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Biomedical subjects

Katsumasa Takahashi

Publications and source records attributed to Katsumasa Takahashi.

12 recordsLinked to original sources

A case of squamous cell carcinoma of the head and neck producing granulocyte-colony stimulating factor with marked leukocytosis.

In squamous cell carcinoma of the head and neck (SCCHN), tumor cells have been shown to secrete detectable amounts of various cytokines, such as interleukin (IL)-6, IL-10, and transforming growth factor (TGF)-beta. These tumor-derived factors might be responsible for promoting malignancy. Here, we describe a SCCHN patient with tumor produced G-CSF and characterized by marked leukocytosis. In this 45-year-old man, severe leukocytosis developed in parallel with aggressive tumor growth. G-CSF production by the tumor was confirmed by immunohistochemistry (IHC). Serum G-CSF levels were elevated. The leukocyte counts and the blood G-CSF level decreased following a course of radiotherapy. Tumor cells were also positive for G-CSF receptor, suggesting autocrine growth regulation by G-CSF. Moreover, the tumor cells were also investigated by IHC with anti-p53, anti-P-glycoprotein (P-gp), anti-thymidylate synthase (TS), and anti-dihydropyrimidine dehydrogenase (DPD), which molecules are thought to contribute the acquisition of therapeutic resistance. The tumor cells were positively stained for TS and DPD, but neither p53 nor P-gp. These results suggest that a variety of molecules may be responsible for acquisition of high malignancy.

Abscess↗

Temporal bone histopathologic abnormalities associated with mitochondrial mutation T7511C.

OBJECTIVES: We previously reported a mitochondrial T7511C mutation in the tRNA gene in a Japanese family with nonsyndromic hearing loss (HL). However, the temporal bone histopathology associated with T7511C has not been reported. The aim of the present study is to report histopathologic findings of a temporal bone from a patient in the Japanese family with this mutation. STUDY DESIGN: Single case study. METHODS: A temporal bone was obtained from the right ear of a male subject with progressive HL from 5 years of age and who died at 60 years of age from cerebral infarction. The bone was embedded, sectioned, and stained with hematoxylin-eosin for light microscopic study. Graphic reconstruction of the cochlea was performed using the method described by Schuknecht to determine loss of the stria vascularis and neurosensory elements including hair cells and spiral ganglion neurons. RESULTS: The most significant histopathologic finding was severe loss of spiral ganglion cells in all turns of the cochlea. Severe loss of neuronal filaments in Rosenthal's canal was also observed. The organ of Corti showed scattered loss of inner and outer hair cells in the basal turn. Partial atrophy of the stria vascularis was observed in all turns of the cochlea. CONCLUSION: Our results suggest that severe loss of spiral ganglion cells was the main cause of sensorineural HL associated with the T7511C mutation.

Atrophy↗

Maturation of circulating dendritic cells and imbalance of T-cell subsets in patients with squamous cell carcinoma of the head and neck.

Interactions between dendritic cells (DCs) and T cells play a pivotal role in the regulation and maintenance of immune responses. In cancer patients, various immunological abnormalities have been observed in these immune cells. Here, we investigated proportions and the phenotype of DCs and the cytokine profile of T-cell subsets in the peripheral blood of patients with squamous cell carcinoma of the head and neck (SCCHN), using multicolor flow cytometry. The percentage of myeloid (CD11c(+)), but not plasmacytoid (CD123(+)) DCs, was significantly lower (P<0.05) and expression of HLA-DR was significantly decreased in total and myeloid DCs of cancer patients compared to healthy donors. Simultaneous analyses of T-cell subsets in the patients' circulation showed significantly increased proportions of CD4(+) T cells expressing Th1 and Th2 cytokines after ex vivo stimulation without any skewing in the Th1/Th2 ratio. The relative level of HLA-DR expression on myeloid or total DCs positively correlated with the Th1/Th2 ratio (P<0.01), and the proportion of total circulating DCs was inversely correlated with that of regulatory CD4(+)CD25+() T cells (P<0.01). These results suggest that the decreased proportion of circulating DCs and decreased HLA-DR expression in DCs may have a major impact on systemic immune responses in patients with SCCHN.

Adult↗

Sexually dimorphic expression of the novel germ cell antigen TEX101 during mouse gonad development.

Prospermatogonia, or gonocytes, are the cells that differentiate from primordial germ cells to the first mature type of spermatogonia in the developing testis. Although prospermatogonia play a central role in this stage (i.e., prespermatogenesis), the details regarding their characterization have not been fully elucidated. Recently, we identified a novel mouse testicular germ cell-specific antigen, TES101 reactive protein (TES101RP), in the adult mouse testis. The protein TES101RP is also designated as protein TEX101. In the present study, we investigated the expression of TEX101 on germ cells in developing mouse gonads using histochemical techniques (i.e., immunohistochemistry, BrdU labeling, and TUNEL staining) and reverse transcription-polymerase chain reaction. TEX101 appeared on germ cells in both male and female gonads after the pregonadal period. In the testis, TEX101 was expressed constitutively on surviving prospermatogonia during prespermatogenesis. After the initiation of spermatogenesis, the prospermatogonia differentiated into spermatogonia. TEX101 expression disappeared from the spermatogonia, but reappeared on spermatocytes and spermatids. In the ovary, TEX101 was expressed on germ cells until the start of folliculogenesis; TEX101 was not detected on oocytes that were surrounded by follicular cells. These findings indicate that TEX101 is a specific marker for both male and female germ cells during gonadal development. Because the on and off switching of TEX101 expression in germ cells almost parallels the kinetics of gametogenesis, TEX101 may play an important physiological role in germ cell development.

Animals↗

Infiltration of dendritic cells and NK cells into the sentinel lymph node in oral cavity cancer.

The sentinel lymph node (SLN) is regarded as the first tumor-draining lymph node, which may be the initial site activated by tumor antigens. To clarify the immunological functions of SLNs, a total of 89 tumor-free regional lymph nodes (41 SLNs and 48 non-SLNs) were obtained from 12 patients with oral cavity cancer, and infiltration of both DCs and NK cells was determined by immunohistochemistry. S-100+ and CD1a+ DCs infiltrated significantly into SLNs compared to non-SLNs. Analysis in each of the pN0 and pN+ patients showed that all the DC markers in pN0 patients and only S-100+ in pN+ patients were significantly more abundant in SLNs. Moreover, infiltration of CD83+ DCs was less in pN+ patients than in pN0 patients. These results suggest that more significant immune responses against cancer occur in SLNs than in non-SLNs. However the progression of disease including nodal disease may cause systemic immunosuppression.

Adult↗

Novel method for recording vestibular evoked myogenic potential: minimally invasive recording on neck extensor muscles.

OBJECTIVES: Vestibular evoked myogenic potential (VEMP) has been used to test vestibulocollic reflex. However, VEMP is not stable on elderly patients because of their weak muscular strength. In this study, we tried to record VEMP on median neck extensor muscles with weak muscular contraction STUDY DESIGN: We recorded VEMP from normal subjects and patients by novel and conventional methods. METHOD: Thirty-one normal subjects and 56 patients with vertigo or hearing loss were tested in a seated or prone position without muscular tension. The different electrodes were placed on the median surface at the palpable bottom of the occipital bone. RESULTS: Our response showed a clear negative peak at 13 ms on normal subjects, with reversed polarity compared with VEMP on the sternocleidomastoid muscle. This potential is defined as VEMP caused by the proper latencies, dependency of the strength on sound stimulation, and independence of hearing ability. In the cases of acoustic neurinoma, onset latencies were prolonged or nonexistent. The responses on neck extensor muscles could not be recorded on some elderly patients. CONCLUSION: This new method of recording VEMP is less invasive and suitable for elderly patients.

Adolescent↗

A preliminary study on sentinel lymph node biopsy: feasibility and predictive ability in oral cavity cancer.

The main factor that affects the prognosis of patients with head and neck cancer (HNC) is regional lymph node metastases. For this reason, the accurate evaluation of neck metastases is required for neck management. This study investigates the sentinel lymph node identification and the accuracy of the histopathology of the sentinel lymph node in patients with HNC. Eleven patients with histologically proven oral squamous cell carcinoma accessible to radiocolloid injection were enrolled in this study. Using both lymphoscintigraphy and a handheld gamma probe, the sentinel lymph node could be identified in all 11 patients. Subsequently, the sentinel lymph nodes and the neck dissection specimen were examined for lymph node involvement due to tumor. The histopathology of sentinel lymph nodes was consistent with the pathological N classification in all 11 patients. Furthermore, the histopathology of sentinel lymph nodes was superior to physical examination, computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) scan. The results of this study indicate that sentinel lymph node identification is technically feasible and predicts cervical metastases in patients with oral cavity cancer. This may be a useful diagnostic technique for identifying lymph node disease in staging lymph node dissection.

Adult↗

Diagnosis of tumor in the nasal cavity and paranasal sinuses with [11C]choline PET: comparative study with 2-[18F]fluoro-2-deoxy-D-glucose (FDG) PET.

[11C]choline (11C-choline) positron emission tomography (PET) was performed to evaluate its clinical utility in the diagnosis of tumors in the nasal cavity and paranasal sinuses. We studied 22 patients with suspicion of malignant tumors in the nasal cavity and paranasal sinuses. Tumor uptake of 11C-choline was measured with standardized uptake value (SUV) and correlated with the pathological diagnosis. 2-[18F]fluoro-2-deoxy-D-glucose (FDG) PET was performed in all patients for comparison. Both 11C-choline and FDG PET depicted squamous cell carcinoma showing an increased activity significantly higher than that of normal tissue, and these SUVs were significantly higher than those of benign lesions. FDG uptake in malignant tumors as a whole was variable. Although 11C-choline uptake in squamous cell carcinoma was lower than FDG uptake, 11C-choline uptake in malignant tumors was relatively uniform and statistical significance was found. PET with 11C-choline may be useful to diagnosis tumors in the nasal cavity and paranasal sinuses.

Adult↗

Acute otitis media caused by drug-resistant bacteria: correlation with antibiotic treatment.

OBJECTIVE: Although acute otitis media (AOM) is the commonest infectious disease of childhood, the emergence of drug-resistant bacteria has dramatically changed its clinical outcome. Here, we report the trend of AOM due to drug-resistant Staphylococcus pneumoniae (DRSP) and beta-lactamase-negative ampicillin-resistant Haemophilus influenzae (BLNAR), and the relation between antibiotics used for the management of AOM and the isolation of bacterial pathogens. MATERIAL AND METHODS: Bacterial isolation and susceptibility tests were performed on specimens from children with AOM. Clinical information, including antibiotic treatment within the previous 30 days, was analyzed. RESULTS: DRSP was detected in 59.3% of Pneumococci isolates and BLNAR in 26.0% of H. influenzae isolates. As expected, the incidence of AOM caused by such drug-resistant bacteria has been increasing year on year, and 32% of cases have been treated with inappropriate antibiotics. In contrast, 32% of cases of AOM caused by DRSP and 50% caused by BLNAR were given antibiotics with high susceptibility to drug-resistant bacteria. CONCLUSION: In order to ensure the most appropriate use of antibiotics, clinicians should consider performing tympanocentesis or myringotomy, with subsequent submission of the middle ear fluid for susceptibility testing. Furthermore, these results suggest that, as well as the selection of antibiotics, the dosage and period of dosing should also be considered in the management of AOM. In addition, other factors, in particular horizontal transmission from other infants in day care or nursery school, may affect the rapid spread of such drug-resistant bacteria.

Acute Disease↗

Tone burst-evoked myogenic potentials in rat neck extensor and flexor muscles.

Vestibular evoked myogenic potential (VEMP) has been used to test the vestibulocollic reflex. This study establishes a stable recording of VEMPs of animals, and presents useful parameters for vestibular ability. In an acute experiment, rats were decerebrated, and myogenic potential from neck extensor muscles was recorded. The myogenic potentials elicited by a tone-burst stimulus showed a biphasic response in the ipsilateral muscle, and the mean latency of the response was 3.56 ms, the positive peak appearing at 4.63 ms. The onset latencies of the response lengthen as the stimulus becomes weaker; this is the most suitable parameter of vestibular ability. The latencies of the monophasic response from the spinal cord were shorter than those of muscle. After injection of a muscle relaxant, myogenic potentials disappeared immediately, but the spinal cord response remained. We succeeded in recording responses not only from acute experimental animals but also from free-moving animals for the first time. These myogenic potentials were similar to VEMPs in humans; because the threshold of the response was higher than the auditory brainstem response threshold by 40-45 dB, the response could only be recorded with very high spontaneous muscle activity and the latency was shorter than the startle reflex.

Acoustic Stimulation↗

Temporal bone histopathological and quantitative analysis of mitochondrial DNA in MELAS.

OBJECTIVES/HYPOTHESIS: Although hearing loss is common in MELAS (syndrome of mitochondrial encephalopathy, lactic acidosis and stroke-like episodes), the histopathology of the temporal bone has not been reported. The majority of cases of MELAS are linked to a mitochondrial DNA (mtDNA) mutation at nucleotide 3243. In MELAS, normal mtDNA and mutant mtDNA coexist in a heteroplasmic manner. The purpose of the study was to report the otopathological findings from two patients with MELAS and quantitative mtDNA analysis in the inner ear of one of these patients. STUDY DESIGN: Basic scientific histopathological examination and quantitative mtDNA analysis of the temporal bone. METHODS: Temporal bones were embedded in celloidin and sectioned for light microscopic study. Graphic reconstruction of the cochlea was performed using the method described by Schuknecht. For quantitative mtDNA analysis, total DNA from the membranous part of the inner ear was collected, amplified by polymerase chain reaction, and digested with the restriction enzyme. The percentage of mutant/total mtDNA was measured by the ratio of fluorescence intensity. RESULTS: Histopathological examination revealed severe degeneration of the stria vascularis and degenerative change of spiral ganglion cells in both patients. The quantitative DNA studies showed that the proportion of mutant to wild-type mtDNA was similar in both histologically affected and histologically unaffected tissues within the inner ear. CONCLUSION: Dysfunction of the stria vascularis and spiral ganglion cells causes sensorineural hearing loss in MELAS.

Adult↗

Nonsyndromic hearing loss caused by a mitochondrial T7511C mutation.

OBJECTIVES: The aims of the present study were to identify a mutation in a Japanese family showing nonsyndromic sensorineural hearing loss and to relate the mutation to characteristics of patients, including audiovestibular findings. STUDY DESIGN: Familial cohort study. METHODS: Mutation analysis was performed using genomic DNA extracted from blood samples. Subjects underwent audiovestibular examinations, including pure-tone audiograms, tympanometry, self-recording audiometry, acoustic reflex threshold, speech discrimination testing, evoked and distortion-product otoacoustic emissions, auditory brainstem responses, and caloric testing. RESULTS: We identified a T7511C mutation in the mitochondrial tRNA(Ser(UCN)) gene previously reported in one other family. The degree of heteroplasmy for the T7511C mutation ranged from 84% to 92%, and did not correlate with age at examination or severity of hearing loss. Extensive audiologic evaluation suggested both cochlear and retrocochlear involvement. CONCLUSION: Families with maternally transmitted nonsyndromic hearing loss should be investigated for mutations in the tRNA(Ser(UCN)) gene.

Adult↗