bluuebunny/crossref_metadata_2025 huggingface dataset:
Suppression of breast cancer cell growth by Na+/H+ exchanger regulatory factor 1 (NHERF1)
Authors: Pan Yong , Wang Lei , Le Dai Jia
Published: November 2006

Introduction

Na+/H+ exchanger regulatory factor 1 (NHERF1, also known as EBP50 or NHERF) is a putative tumour suppressor gene in human breast cancer. Located at 17q25.1, NHERF1 is frequently targeted during breast tumourigenesis. Loss of heterozygosity (LOH) at the NHERF1 locus is found in more than 50% of breast tumours. In addition, NHERF1 is mutated in a subset of primary breast tumours and breast cancer cell lines. LOH at the NHERF1 locus is strongly associated with aggressive features of breast tumours, implicating NHERF1 as a haploinsufficiency tumour suppressor gene. However, the putative NHERF1 tumour suppressor activity has not been functionally verified.

Methods

To confirm the NHERF1 tumour suppressor activity suggested by our genetic analyses, we used retrovirus-transduced short hairpin RNA (shRNA) to knock down NHERF1 expression in breast cancer cell lines MCF7 and T47D. These cells were then assessed for cell growth in vitro and in vivo. The control and NHERF1 knockdown cells were also serum-starved and re-fed to compare their cell cycle progression as measured by fluorescence-activated cell sorting analyses.

Results

We found that downregulation of the endogenous NHERF1 in T47D or MCF7 cells resulted in enhanced cell proliferation in both anchorage-dependent and -independent conditions compared with that of the vector control cells. NHERF1 knockdown T47D cells implanted at mammary fat pads of athymic mice formed larger tumours than did control cells. We found that serum-starved NHERF1 knockdown cells had a faster G1-to-S transition after serum re-stimulation than the control cells. Immunoblotting showed that the accelerated cell cycle progression in NHERF1 knockdown cells was accompanied by increased expression of cyclin E and elevated Rb phosphorylation level.

Conclusion

Our findings suggested that the normal NHERF1 function in mammary epithelial cells involves blockage of cell cycle progression. Our study affirmed the tumour suppressor activity of NHERF1 in breast which may be related to its regulatory effect on cell cycle. It warrants future investigation of this novel tumour suppressor pathway in human breast cancer which may turn up therapeutic opportunities.
GATA3 protein as a MUC1 transcriptional regulator in breast cancer cells
Authors: Abba Martín C , Nunez María I , Colussi Andrea G , Croce María V , Segal-Eiras Amada , Aldaz C Marcelo
Published: November 2006

Introduction

Recent studies have demonstrated that members of the GATA-binding protein (GATA) family (GATA4 and GATA5) might have pivotal roles in the transcriptional upregulation of mucin genes (MUC2, MUC3 and MUC4) in gastrointestinal epithelium. The zinc-finger GATA3 transcription factor has been reported to be involved in the growth control and differentiation of breast epithelial cells. In SAGE (serial analysis of gene expression) studies we observed an intriguing significant correlation between GATA3 and MUC1 mRNA expression in breast carcinomas. We therefore designed the present study to elucidate whether MUC1 expression is regulated by GATA3 in breast cancer cells.

Methods

Promoter sequence analysis of the MUC1 gene identified six GATA cis consensus elements in the 5' flanking region (GATA1, GATA3 and four GATA-like sequences). Chromatin immunoprecipitation and electrophoretic mobility-shift assays were employed to study the presence of a functional GATA3-binding site. GATA3 and MUC1 expression was analyzed in vitro with a GATA3 knockdown assay. Furthermore, expression of GATA3 and MUC1 genes was analyzed by real-time RT-PCR and immunohistochemistry on breast cancer-specific tissue microarrays.

Results

We confirmed the presence of a functional GATA3-binding site on the MUC1 promoter region in the MCF7 cell line. We determined that GATA3 knockdown assays led to a decrease in MUC1 protein expression in MCF7 and T47D cells. In addition, we detected a statistically significant correlation in expression between GATA3 and MUC1 genes at the mRNA and protein levels both in normal breast epithelium and in breast carcinomas (p = 0.01). GATA3 expression was also highly associated with estrogen receptor and progesterone receptor status (p = 0.0001) and tumor grade (p = 0.004) in breast carcinomas.

Conclusion

Our study provides evidence indicating that GATA3 is probably a mediator for the transcriptional upregulation of MUC1 expression in some breast cancers.
Monocytes infected withMycobacterium tuberculosisregulate MAP kinase-dependent astrocyte MMP-9 secretion
Authors: Harris James E , Green Justin A , Elkington Paul T , Friedland Jon S
Published: November 2006

Tuberculosis (TB) of the CNS (CNS-TB) carries a high mortality. Disease pathology is characterized by widespread destruction of CNS tissues. Matrix metalloproteinase-9 (MMP-9) is able to catabolyze specific components of the CNS tissue matrix and blood-brain barrier. Increased cerebrospinal fluid MMP-9 concentrations are associated with tissue damage, leukocyte infiltration, and death in CNS-TB. Using zymography, Western analysis, and transcription factor assays, we investigated mechanisms regulating MMP-9 activity in CNS-TB. We demonstrate that conditioned media from monocytes infected with Mycobacterium tuberculosis (CoMTB) induce MMP-9 secretion from astrocytes (U373-MG). IL-1β and TNF-α are necessary but not sufficient for such induction of astrocyte MMP-9 secretion. CoMTB up-regulates AP-1 DNA-binding activity, and the c-Jun, FosB, and JunB subunits are particularly increased. MMP-9 secretion from CoMTB-stimulated astrocytes is dependent on the activity of p38, Erk, and Jnk MAPKs. Phosphorylation of p38, Erk, and Jnk is activated rapidly, peaking 30 min poststimulation with CoMTB. Inhibition of IL-1β but not TNF-α in CoMTB decreases p38, Erk, and Jnk activity in astrocytes. Consistently, IL-1β signals through the MAPK cascade at physiological levels, whereas TNF-α, IL-6, IL-10, CCL-2, CCL-5, and CXCL-8 (all present in CoMTB) do not. In summary, the data suggest that monocyte-dependent cytokine networks may play a key role in the development of a matrix-degrading environment during CNS-TB.
ΔNp63 plays an anti-apoptotic role in ventral bladder development
Authors: Cheng Wei , Jacobs W. Bradley , Zhang Jennifer J. R. , Moro Anne , Park Jin-Hyung , Kushida Michelle , Qiu Wei , Mills Alea A. , Kim Peter C. W.
Published: November 2006

The bladder, the largest smooth-muscle organ in the human body, is responsible for urine storage and micturition. P63, a homolog of the p53 tumor-suppressor gene, is essential for the development of all stratified epithelia, including the bladder urothelium. The N-terminal truncated isoform of p63, ΔNp63, is known to have anti-apoptotic characteristics. We have established that ΔNp63is not only the predominant isoform expressed throughout the bladder, but is also preferentially expressed in the ventral bladder urothelium during early development. We observed a host of ventral defects in p63-/- embryos, including the absence of the abdominal and ventral bladder walls. This number of ventral defects is identical to bladder exstrophy, a congenital anomaly exhibited in human neonates. In the absence of p63, the ventral urothelium was neither committed nor differentiated,whereas the dorsal urothelium was both committed and differentiated. Furthermore, in p63-/- bladders, apoptosis in the ventral urothelium was significantly increased. This was accompanied by the upregulation of mitochondrial apoptotic mediators Bax and Apaf1, and concurrent upregulation of p53. Overexpression ofΔ Np63γ and ΔNp63β in p63-/- bladder primary cell cultures resulted in a rescue,evidenced by significantly reduced expressions of Bax and Apaf1. We conclude that ΔNp63 plays a crucial anti-apoptotic role in normal bladder development.
Bchs, a BEACH domain protein, antagonizes Rab11 in synapse morphogenesis and other developmental events
Authors: Khodosh Rita , Augsburger Adela , Schwarz Thomas L. , Garrity Paul A.
Published: November 2006

BEACH proteins, an evolutionarily conserved family characterized by the presence of a BEACH (Beige and Chédiak-Higashi) domain, have been implicated in membrane trafficking, but how they interact with the membrane trafficking machinery is unknown. Here we show that the DrosophilaBEACH protein Bchs (Blue cheese) acts during development as an antagonist of Rab11, a small GTPase involved in vesicle trafficking. We find that reduction in, or loss of, bchs function restores viability and normal bristle development in animals with reduced rab11 function, while reductions in rab11 function exacerbate defects caused by bchsoverexpression in the eye. Consistent with a role for Bchs in modulating Rab11-dependent trafficking, Bchs protein is associated with vesicles and extensively colocalized with Rab11 at the neuromuscular junction (NMJ). At the NMJ, we find that rab11 is important for synaptic morphogenesis, as reductions in rab11 function cause increases in bouton density and branching. These defects are also suppressed by loss of bchs. Taken together, these data identify Bchs as an antagonist of Rab11 during development and uncover a role for these regulators of vesicle trafficking in synaptic morphogenesis. This raises the interesting possibility that Bchs and other BEACH proteins may regulate vesicle traffic via interactions with Rab GTPases.
Frizzled3a and Celsr2 function in the neuroepithelium to regulate migration of facial motor neurons in the developing zebrafish hindbrain
Authors: Wada Hironori , Tanaka Hideomi , Nakayama Satomi , Iwasaki Miki , Okamoto Hitoshi
Published: November 2006

Migration of neurons from their birthplace to their final target area is a crucial step in brain development. Here, we show that expression of the off-limits/frizzled3a (olt/fz3a) and off-road/celsr2 (ord/celsr2) genes in neuroepithelial cells maintains the facial (nVII) motor neurons near the pial surface during their caudal migration in the zebrafish hindbrain. In the absence of olt/fz3a expression in the neuroepithelium, nVII motor neurons extended aberrant radial processes towards the ventricular surface and mismigrated radially to the dorsomedial part of the hindbrain. Our findings reveal a novel role for these genes, distinctive from their already known functions, in the regulation of the planar cell polarity (i.e. preventing integration of differentiated neurons into the neuroepithelial layer). This contrasts markedly with their reported role in reintegration of neuroepithelial daughter cells into the neuroepithelial layer after cell division.
Sequence of Atlantic cod (Gadus morhua) GLUT4, GLUT2 and GPDH:developmental stage expression, tissue expression and relationship to starvation-induced changes in blood glucose
Authors: Hall Jennifer R. , Short Connie E. , Driedzic William R.
Published: November 2006

cDNAs of putative glucose transporters, GLUT4 and GLUT2, were cloned from Atlantic cod (Gadus morhua). The GLUT4 cDNA encodes a 503 amino acid and the GLUT2 cDNA a 506 amino acid protein. Phylogenetic analysis, amino acid sequence alignment, and tissue distribution support categorizing them as homologues of mammalian GLUT4 and 2. GLUT4 clusters with GLUT4s from fish and other vertebrates. It shows 84% amino acid identity to GLUT4 from coho salmon and brown trout and 65% identity with other vertebrates. It is most highly expressed in heart, strongly expressed in red and white skeletal muscle and present at lower levels in gill, gonad, intestine, and kidney. GLUT2 clusters with GLUT2 from rainbow trout and other vertebrates. It shows 75% amino acid identity with rainbow trout and 62% identity with chicken GLUT2. In Atlantic cod, GLUT2 is most highly expressed in liver with lower levels noted in intestine and kidney.

Food deprivation for 2 months was used as a vehicle to monitor GLUT expression at different blood glucose levels. Starvation resulted in a decrease in blood glucose and liver glycogen that recovered following 20 days of re-feeding. GLUT4 expression in heart was decreased with starvation and increased with re-feeding. GLUT4 mRNA level in heart correlated with blood glucose. It is suggested that this relationship is related to insulin responsiveness. GLUT4 expression in white muscle increased with starvation and decreased with re-feeding. It is proposed that this is due to the necessity to maintain high levels of the glucose transporter protein in the face of starvation-associated proteolysis. GLUT2 expression in liver correlated with blood glucose, consistent with higher rates of glucose transport from liver to blood in the fed state than in the food-deprived state.

Glycerol-3-phosphate dehydrogenase (GPDH) cDNA was also cloned. It encodes a 351 amino acid protein, which is 73-90% identical to GPDH from numerous other fish species. GPDH is ubiquitously expressed. Expression in heart decreased with starvation and increased with refeeding, whereas expression in liver did not change with starvation.

In other studies, gene expression was monitored at nine time points from fertilization of eggs to larval development. GLUT4 is detectable in fertilized eggs and is fully expressed by the halfway to hatching point. GLUT2 is not evident at fertilization, is detectable at halfway to hatching, and fully expressed at hatching. GPDH expression was evident from fertilization.
The controversy of warthin's tumor
Authors: Chapnik Jerry S.
Published: November 2006

Warthin's tumor is controversial. This controversy is multifaceted and relates to all aspects of the tumor from its historical beginnings to its pathogenesis, investigations, and treatments.

In this paper, an in depth study of Warthin's tumor has been made to help clarify these controversies.
Laryngeal pseudosarcoma
Authors: Giordano Anthony M. , Ewing Steve , Adams George , Maisel Robert
Published: November 2006

In the past laryngeal pseudosarcomas have been diagnosed as a. carcinosarcomas, b. pleomorphic or spindle cell carcinomas, or c. squamous cell carcinomas with pseudosarcomatous reactive stroma. Arguments have centered around the nature of the sarcomatous stroma. Because of this confusion there is disagreement as to the treatment and prognosis of these tumors.

Seven pseudosarcomas were treated between 1969–1979, 4 were pedunculated and 3 exophytic. Treatment consisted of primary CO60 irradiation in 2 patients, surgery in 3 cases and combined therapy in 2 cases with no recurrences. Three of the 7 have died, 1 of a poorly differentiated adenosquamous carcinoma of the right main stem bronchus and the other 2 of natural causes at ages 77 and 85.

From a review of the literature as well as our experience, we have reached the following conclusions. 1. Stromal cells are a malignant morphologic variant of the squamous cell and are best termed spindled cells. 2. Neck metastasis at any time is a poor prognostic sign. 3. The pattern of metastasis and survival seems to parallel laryngeal squamous cell carcinoma, and thus treatment should be similar for given stages.
Application of posterior neck dissection in treating malignant melanoma of the posterior scalp
Authors: Fisher Samuel R. , Cole T. Boyce , Seigler Hilliard F.
Published: November 2006

Utilization of a posterior neck dissection in the treatment of nine patients with malignant melanoma of the posterior scalp is presented. Seven of nine patients presented with metastatic disease present in the posterior neck after initial treatment elsewhere. Four of the seven patients developed regional disease 4 months to 4 years following initial diagnosis. Variables dictating surgical treatment included the Clark's level, Breslow depth of invasion of original lesion, evidence of metastatic disease, and type of melanoma. The surgical technique of the posterior neck dissection is graphically depicted and the indications outlined. The posterior neck dissection is mandatory to adequately resect the primary lymphatics of the posterior scalp. Controlled studies are urged to determine the efficacy of prophylactic surgical lymphadenectomy in malignant melanoma of the head and neck.
Serial section reconstruction of the neural poles of hair cells in the human organ of corti. II. outer hair cells
Authors: Nadol Joseph B.
Published: November 2006

Study of the anatomy of the cochlea, and in particular the morphology of synaptic relationships between hair cells and cochlear neurons, is essential for elucidation of the mechanisms of transduction of mechanical acoustic signals into electrical neural events. Because considerable gaps remain in our understanding of the microscopic anatomy of these synapses, particularly in the human, a reconstruction of the neural pole of outer hair cells of the human organ of Corti was performed. The data are based on 577 serial sections from the basal turn and 368 sections from the middle turn. This provided complete data on 11 and partial data on 9 outer hair cells.

Terminal size of afferent fibers on outer hair cells was much more uniform than that found at the base of inner hair cells. Only small bouton‐like terminals were found. Branching of afferent fibers was also seen at the base of outer hair cells. Each outer hair cell received approximately two to eight afferent nerve terminals. Multiple synaptic contacts between a single afferent terminal and an outer hair cell were common.

Junctional membrane specialization consisted of synapses, desmosomes, coated vesicles and arrays of microtubules and membrane cisternae. Specialization at synapses consisted of asymmetrical membrane thickening. At outer hair cells the presynaptic membrane was thicker than the postsynaptic membrane. At inner hair cells the converse was true. At outer hair cells 35% of synapses had presynaptic bodies, compared to 83% of synapses at inner hair cells. Reciprocal synapses, with both hair cell to neuron and neuron to hair cell polarities, were found only on outer hair cells.

Vesiculated efferent terminals were common at the base of outer hair cells. Both axosomatic and axodendritic efferent synapses were found. In addition, the same efferent fibers were found to synapse both on an outer hair cell and on an afferent dendrite.

One example of a probable dendro‐dendritic synapse in the outer spiral bundle is presented.
Hydrops following perilymph fistula repair
Authors: Potter Charles R. , Conner George H.
Published: November 2006

A series of 15 ears were explored for perilymph fistulas. Fifteen fistulas were found in 13 ears. Two cases are presented which developed hydrops‐like symptoms only after closure of their fistulas. Closure of the other patients' fistulas was successful in relieving vertiginous symptoms, although hearing seldom improved. There were no significant complications of surgery. Fat failed as a graft material 4 of 10 times, whereas vein and perichondrium were not associated with recurrence of symptoms. The ENG‐fistula test, as described by Daspit and associates, correctly predicted the presence or absence of a fistula in 7 of 8 ears tested. Hennebert's sign correctly predicted fistulae in 2 ears, and Hennebert's symptom was associated with proven fistulae in 9 of the 10 times it was present.

Because of the low morbidity and the high success rate of surgery, a patient with a history suggestive of a perilymph fistula should have exploratory tympanotomy, particularly if the ENG‐fistula test is positive.
Astemizole: Its use in patients with chronic vertigo and eng signs … A pilot study of a new drug.
Authors: Turner John S. , Jackson Richard T.
Published: November 2006

Astemizole, a new H1 antihistamine, was tested on 10 patients with chronic dizziness and either spontaneous or positional nystagmus. Patients with Meniere's disease were excluded from the study. The patients took 10 mg of astemizole per day for 30 days. Four ENGs were performed; one pre‐drug, one after 2 weeks of drug, one after 4 weeks of drug and one post‐drug ENG.

Six of the 10 patients showed a clear decrease in spontaneous and/or positional nystagmus at the second and third ENG and a rebound of nystagmus when the drug was stopped. There was a positive relation between subjective symptoms and nystagmus. No side‐effects were observed.
The elusive henry jones shrapnell.
Authors: Mcgovern Francis H.
Published: November 2006

In a small series of articles published in The London Gazette in 1830 Henry Jones Shrapnell, surgeon, first described the correct form and structure of the tympanic membrane. He divided the drum membrane into two parts, the pars tensa and the pars flaccida. To this day the latter structure is known to every otologist and to most medical students as Shrapnell's membrane. In addition he wrote on the function of the membrana tympani, the nerves of the ear, and the true anatomy of the os incus. Heretofore the lenticular process of the incus was considered a separate bone in the ossicular chain.

In spite of his distinctive contribution to medicine, a search of over a decade failed to uncover little basic information about Shrapnell's life, and for this reason he has been called by a distinguished librarian, the elusive Mr. Shrapnell. Recently, from my continued investigation, and with the help of many fine London scholars, a clearer picture has emerged of Shrapnell's forebearers, his family, his education and his death.
Reliability and validity of industrial audiometry: Implications for hearing conservation program design.
Authors: Dobie Robert A.
Published: November 2006

Hearing conservation in industry relies heavily on monitoring audiometry to detect early noise‐induced hearing loss in workers who are exposed to potentially damaging noise, with or without hearing protectors. The “real‐world” reliability and validity of these measurements, as well as otoscopic observations in industry, have not been extensively investigated. In addition, there is considerable controversy over the selection of a definition of “significant threshold shift” in industrial audiometry. These and related issues were considered in a series of three studies utilizing data from an active hearing conservation program. Test‐retest variability in industry is much higher than has been reported for clinical settings; this variability is reduced by pure‐tone averaging. Workers referred for otologic evaluation were found to have hearing levels which were, on the average, about 5 dB better than indicated by plant audiometry, even without excluding 4% of referred workers who had unilateral deafness and showed “shadow curves” on the plant audiograms. Otoscopic data obtained by the plant audiometrists were uncorrelated with the results of otoscopy by consultant otologists. Techniques borrowed from decision theory and signal detection theory were used to evaluate possible criteria for significant threshold shift. Criteria based on pure‐tone averaging were superior to those based on a certain amount of threshold shift for any frequency tested.

It is proposed that a significant threshold shift be defined as a 10 dB or greater change for the worse for either the 0.5, 1,2 kHz pure‐tone average or the 3, 4, 6 kHz pure‐tone average, in either ear, and that such shifts be validated by prompt retesting. Even with this criterion, a substantial number of shifts (most shifts, in some situations) will be either spurious or attributable to disorders other than noise‐induced hearing loss, such as presbycusis. Otologic referral in cases of large or repeated shifts may prevent unjustified administrative actions, to the advantage of both workers and management. A practical consequence of the use of monitoring audiometry may be a de facto lowering of the permissible exposure level to 85 dBA TWA.
Bacteriological study in chronic maxillary sinusitis.
Authors: Su Wen‐Yang , Liu Chen , Hung Shuian‐Yeng , Tsai Wei‐Fu
Published: November 2006

The bacterial findings of 73 maxillary sinuses in 48 patients with chronic maxillary sinusitis, together with 7 non‐inflamed sinuses, are reported. Employing an intraoperative technique and simultaneous collection of 3 different types of specimens in the present investigation made possible comparison of their bacterial characteristics. The results indicated that intraoperative culture of antral mucosa seems to provide the most reliable finding of bacterial flora in chronic maxillary sinusitis.

The anaerobic bacteria were never found in the mucosal culture of non‐inflamed sinus. The anaerobes appeared to invade the sinus cavity following the sealing of the ostium through the lymphatic or venous system and maintain the inflammatory process. Microbiological analysis of the results between the infected and non‐inflamed sinuses established anerobic bacteria as the most important pathogen in chronic maxillary sinusitis. The predominant anaerobes recovered in descending order of frequency were Veillonella sp., Peptococcus sp., Propionibacterium acne and anaerobic nonspore‐forming GPB.

Statistical analysis of the results of mucosal culture of inflamed and control materials demonstrated that those aerobic and faculatative bacteria recovered in the inflamed sinus appeared to be the normal inhabitants of non‐inflamed sinus mucosa. The presence of normal flora in the normal healthy sinus mucosa may explain the chain of events that follows the occlusion of the ostium. These aerobic bacteria may become pathogenic and play a role in the pathogenesis of sinusitis.
Malignant melanoma of cervical and parotid lymph nodes with an unknown primary site
Authors: Nasri Sina , Namazie Ali , Dulguerov Pavel , Mickel Robert
Published: November 2006

Forty‐six patients with malignant melanoma metastatic to cervical or parotid lymph nodes with an unknown primary site were treated at UCLA Medical Center from 1964 through 1991. Treatment consisted of parotidectomy and/or neck dissection with or without adjuvant therapy. The initial presentation was a cervical mass in 74% and a parotid mass in 26% of patients. Metastasis distal to the head and neck nodal basins developed in 22% of patients.

Involvement of more than four cervical or parotid nodes resulted in a significant increase in distant metastasis (P>.01). Adjuvant therapy was found to have no significant effect on survival rates. However, age at the time of diagnosis influenced the survival rates. The significance of the improved survival of these patients as compared to those with a known primary melanoma is discussed.
Distant metastases from head and neck squamous cell carcinomas
Authors: Calhoun Karen H. , Fulmer Paul , Weiss Raymond , Hokanson James A.
Published: November 2006

Distant metastases (DMs) occurred in 83 (11.4%) of 727 retrospectively studied head and neck cancer patients. Primary tumor location and initial treatment did not influence DM development; larger primaries (P<.04) or more extensive neck disease (P<.007) more often caused DMs. Initial diagnosis to DMs averaged 11.7 months (range, 0 to 60 months), with 84% diagnosed within 24 months. With the exception of laryngeal primaries, no facet of tumor, host, or initial treatment influenced where or how rapidly DMs developed. Lung was the most common DM site (83.4%), then bone (31.1%) and liver (6.0%). Survival with DMs averaged 4.3 months (range, 1 day to 2.7 years); 86.7% died within 1 year. This report yields the following conclusions: 1. Initial tumor size and neck disease are the only predictors of DMs. 2. DMs usually occur within 2 years of the initial diagnosis. 3. Lung is the most common DM site, making chest x‐ray the most effective DM screen. 4. Survival with DMs is usually less than a year.
Congenital Aural Atresia
Authors: Bauer George P. , Wiet Richard J. , Zappia John J.
Published: November 2006

Congenital aural atresia is an unusual anomaly that is difficult to surgically correct. Altered anatomical landmarks, especially of the facial nerve, and variability of the middle ear configuration, contribute to the difficulty of the procedure. In addition, the unpredictable healing process can make for variable outcomes. Choosing appropriate candidates for surgical repair minimizes risks and enhances patient care.

This report reviews the outcome with evaluation and management of 17 patients with congential aural atresia. Surgical techniques for repair, including use of a hydroxylapatite canal wall prosthesis to help reconstruct the posterior canal wall are described. As expected, patients with less severe anomalies had better postoperative hearing results. Lateralized tympanic membrane, canal stenosis, and meatal narrowing were complications encountered. The anatomy and embryology of the ear and facial nerve are reviewed to assist surgeons in safe, successful surgery.
Localization of il‐1β mrna and cell adhesion molecules in the maxillary sinus mucosa of patients with chronic sinusitis
Authors: Tokushige Eiichiro , Itoh Kazunori , Ushikai Miharu , Katahira Shoko , Fukuda Katsunori
Published: November 2006

Interleukin‐1β (IL‐1β) is a predominant cytokine in retained paranasal sinus fluid of chronic sinusitis where infiltration by polymorphonuclear neutrophils (PMNs) of nasal and paranasal mucosa is characteristic. The authors investigated the localization of IL‐1β messenger RNA (mRNA) in the maxillary sinus mucosa of patients with chronic sinusitis, using digoxigenin‐labeled oligonucleotide probes. IL‐1β mRNA was detected in some extravascular PMNs and small numbers of mononuclear leukocytes but was not detected in other tissue cells or intravascular leukocytes. The expression and distribution of the cell adhesion molecules, intercellular adhesion molecule‐1 (ICAM‐1) and endothelial‐leukocyte adhesion molecule‐1 (ELAM‐1), were also studied in cultured human mucosal microvascular endothelial cells and in the maxillary sinus mucosa in chronic sinusitis by immunohistochemistry using monoclonal antibodies against these cell adhesion molecules. Only ICAM‐1 was expressed on cultured human mucosal microvascular endothelial cells without IL‐1β stimulation. With IL‐1β activation of these cells, ELAM‐1 was expressed strongly and the expression of ICAM‐1 was enhanced. In the maxillary sinus mucosa, ICAM‐1 was strongly and universally expressed on endothelial cells of all small vessels, whereas ELAM‐1 was expressed only in the subepithelial region. These findings suggest that IL‐1β, one of mediators in chronic sinusitis, is produced by PMNs, induces the expression of ICAM‐1 and ELAM‐1 on endothelial cells, and, thereby, stimulates PMN infiltration in chronic sinusitis.
Is the older ear more susceptible to noise damage?
Authors: Sun John C. , Bohne Barbara A. , Harding Gary W.
Published: November 2006

Eight chinchillas aged 8.9 to 12.8 years were used to examine the effect of noise on the aging ear. The left malleus/incus complex was removed to produce a 50‐dB conductive hearing loss which protected those ears from noise damage. The animals were then exposed for 36 days to an octave band of noise with a center frequency of 0.5 kHz and a sound pressure level of 95 dB. After 1 hour (n=2) or 1 month (n=6) of recovery, their cochleas were prepared for microscopic examination. The percentages of missing inner hair cells (IHCs) were 7.4 ± 6.0% and 7.8 &PM; 5.1% for their protected and exposed ears, respectively. Outer hair cell (OHC) loss was 12.8 &PM; 8.7% and 20.6 &PM; 7.8% for their protected and exposed ears, respectively. A paired sample Student's t test revealed that OHC loss was significantly greater (P=.003) in the older‐exposed compared to the older‐protected ears whereas IHC loss was not significantly different. For younger‐exposed ears (i.e., 1 to 3 years), the percentages of missing IHCs and OHCs averaged 2.6 &PM; 2.0% and 12.3 &PM; 4.6%, respectively. When the aging‐related cell loss was subtracted from total loss in the younger‐and older‐exposed ears, the noise‐induced loss of sensory cells in the older ears was not significantly different from that in the younger ears. Therefore, it is concluded that older chinchilla ears are not more susceptible to noise damage than younger ears.
Choosing the Lesser of Two Evils, the Better of Two Goods: Specifying the Roles of Ventromedial Prefrontal Cortex and Dorsal Anterior Cingulate in Object Choice
Authors: Blair Karina , Marsh Abigail A. , Morton John , Vythilingam Meena , Jones Matthew , Mondillo Krystal , Pine Daniel C. , Drevets Wayne C. , Blair James R.
Published: November 2006

The ventromedial prefrontal cortex (vmPFC) and dorsal anterior cingulate cortices (ACd) are considered important for reward-based decision making. However, work distinguishing their individual functional contributions has only begun. One aspect of decision making that has received little attention is that making the right choice often translates to making the better choice. Thus, response choice often occurs in situations where both options are desirable (e.g., choosing between mousse au chocolat or crème caramel cheesecake from a menu) or, alternatively, in situations where both options are undesirable. Moreover, response choice is easier when the reinforcements associated with the objects are far apart, rather than close together, in value. We used functional magnetic resonance imaging to delineate the functional roles of the vmPFC and ACd by investigating these two aspects of decision making: (1) decision form (i.e., choosing between two objects to gain the greater reward or the lesser punishment), and (2) between-object reinforcement distance (i.e., the difference in reinforcements associated with the two objects). Blood oxygen level-dependent (BOLD) responses within the ACd and vmPFC were both related to decision form but differentially. Whereas ACd showed greater responses when deciding between objects to gain the lesser punishment, vmPFC showed greater responses when deciding between objects to gain the greater reward. Moreover, vmPFC was sensitive to reinforcement expectations associated with both the chosen and the forgone choice. In contrast, BOLD responses within ACd, but not vmPFC, related to between-object reinforcement distance, increasing as the distance between the reinforcements of the two objects decreased. These data are interpreted with reference to models of ACd and vmPFC functioning.
Proteasome Inhibition Triggers Activity-Dependent Increase in the Size of the Recycling Vesicle Pool in Cultured Hippocampal Neurons
Authors: Willeumier Kristen , Pulst Stefan M , Schweizer Felix E
Published: November 2006

The ubiquitin proteasome system, generally known for its function in protein degradation, also appears to play an important role in regulating membrane trafficking. A role for the proteasome in regulating presynaptic release and vesicle trafficking has been proposed for invertebrates, but it remains to be tested in mammalian presynaptic terminals. We used the fluorescent styrylpyridinium dye FM4-64 to visualize changes in the recycling pool of vesicles in hippocampal culture under pharmacological inhibition of the proteasome. We found that a 2 h inhibition increases the recycling pool of vesicles by 76%, with no change in the rate or total amount of dye release. Interestingly, enhancement did not depend on protein synthesis but did depend on synaptic activity; blocking action potentials during proteasome inhibition abolished the effect whereas increasing neuronal activity accelerated the effect with an increased recycling pool evident after 15 min. We propose that the proteasome acts as a negative-feedback regulator of synaptic transmission, possibly serving a homeostatic role.
The Dynamic Distribution of TrkB Receptors before, during, and after Synapse Formation between Cortical Neurons
Authors: Gomes Raquel A. , Hampton Cara , El-Sabeawy Faten , Sabo Shasta L. , McAllister A. Kimberley
Published: November 2006

Although brain-derived neurotrophic factor (BDNF) potently regulates neuronal connectivity in the developing CNS, the mechanism by which BDNF influences the formation and/or maintenance of glutamatergic synapses remains unknown. Details about the subcellular localization of the BDNF receptor, TrkB, relative to synaptic and nonsynaptic proteins on excitatory neurons should provide insight into how BDNF might exert its effects during synapse formation. Here, we investigated the subcellular localization of tyrosine kinase receptor B (TrkB) relative to synaptic vesicle-associated proteins and NMDA receptors using immunocytochemistry, confocal microscopy, and time-lapse imaging in dissociated cultures of cortical neurons before, during, and after the peak of synapse formation. We find that TrkB is present in puncta on the surface and intracellularly in both dendrites and axons throughout development. Before synapse formation, some TrkB puncta in dendrites colocalize with NMDA receptors, and almost all TrkB puncta in axons colocalize with synaptic vesicle proteins. Clusters of TrkB fused to the enhanced green fluorescent protein (TrkB-EGFP) are highly mobile in both axons and dendrites. In axons, TrkB-EGFP dynamics are almost identical to vesicle-associated protein (VAMP2-EGFP), and these proteins are often transported together. Finally, surface TrkB is found in structures that actively participate in synapse formation: axonal growth cones and dendritic filopodia. Over time, surface TrkB becomes enriched at glutamatergic synapses, which contain both catalytic and truncated TrkB. These results suggest that TrkB is in the right place at the right time to play a direct role in the formation of glutamatergic synapses between cortical neurons.
Anterolateral Prefrontal Cortex Mediates the Analgesic Effect of Expected and Perceived Control over Pain
Authors: Wiech Katja , Kalisch Raffael , Weiskopf Nikolaus , Pleger Burkhard , Stephan Klaas Enno , Dolan Raymond J.
Published: November 2006

Perceived control attenuates pain and pain-directed anxiety, possibly because it changes the emotional appraisal of pain. We examined whether brain areas associated with voluntary reappraisal of emotional experiences also mediate the analgesic effect of perceived control over pain. Using functional magnetic resonance imaging, we compared self-controlled noxious stimuli with physically identical stimuli that were externally controlled. Self-controlled stimulation was accompanied by less pain and anxiety and higher activation in dorsal anterior cingulate (dACC), right dorsolateral, and bilateral anterolateral prefrontal (alPFC) cortices. Activation in dACC and right alPFC was negatively correlated with pain intensity ratings. For externally controlled pain, activation in right alPFC was inversely correlated with the participants' general belief to have control over their lives. Our results are consistent with a reappraisal view of control and suggest that the analgesic effect of perceived control relies on activation of right alPFC. Failure to activate right alPFC may explain the maladaptive effects of strong general control beliefs during uncontrollable pain.
Enhancing GABAAReceptor α1 Subunit Levels in Hippocampal Dentate Gyrus Inhibits Epilepsy Development in an Animal Model of Temporal Lobe Epilepsy
Authors: Raol YogendraSinh H , Lund Ingrid V , Bandyopadhyay Sabita , Zhang Guojun , Roberts Daniel S , Wolfe John H , Russek Shelley J , Brooks-Kayal Amy R
Published: November 2006

Differential expression of GABAAreceptor (GABR) subunits has been demonstrated in hippocampus from patients and animals with temporal lobe epilepsy (TLE), but whether these changes are important for epileptogenesis remains unknown. Previous studies in the adult rat pilocarpine model of TLE found reduced expression of GABR α1 subunits and increased expression of α4 subunits in dentate gyrus (DG) of epileptic rats compared with controls. To investigate whether this altered subunit expression is a critical determinant of spontaneous seizure development, we used adeno-associated virus type 2 containing the α4 subunit gene (GABRA4) promoter to drive transgene expression in DG after status epilepticus (SE). This novel use of a condition-dependent promoter upregulated after SE successfully increased expression of GABR α1 subunit mRNA and protein in DG at 1–2 weeks after SE. Enhanced α1 expression in DG resulted in a threefold increase in mean seizure-free time after SE and a 60% decrease in the number of rats developing epilepsy (recurrent spontaneous seizures) in the first 4 weeks after SE. These findings provide the first direct evidence that altering GABR subunit expression can affect the development of epilepsy and suggest that α1 subunit levels are important determinants of inhibitory function in hippocampus.
Breastfeeding and Verbal Ability of 3-Year-Olds in a Multicity Sample
Authors: Gibson-Davis Christina M. , Brooks-Gunn Jeanne
Published: November 2006

OBJECTIVES. Our goal was to analyze the effect of maternal verbal ability and education on the association between breastfeeding and children’s cognitive functioning. First, we hypothesized that maternal verbal abilities account for a large portion of the association between breastfeeding and child verbal abilities. Second, we hypothesized that after adjusting for maternal verbal abilities, a positive effect of breastfeeding will be most evident among highly educated mothers, because these mothers may have more opportunity to engage in cognitively stimulating parenting than do mothers with less education.

PATIENTS AND METHODS. With data on 1645 American-born mothers participating in a longitudinal birth cohort study, we used linear regression to determine the influence of breastfeeding for at least 1 month on the Peabody Picture Vocabulary Test-Third Edition scores of 3-year-old children. Models were adjusted for an extensive set of demographic characteristics, including mother’s Peabody Picture Vocabulary Test and the Home Observation for Measurement of the Environment score. Mothers were categorized into 1 of 3 educational-status groups: no high school diploma, high school diploma, and some post–secondary education.

RESULTS. In unadjusted mean comparisons, breastfed children had Peabody Picture Vocabulary Test scores that were 6.6 points higher than children who were not breastfed. After adjusting for demographic characteristics and maternal verbal ability, the coefficient dropped to 1.72. Among mothers with education beyond high school, the children’s Peabody Picture Vocabulary Test scores in adjusted models were 2.2 points higher for breastfed children. Among mothers with a high school diploma or less, there were no significant differences in the children’s Peabody Picture Vocabulary Test scores by breastfeeding status. These results were consistent in white, black, and Hispanic children.

CONCLUSIONS. Maternal Peabody Picture Vocabulary Test scores mediate much of the association between breastfeeding and child verbal abilities. The beneficial effects of breastfeeding on children’s cognition may emerge only when breastfeeding is done in conjunction with other positive parenting behaviors. The advantageous effects of breastfeeding do not seem to be solely attributable to the superior nutrient content of breast milk.
Changes in the Use of Postnatal Steroids for Bronchopulmonary Dysplasia in 3 Large Neonatal Networks
Authors: Walsh Michele C. , Yao Qing , Horbar Jeffrey D. , Carpenter Joseph H. , Lee Shoo K. , Ohlsson Arne
Published: November 2006

BACKGROUND. Postnatal corticosteroids were widely used in the 1990s in an attempt to reduce the incidence of bronchopulmonary dysplasia. However, high rates of short-term adverse effects and impaired neurodevelopmental outcomes were seen. In early 2002, a joint statement of the American Academy of Pediatrics and Canadian Paediatric Society called for limitation in the use of postnatal corticosteroids. The impact of this statement is not known.

OBJECTIVES. The purpose of this work was to determine the frequency of postnatal corticosteroid use and mortality and morbidities over time, particularly before and after the joint statement.

DESIGN/METHODS. We conducted a retrospective analysis of cohort data within 3 large network registries (the National Institute of Child Health and Development Neonatal Research Network [18 centers], the Vermont Oxford Network [444 centers], and the Canadian Neonatal Network [10 centers]) for the following 3 periods: prestatement (2001), statement (2002), and poststatement (2003) of very low birth-weight infants (501–1500 g). The National Institute of Child Health and Development Neonatal Research Network and the Vermont Oxford Network were also analyzed for longer-term trends from 1990 to 2003. Postnatal corticosteroid use, mortality at discharge, and neonatal morbidities (bronchopulmonary dysplasia at 36 weeks, late-onset infection >72 hours of age, necrotizing enterocolitis treated with surgery, and length of stay) between periods were compared.

RESULTS. Mean birth weight (range: 1022–1060 g), postmenstrual age (28 weeks), and gender (51% male) were similar between the networks. Race differed with more black infants in the National Institute of Child Health and Development Neonatal Research Network than the Vermont Oxford Network (38% vs 24%). Antenatal steroid use was similar (range: 61%–75%). Postnatal corticosteroid use rose from 1990 (8%–16%), peaked in 1996–1998 (24%–28%), and began to decline in 1999. Use in 2003 was significantly less than in 2001. Mortality and major morbidities were similar.

CONCLUSIONS. Postnatal corticosteroid use had decreased significantly in 3 large neonatal networks before the joint statement with further decreases after the statement with no apparent impact on mortality and short-term morbidity. Despite substantial decreases, ∼8% of very low birth-weight infants continue to be treated with postnatal corticosteroid.
Racial/Ethnic Differences in Breastfeeding Initiation and Continuation in the United Kingdom and Comparison With Findings in the United States
Authors: Kelly Yvonne J. , Watt Richard G. , Nazroo James Y.
Published: November 2006

OBJECTIVE. Patterns of breastfeeding vary considerably across different racial/ethnic groups; however, little is known about factors that might explain differences across and within different racial/ethnic groups. Here we examine patterns of breastfeeding initiation and continuation among a racially/ethnically diverse sample of new mothers and compare this with patterns seen in the United States. The effects of demographic, social, economic, and cultural factors on racial/ethnic differences in breastfeeding practices are assessed.

METHODS. The sample includes all singleton infants whose mothers participated in the first survey of the United Kingdom Millennium Cohort Study. Missing data reduced the sample to 17474 (96%) infants with complete data.

RESULTS. After adjustment for demographic, economic, and psychosocial factors, logistic regression models showed that Indian, Pakistani, Bangladeshi, black Caribbean, and black African mothers were more likely to initiate breastfeeding compared with white mothers. Further adjustment for a marker of cultural tradition attenuated these relationships, but all remained statistically significant, suggesting that some of the difference was a consequence of cultural factors. After adjustment for demographic, economic, and psychosocial factors, Indian, Pakistani, Bangladeshi, black Carribbean, and black African mothers were more likely to continue breastfeeding at 3 months compared with white mothers. Additional adjustment for a marker of cultural tradition attenuated the relationship for Indian, Pakistani, Bangladeshi, and black African mothers, but all remained statistically significant. Models run for breastfeeding continuation at 4 and 6 months were consistent with these results.

CONCLUSIONS. We have shown that in the United Kingdom the highest breastfeeding rates are among black and Asian mothers, which is in stark contrast to patterns in the United States, where the lowest rate is seen among non-Hispanic black mothers. The contrasting racial/ethnic patterns of breastfeeding in the UnitedKingdom and United States necessitate very different public health approaches to reach national targets on breastfeeding and reduce health disparities. Those who implement future policies aimed at increasing breastfeeding rates need to pay attention to different social, economic, and cultural profiles of all racial/ethnic groups.