member TACI is a high affinity receptor for TNF family members APRIL and BLyS.

An expression cloning approach was employed to identify the receptor for B-lymphocyte stimulator (BLyS) and identified the tumor necrosis factor receptor superfamily member TACI as a BLyS-binding protein. Expression of TACI in HEK293T cells confers on the cells the ability to bind BLyS with subnanomolar affinity. Furthermore, a TACI-Fc fusion protein recognizes both the cleaved, soluble form of BLyS as well as the membrane BLyS present on the cell surface of a recombinant cell line. TACI mRNA is found predominantly in B-cells and correlates with BLyS binding in a panel of B-cell lines. We also demonstrate that TACI interacts with nanomolar affinity with the BLyS-related tumor necrosis factor homologue APRIL for which no clear in vivo role has been described. BLyS and APRIL are capable of signaling through TACI to mediate NF-kappaB responses in HEK293 cells. We conclude that TACI is a receptor for BLyS and APRIL and discuss the implications for B-cell biology.

B-Cell Activation Factor Receptor↗
PubMed1999

The health and cost effects of substituting home care for inpatient acute care: a review of the evidence.

BACKGROUND: There is much interest in reducing hospital stays by providing some health care services in patients' homes. The authors review the evidence regarding the effects of this acute care at home (acute home care) on the health of patients and caregivers and on the social costs (public and private costs) of managing the patients' health conditions. METHODS: MEDLINE and HEALTHSTAR databases were searched for articles using the key term "home care." Bibliographies of articles read were checked for additional references. Fourteen studies met the selection criteria (publication between 1975 and early 1998, evaluation of an acute home care program for adults, and use of a control group to evaluate the program). Of the 14, only 4 also satisfied 6 internal validity criteria (patients were eligible for home care, comparable patients in home care group and hospital care group, adequate patient sample size, appropriate analytical techniques, appropriate health measures and appropriate costing methods). RESULTS: The 4 studies with internal validity evaluated home care for 5 specific health conditions (hip fracture, hip replacement, chronic obstructive pulmonary disease [COPD], hysterectomy and knee replacement); 2 of the studies also evaluated home care for various medical and surgical conditions combined. Compared with hospital care, home care had no notable effects on patients' or caregivers' health. Social costs were not reported for hip fracture. They were unaffected for hip and knee replacement, and higher for COPD and hysterectomy; in the 2 studies of various conditions combined, social costs were higher in one and lower in the other. Effects on health system costs were mixed, with overall cost savings for hip fracture and higher costs for hip and knee replacement. INTERPRETATION: The limited existing evidence indicates that, compared with hospital care, acute home care produces no notable difference in health outcomes. The effects on social and health system costs appear to vary with condition. More well-designed evaluations are needed to determine the appropriate use of acute home care.

Acute Disease↗
PubMed1999

Characterization of the Tribolium Deformed ortholog and its ability to directly regulate Deformed target genes in the rescue of a Drosophila Deformed null mutant.

We have analyzed the Tribolium castaneum ortholog of the Drosophila homeotic gene Deformed (Dfd) and determined its expression pattern during embryogenesis in this beetle. Tc Deformed (Tc Dfd) is expressed in the blastoderm and the condensing germ rudiment in a region that gives rise to gnathal segments. During germ band extension Tc Dfd is expressed in the mandibular and maxillary segments, their appendages, and the dorsal ridge. Comparison of insect Dfd protein sequences reveals several highly conserved regions. To determine whether common molecular features reflect conserved regulatory functions we used the Gal4 system to express the Tribolium protein in Drosophila embryos. When Tc Dfd is expressed throughout embryonic ectoderm under the control of P69B, the beetle protein autoregulates the endogenous Dfd gene. In addition, the Drosophila proboscipedia gene (a normal target of Dfd) is ectopically activated in the antennal and thoracic segments. We also compared the ability of the beetle and fly proteins to rescue defects in Dfd- mutants by expressing each throughout the embryonic during embryogenesis. Both proteins rescued Dfd- defects to the same extent in that they each restore the development of mouth hooks and cirri, as well as cause gain-of-function abnormalities of posterior mouth parts. As before, pb was ectopically activated in the antennal segment. This is the first demonstration of the ability of a heterologous homeotic selector protein to directly regulate a target gene independent of an endogenous Drosophila autoregulatory loop.

Amino Acid Sequence↗
PubMed1999

Immediate autografting of bone in open fractures with bone loss of the hand: a preliminary report. Case reports.

Three patients with open fractures of the hand associated with bone loss were treated within four to six hours of injury by corticocancellous bone grafting and soft tissue coverage after meticulous debridement, copious irrigation of the wounds, and broad-spectrum antibiotics given intravenously. Long term follow-up was uneventful and showed that the graft had taken and healed well with early and full restoration of function and a good cosmetic result. Immediate corticocancellous bone grafting of an injured hand could be used in selected cases with well-debrided, surgically clean wounds as long as there is a rich blood supply. Adequate bone fixation, soft tissue coverage, and broad-spectrum antibiotics given intravenously will remove the risk of infection. Hand architecture is corrected while wound contracture and secondary deformity are avoided. Both patients' discomfort and hospital costs are considerably reduced.

Adult↗
PubMed1998

Augmented therapy of extensive Hodgkin's disease: radiation to known disease or prolongation of induction chemotherapy did not improve survival--results of a Cancer and Leukemia Group B study.

PURPOSE: This prospective randomized trial in extensive untreated Hodgkin's disease was undertaken to assess the potential benefit of augmented therapy (12 months chemotherapy or radiation to known disease) compared to standard 6 months chemotherapy. PATIENT AND METHODS: A total of 258 patients, mostly Stage IV, were randomized to four treatment regimens consisting of six cycles of CCNU, vinblastine, procarbazine, and prednisone (CVPP); 12 cycles of CVPP; six cycles of CVPP followed by 25 Gy radiotherapy; or three cycles CVPP, 25 Gy radiotherapy, and three cycles CVPP. RESULTS: Complete remissions were achieved in 65% of all patients. A 58% overall 5-year survival rate was obtained. Relapses in irradiated areas of known disease occurred in only 6% of responding patients. There was, however, no statistical difference in response frequency, disease-free survival, or overall survival among the four regimens. Elderly patients responded less frequently. CONCLUSION: While radiotherapy provided control of local (known) disease, no impact on overall survival was apparent. Likewise, doubling the duration of chemotherapy did not improve response or survival. Augmentation of therapy with either radiotherapy or more chemotherapy in this study was of no benefit compared to the standard 6 months of treatment.

Adult↗
PubMed1997

Care for Canada's frail elderly population: fragmentation or integration?

Budget constraints, technological advances and a growing elderly population have resulted in major reforms in health care systems across Canada. This has led to fewer and smaller acute care hospitals and increasing pressure on the primary care and continuing care networks. The present system of care for the frail elderly, who are particularly vulnerable, is characterized by fragmentation of services, negative incentives and the absence of accountability. This is turn leads to the inappropriate and costly use of health and social services, particularly in acute care hospitals and long-term care institutions. Canada needs to develop a publicly managed community-based system of primary care to provide integrated care for the frail elderly. The authors describe such a model, which would have clinical and financial responsibility for the full range of health and social services required by this population. This model would represent a major challenge and change for the existing system. Demonstration projects are needed to evaluate its cost-effectiveness and address issues raised by its introduction.

Aged↗
PubMed1997

FlyBase: a Drosophila database. The FlyBase consortium.

FlyBase is a database of genetic and molecular data concerning Drosophila. FlyBase is maintained as a relational database (in Sybase) and is made available as html documents and flat files. The scope of FlyBase includes: genes, alleles (and phenotypes), aberrations, transposons, pointers to sequence data, clones, stock lists, Drosophila workers and bibliographic references. The Encyclopedia of Drosophila is a joint effort between FlyBase and the Berkeley Drosophila Genome Project which integrates FlyBase data with those from the BDGP.

Animals↗
PubMed1997

Ulnar nerve injury at the elbow after steroid injection for medial epicondylitis.

We describe an accidental injury to the ulnar nerve at the elbow following steroid injection for medial epicondylitis in a patient with undetected recurrent dislocation of the nerve. The chalky substance found on exploration to intermingle with the nerve fascicles was removed and the nerve was placed under the flexor-pronator mass. After surgery, complete resolution of the epicondylar pain was noted, along with significant improvement in two-point discrimination of the ulnar digits. We recommend clinical assessment of the ulnar nerve location prior to injection to avoid injury. Should recurrent dislocation of the nerve be diagnosed, injection should be given cautiously, preferably with the elbow in an extended or semiflexed position.

Adult↗
PubMed1997

Partial lacerations of flexor tendons in children. Primary repair versus conservative treatment.

We compared the outcome of 17 partially lacerated (less than 75% of cross-sectional area) flexor tendons in children treated by surgical repair to that of 19 tendons treated conservatively by early mobilization. The outcome of both groups was similarly favourable. No complications, such as triggering or complete tendon tear, were found in either group. We advocate early mobilization in children in whom a partial division of the flexor tendon is diagnosed clinically. Exploration should be carried out only in doubtful cases to exclude complete division of the tendon.

Child↗
PubMed1997

The efficacy of an injection of steroids for medial epicondylitis. A prospective study of sixty elbows.

We report the details of a prospective, randomized, double-blind study that was undertaken to analyze the short-term and long-term effects of the local injection of methylprednisolone to treat medial epicondylitis. Fifty-eight patients (sixty elbows) were assigned to receive a single injection of 1 per cent lidocaine with either forty milligrams of methylprednisolone (experimental group) or saline solution (control group); both groups were also managed with physical therapy and the use of non-steroidal anti-inflammatory drugs. The two groups were not significantly different with regard to the age and gender of the patients, the duration of the symptoms, the degree of pain before the injection, or the number of dominant upper limbs involved. Six weeks after the injection, the experimental group had significantly less pain than the control group (p < 0.03), as determined with a modification of the grading system of Nirschl and Pettrone. However, the groups did not differ with regard to pain at three months and at one year. The intensity of pain, as measured on a visual-analog scale, did not differ between the two groups six weeks and one year after the injection. We believe that the improvement observed in both groups primarily reflects the natural history of the disorder, and we conclude that the local injection of steroids provides only short-term benefits in the treatment of medial epicondylitis.

Adult↗
PubMed1990

Feed that burn.

Explore the source record for details and available documents.

Burns↗
PubMed1990

Deep partial skin thickness burns: a reproducible animal model to study burn wound healing.

A reproducible deep partial skin thickness burn model using guinea-pigs to study the healing process of this injury is described. Round aluminium templates heated to 75 degrees C and applied for 5 s to the moistened, clipped and depilated dorsal skin produced the desired depth of injury. This model is applicable for the study of the three main components of the burn wound healing process: epithelialization, contraction and scar formation. It is recommended that the India ink injection technique be used to confirm the depth of the burn wound.

Animals↗
PubMed1989

Is postburn dermal ischaemia enhanced by oxygen free radicals?

The accumulated data suggest that oxygen free radicals are actively involved in the pathophysiology of the wound healing process. Since OH. and O2- directly correlate with the release of arachidonic acid and catalyse some of the enzymes participating in its cascade, their involvement in the enhancement of dermal ischaemia in the stasis zone is postulated. Experimental data using topically applied scavengers of superoxide have shown their beneficial effects on the burn wound healing process.

Burns↗