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Biomedical subjects

Y Iino

Publications and source records attributed to Y Iino.

At least 19 recordsLinked to original sources

The Ras-MAPK pathway is important for olfaction in Caenorhabditis elegans.

The Ras-MAPK (mitogen-activated protein kinase) signal transduction pathway is well known to control cellular proliferation and differentiation in response to extracellular signals, but its other functions are less understood. In Caenorhabditis elegans this pathway regulates several developmental events, such as vulval induction and progression of meiosis, but its function in the nervous system is unknown. Here we report that the Ras-MAPK pathway is involved in olfaction in this organism. Mutational inactivation and hyperactivation of this pathway impairs efficiency of chemotaxis to a set of odorants. Experiments in which let-60 ras was expressed using a heat-shock promoter and a cell-specific promoter show that a normal activity of LET-60 Ras is required in mature olfactory neurons. Application of the odorant isoamylalcohol to wild-type animals leads to the activation of MAP kinase in olfactory neurons within 10 seconds. This induction is dependent on the function of the nucleotide-gated channel TAX-2/TAX-4 and the voltage-activated calcium channel subunit UNC-2. These results suggest a dynamic regulatory role for the Ras-MAPK pathway in perception and transmission of sensory signals in olfactory neurons.

Animals

Invasive verrucous carcinoma: a temporal bone histopathology report.

Only nine cases of primary verrucous carcinoma of the temporal bone have been reported in the English literature. We describe histopathologic findings in a 78-year-old man dying of intracranial complications of primary verrucous carcinoma of the external auditory canal. Following autopsy the temporal bone was prepared for light microscopic examination. The temporal bone was serially sectioned horizontally after fixation, decalcification, and embedding, and each 10th section was stained with hematoxylin and eosin and examined by light microscopy. The carcinoma originated from the external auditory canal, infiltrating the mastoid cavity, the middle ear, tissue adjacent to the internal carotid artery, and the posterior cranial fossa, where it invaded the right cerebellum and produced an abscess. The labyrinth and internal auditory canal were not infiltrated. Metastasis to lymph nodes or distant sites was not identified. In the present case, the verrucous carcinoma originating from the external auditory canal extended into the posterior cranial fossa, while it did not invade the membranous labyrinth.

Aged

A scheme for challenging cholesteatoma in children.

In order to secure both long-lasting carefree ears and hearing-preservation/restoration, the best method to apply is the closed-method tympanoplasty, especially for cholesteatomatous otitis media in children. We agree with this method, in spite of the high percentages of postoperative residual cholesteatoma in children. Until a better way of irradicating cholesteatoma becomes available, either staged operations or periodical check-ups for many years are mandatory. While postoperative attic retraction/cholesteatoma formation seems to be preventable in most cases, the rate of residual cholesteatoma is very high in our data and in other reports. Looking for a reason, the differences between the cholesteatoma in children and those in adults are to be investigated in macro-, micro- and ultramicroscopic observations. In addition, basic rather than clinical studies on cholesteatoma in children are requested.

Child

Efficacy of tympanostomy tube insertion for otitis media with effusion in children with Down syndrome.

OBJECTIVE: Although the insertion of tympanostomy tubes is regarded as an effective treatment for otitis media with effusion in the general population, it remains to be determined whether tympanostomy tube insertion is also effective for otitis media with effusion in children with Down syndrome. The present study was carried out to determine the efficacy of tympanostomy tube insertion in children with Down syndrome. PATIENTS AND METHODS: We studied 28 children (18 males and ten females) with Down syndrome and 28 age-matched control children who underwent tympanostomy tube insertion and were followed up for more than 2 years, up to 7 years of age or older. The children were followed up every month for 6 months after the operation and every 2 months thereafter. The tympanostomy tubes were not removed unless granulation tissue appeared around the ventilation tubes. RESULTS: The cure rate for otitis media with effusion was lower in the children with Down syndrome than in the age-matched control children. Sequelae of otitis media with effusion (atelectatic eardrum, permanent perforation of the eardrum and middle ear cholesteatoma) were significantly often encountered in the former group. The children with Down syndrome had more frequent episodes of otorrhea from the tympanostomy tubes than the control children and antibiotic-resistant-bacteria were frequently isolated. Moreover, improvement in hearing acuity after the placement of tympanostomy tubes was not always achieved in children with Down syndrome. CONCLUSION: The efficacy of the tympanostomy tube insertion for children with Down syndrome was much lower than in control children. We propose that in children with Down syndrome conservative management should be the treatment of first choice and that the insertion of tympanostomy tubes should be indicated only when hearing loss due to middle ear effusion is in a severe degree and when pathological changes of the eardrum, such as adhesion and deep retraction pocket formation, are going to occur.

Adolescent

A Caenorhabditis elegans JNK signal transduction pathway regulates coordinated movement via type-D GABAergic motor neurons.

The c-Jun N-terminal kinase (JNK) of the MAP kinase superfamily is activated in response to a variety of cellular stresses and is involved in apoptosis in neurons. However, the roles of the JNK signaling pathway in the nervous system are unknown. The genes for the Caenorhabditis elegans homolog of JNK, JNK-1, and its direct activator, JKK-1, were isolated based on their abilities to function in the Hog1 MAP kinase pathway in yeast. JKK-1 is a member of the MAP kinase kinase superfamily and functions as a specific activator of JNK. Both jnk-1 and jkk-1 are expressed in most neurons. jkk-1 null mutant animals exhibit defects in locomotion that can be rescued by the conditional expression of JKK-1 in mutant adults, suggesting that the defect is not due to a developmental error. Furthermore, ectopic expression of JKK-1 in type-D motor neurons is sufficient to rescue the movement defect. Thus, the C.elegans JNK pathway functions in type-D GABAergic motor neurons and thereby modulates coordinated locomotion.

Amino Acid Sequence

The efficacy of technetium-99m-MIBI scan and intraoperative methylene blue staining for the localization of abnormal parathyroid glands.

The efficacy of the technetium-99m-2-methoxyisobutylisonitrile (Tc-MIBI) scan and intraoperative methylene blue staining was analyzed in a consecutive series of 15 patients with primary hyperparathyroidism who underwent neck surgical exploration. A total of 17 abnormal parathyroid glands were removed, 7 of which were confirmed histologically as adenomas and 10 as hyperplasias. The Tc-MIBI scan and the thallium-201-technetium-99m subtraction (Tl/Tc) scan preoperatively localized 11 (69%) of 16, and 6 (40%) of 15 abnormal parathyroid glands, respectively. The Tc-MIBI scan correctly localized two ectopic abnormal parathyroid glands which were not localized by the Tl/Tc scan or ultrasonography (US). However, it also demonstrated false-positive accumulations caused by thyroid diseases in two patients. There were 4 abnormal parathyroid glands not detected by the preoperative imaging techniques, whereas all 17 abnormal parathyroid glands were stained with methylene blue, the infusion of which caused no adverse effects or toxicity. In conclusion, Tc-MIBI scanning and intraoperative methylene blue staining are effective techniques for the localization of abnormal parathyroid glands in patients with primary hyperparathyroidism.

Adenoma

kel-1, a novel Kelch-related gene in Caenorhabditis elegans, is expressed in pharyngeal gland cells and is required for the feeding process.

BACKGROUND: Kelch-related proteins constitute an expanding family, members of which carry two conserved motifs named the BTB/POZ and the kelch repeat domains. The best-characterized member, Drosophila Kelch, constitutes the ring canals in the egg chamber in association with actin. However, physiological and biochemical functions of the members of this family remain largely uncharacterized. RESULTS: We identified the kel-1 gene encoding a Kelch-related protein in the nematode Caenorhabditis elegans. The deduced KEL-1 protein had 618 amino acid residues and was most similar to Drosophila Kelch. Loss of kel-1 function caused growth arrest at an early larval stage, most likely at the beginning of L2. The kel-1 deletion mutant appeared normal in morphology, movement and pumping action for the initial two to three days after hatching, but it failed to convey foods effectively to intestine and could hardly increase in body size. Analyses using immunostaining and reporter gene expression indicated that kel-1 was expressed almost exclusively in the g1 pharyngeal gland cells during late embryogenesis and at all developmental stages thereafter. CONCLUSIONS: C. elegans KEL-1 protein is essential for the larval development, probably performing a function required for feeding in the pharyngeal g1 gland cells, which are supposed to secrete materials aiding digestion.

Amino Acid Sequence

Fission yeast Pob1p, which is homologous to budding yeast Boi proteins and exhibits subcellular localization close to actin patches, is essential for cell elongation and separation.

The fission yeast pob1 gene encodes a protein of 871 amino acids carrying an SH3 domain, a SAM domain, and a PH domain. Gene disruption and construction of a temperature-sensitive pob1 mutant indicated that pob1 is essential for cell growth. Loss of its function leads to quick cessation of cellular elongation. Pob1p is homologous to two functionally redundant Saccharomyces cerevisiae proteins, Boi1p and Boi2p, which are necessary for cell growth and relevant to bud formation. Overexpression of pob1 inhibits cell growth, causing the host cells to become round and swollen. In growing cells, Pob1p locates at cell tips during interphase and translocates near the division plane at cytokinesis. Thus, this protein exhibits intracellular dynamics similar to F-actin patches. However, Pob1p constitutes a layer, rather than patches, at growing cell tips. It generates two split discs flanking the septum at cytokinesis. The pob1-defective cells no longer elongate but swell gradually at the middle, eventually assuming a lemon-like morphology. Analysis using the pob1-ts allele revealed that Pob1p is also essential for cell separation. We speculate that Pob1p is located on growing plasma membrane, possibly through the function of actin patches, and may recruit proteins required for the synthesis of cell wall.

Actins

Natural history of fibroadenomas based on the correlation between size and patient age.

BACKGROUND: Several recent studies have reported that most fibroadenomas remain static or regress when they are managed conservatively; however, no such studies have evaluated the breast disorder in Japanese women. To understand the natural history of fibroadenomas in Japanese women, we examined the correlation between the sizes of the fibroadenomas and the women's age. METHODS: Fifty-eight consecutive patients (age range, 17-51 years; mean, 33.9 years) with histologically confirmed fibroadenoma were enrolled in this study. The sizes of the excised fibroadenomas were analyzed in relation to the women's ages. RESULTS: The fibroadenomas decreased significantly in size (Y, mm) with patient age (X, years) (P = 0.0012) according the equation Y = -0.340X + 27.0 (95% confidence limits for the slope, -0.139 to -0.540). From this equation, the mean sizes of the fibroadenoma in women aged 20, 30 and 40 years were expected to be 20.2 mm (95% confidence interval, 16.2-24.2 mm), 16.8 mm (95% confidence interval, 10.8-22.8 mm) and 13.4 mm (95% confidence interval, 5.4-21.4 mm), respectively. The mean annual decrease in the size of the fibroadenomas was 0.340 mm. CONCLUSIONS: Our results indicate that in Japanese women fibroadenomas increase in size more frequently in younger than in older women. Moreover, it is speculated that most fibroadenomas might stop growing when they reach an approximate maximum diameter of 20 mm, after which time they might remain static or regress.

Adolescent

Amplification of RNA from archival human temporal bone sections.

BACKGROUND: The amplification of DNA from celloidin-embedded human temporal bone sections by polymerase chain reaction (PCR) has been applied to some auditory diseases, such as herpes zoster oticus and hearing loss caused by the mutations of mitochondrial DNA. However, few studies have reported detection of RNA from temporal bone sections. OBJECTIVES: Because RNA analysis from temporal bone sections may elucidate the development of the diseases in the auditory, vestibular, and facial nerves, the authors investigated whether RNA in these sections can be amplified by reverse transcription (RT)-PCR. METHODS: Sections that were formalin-fixed, decalcified, and embedded between 1972 and 1986 were used. Nucleic acid was extracted from the celloidin-embedded temporal bone sections and subjected to RT-PCR. Human alpha-tubulin RNA was reverse transcribed to cDNA and amplified by nested PCR using two sets of primers that were designed to distinguish cDNA from genomic DNA based on the presence of an intron between the primers. RESULTS: Human alpha-tubulin RNA was detected in 11 of 14 temporal bone sections (79%) by RT-PCR. RNA was detected in even the oldest sections, which were processed in 1972. CONCLUSIONS: These results indicate that RNA can be analyzed from archival celloidin-embedded human temporal bone sections.

Archives

Human temporal bone study on the postnatal ossification process of auditory ossicles.

OBJECTIVE: In infancy the head of the malleus and body of the incus normally contain bone marrow, which is gradually replaced by bone and converted into vascular channels with age. This study was carried out to clarify the age at which ossification of the ossicles is complete and to examine factors influencing the ossification process. STUDY DESIGN: Human temporal bone sections from 32 infants and children with or without congenital anomalies, aged 1 day to 9 years, who were born at term were studied. METHODS: The percentage bone marrow area occupying the head of the malleus and body of the incus was calculated in three horizontal temporal bone sections for each case, using computer-aided digital processing of images. RESULTS: Bone marrow was observed in both the malleus and incus in children until 25 months of age, while after the age of 25 months no bone marrow tissue was present in either of the ossicles. It appeared that the bone marrow space disappeared somewhat earlier in the malleus than in the incus. The bone marrow space around the otic capsule disappeared much earlier than that within the ossicles. The age at completion of ossification was correlated with neither the presence of congenital anomalies nor the presence of residual mesenchyme in the middle ear. CONCLUSIONS: Ossification of the ossicles seems to occur steadily throughout fetal life and after birth during development of the middle ear. Although the clinical significance of postnatal residual bone marrow within the ossicles is not known, it possibly plays a role as a blood-forming organ in early infancy.

Bone Marrow

A randomized controlled comparative study of oral medroxyprogesterone acetate 1,200 and 600 mg in patients with advanced or recurrent breast cancer.

A randomized controlled comparative study of oral medroxyprogesterone acetate (MPA) 1,200 mg (arm I) and 600 mg (arm II) was conducted in 80 patients with advanced or recurrent breast cancer. There were no significant differences between arm I and arm II in terms of response rate, duration of response and survival, or in terms of incidence and severity of adverse reactions. The lowest serum MPA concentration in responders tended to be higher than that in nonresponders. In the cohort of this study, the lowest concentration in partial response was 17.4 ng/ml, suggesting that this level may be the required minimum serum concentration.

Antineoplastic Agents, Hormonal

Left colon substitution with His' angle following total gastrectomy. Surgical technique using stapling devices.

To resolve the disadvantages of jejunal Roux-en-Y reconstruction following total gastrectomy, we attempted the use of left colon substitution with all anastomoses conducted using mechanical stapling devices. A His' angle was formed to reduce regurgitation esophagitis. About 25 cm of the left colon with the ascending branch of the left colic artery with an adequate blood supply was brought up to the remnant esophagus without tension on the mesentery. The colon graft was interposed between the esophagus and duodenum in an isoperistaltic fashion. Three anastomoses, esophagocolic, duodenocolic and colocolic, were completed with a circular stapling device. An end-to-side esophagocolonostomy was positioned about 3 cm distal from the blind end of the proximal colon stump. The proximal end of the left colon was pexied to the esophagus using 3-4 stitches to make a new His' angle. Gastrointestinal continuity was restored by a side-to-end colonoduodenostomy and an end-to-end colonocolonostomy. Fifteen gastric cancer patients underwent left colon substitution following total gastrectomy. The circular staple used for esophagocolonostomy and colonoduodenostomy was 25 mm in all patients, and for colonocolonostomy was 29 mm in 9 patients and 33 mm in 6 patients. No problems were encountered in any steps of the procedure, and faulty stapling was avoided. Neither anastomotic leakage nor necrosis of the interposed colon segment was seen, nor was late anastomotic stricture, in any patient. Barium radiograms of the interposed colon segment showed that the capacity and passage of the interposed colon were adequate, and regurgitation did not occur. Diet volume was satisfactory and weight loss minimal.

Adult

Mitogen-activated protein kinase cascade in breast cancer.

The mitogen-activated protein (MAP) kinase is considered to play a central role in diverse cellular events including carcinogenesis and tumor progression. Indeed, expression of MAP kinase, tyrosine-phosphorylated MAP kinase, and Raf-1 protein was greater in cancerous human tissues than in the surrounding noncancerous glands. In a 7,12-dimethylbenz[a]anthracene-induced rat mammary carcinoma model, estrogen promoted and ovariectomy and antiestrogen, tamoxifen (TAM) inhibited the tumor growth. Ovariectomy suppressed expression of MAP kinase, tyrosine-phosphorylated MAP kinase and Raf-1, whereas estrogen as well as TAM induced expression of MAP kinase and Raf-1 under castrated conditions. Since it was reported that MAP kinase was activated during the progression of breast carcinoma cells, such estrogenic actions of TAM toward the MAP kinase cascade might be responsible for malignant progression.

Animals