ABSTRACT
CONTEXT: Atypical femoral fractures (AFFs) are very rare atraumatic or mild trauma fractures in the subtrochanteric region or femoral shaft. Some unique genetic variants in Asian populations might confer susceptibility to AFF, since the incidence of AFFs is higher in Asian populations. OBJECTIVE: Because rare variants have been found to be causative in some diseases and the roles of osteomalacia causative genes have not been reported, we investigated rare variants in genes causing abnormal mineralization. METHODS: Exome sequencing was performed to detect variants in gene coding and boundary regions, and the frequencies of deleterious rare alleles were compared between Japanese patients with AFF (nâ =â 42) and controls of the 4.7KJPN panel of Tohoku Medical Megabank by whole genome sequencing (nâ =â 4773). RESULTS: The frequency of the deleterious rare allele of ENPP1 was significantly increased in AFF (Pâ =â .0012, corrected P [Pc]â =â .0155, OR 4.73, 95% CI 2.15-10.40). In multigene panel analysis, the frequencies of deleterious rare alleles of candidate genes were increased in AFF (Pâ =â .0025, OR 2.72, 95% CI 1.49-4.93). Principal component analysis of bone metabolism markers identified a subgroup of patients with AFF with higher frequencies of deleterious rare alleles in ENPP1 (Pâ =â 4.69 × 10-5, Pcâ =â .0006, OR 8.47, 95% CI 3.76-19.09) and the candidate genes (Pâ =â 1.08 × 10-5, OR 5.21, 95% CI 2.76-9.86). CONCLUSION: AFF is associated with genes including ENPP1 that cause abnormal mineralization, suggesting that osteomalacia is an underlying condition predisposing to AFF and that higher incident rates of AFFs in Asian populations might be explained by the genetic risk factors including ENPP1.
Subject(s)
Bone Density Conservation Agents , Bone Diseases , Familial Hypophosphatemic Rickets , Femoral Fractures , Osteomalacia , Alleles , Bone Density Conservation Agents/adverse effects , Bone Diseases/genetics , Diphosphonates/adverse effects , Familial Hypophosphatemic Rickets/complications , Female , Femoral Fractures/epidemiology , Femoral Fractures/genetics , Humans , Male , Osteomalacia/geneticsABSTRACT
BACKGROUND: Group A Streptococcus pyogenes (GAS) causes necrotizing soft tissue infections (NSTIs) necessitating exploration, surgical debridement, and possibly limb amputation. CASE PRESENTATION: A 45-year-old man presented with traumatic injury of the left carpal region, vomiting, and diarrhea. The swelling and pain in the left forearm worsened with sensorimotor deficits, and his skin color deteriorated. Emergent exploration was performed for limb preservation; GAS was detected in an exudate, and debridement was performed on postoperative day 2 for streptococcal toxic shock syndrome. He recovered uneventfully and was discharged; however, he returned after 2 months with GAS-induced STI at the same site and received antimicrobial treatment. CONCLUSION: Exploration and subsequent debridement are crucial for effective treatment of NSTI.
ABSTRACT
Ischemic neuropathy is common in subjects with critical limb ischemia, frequently causing chronic neuropathic pain. However, neuropathic pain caused by ischemia is hard to control despite the restoration of an adequate blood flow. Here, we used a rat model of ischemic-reperfusion nerve injury (IRI) to investigate possible effects of hepatocyte growth factor (HGF) against ischemic neuropathy. Hemagglutinating virus of Japan (HVJ) liposomes containing plasmids encoded with HGF was delivered into the peripheral nervous system by retrograde axonal transport following its repeated injections into the tibialis anterior muscle in the right hindlimb. First HGF gene transfer was done immediately after IRI, and repeated at 1, 2 and 3 weeks later. Rats with IRI exhibited pronounced mechanical allodynia and thermal hyperalgesia, decreased blood flow and skin temperature, and lowered thresholds of plantar stimuli in the hind paw. These were all significantly improved by HGF gene transfer, as also were sciatic nerve conduction velocity and muscle action potential amplitudes. Histologically, HGF gene transfer resulted in a significant increase of endoneurial microvessels in sciatic and tibial nerves and promoted nerve regeneration which were confirmed by morphometric analysis. Neovascularization was observed in the contralateral side of peripheral nerves as well. In addition, IRI elevated mRNA levels of P2X3 and P2Y1 receptors, and transient receptor potential vanilloid receptor subtype 1 (TRPV1) in sciatic nerves, dorsal root ganglia and spinal cord, and these elevated levels were inhibited by HGF gene transfer. In conclusion, HGF gene transfer is a potent candidate for treatment of acute ischemic neuropathy caused by reperfusion injury, because of robust angiogenesis and enhanced nerve regeneration.
Subject(s)
Genetic Therapy/methods , Hepatocyte Growth Factor/genetics , Neuralgia/therapy , Reperfusion Injury/therapy , Animals , Disease Models, Animal , Ganglia, Spinal/metabolism , Gene Transfer Techniques , Genetic Vectors , Hepatocyte Growth Factor/metabolism , Humans , Hyperalgesia/metabolism , Liposomes/metabolism , Male , Rats , Rats, Wistar , Sciatic Nerve/metabolism , Sendai virus/genetics , Treatment OutcomeABSTRACT
BACKGROUND: Plate fixation is an established method for treating unstable distal clavicle fractures. However, the appropriate timing of surgery for acute distal clavicle fractures remains unclear. The present study aimed to evaluate the clinical outcomes of osteosynthesis using a Scorpion plate and to assess the influence of surgery timing on the surgical outcomes for acute unstable distal clavicle fractures. METHODS: We retrospectively reviewed 105 patients who underwent fixation for acute unstable distal clavicle fractures (Neer type II and V) using the Scorpion plate between 2008 and 2018. Patients were divided into early (45 patients) and delayed (60 patients) treatment groups based on the timing of the surgical intervention (within or after 7 days). The outcomes were postoperative complications (nonunion, peri-implant fracture, plate loosening, plate-related pain, and stiffness). We evaluated the outcomes from X-ray radiographs and clinical notes. RESULTS: Among the 105 patients, nonunion, plate loosening, plate-related pain, and stiffness were observed in six patients (5.7%), four patients (3.8%), seven patients (6.7%), and one patient (1.0%), respectively. The nonunion rate was significantly higher in the delayed treatment group than that in the early treatment group (P = 0.036). Although the difference was not significant, plate loosening and stiffness were only observed in the delayed treatment group. CONCLUSION: Our results demonstrated that osteosynthesis using Scorpion plates achieved satisfactory surgical outcomes for unstable distal clavicle fractures. In addition, this study suggested that performing surgery within 6 days after injury is recommended to reduce postoperative complications.
Subject(s)
Bone Plates , Clavicle/injuries , Clavicle/surgery , Fracture Fixation, Internal/methods , Fractures, Bone/surgery , Operative Time , Adolescent , Adult , Aged , Aged, 80 and over , Clavicle/diagnostic imaging , Cohort Studies , Female , Fracture Fixation, Internal/instrumentation , Fractures, Bone/diagnostic imaging , Humans , Male , Middle Aged , Retrospective Studies , Treatment Outcome , Young AdultABSTRACT
BACKGROUND: Abscess formation in the subscapularis muscle is a rare clinical condition. Few reports are available regarding the treatment methods and surgical approaches for subscapularis intramuscular abscesses. Here, we describe a case of subscapularis intramuscular abscess that was treated successfully via surgical drainage using a new approach, the "dorsal subscapularis approach". CASE PRESENTATION: A 67-year-old woman presented to our hospital with complaints of fever and disturbance of consciousness. Two days prior to visiting our hospital, right shoulder pain and limited range of motion in the shoulder were noted. Cerebrospinal fluid examination and contrast-enhanced computed tomography (CT) imaging on admission revealed a right subscapularis intramuscular abscess with concomitant bacterial meningitis. The patient's clinical symptoms improved after antibiotic administration for 3 weeks, but the right shoulder pain persisted. Contrast-enhanced CT imaging performed after antibiotic administration revealed an abscess in the right shoulder joint space, in addition to a capsule of the abscess in the right subscapularis muscle. We performed open surgical drainage for the abscess, which had spread from the subscapularis muscle to the glenohumeral joint. Using the deltoid-pectoral approach, we detected exudate and infected granulation tissue in the joint cavity. Furthermore, we separated the dorsal side of the subscapularis muscle from the scapula using a raspatory and detected infected granulation tissue in the subscapularis muscle belly. We performed curettage and washed as much as possible. After surgery, antibiotic administration continued for 2 weeks. The patient's right shoulder pain subsided and CT performed 2 months after surgery revealed no recurrence of infection. CONCLUSIONS: The present case indicated that a subscapularis intramuscular abscess could lead to severe concomitant infections of other organs via the hematogenous route. Thus, early detection and treatment are necessary. Moreover, in this case, surgical drainage using a dorsal subscapularis approach was beneficial to treating the abscess, which had spread from the subscapularis muscle to the glenohumeral joint.
Subject(s)
Abscess/therapy , Arthritis, Infectious/therapy , Drainage/methods , Meningitis, Pneumococcal/therapy , Myositis/therapy , Shoulder Pain/surgery , Abscess/blood , Abscess/complications , Abscess/microbiology , Aged , Anti-Bacterial Agents/therapeutic use , Arthritis, Infectious/blood , Arthritis, Infectious/complications , Arthritis, Infectious/microbiology , Female , Humans , Meningitis, Pneumococcal/blood , Meningitis, Pneumococcal/diagnosis , Meningitis, Pneumococcal/microbiology , Myositis/microbiology , Rotator Cuff/diagnostic imaging , Rotator Cuff/microbiology , Rotator Cuff/surgery , Shoulder Joint/diagnostic imaging , Shoulder Joint/microbiology , Shoulder Joint/surgery , Shoulder Pain/etiology , Streptococcus pneumoniae/isolation & purification , Tomography, X-Ray Computed , Treatment OutcomeABSTRACT
BACKGROUND: Superior shoulder dislocation is a rare type of shoulder dislocation. Its occurrence is thought to be associated with rupture of the deltoid; however, few reports are available on the mechanism of onset and the treatment of a superior shoulder dislocation. Here we describe a case of dislocation in the direction of the posterior acromion, referred to as posterosuperior shoulder dislocation, caused by the traumatic rupture of deltoid posterior fibers. CASE PRESENTATION: An 83-year-old woman who fell on her right elbow in the hospital presented to our department with complaints of right shoulder pain. She had been undergoing conservative treatment for a massive rotator cuff tear and a rupture of the long head of biceps tendon 5 years previously. X-ray radiography images at the time of the trauma revealed that the right humeral head was dislocated upwards and in the direction of the posterior acromion. Magnetic resonance imaging (MRI) revealed newly ruptured deltoid posterior fibers, in addition to the massive rotator cuff tear. Closed reduction was performed and the shoulder joint was held in external rotation at 30 degrees for 6 weeks. However, re-dislocation was observed at an early stage after the removal of the orthosis and marked instability remained. CONCLUSIONS: This is the first case of posterosuperior shoulder dislocation. It suggests that rupture of the deltoid posterior fibers contributes to the onset of posterosuperior shoulder dislocation in patients with a massive rotator cuff tear. Moreover, in superior shoulder dislocation, conservative treatment may result in continuing instability which requires surgical treatment.
Subject(s)
Accidental Falls , Closed Fracture Reduction/instrumentation , Rotator Cuff Injuries/complications , Shoulder Dislocation/etiology , Aged, 80 and over , Female , Humans , Magnetic Resonance Imaging , Orthotic Devices , Recurrence , Rotator Cuff Injuries/diagnostic imaging , Rotator Cuff Injuries/surgery , Shoulder Dislocation/diagnostic imaging , Shoulder Dislocation/surgery , Treatment OutcomeABSTRACT
BACKGROUND: Intraosseous suture-button devices have been used for acromioclavicular joint reconstruction due to its relative simplicity compared with other procedures. However, the complications of acromioclavicular joint reconstruction using a suture-button are not fully understood. Here, we describe a case of a clavicle fracture at the suture hole following acromioclavicular joint reconstruction using a suture-button and hook plate. CASE PRESENTATION: A 28-year-old man presented at our hospital after a fall from his bicycle. The patient had a history of acromioclavicular joint reconstruction with a suture-button and a hook plate for right acromioclavicular joint dislocation, seven months ago at another hospital. The hook plate had been removed four months ago, while X-ray radiography before removal had shown the widening of a suture hole. In the current fall from the bicycle, X-ray radiography revealed a clavicle fracture through the previous drill hole for suture-button. We removed the suture-button and performed an open reduction and internal fixation for the clavicle fracture. CONCLUSION: The present case indicated that a clavicle fracture at the suture hole, although rare, is one of the complications after an acromioclavicular joint reconstruction using a suture-button. This case suggested that drilling to the necessary minimum when making suture holes and paying attention to the widening of suture holes are important to prevent a postoperative clavicle fracture.
Subject(s)
Acromioclavicular Joint/surgery , Clavicle/injuries , Fractures, Bone/etiology , Postoperative Complications/etiology , Suture Techniques/adverse effects , Accidental Falls , Acromioclavicular Joint/injuries , Adult , Bicycling , Clavicle/surgery , Humans , Joint Dislocations/surgery , Male , Suture Techniques/instrumentationABSTRACT
BACKGROUND: The epidemiological patterns of musculoskeletal injuries or disorders in military personnel have not been well documented and a better understanding is required for proper preventative measures and treatment. Here, we investigated musculoskeletal injuries or disorders among members of the Japan Self-Defense Forces. METHODS: All orthopedic patients (n = 22,340) who consulted to Japan Self-Defense Forces Hospitals were investigated for their type of injury or disorder, the injured body part, the mechanism, and the cause of injuries. RESULTS: Thirty-nine percent of the cases were classified as traumatic injuries, and 61% were classified as non-traumatic disorders. Of the traumatic injury patients, the injured body part was the upper extremity in 32%, the trunk in 23%, and the lower extremities in 45% of the cases. The most common injured body location was the knee followed by the hand/finger and ankle. Exercise was the most common cause of injury, followed by traffic accident and military training. Contusions were the most common traumatic injuries, followed by sprains and fractures. Of non-traumatic disorders, the lower extremities were reported as the injured part in 43% of the disorders. Lumbar spine disorders were the most common non-traumatic disorders, followed by tendon and joint disorders. CONCLUSIONS: Over one-third of orthopedic cases among members of the Japan Self-Defense Forces are traumatic injuries, with the knee being the body part most commonly injured and exercise being the leading cause of injury.
ABSTRACT
BACKGROUND: Shoulder rotational muscles act as dynamic stabilizers of the glenohumeral joint, and the recovery of muscle strength plays an important role in stabilizing the joint during postoperative rehabilitation. However, temporal changes in muscle strength after arthroscopic Bankart repair have not been clarified. PURPOSE: To better understand the temporal recovery of shoulder rotational muscle strength after arthroscopic Bankart repair. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Isokinetic concentric shoulder rotational muscle strength was evaluated in 50 patients who were diagnosed with recurrent dislocations of the glenohumeral joint and treated with arthroscopic Bankart repair. RESULTS: The mean peak torque/weight and total work were reduced significantly at 1.5 months after surgery (P < .0001) and returned to preoperative levels by 6 months for external rotation and 4.5 months for internal rotation. The contralateral peak torque ratios reached preoperative levels by 6 months after surgery. The ipsilateral peak torque ratios were reduced between 1.5 and 3 months after surgery and returned to preoperative levels at 6 months for external rotation and 4.5 months for internal rotation. CONCLUSION: Isokinetic shoulder rotational muscle strength after arthroscopic Bankart repair recovered to preoperative levels by 6 months for external rotation and 4.5 months for internal rotation.
ABSTRACT
Little is known regarding the incidence of the shoulder instability in Japan. The aim of this study was to evaluate the incidence of traumatic shoulder instability among Japanese military cadets. A prospective cohort study was performed to capture all traumatic shoulder instability events between 2009 and 2012 among cadets in a military educational academy of the Japan Self Defense Forces. The total number of cadets in the cohort was 5,402 (average age 20.6 years). The incidence of instability events, including dislocation or subluxation, was calculated. Chronicity, demographics of participants, mechanism of injury, and athletic events were also evaluated. The incidence of traumatic dislocation was 4.1/1,000 person-years and that of subluxation was 6.1/1,000 person-years. The incidence of primary dislocation or subluxation was 5.4/1,000 person-years and that of recurrent dislocation or subluxation was 4.7/1,000 person-years. Of first dislocations or subluxations, 92% occurred during sports activities, including after-school sports activities, military training, and gym classes. In conclusion, the overall incidence of shoulder instability events among Japanese military cadets was 10.3/1,000 person-years, and was extremely high. Most shoulder instability events occurred during sports activities, and a program to prevent such injuries during sports activities is necessary for young participants.
Subject(s)
Joint Instability/epidemiology , Military Personnel/statistics & numerical data , Shoulder Injuries , Adolescent , Athletic Injuries/epidemiology , Cohort Studies , Female , Humans , Incidence , Japan/epidemiology , Joint Dislocations/complications , Male , Prospective Studies , Risk Factors , Young AdultABSTRACT
A 55-year-old woman with incomplete spontaneous posterior interosseous nerve (PIN) palsy underwent interfascicular neurolysis and tendon transfer, 17 years after its onset. After one year, her nerve function partially recovered electrophysiologically. This case suggests that incomplete spontaneous PIN palsy may recover by interfascicular neurolysis, even with a long preoperative delay.
Subject(s)
Fingers/innervation , Nerve Block/methods , Paralysis/therapy , Peripheral Nerves/drug effects , Peripheral Nerves/surgery , Recovery of Function , Tendon Transfer/methods , Electromyography , Female , Follow-Up Studies , Humans , Middle Aged , Paralysis/diagnosis , Paralysis/physiopathology , Peripheral Nerves/physiopathology , Time FactorsABSTRACT
A 32-year-old male patient was admitted to the hospital with a pulsing mass of the right palm. He was an electrical construction engineer who frequently used a screwdriver. Computed tomography (CT) examination revealed a 22- × 30-mm saccular aneurysm of the right ulnar artery. The ulnar artery aneurysm was resected, and we could perform direct anastomosis of the ulnar artery. The dilated true aneurysm was compatible with a traumatic origin. A postoperative enhanced CT examination showed smooth reconstruction of the palmar arch. An occupational true aneurysm of the ulnar artery could be treated by resection and direct anastomosis.
ABSTRACT
Glucagon-like peptide-1 (GLP-1) is glucose-dependent insulinotropic hormone secreted from enteroendocrine L cells. Its long-acting analogue, exendin-4, is equipotent to GLP-1 and is used to treat type 2 diabetes mellitus. In addition, exendin-4 has effects on the central and peripheral nervous system. In this study, we administered repeated intraperitoneal (i.p.) injections of exendin-4 to examine whether exendin-4 is able to facilitate the recovery after the crush nerve injury. Exendin-4 injection was started immediately after crush injury and was repeated every day for subsequent 14 days. Rats subjected to sciatic nerve crush exhibited marked functional loss, electrophysiological dysfunction, and atrophy of the tibialis anterior muscle (TA). All these changes, except for the atrophy of TA, were improved significantly by the administration of exendin-4. Functional, electrophysiological, and morphological parameters indicated significant enhancement of nerve regeneration 4 weeks after nerve crush. These results suggest that exendin-4 is feasible for clinical application to treat peripheral nerve injury.
Subject(s)
Nerve Crush , Nerve Regeneration/drug effects , Peptides/pharmacology , Peptides/therapeutic use , Receptors, Glucagon/agonists , Sciatic Nerve/drug effects , Sciatic Nerve/physiopathology , Venoms/pharmacology , Venoms/therapeutic use , Animals , Axons/drug effects , Axons/pathology , Electrophysiological Phenomena/drug effects , Exenatide , Glucagon-Like Peptide-1 Receptor , Muscle, Skeletal/drug effects , Muscle, Skeletal/innervation , Muscle, Skeletal/pathology , Muscle, Skeletal/physiopathology , Myelin Sheath/drug effects , Myelin Sheath/pathology , Rats , Rats, Wistar , Sciatic Nerve/ultrastructureABSTRACT
In the field of orthopaedic surgery, an orthopaedic surgeon sometimes requires to suppress excessive bone formation, such as ectopic bone formation, ossifying myositis and radio-ulnar synostosis, etc. Ultraviolet (UV) light irradiation of a photocrosslinkable chitosan (Az-CH-LA) generates an insoluble hydrogel within 30 s. The purpose of this study was to evaluate the ability of the photocrosslinked chitosan hydrogel (PCH) to inhibit bone formation in an experimental model of bone defect. Rat calvarium and fibula were surgically injured and PCH was implanted into the resultant bone defects. The PCH implants significantly prevented bone formation in the bone defects during the 4 and 8 week observation periods. In the PCH-treated defects, fibrous tissues infiltrated by inflammatory cells were formed by day 7, completely filling the bone defects. In addition to these findings, expression of osteocalcin and runt-related gene 2 (RUNX2) mRNA, both markers of bone formation, was lower in the PCH-treated defects than in the controls. In contrast, collagen type 1α2 and α-smooth muscle actin (α-SMA) mRNA levels were significantly higher in the PCH-treated defects after 1 week. PCH stimulated the formation of fibrous tissue in bone defects while inhibiting bone formation. Thus, PCH might be a promising new therapeutic biomaterial for the prevention of bone formation in orthopaedic surgery.
Subject(s)
Chitosan/chemistry , Fibula/pathology , Hydrogels , Ossification, Heterotopic/prevention & control , Skull/pathology , Synostosis/prevention & control , Ultraviolet Rays , Animals , Biocompatible Materials/chemistry , Chitin/chemistry , Cross-Linking Reagents/chemistry , Gene Expression Profiling , Immunohistochemistry , Inflammation , Light , Male , Orthopedics/methods , Polymers/chemistry , Rats , Rats, Sprague-Dawley , Time FactorsABSTRACT
BACKGROUND: Gene transduction has been considered advantageous for the sustained delivery of proteins to specific target tissues. However, in the case of hard tissues, such as bone, local gene delivery remains problematic owing to anatomical accessibility limitations of the target sites. METHODOLOGY/PRINCIPAL FINDINGS: Here, we evaluated the feasibility of exogenous gene transduction in the interior of bone via axonal transport following intramuscular administration of a nonviral vector. A high expression level of the transduced gene was achieved in the tibia ipsilateral to the injected tibialis anterior muscle, as well as in the ipsilateral sciatic nerve and dorsal root ganglia. In sciatic transection rats, the gene expression level was significantly lowered in bone. CONCLUSIONS/SIGNIFICANCE: These results suggest that axonal transport is critical for gene transduction. Our study may provide a basis for developing therapeutic methods for efficient gene delivery into hard tissues.
Subject(s)
Axonal Transport , Bone and Bones/metabolism , Genetic Therapy/methods , Transduction, Genetic/methods , Animals , Genetic Vectors/genetics , Genetic Vectors/metabolism , Male , Plasmids/genetics , Plasmids/metabolism , Rats , Rats, WistarABSTRACT
Musician's dystonia is a type of task specific dystonia for which the pathophysiology is not clear. In this study, we performed functional magnetic resonance imaging to investigate the motor-related brain activity associated with musician's dystonia. We compared brain activities measured from subjects with focal hand dystonia and normal (control) musicians during right-hand, left-hand, and both-hands tapping tasks. We found activations in the thalamus and the basal ganglia during the tapping tasks in the control group but not in the dystonia group. For both groups, we detected significant activations in the contralateral sensorimotor areas, including the premotor area and cerebellum, during each tapping task. Moreover, direct comparison between the dystonia and control groups showed that the dystonia group had greater activity in the ipsilateral premotor area during the right-hand tapping task and less activity in the left cerebellum during the both-hands tapping task. Thus, the dystonic musicians showed irregular activation patterns in the motor-association system. We suggest that irregular neural activity patterns in dystonic subjects reflect dystonic neural malfunction and consequent compensatory activity to maintain appropriate voluntary movements.
Subject(s)
Dystonic Disorders/physiopathology , Hand/physiopathology , Movement Disorders/physiopathology , Music/psychology , Nerve Net/physiopathology , Occupational Diseases/physiopathology , Adult , Cerebellum/anatomy & histology , Cerebellum/physiopathology , Dystonic Disorders/diagnosis , Evoked Potentials, Motor/physiology , Female , Functional Laterality/physiology , Hand/innervation , Humans , Magnetic Resonance Imaging , Male , Motor Cortex/anatomy & histology , Motor Cortex/physiopathology , Movement Disorders/diagnosis , Nerve Net/anatomy & histology , Neuropsychological Tests , Occupational Diseases/diagnosis , Psychomotor Performance/physiology , Young AdultABSTRACT
When the CD4(+)CD8(+) thymic lymphoma cells were treated with puromycin, we found that most of the cells died at 0.3-1 microg/ml of puromycin within 24h. However, cell death was greatly reduced when the dose of puromycin was increased. Similar dose-pattern of cell death was observed in thymocytes and the sensitivity to puromycin was greater in CD4(+)CD8(+) thymocytes than CD4(+)CD8(-) thymocytes. The induction of apoptosis was blocked by the protein synthesis inhibitor cycloheximide, and to some extent by transfection of Bcl-xL or Bcl-2 genes. Expression of GRP78 was up-regulated after treatment with a small dose of puromycin, and the cell death by puromycin was blocked in the presence of caspase 12 inhibitor. These results indicated that the induction of cell death by low-dose puromycin was due to endoplasmic reticulum stress. Furthermore, we found that dexamethasone, a synthetic glucocorticoid, and puromycin worked synergistically to induce cell death in thymocytes.