Morbidity and Mortality Trends in Preterm Infants of <32 Weeks Gestational Age with Severe Intraventricular Hemorrhage : A 14-Year Single-Center Retrospective Study

Objective@#: Owing to advances in critical care treatment, the overall survival rate of preterm infants born at a gestational age (GA) 7 days after birth) for infants with severe IVH significantly improved over time, decreasing from 39.1% in phase I to 14.3% in phase II (p=0.043). A history of hypotension treated with vasoactive medication within 1 week after birth (adjusted odds ratio, 7.39; p=0.025) was found to be an independent risk factor for mortality. When comparing major morbidities of surviving infants, those in phase II were significantly more likely to have undergone surgery for necrotizing enterocolitis (NEC) (29.2% vs. 0.0%; p=0.027). Additionally, rates of late-onset sepsis (45.8% vs. 14.3%; p=0.049) and central nervous system infection (25.0% vs. 0.0%; p=0.049) were significantly higher in phase II survivors than in phase I survivors. @*Conclusion@#: In-hospital mortality in preterm infants with severe IVH decreased over the last decade, whereas major neonatal morbidities increased, particularly surgical NEC and sepsis. This study suggests the importance of multidisciplinary specialized medical and surgical neonatal intensive care in preterm infants with severe IVH.

Intraventricular Antimicrobial Therapy for Intractable Ventriculitis:Two Case Reports

It is challenging to treat ventriculitis with parenteral treatment alone in some cases because of the difficulty involved in maintaining an appropriate level of antibiotics in cerebrospinal fluid (CSF). We report two cases of ventriculitis who did not respond to intravenous (IV) antibiotics but were successfully treated with intraventricular antibiotics using IV agents. The first case was a four-month-old male patient with X-linked hydrocephalus.He showed ventriculitis due to Klebsiella pneumoniae not producing extended-spectrum β-lactamase and susceptible to third-generation cephalosporins and gentamicin, following ventriculoperitoneal (VP) shunt. His condition did not improve during the 47 days of treatment with IV cefotaxime and meropenem. We achieved improvement in clinical presentation and CSF profile after three times of intraventricular gentamicin injection. The patient was discharged from the hospital with antiepileptic drugs. The second case was a six-month-old female patient with a history of neonatal meningitis complicated with hydrocephalus at one month of age, VP shunt at two months of age, followed by a methicillinresistant coagulase-negative staphylococci (CoNS) shunt infection with ventriculitis after the shunt operation. CoNS ventriculitis recurred four weeks later. We failed to treat intractable methicillin-resistant CoNS ventriculitis with IV vancomycin for ten days, and thus intraventricular antimicrobial treatment was considered. Five times of intraventricular vancomycin administration led to improvement in clinical parameters. There were only neurological sequelae of delayed language development but no other major complications. Patients in these two cases responded well to intraventricular antibiotics, with negative CSF culture results, and were successfully treated for ventriculitis without serious complications.

Pediatric Minor Traumatic Brain Injury : Growing Skull Fracture, Traumatic Cerebrospinal Fluid Leakage, Concussion

Traumatic brain injury (TBI) is a major public health issue that causes significant morbidity and mortality in the pediatric population. Pediatric minor TBIs are the most common and are widely underreported because not all patients seek medical attention. The specific management of these patients is distinct from that of adult patients because of the different physiologies in these age groups. This article focuses on minor TBIs, particularly growing skull fractures, traumatic cerebrospinal fluid leakage, and concussion.

Human Induced Pluripotent Stem Cells: Clinical Significance and Applications in Neurologic Diseases

The generation of human induced pluripotent stem cells (iPSCs) from somatic cells using gene transfer opens new areas for precision medicine with personalized cell therapy and encourages the discovery of essential platforms for targeted drug development. iPSCs retain the genome of the donor, may regenerate indefinitely, and undergo differentiation into virtually any cell type of interest using a range of published protocols. There has been enormous interest among researchers regarding the application of iPSC technology to regenerative medicine and human disease modeling, in particular, modeling of neurologic diseases using patient-specific iPSCs. For instance, Parkinson’s disease, Alzheimer’s disease, and spinal cord injuries may be treated with iPSC therapy or replacement tissues obtained from iPSCs. In this review, we discuss the work so far on generation and characterization of iPSCs and focus on recent advances in the use of human iPSCs in clinical setting.

Human Induced Pluripotent Stem Cells: Clinical Significance and Applications in Neurologic Diseases

The generation of human induced pluripotent stem cells (iPSCs) from somatic cells using gene transfer opens new areas for precision medicine with personalized cell therapy and encourages the discovery of essential platforms for targeted drug development. iPSCs retain the genome of the donor, may regenerate indefinitely, and undergo differentiation into virtually any cell type of interest using a range of published protocols. There has been enormous interest among researchers regarding the application of iPSC technology to regenerative medicine and human disease modeling, in particular, modeling of neurologic diseases using patient-specific iPSCs. For instance, Parkinson’s disease, Alzheimer’s disease, and spinal cord injuries may be treated with iPSC therapy or replacement tissues obtained from iPSCs. In this review, we discuss the work so far on generation and characterization of iPSCs and focus on recent advances in the use of human iPSCs in clinical setting.

S100ß, Matrix Metalloproteinase-9, D-dimer, and Heat Shock Protein 70 Are Serologic Biomarkers of Acute Cerebral Infarction in a Mouse Model of Transient MCA Occlusion

OBJECTIVE: Diagnosing acute cerebral infarction is crucial in determining prognosis of stroke patients. Although many serologic tests for prompt diagnosis are available, the clinical application of serologic tests is currently limited. We investigated whether S100β, matrix metalloproteinase-9 (MMP-9), D-dimer, and heat shock protein 70 (HSP70) can be used as biomarkers for acute cerebral infarction.METHODS: Focal cerebral ischemia was induced using the modified intraluminal filament technique. Mice were randomly assigned to 30-minute occlusion (n=10), 60-minute occlusion (n=10), or sham (n=5) groups. Four hours later, neurological deficits were evaluated and blood samples were obtained. Infarction volumes were calculated and plasma S100β, MMP-9, D-dimer, and HSP70 levels were measured using enzyme-linked immunosorbent assay.RESULTS: The average infarction volume was 12.32±2.31 mm³ and 46.9±7.43 mm³ in the 30- and 60-minute groups, respectively. The mean neurological score in the two ischemic groups was 1.6±0.55 and 3.2±0.70, respectively. S100β, MMP-9, and HSP70 expressions significantly increased after 4 hours of ischemia (p=0.001). Furthermore, S100β and MMP-9 expressions correlated with infarction volumes (p < 0.001) and neurological deficits (p < 0.001). There was no significant difference in D-dimer expression between groups (p=0.843). The area under the receiver operating characteristic curve (AUC) showed high sensitivity and specificity for MMP-9, HSP70 (AUC=1), and S100β (AUC=0.98).CONCLUSION: S100β, MMP-9, and HSP70 can complement current diagnostic tools to assess cerebral infarction, suggesting their use as potential biomarkers for acute cerebral infarction.

The Potential of Diffusion-Weighted Magnetic Resonance Imaging for Predicting the Outcomes of Chronic Subdural Hematomas

OBJECTIVE: Diffusion-weighted magnetic resonance imaging (DW-MRI) has proven useful in the study of the natural history of ischemic stroke. However, the potential of DW-MRI for the evaluation of chronic subdural hematoma (CSDH) has not been established. In this study, we investigated DW-MRI findings of CSDH and evaluated the impact of the image findings on postoperative outcomes of CSDH.METHODS: We studied 131 CSDH patients who had undergone single burr hole drainage surgery. The images of the subdural hematomas on preoperative DW-MRI and computed tomography (CT) were divided into three groups based on their signal intensity and density: 1) homogeneous (iso or low) density on CT and homogeneous low signal intensity on DW-MRI; 2) homogeneous (iso or low) density on CT and mixed signal intensity on DW-MRI; and 3) heterogeneous density on CT and mixed signal intensity on DW-MRI. On the basis of postoperative CT, we also divided the patients into 3 groups of surgical outcomes according to residual hematoma and mass effect.RESULTS: Analysis showed statistically significant differences in surgical (A to B: p < 0.001, A to C: p < 0.001, B to C: p=0.129) and functional (A to B: p=0.039, A to C: p < 0.001, B to C: p=0.108) outcomes and treatment failure rates (A to B: p=0.037, A to C: p=0.03, B to C: p=1) between the study groups. In particular, group B and group C showed worse outcomes and higher treatment failure rates than group A.CONCLUSION: CSDH with homogeneous density on CT was characterized by signal intensity on DW-MRI. In CSDH patients, performing DW-MRI as well as CT helps to predict postoperative treatment failure or complications.

S100ß, Matrix Metalloproteinase-9, D-dimer, and Heat Shock Protein 70 Are Serologic Biomarkers of Acute Cerebral Infarction in a Mouse Model of Transient MCA Occlusion

OBJECTIVE: Diagnosing acute cerebral infarction is crucial in determining prognosis of stroke patients. Although many serologic tests for prompt diagnosis are available, the clinical application of serologic tests is currently limited. We investigated whether S100β, matrix metalloproteinase-9 (MMP-9), D-dimer, and heat shock protein 70 (HSP70) can be used as biomarkers for acute cerebral infarction. METHODS: Focal cerebral ischemia was induced using the modified intraluminal filament technique. Mice were randomly assigned to 30-minute occlusion (n=10), 60-minute occlusion (n=10), or sham (n=5) groups. Four hours later, neurological deficits were evaluated and blood samples were obtained. Infarction volumes were calculated and plasma S100β, MMP-9, D-dimer, and HSP70 levels were measured using enzyme-linked immunosorbent assay. RESULTS: The average infarction volume was 12.32±2.31 mm³ and 46.9±7.43 mm³ in the 30- and 60-minute groups, respectively. The mean neurological score in the two ischemic groups was 1.6±0.55 and 3.2±0.70, respectively. S100β, MMP-9, and HSP70 expressions significantly increased after 4 hours of ischemia (p=0.001). Furthermore, S100β and MMP-9 expressions correlated with infarction volumes (p < 0.001) and neurological deficits (p < 0.001). There was no significant difference in D-dimer expression between groups (p=0.843). The area under the receiver operating characteristic curve (AUC) showed high sensitivity and specificity for MMP-9, HSP70 (AUC=1), and S100β (AUC=0.98). CONCLUSION: S100β, MMP-9, and HSP70 can complement current diagnostic tools to assess cerebral infarction, suggesting their use as potential biomarkers for acute cerebral infarction.

The Potential of Diffusion-Weighted Magnetic Resonance Imaging for Predicting the Outcomes of Chronic Subdural Hematomas

OBJECTIVE: Diffusion-weighted magnetic resonance imaging (DW-MRI) has proven useful in the study of the natural history of ischemic stroke. However, the potential of DW-MRI for the evaluation of chronic subdural hematoma (CSDH) has not been established. In this study, we investigated DW-MRI findings of CSDH and evaluated the impact of the image findings on postoperative outcomes of CSDH. METHODS: We studied 131 CSDH patients who had undergone single burr hole drainage surgery. The images of the subdural hematomas on preoperative DW-MRI and computed tomography (CT) were divided into three groups based on their signal intensity and density: 1) homogeneous (iso or low) density on CT and homogeneous low signal intensity on DW-MRI; 2) homogeneous (iso or low) density on CT and mixed signal intensity on DW-MRI; and 3) heterogeneous density on CT and mixed signal intensity on DW-MRI. On the basis of postoperative CT, we also divided the patients into 3 groups of surgical outcomes according to residual hematoma and mass effect. RESULTS: Analysis showed statistically significant differences in surgical (A to B: p < 0.001, A to C: p < 0.001, B to C: p=0.129) and functional (A to B: p=0.039, A to C: p < 0.001, B to C: p=0.108) outcomes and treatment failure rates (A to B: p=0.037, A to C: p=0.03, B to C: p=1) between the study groups. In particular, group B and group C showed worse outcomes and higher treatment failure rates than group A. CONCLUSION: CSDH with homogeneous density on CT was characterized by signal intensity on DW-MRI. In CSDH patients, performing DW-MRI as well as CT helps to predict postoperative treatment failure or complications.

Clinical Results of Odontoid Fractures according to a Modified, Treatment-Oriented Classification

OBJECTIVE: Odontoid fracture is common in cervical injury, representing about 20% of total cervical fractures. Classic odontoid fracture classification focused on anatomy of fracture site has no treatment recommendation and a modified treatment-oriented classification of odontoid fracture was suggested in 2005. We reviewed our odontoid fracture patients to assess the feasibility and efficacy of Grauer's classification. METHODS: Between October 2000 and September 2015, we collected data from patients who came to our institute for odontoid fracture. Demographic data of patients was reviewed, and neck visual analog scale (VAS) score and fusion rate were assessed by reviewing electronic medical records retrospectively. RESULTS: Sixty-nine patients out of a total of eighty two odontoid fracture patients were reviewed according to Grauer's classification. Neck VAS of all subtypes in odontoid fracture classification were decreased at last follow-up (p=0.001). Overall fusion rate was 88.4% at last follow-up. Concordance rate between Grauer's recommendation and our treatment was 69.9%, especially in type II with the concordance higher than 80%. Complication was minimal representing 7.2%, only in types I and III. CONCLUSION: In this study, there were statistically significant improvement in all subtypes in terms of neck VAS at the last follow up, especially in types II and III. Grauer's classification appears to be meaningful to decide treatment plan for odontoid fractures, especially type II odontoid fracture.

Associations of Upper Arm and Thigh Circumferences with Dementia and Depression in Korean Elders

OBJECTIVE: Previous studies have reported an association between weight loss and cognitive impairment. Changes in anthropometric measurements, such as arm and thigh circumferences, are associated with body mass changes and physical activity. Our aim was to investigate the association of upper arm and thigh circumferences with dementia and depression in the community-dwelling elderly population. METHODS: In total, 2,498 community residents aged 65 years or over were clinically assessed for dementia using the Korean version of the Community Screening Interview for Dementia. Depression was also assessed using the Korean version of the Geriatric Mental State Schedule B3. Arm and thigh circumferences were measured. Complex sample logistic regression was performed to evaluate associations of changes in anthropometric measurements with dementia/depression after controlling for other covariates. RESULTS: In the adjusted analyses, there was an independent association between dementia and arm circumference (OR=1.12; 95% CI=1.06–1.19). This association was significant in the females (OR=1.12; 95% CI=1.05–1.19) but not in males (OR=1.07; 95% CI=0.93–1.28). The association between dementia and thigh circumference was not significant in the adjusted analysis (OR=1.03; 95% CI=0.99–1.07). No significant association was found between either upper arm or thigh circumference and depression. CONCLUSION: In the older female Korean population, decreased upper arm circumference was associated with dementia and may represent a biological marker for this condition. This association may be explained by nutritional deficits or decreased physical activity.

Subdural Hematoma without Subarachnoid Hemorrhage Caused by the Rupture of Middle Cerebral Artery Aneurysm

Pure subdural hematomas caused by a ruptured intracranial aneurysm are extremely rare. We describe the case of a 42-year-old woman who presented with headache without evidence of head trauma. Magnetic resonance angiography and conventional cerebral angiography revealed a ruptured aneurysm at the right middle cerebral artery bifurcation. The patient underwent surgical treatment and had a good outcome without any neurological deficit. The mechanisms and clinical characteristics of this condition are discussed.

The Use of Gentamicin-Impregnated Collagen Sponge for Reducing Surgical Site Infection after Spine Surgery

OBJECTIVE: Surgical site infection (SSI) is the one of the most frequent complications in hospitalized patients, and it extends hospital stays and causes extra morbidities. To reduce SSI after spine surgery, we applied the gentamicin-impregnated collagen sponge (Collatamp G) during the operation and analyzed the results retrospectively. METHODS: Between October 2012 and December 2015, we collected data who applied the Collatamp G in spine surgery at a single institution. Demographic data of patients and another possible risk factors of SSI were also included, and we assessed the correlation between the risk factors and the developing of SSI by reviewing electronic medical records retrospectively. RESULTS: Three percent of all patients (10 of 280) developed the SSI and only 0.8% of patients who applied Collatamp G developed SSI (1 of 119). Otherwise, 5% of patients who did not apply Collatamp G developed SSI (9 of 161) (p=0.034). We also analyzed the correlation between SSI and other potential risk factors but nothings showed statistical correlation with SSI. CONCLUSION: In this study, there were statistically significant results that SSI rate was decreased in the group of patients using Collatamp G in spine surgery generally. However, further studies are required to resolve some limitations in the future.

Closure of Myelomeningocele Defects Using a Limberg Flap or Direct Repair

BACKGROUND: The global prevalence of myelomeningocele has been reported to be 0.8-1 per 1,000 live births. Early closure of the defect is considered to be the standard of care. Various surgical methods have been reported, such as primary skin closure, local skin flaps, musculocutaneous flaps, and skin grafts. The aim of this study was to describe the clinical characteristics of myelomeningocele defects and present the surgical outcomes of recent cases of myelomeningocele at our institution. METHODS: Patients who underwent surgical closure of myelomeningocele at our institution from January 2004 to December 2013 were included in this study. A retrospective chart review of their medical records was performed, and comorbidities, defect size, location, surgical procedures, complications, and the final results were analyzed. RESULTS: A total of 14 patients underwent surgical closure for myelomeningocele defects. Twelve cases were closed with direct skin repair, while two cases required local skin flaps to cover the skin defects. Three cases of infection occurred, requiring incision and either drainage or removal of allogenic materials. One case of partial flap necrosis occurred, requiring secondary revision using a rotational flap and a full-thickness skin graft. Despite these complications, all wounds eventually healed completely. CONCLUSIONS: Most myelomeningocele defects can be managed by direct skin repair alone. In cases of large defects, in which direct repair is not possible, local flaps may be used to cover the defect. Complications such as wound dehiscence and partial flap necrosis occurred in this study; however, all such complications were successfully managed with simple ancillary procedures.

Development of a Korean Version of the Perceived Deficits Questionnaire-Depression for Patients with Major Depressive Disorder

OBJECTIVE: Cognitive symptoms are an important component of depression and the Perceived Deficits Questionnaire-Depression is one of only a few instruments available for the subjective assessment of cognitive dysfunction in depression. Thus, the present study aimed to validate a Korean version of the PDQ-D (K-PDQ-D) using patients with major depressive disorder (MDD). METHODS: This study included 128 MDD patients who were assessed at study entry and 86 of these patients were then completed 12 weeks of antidepressant monotherapy. All subjects were assessed with the K-PDQ-D, the Montgomery-Asberg Depression Rating Scale (MADRS), the Sheehan Disability Scale (SDS), the EuroQol-5 dimensions questionnaire (EQ-5D), and the number of sick leave days taken in the previous week. The internal consistency, Guttman's split-half and test-retest reliabilities, factorial analyses, and concurrent and predictive validities of the K-PDQ-D were investigated. RESULTS: The K-PDQ-D exhibited excellent internal consistency and reliabilities, and was composed of four factors with high coefficients of determination. The concurrent validity analyses revealed that the K-PDQ-D scores were significantly correlated with the MADRS, SDS, and EQ-5D scores and the number of sick leave days taken. The K-PDQ-D scores at study entry significantly predicted changes in sick leave days and EQ-5D score from study entry to the 12-week endpoint. CONCLUSION: The newly developed K-PDQ-D is a reliable and valid instrument for the evaluation of subjective cognitive symptoms in MDD patients. The K-PDQ-D may assist in the gathering of unique information regarding subjective cognitive complaints, which is important for the comprehensive evaluation of patients with MDD.

Development and Growth of the Normal Cranial Vault : An Embryologic Review

Understanding the development of a skull deformity requires an understanding of the normal morphogenesis of the cranium. Craniosynostosis is the premature, pathologic ossification of one or more cranial sutures leading to skull deformities. A review of the English medical literature using textbooks and standard search engines was performed to gather information about the prenatal development and growth of the cranial vault of the neurocranium. A process of morphogenic sequencing begins during prenatal development and growth, continues postnatally, and contributes to the basis for the differential manner of growth of cranial vault bones. This improved knowledge might facilitate comprehension of the pathophysiology of craniosynostosis.

Is Routine Repeated Head CT Necessary for All Pediatric Traumatic Brain Injury?

OBJECTIVE: Repeated computed tomography (CT) follow up for traumatic brain injury (TBI) patients is often performed. But there is debate the indication for repeated CT scans, especially in pediatric patients. Purpose of our study is to find risk factors of progression on repeated CT and delayed surgical intervention based on the repeated head CT. METHODS: Between March, 2007 and December, 2013, 269 pediatric patients (age 0-18 years) had admitted to our hospital for head trauma. Patients were classified into 8 subgroups according to mechanisms of injury. Types, amount of hemorrhage and amount changes on repeated CT were analyzed as well as initial Glasgow Coma Scale (GCS) scores. RESULTS: Within our cohort of 269 patients, 174 patients received repeat CT. There were progression in the amount of hemorrhage in 48 (27.6%) patients. Among various hemorrhage types, epidural hemorrhage (EDH) more than 10 cc measured in initial CT was found to be at risk of delayed surgical intervention significantly after routine repeated CT with or without neurological deterioration than other types of hemorrhage. Based on initial GCS, severe head trauma group (GCS 3-8) was at risk of delayed surgical intervention after routine repeated CT without change of clinical neurologic status. CONCLUSION: We suggest that the patients with EDH more than 10 cc or GCS below 9 should receive repeated head CT even though absence of significant clinical deterioration.

Unusual Presentation of Cerebral Cavernous Malformation

Cerebral cavernous malformations (CMs) are vascular malformations of the central nervous system, which can be detected in the absence of any clinical symptoms. Nodules and cysts with mixed signal intensity and a peripheral hemosiderin rim are considered brain magnetic resonance imaging (MRI) findings typical of CMs. A 48-year-old man was admitted to our hospital because of abnormal MRI findings without significant neurological symptoms. A cyst with an internal fluid-fluid level was found in the left basal ganglia on the initial brain MRI. We decided to observe the natural course of the asymptomatic lesion with serial MRI follow-up. On MRI at the 5-month follow-up, the cystic mass was enlarged and showed findings consistent with those of cystic CM. Surgical resection was performed and the pathological diagnosis was CM. Our experience suggests that the initial presentation of a CM can be a pure cyst and neurosurgeons should consider the likelihood of CMs in cases of cystic cerebral lesions with intracystic hemorrhage.

Predictors of Outcome in Patients with Cervical Spondylotic Myelopathy Undergoing Unilateral Open-Door Laminoplasty

OBJECTIVE: This study aimed to analyze prognostic factors affecting surgical outcomes of expansive laminoplasty for cervical spondylotic myelopathy (CSM). METHODS: Using the Frankel scale and Japanese Orthopaedic Association (JOA) scale, we retrospectively reviewed the outcomes of 45 consecutive patients who underwent modified unilateral open-door laminoplasty using hydroxyapatite spacers and malleable titanium miniplates between June 2008 and May 2014. The patients were assigned to the good and poor clinical outcome groups, with good outcome defined as a JOA recovery rate >75%. RESULTS: The mean preoperative JOA scale was significantly higher in the good outcome group (14.95+/-3.21 vs. 10.78+/-6.07, p<0.001), whereas the preoperative cervical range of motion (ROM) in this group was significantly lower (29.89degrees+/-10.11 vs. 44.35degrees+/- 8.88, p<0.001). In univariate analysis, a high preoperative JOA scale (odds ratio (OR) 1.271, 95% confidence interval (CI) 1.005-1.607) and low preoperative cervical ROM(OR 0.858, 95% CI 0.786-0.936) were statistically correlated with good outcomes. Furthermore, these factors demonstrated an independent association with clinical outcomes (preoperative JOA scale: OR 1.344, 95% CI 1.019-1.774, p=0.036; preoperative cervical ROM: OR 0.860, 95% CI 0.788-0.940, p=0.001). CONCLUSION: In this study, a high preoperative JOA scale was associated with good clinical outcome after laminoplasty, whereas a higher preoperative cervical spine ROM was associated with poor clinical outcome. This may suggests that cervical mobility and preoperative neurological status affect clinical outcomes of laminoplasty.

Insulin Phosphorylates Tyrosine Residue 464 of Tub and Translocates Tubby into the Nucleus in HIRcB Cells

BACKGROUND: The tubby protein has a motif that might be relevant for its action in the insulin signaling pathway. Previous studies have indicated that tubby undergoes phosphorylation on tyrosine residues in response to several stimuli and is known to localize in the nucleus as well as in the plasma membrane. However, the relationship between phosphorylation and nuclear translocation is not well understood. Here, we report that insulin directly phosphorylates tubby, which translocates into the nucleus. METHODS: The effects of insulin on Tubby were performed with Western blot. The immunoprecipitation and confocal microscopy were performed to prove phosphorylation and nuclear translocation. RESULTS: Mutation study reveals that tyrosine residue 464 of tubby gene (Tub) is a phosphorylation site activated by insulin. In addition, major portions of tubby protein in the plasma membrane are translocated into the nucleus after insulin treatment. Tyrosine kinase inhibitor pretreatment blocked insulin-induced tubby translocation, suggesting that phosphorylation is important for nuclear translocation. Moreover, mutant tyrosine residue 464 did not translocate into the nucleus in respond to insulin. These findings demonstrate that insulin phosphorylates tyrosine residue 464 of Tub, and this event is important for insulin-induced tubby nuclear translocation. CONCLUSION: Insulin phosphorylates tyrosine residue 464 of Tub and translocates tubby into the nuclei of HIRcB cells.