Sound-evoked neurogenic responses with short latency of vestibular origin.

OBJECTIVE: In ABR recording, a large negative deflection with a latency of 3 ms (N3) has been recorded in patients with peripheral profound deafness. It has been suggested that N3 might be of vestibular origin. So far, N3 has been recorded only in patients with peripheral profound deafness. If we can record N3 potentials in subjects with preserved hearing, recording N3 potentials might be a new clinical test of the vestibular system. To record neurogenic potentials (N3) of vestibular origin in healthy volunteers and patients with vestibular disorders. METHODS: Twelve healthy volunteers (10 men and two women, aged 23-37 years) and 12 patients with vestibular disorders (6 men and 6 women, aged 29-71 years) were enrolled in this study. To record responses, surface electrodes were placed on the ipsilateral mastoid and the vertex. An electrode on the nasion served as the ground. Recording was performed using an auditory evoked potential recording system with a mini-mixer and a stereo-amplifier. Signals at the vertex to the ispilateral mastoid were amplified and bandpass filtered (100-3000 Hz). One thousand-hertz short tone bursts (1 kHz STB; rise/fall time=0.5 ms, plateau time=1 ms) were presented to either ear through a headphone with or without white noise (WN) ipsilateral to the stimulated ear. The stimulation rate was 10 Hz, and the analysis time was 10 ms. The responses to 500 stimuli were averaged twice. RESULTS: When 1 kHz STB (95 dBnHL, equivalent to 130 dBSPL) were presented with 100 dBSPL WN (ipsilateral to the stimulated ear), a negative peak with 3-4 ms latency (N3) was observed in 23 of the 24 ears (95.8%) with reproducibility in healthy subjects. Without WN, N3 was observed in 17 of the 24 ears (70.8%). The threshold of N3 was 90.2 dBnHL on the average. The presence of N3 in the patients was in agreement with the presence of the VEMP, which were also recorded. CONCLUSIONS: Using techniques of WN exposure ipsilateral to the stimulated ear, we recorded N3 in healthy subjects and in vestibular disorder patients with preserved hearing. This negative peak is likely to be of vestibular origin. SIGNIFICANCE: N3 may be measured from subjects who cannot contract neck muscles due to their ages, mental states, or consciousness disorders. In other words, N3 may be measured from subjects from whom VEMP cannot be recorded. In combination with VEMP, N3 may be useful for the detection of lesion sites.     

The intracranial pressure of the patients with mild form of craniosynostosis

Introduction While raised intracranial pressure (ICP) is a well recognized complication affecting children with syndromic craniosynostosis, certain percentage of the patients with non-syndromic craniosynostosis may have some problems related to increased ICP, such as developmental delay or visual problem. However, it is still not clear how many percent of and/or which types of craniosynostosis patients suffer from those symptoms, especially in older patients. Objective The aim of this study was to examine the ICP of older children with mild form of craniosynostosis to determine if any of them should be surgically treated. Materials and methods We measured ICP before making the decision for surgical intervention. Results Twenty-five of thirty-six patients had raised ICP in our series. Discussion All of the 25 patients were treated surgically and followed-up after more than 1 year. All patients improved in some degree. Further investigations should be performed to determine what is the threshold for raised ICP in children. Presented at the Consensus Conference on Pediatric Neurosurgery, Rome, 1–2 December 2006.     

Response of guinea pig vestibular nucleus neurons to clicks

Responses of single neurons in the vestibular nuclei to clicks were studied by extracellular recording in anaesthetised guinea pigs. Eighty-four neurons in the ipsilateral vestibular nuclei were activated with an average latency of 1.75±0.30 ms, which is about 0.9 ms longer than the mean latency of activation of click-sensitive vestibular afferents to intense clicks. The threshold of clicks for evoking the response of these neurons was around 70 dB above the auditory brainstem response threshold. Earlier studies have indicated that click-sensitive vestibular afferents are tilt-sensitive and likely to originate from saccular receptors, and in the present study nine of the click-sensitive vestibular nucleus neurons were tilt-sensitive, suggesting that these central neurons receive monosynaptic input from the corresponding saccular afferents. Recording sites were marked by means of iontophoretic injection of FCF green dye; they were located in the lateral portion of the descending vestibular nucleus and the caudal and ventral regions of the lateral vestibular nucleus.     

Adrenocorticotropin and growth hormone secretions after intracerebroventricular administration of neostigmine in rats: their relationships to hypothalamic monoaminergic neuronal activities

Serum adrenocorticotropic hormone (ACTH) and growth hormone (GH) concentrations were assessed simultaneously with hypothalamic neuronal activities of norepinephrine (NE), dopamine (DA), and serotonin (5-HT) 60 min after the third cerebroventricular administration of neostigmine (a cholinesterase inhibitor) in awake rats. Serum ACTH and GH concentrations were significantly increased and decreased, respectively. Neostigmine caused significant increases in hypothalamic NE and DA activities and a significant decrease in hypothalamic 5-HT activity. The reciprocal changes of serum ACTH and GH cencentrations were similar to those of hypothalamic NE and 5-HT activities. Multiple regression analyses with stepwise procedure revealed that hypothalamic NE and 5-HT activities were respectively significant determinants of serum ACTH and GH concentrations. Apart from the direct influence of neostigmine on ACTH and GH secretions, it is suggested that the changes in hypothalamic monoaminergic activities play an important role in modulating ACTH and GH secretions following the administration of neostigmine.     

Clotrimazole, an antifungal drug possessing diverse actions, increases membrane permeation of cadmium in rat thymocytes

In previous study, clotrimazole, an antifungal drug, exerted potent cytotoxic action on rat thymocytes in presence of metal divalent cations such as Cd²⁺ and Pb²⁺. To reveal one of toxicological characteristics of clotrimazole, we examined the effect of clotrimazole on intracellular concentration of metal divalent cations by flow cytometer with fluo-3, a fluorescent. Simultaneous application of clotrimazole and CdCl₂ significantly decreased the cell viability although their concentrations were not cytotoxic, respectively. Clotrimazole alone increased the intensity of fluo-3 fluorescence, suggesting an increased concentration of intracellular Ca²⁺. The intensity of fluo-3 fluorescence augmented by the combination of clotrimazole and CdCl₂ was much higher than that by respective agents. Removal of external Ca²⁺ further increased the intensity of fluorescence augmented by the combination. Furthermore, the application of MnCl₂ did not attenuate the intensity in the presence of CdCl₂. Therefore, it is suggested that the augmentation of fluo-3 fluorescence in the simultaneous presence of clotrimazole and CdCl₂ is Cd²⁺-dependent. Clotrimazole may increase membrane permeation of Cd²⁺.     

Successful chemotherapy with carboplatin and docetaxel for an elderly patient with advanced non-small cell lung cancer

A 79-year-old man was admitted to our hospital with right hypochondrium pain. His chest X-ray and CT scan showed a mass lesion on the left upper lobe, and multiple metastases in the liver. The diagnosis was non-small cell carcinoma of the lung. He received 4 courses of combined chemotherapy of carboplatin and docetaxel every 4 weeks. At the end of 4 courses, a partial response was achieved. Two courses of a in similar regimen were added at the time of a later recurrence, and the effect was a partial response. Carboplatin+docetaxel combined chemotherapy, which can be conducted relatively safely on an outpatient basis, may be an effective treatment for non-small cell lung cancer in the elderly.     

The pathological findings of vasculitis simultaneously occurring with carcinoma, invasive breast carcinoma in a patient with behçet’s disease

We present a rare case of invasive right breast carcinoma in a 72-year-old woman with Behçet’s disease (BD). A radical modified right mastectomy and axillary lymphadenectomy were performed and postoperative hormonal therapy with the aromatase inhibitor anastrozole was administered for adjuvant therapy. At 10 months follow-up the patient remains disease free. Malignancies associated with BD are very uncommon. The pathological findings showed small vessel vasculitis and lobulitis of the breast in association with invasive carcinoma.     

Genetic polymorphisms of human ABC transporter ABCG2: development of the standard method for functional validation of SNPs by using the Flp recombinase system

The vector-mediated introduction of cDNA into mammalian cells by calcium phosphate co-precipitation or permeation with lipofectamine is widely used for the integration of cDNA into genomic DNA. However, integration of cDNA into the host's chromosomal DNA occurs randomly at unpredictable sites, and the number of integrated recombinant DNAs is not controllable. To investigate the effect of genetic polymorphisms of ABCG2 on the protein expression and the drug resistance profile, we developed the Flp-In method to integrate one single copy of ABCG2 variant-cDNA into FRT-tagged genomic DNA. More than 20 metaphase spreads were examined for both fluorescence in situ hybridization (FISH) mapping and multicolor-FISH analysis, and it has been revealed that ABCG2 cDNA was incorporated into the telomeric region of the short arm on one of chromosomes 12 in Flp-In-293 cells. Based on the currently available SNP data for human ABCG2, we have created a total of seven variants by site-directed mutagenesis and stably expressed them in Flp-In-293 cells. While mRNAs of those integrated ABCG2 variants and wild type were evenly expressed in Flp-In-293 cells, the protein expression levels of F208S and S441N variants were found to be markedly low. It is suggested that the protein instability due to enhanced degradation resulted in the low levels of their protein expression. Thus, the Flp recombinase system would provide a useful tool to validate the effect of nonsynonymous SNPs on the protein stability and post-translational modification of ABCG2.     

Functional validation of the genetic polymorphisms of human ATP-binding cassette (ABC) transporter ABCG2: identification of alleles that are defective in porphyrin transport

The ATP-binding cassette (ABC) transporter ABCG2 has been implicated to play a significant role in the response of patients to medication and/or the risk of diseases. To clarify the possible physiological or pathological relevance of ABCG2 polymorphisms, we have functionally validated single nucleotide polymorphisms (SNP) of ABCG2. In the present study, based on the currently available data on SNPs and acquired mutations, we have created a total of 18 variant forms of ABCG2 (V12M, G51C, Q126stop, Q141K, T153M, Q166E, I206L, F208S, S248P, E334stop, F431L, S441N, R482G, R482T, F489L, F571I, N590Y, and D620N) by site-directed mutagenesis and expressed them in insect cells. Because porphyrins are considered to be endogenous substrates for ABCG2, we have investigated the porphyrin transport activity of those variant forms in vitro. We herein provide evidence that the variants Q126stop, F208S, S248P, E334stop, and S441N are defective in porphyrin transport, whereas F489L exhibited impaired transport, approximately 10% of the activity observed for the wild type. Furthermore, Flp-In-293 cells expressing those variants were photosensitive. Thus, among those genetic polymorphisms of ABCG2, at least the hitherto validated alleles of Q126stop, S441N, and F489L are suggested to be of clinical importance related to the potential risk of porphyria.     

Reciprocal effects of glucose on the process of cell death induced by calcium ionophore or H2O2 in rat lymphocytes

We have examined the effects of glucose at high concentrations on the process of cell death induced by excessive increase in intracellular Ca(2+) concentration ([Ca(2+)](i)) or oxidative stress in rat lymphocytes. The cell death elicited by the excessive increase in [Ca(2+)](i) seemed to be induced by an activation of Ca(2+)-dependent K(+) channels because the inhibitors for Ca(2+)-dependent K(+) channels attenuated the decrease in cell viability. Glucose at 30-50mM augmented the decrease in cell viability by the excessive increase in [Ca(2+)](i). It was not specific for glucose because it was the case for sucrose or NaCl, suggesting an involvement of increased osmolarity in adverse action of glucose. On the contrary, glucose protected the cells suffering from oxidative stress induced by H(2)O(2), one of reactive oxygen species. It was also the case for fructose or sucrose, but not for NaCl. The process of cell death induced by H(2)O(2) started, being independent from the presence of glucose. Glucose delayed the process of cell death induced by H(2)O(2). Sucrose and fructose also protected the cells against oxidative stress. The reactivity of sucrose to reactive oxygen species is lower than those of glucose and fructose. The order in the reactivity cannot explain the protective action of glucose. Glucose at high concentrations exerts reciprocal actions on the process of cell death induced by the oxidative stress and excessive increase in [Ca(2+)](i).