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Biomedical subjects

K Makishima

Publications and source records attributed to K Makishima.

At least 19 recordsLinked to original sources

Effects of histamine and interleukin-4 synthesized in arterial intima on phagocytosis by monocytes/macrophages in relation to atherosclerosis.

We investigated the localization of histidine decarboxylase (HDC), which is the rate-limiting enzyme that generates histamine from histidine, in human aorta/coronary artery. RT-PCR and immunohistochemical staining revealed that the HDC gene was expressed in monocytes/macrophages and T cells in the arterial intima but not in smooth muscle cells in either the arterial intima or the media. A luciferase promoter assay with U937 and Jurkat cells demonstrated that interleukin-4 (IL-4) inhibited the expression of the HDC gene. In contrast, among a scavenger receptor family, IL-4 as well as histamine up-regulated U937 cells to express the LOX-1 gene but not the SR-A gene, which genes encode receptors that scavenge oxidized lipids. These findings suggest that histamine synthesized in the arterial wall participates in the initiation and progression of atherosclerosis and that IL-4 can act as an important inhibitory and/or stimulatory factor in the function of monocytes/macrophages modulated by histamine in relation to the process of atherosclerosis.

Arteriosclerosis↗

Transcriptional activation of the human HMG1 gene in cisplatin-resistant human cancer cells.

The nonhistone chromosomal protein, high mobility group 1 (HMG1), which is ubiquitously expressed in higher eukaryotic cells, preferentially binds to cisplatin-modified DNA. The observation that HMG1 is overexpressed in cisplatin-resistant human cancer cells suggests that cisplatin resistance may be closely associated with HMG1. To decipher the mechanism of HMG1 overexpression in cisplatin-resistant cells, we isolated two overlapping genomic DNA clones containing the entire human HMG1 gene. These clones, which span approximately 15 kb of contiguous DNA, include 5 kb of the 5' flanking region as well as the entire coding sequence. We sequenced 1500 bp upstream of the first exon. The segment proximal to the transcription initiation site did not contain a TATA box but did possess an activating transcription factor site, an activator protein-2 site, one CCAAT box, and two CCAAT-binding transcription factor/nuclear factor-1 (CTF/NF-1) sites. HMG1 promoter activity was 3-10-fold higher in cisplatin-resistant KB-CP20 cells than in parental KB cells. An in vivo footprint experiment showed several differences of dimethyl sulfate modifications between KB and KB-CP20 cells in the area around the CTF/NF-1 sites. In addition, electrophoretic gel mobility shift assays showed that binding of a nuclear factor from cisplatin-resistant cells to the CTF/NF-1 site was significantly higher than the binding of the same factor from parental cells. Semiquantitative reverse transcription-PCR and Western blot analysis also showed that expression of CTF/NF-1 was 3-20-fold higher in the resistant cell line than in its parental counterpart. These findings suggest that, in cisplatin-resistant cells, the expression of HMG1 gene product is enhanced at the transcriptional level and that this probably occurs through the enhanced expression of the CCAAT binding factor, CTF/NF-1.

Antineoplastic Agents↗

Significance of airborne transmission of methicillin-resistant Staphylococcus aureus in an otolaryngology-head and neck surgery unit.

OBJECTIVES: To quantitatively investigate the existence of airborne methicillin-resistant Staphylococcus aureus (MRSA) in a hospital environment and to perform phenotyping and genotyping of MRSA isolates to study MRSA epidemiology. DESIGN: Prospective surveillance of patients with MRSA infections or colonizations was performed, as was an observational study of environmental airAirborne samples were taken by an air sampler; samples were obtained from object surfaces by stamping or swabbing. Epidemiological study of MRSA isolates was performed with an antibiotic susceptibility test, coagulase typing, and pulsed-field gel electrophoresis. SETTING: Three single-patient rooms in a 37-bed otolaryngology-head and neck surgery unit. PATIENTS: Three patients with squamous cell head and neck cancer were observed to have been colonized or infected with MRSA after surgery. RESULTS: The MRSA samples were collected from the air in single-patient rooms during both a period of rest and when bedsheets were being changed. Isolates of MRSA were detected in all stages (from stage 1 [>7 microm] to stage 6 [0.65-1.1 microm]). About 20% of the MRSA particles were within a respirable range of less than 4 microm. Methicillin-resistant S aureus was also isolated from inanimate environments, such as sinks, floors, and bedsheets, in the rooms of the patients with MRSA infections as well as from the patients' hands. An epidemiological study demonstrated that clinical isolates of MRSA in our ward were of one origin and that the isolates from the air and from inanimate environments were identical to the MRSA strains that caused infection or colonization in the inpatients. CONCLUSIONS: Methicillin-resistant S aureus was recirculated among the patients, the air, and the inamimate environments, especially when there was movement in the rooms. Airborne MRSA may play a role in MRSA colonization in the nasal cavity or in respiratory tract MRSA infections. Measures should be taken to prevent the spread of airborne MRSA to control nosocomial MRSA infection in hospitals.

Carcinoma, Squamous Cell↗

[Clinical and bacteriological significance of the Streptococcus milleri group in deep neck abscesses].

Streptococcus constellatus, S. intermedius, and S. anginosus, the three species of the S. milleri group, form part of the normal flora most commonly found in the mouth, throat, gastrointenstinal tract, and genital tract. The S. milleri group has become known as an important pathogen in abscess disease, but little attention has been paid to their role in deep neck abscesses. We have treated 9 patients with deep neck abscesses relating to the S. milleri group since 1991, and regarded this group as an important pathogen also in these abscesses. We studied the frequency of the S. milleri group isolated from deep neck abscesses in our cases and from the literature and discuss clinical significance and bacteriological pathogenesis. Cases numbered 27 treated at our facility since 1991 and 200 cases reported in the Japanese literature since 1990. Of our 9 cases, 4 originated from acute pharyngitis, 3 from peritonsillar abscesses, and 2 from odontogenic infection. Serious complications such as mediastinitis, cervical necrotizing fasciitis, sepsis accompanied by disseminated intravascular coagulation, and spondylitis of the cervical vertebrae were seen in 4 cases. Among organisms isolated, the S. milleri group appeared to be a pathogen contributing to abscess formation and to serious complications. The genus Streptococcus was most frequently isolated both in our 27 cases (66.7%) and the 200 in the literature (45.5%). Among species of the genus Streptococcus, the S. milleri group numbered the highest in our cases at 33.3% but only 8.5% in the literature. Cases in the literature, however, contained many unknown species of Streptococci--31.5% vs. 18.5% in our cases. alpha-streptococcus was frequently reported in the literature among unknown species of Streptococci--36 of 63. Culture-negative cases were also numbered more in the literature than in our case--29.0% vs. 18.5%. Special conditions and procedures are required to suitably isolate and detect the S. milleri group. Since not all facilities use identical techniques in routine bacteriological examination, a considerable number of the S. milleri group could be missed in unknown species of Streptococci or alpha-streptococcus and culture-negative cases. The detailed pathogenesis of the S. milleri group remains to be clarified. Infection by normal flora on mucosa is thought to occur due to an imbalance between organisms and host defense in deep neck abscesses. Some strains of the S. milleri group have been reported to produce many tissue-destroying enzymes such as collagenase and hyaluronidase. The co-existence of the S. milleri group with some anaerobe strains has also been suggested to accelerate inflammation. We discuss the mechanism inducing the massive release of cytokines through T cell response to certain exotoxins produced by S. milleri group, as reported in toxic shock-like syndrome due to the group A beta-streptococcus and in alpha-streptococcal shock syndrome due to viridans streptococci (alpha-streptococci).

Abscess↗

Relationship of nasal carriage of Staphylococcus aureus to pathogenesis of perennial allergic rhinitis.

BACKGROUND: Several studies have previously shown some factors that modify the pathogenesis of perennial allergic rhinitis (PAR). However, the association between bacterial colonization and PAR has not been well understood. OBJECTIVE: We sought to study the association between superantigen-producing Staphylococcus aureus and PAR. METHODS: S aureus colonization in the nasal cavity and its superantigen production were studied in 65 patients with PAR and 45 nonallergic control subjects. The nasal symptom scores of the patients were evaluated. Furthermore, we examined the response to staphylococcal enterotoxin B or toxic shock syndrome toxin 1 of peripheral blood lymphocytes from both patients and control subjects by measuring proliferative responses and production of cytokines (IFN-gamma, IL-4, and IL-5). RESULTS: The rate of nasal carriage of S aureus in the patients (44%) was significantly higher than that of the control subjects (20%, P <.01). Moreover, the rate of nasal carriage of superantigen-producing S aureus in the patients (22%) was significantly higher than that of the control subjects (6.7%, P <.05). The nasal symptom scores of the S aureus -positive patients were significantly higher than those of the S aureus -negative patients (P <.05), although there was no significant association between symptom scores and superantigen production. Peripheral blood lymphocytes from the patients showed significantly higher proliferative responses and were more likely to produce T(H2 )type cytokines in response to superantigens (P <.01), but the responses were not different among the patients with S aureus carriage and superantigen production. CONCLUSION: This study suggests that PAR leads to a higher carriage rate of S aureus, and nasal carriage of S aureus may aggravate PAR.

Adolescent↗

[The effects of sleep position change in sleep apnea syndrome].

Changing the sleep position from supine to non-supine is a simple but effective treatment for some patients with sleep apnea syndrome. In the present study, we compared the clinical data for good responders (GRs), those who responded well to the sleep position change, with those for poor responders (PRs), and also evaluated the effect of surgical treatment on the positional improvement of ventilation in the PR group. Forty-one adult patients with sleep apnea syndrome (mean age: 47.1 years, mean obesity index: 125.8%) were divided into two groups based on their polysomnographic responses to sleep position change. Thirty-two patients were classified as the GR group, whose apnea-hypopnea index (AHI) in the non-supine position declined to less than half of their AHI in the supine position, and nine whose non-supine AHI remained greater than half of their supine AHI were classified as the PR group. The AHI and the desaturation index (DI) for the PR group were significantly higher than those for the GR group, and the obesity index was also higher in the PR group. For the eight PRs who had surgical therapy, their polysomnographic data improved much more in the non-supine position than in the supine position. Of six patients whose total AHI was still 10 or more after surgery, four changed into GRs. The combination of surgery and sleep position change seemed to be an effective treatment even for patients with a little improvement before surgery.

Female↗

Immunoreactivity of endothelins and endothelin receptor in the stria vascularis of the mouse cochlea.

Immunoreactivities of endothelin-1, endothelin-3, endothelin receptor type A, and Na,K-ATPase were investigated in the stria vascularis of adult male WBB6F1 +/+ mice and in that of W/Wv mutants lacking strial intermediate cells. In the +/+ mice, electron microscopic immunoreactivity for the endothelins was seen on the rough endoplasmic reticulum, Golgi apparatus, cytoplasmic vesicles and lysosomes exclusively in the strial intermediate cells by the postembedment method. Immunoreactive endothelin receptor A was localized along the plasma membrane of strial marginal cells of both wild and mutant types although the immunoreactivity of the latter was much less than that of the former by the preembedment method. These findings suggest that the endothelins, which are produced in the strial intermediate cells, may play a role in the maintenance of the stria vascularis function in the +/+ mice. Since the plasma membrane of the marginal cells of the W/Wv mice, which do not generate a high positive endocochlear potential, also showed immunoreactivity for Na,K-ATPase, it seems likely that the endothelins are involved in the activation of sodium pump of the strial marginal cells by mediation of endothelin receptor A. In addition, the role of lysosomes in the crinophagy of the endothelins in the strial intermediate cells is proposed in the +/+ mice.

Animals↗

[Effects of salicylate on electrically evoked otoacoustic emissions in the guinea pig].

Clinically, salicylates have been known to have a ototoxic side effect of reversible hearing loss and to reduce the voltage-dependent length change (electromotility) in experiments on isolated outer hair cells (OHC). In order to clarify how the reduction of OHC electromotility due to salicylates contributes to cochlear dysfunction in vivo, we observed compound action potentials (CAP) threshold as well as the outputs of the electrically evoked otoacoustic emissions (EEOAE) before and after intravenous administration of 500 mg/kg sodium salicylate in a guinea pig model. A silver ball electrode placed on the round window membrane of the animal was used for both recording of the CAP and stimulation to elicit the EEOAE. The CAP threshold to tone bursts with frequencies from 2 to 10 kHz elevated by 13 to 22 dB, and outputs of the EEOAE decreased approximately 4 dB for 5 kHz stimulation, and 12 dB for 8 kHz after salicylate administration. These results suggested that systemically administered salicylate also reduced the electromotility of the OHC, and caused the hearing impairment in vivo.

Action Potentials↗

[Hyperbaric oxygenation therapy in idiopathic sudden sensory neural hearing loss].

We analyzed statistically the prognosis of hearing impairment in patients with idiopathic sudden sensory neural hearing loss. 119 patients (HBO group) were treated with a combination of hyperbaric oxygenation (HBO) and stellate ganglion block (SGB), as well as oral administration of vasodilator and vitamins. Another 107 patients (control group) were treated with various other therapies. Collectively, the therapeutic outcome in the HBO group was better than in the control group. In addition, the recovery rate of hearing in the HBO group was superior to that in the control group for those cases which had severe hearing loss at the first medical examination, had been seen more than two weeks after onset, and had resisted other treatments. As a result of this study, we conclude that HBO is an effective therapeutic tool.

Acute Disease↗

[Importance of AUC of carboplatin in head and neck cancer].

Combination chemotherapy with Carboplatin (CBDCA) and 5-fluorouracil (5-FU) was given to 115 patients with head and neck cancer. The area under the blood concentration-time curve (AUC) of CBDCA was calculated by Calvert's formula for 111 of the 115 patients. A retrospective study was conducted to define the relationship between the clinical outcome of the combination chemotherapy and the AUC of CBDCA. The overall response rate was 58.4% in the 115 patients. The objective response rate for 103 patients with squamous cell carcinoma was 61.9% with eight (7.6%) with complete responses (CR) and 57 (54.3%) with partial responses. The mean AUC for the administration of 300 mg of CBDCA per m2 was 3.91 +/- 0.68 mg/ml.min in the patients with squamous cell carcinoma. Although, there was no statistically significant relationship between the AUC of CBDCA and therapeutic efficacy, all CRs were obtained at an AUC above 3. Thrombocytopenia was the major dose-limiting toxicity in this study. The magnitude of thrombocytopenia increased significantly with increase in AUC values. Severe thrombocytopenia did not seem to occur in the patients with an AUC under 4.5. From these results, the AUC was considered helpful for determining the CBDCA dose to prevent severe side effects. In respect of both therapeutic efficacy and toxicity, AUC values from 3 to 4.5 are recommended for neo-adjuvant chemotherapy with CBDCA and 5-FU. Prospective validation is necessary to settle the question of whether a higher AUC value within this range can improve the outcome.

Antineoplastic Combined Chemotherapy Protocols↗

[Speech audiometry using the American Word Lists for Japanese subjects with normal hearing].

The characteristics of listening to English words for Japanese people were studied in ten normal hearing subjects who had taken English classes to the level of college graduates and had opportunities to learn English continuously. Following pure tone audiometry, speech audiometry was performed using the Central Institute for the Deaf (CID) W-1 and W-22 word lists for English and the 67-S word lists for Japanese. The speech reception thresholds (SRTs) for the CID W-1 lists were significantly higher than average pure tone threshold (PTT), although the SRTs for the 67-S lists were equal to the average PTT. The difference in average SRT between the CID W-1 lists and the 67-S lists was about 15dB, which is statistically significant. The speech discrimination rate for the CID W-22 lists ranged from 78 to 100 percent with an average of 89.5 percent, while all subjects achieved the discrimination rate of 100 percent for the 67-S lists. Analysis with transient matrices of the perceived words demonstrated that the articulation rates were below 90 percent for the consonants /m/, /n/, /p/ and /delta/ . The observed variation in the speech discrimination score and the pattern of confusion among the subjects was assumed to be much more pronounced in noisy conditions.

Adult↗

[Preoperative examination for estimating the course of the facial nerve].

In surgery for a parotid tumor, facial palsy is the most serious complication. Facial palsy tends to occur in the operation in which the facial nerve runs outside of the parotid tumor. Therefore, we developed the facial nerve electric stimulating test (FNEST) to determine more accurately the relationship between the facial nerve and the tumor. The FNEST diagnosed the condition in half of the patients whose facial nerve ran outside of the parotid tumor. Furthermore, a combination of CT and FNEST increased the diagnostic efficiency. The FNEST was a very efficient preoperative examination for estimating the course of the facial nerve.

Adolescent↗

Apical tubules in marginal cells of the differentiating stria vascularis.

BACKGROUND: Apical tubules (ATs) in marginal cells (MCs) of the stria vascularis appear in limited stages of differentiation of the MCs, but their origin and roles remain uncertain. The present study was designed to solve the problem of whether the ATs are intracellular compartments derived from the Golgi apparatus (GA). METHODS: The cochleae of Wistar rats at ages of postnatal days 1, 3, and 5 were prepared for electron microscopy and cytochemistry using thiamine pyrophosphatase (TPPase) and coenzyme A phosphatase (CoA-Pase) as marker enzymes of trans Golgi cisterns and fluorescent labelled lectin, griffonia simplicifolia agglutinin-I (GS-1). RESULTS: The ATs appeared in the apical cytoplasm of the MCs between postnatal days 1 and 5. Reaction products of TPPase and CoA-Pase activities were localized in the trans-Golgi cisterns and the ATs, which were occasionally in a close apposition to the GA. The reaction was found along the apical plasma membrane of the MCs only in case of TPPase. Heavy reactions to GS-1 were seen in the supranuclear region as well as along the apical plasma membrane of the MCs. CONCLUSIONS: The present ultrastructural and cytochemical studies indicate that the ATs, which appear in the MCs at limited perinatal stages, originate from the trans-Golgi cisterns. These ATs may be involved in the apical plasma membrane supply for the differentiation of the MCs prior to the generation of EP.

Animals↗

[Otoacoustic emissions evoked by electrical stimulation].

Otoacoustic emissions evoked by electrical stimulation of the cochlea were measured in guinea pigs. Alternating current with acoustic frequencies was delivered directly to the scala tympani and the vestibuli of the basal turn by using a constant current stimulator made in our laboratory. The amplitude of the electrically evoked otoacoustic emmisson (EEOAE), which was 21.0 dB SPL in response to 2 kHz electrical stimuli of 120 microArms, was decreased gradually with anoxia of the animal and was reduced to below the noise level by extirpation of the ossiculum. The EEOAEs rose with a delay of 100 microseconds from the beginning of the stimulus, and reached maximum amplitude within three cycles. The output of EEOAE was magnified in a linear manner as the stimulus current increased from 10 to 200 microArms. The averages and standard deviations of the EEOAE output at the stimulus level of 170 microArms in six animals were 20.5 +/- 4.1 dB SPL for 1 kHz, 23.3 +/- 4.8 dB SPL for 2 kHz, 10.5 +/- 6.0 dB SPL for 3 kHz, 17.1 +/- 4.7 dB SPL for 4 kHz, 13.6 +/- 4.4 dB for 5 kHz and 18.3 +/- 4.8 dB SPL for 6 kHz. Measurement of EEOAE, in which stable responses could be obtained with simple and easy preparation, was considered a potential procedure for assessing the electromotility of the cochlear outer hair cells in vivo.

Animals↗

[Suppression tuning characteristics of the 2f1-f2 distortion product in cochlear microphonics and otoacoustic emissions].

Suppression of the 2f1-f2 distortion product (DP) by the third tone was measured in cochlear microphonics (CM) and otoacoustic emissions (OAEs) in guinea pigs to clarify the generation site of the DPs. The DPs were elicited by the primary tones with frequencies of 4.62 kHz (f1) and 6 kHz (f2). Five dB-iso-suppression tuning curves (STCs) of the DPs were obtained by plotting the suppressor level as a function of its frequencies. The STCs in both CM DP and DPOAE had the shape of the letter "V" with the tip centering around the frequency of f2. The slopes of the STC on the higher frequency side were steeper than those on the lower side. As the intensity of the primary tones was decreased, the turning of the STC became sharper. These suppression properties indicate that the 2f1-f2 DPs were generated in the area on the basilar membrane where the characteristic frequency corresponded to those of primary tones, especially for the primaries at lower intensities. Because the suppression properties in CM DP and DPOAE were similar to each other, we concluded that these two phenomena had a common generation site.

Acoustic Stimulation↗

Different effects of noise and salicylate and their interactions on the guinea pig cochlea.

We investigated the effects of noise and salicylate on the guinea pig cochlea by monitoring the acoustic nerve compound action potential (CAP) as well as the 2f1-f2 distortion product in the cochlear microphonics (DP-CM). The alterations of DP-CMs by noise and salicylate revealed an apparent difference, even when the noise-induced and salicylate-induced CAP threshold shifts were equal. This result indicated that noise and salicylate might have an effect on different sites in the cochlea. Combined effects were altered by changing the order in which the two agents were applied. The existing noise-induced damage attenuated the additional ototoxicity of salicylate. In contrast, attenuation did not occur when salicylate administration preceded noise exposure. Considering known effects of noise and/or salicylate altering mechano-electrical transduction (MET) and electro-mechanical transduction of the cochlear outer hair cells, our results seem to suggest that the MET plays a key role in the transduction mechanism in the cochlea.

Animals↗

[Experimental study on directional asymmetry of vertical OKN and OKAN].

We studied the directional asymmetry of human vertical optokinetic nystagmus (OKN) and optokinetic after nystagmus (OKAN) based on two experiments conducted in 22 normal subjects. The results of the first experiment indicated that, during upward optokinetic stimulation OKN is produced by the pursuit system and the velocity storage system while during downward optokinetic stimulation the velocity storage system plays no significant role. Up-down asymmetry in vertical OKN seemed to be caused mainly by directional asymmetry of the velocity storage system. Furthermore, as the velocity storage function is very important for producing OKN at a higher stimulation velocity, domination of upward slow phase velocity becomes more apparent with a high stimulation velocity. In our second experiment the subjects were exposed to optokinetic stimulation with or without a stable fixation point. When subjects were exposed to optokinetic stimulation with fixation, they felt a rotating sensation within themselves or a moving sensation of the fixation point. When the stimulation disappeared, most experienced an illusion of small dots moving in the direction opposite the stimulation. In this condition some of the subjects showed after-nystagmus the slow phase of which was in the opposite direction. Subsequently the after-nystagmus became more distinct, with pursuit of the moving dot illusion. This result shows the existence of a mechanism which produces reverse after-nystagmus by mean of a retinal error input. We speculate that these phenomena play causative roles in reverse after-nystagmus (RAN), pursuit reverse after nystagmus (pRAN), and the RAN system.

Adult↗