Endoscopic Modified Medial Maxillectomy for Fungal Ball of the Hypoplastic Maxillary Sinus With Bony Hypertrophy.

Sinus fungal ball is defined as noninvasive chronic rhino-sinusitis with a clump of mold in the paranasal sinuses, typically affecting the maxillary sinus. Fairly good outcomes of endoscopic surgery have been reported where the ball is removed through the antrostomy. However, the affected sinus tends to have a smaller cavity and thicker bony walls. As such, it is often challenging to maintain a window size that is sufficient to control possible recurrence. The endoscopic modified medial maxillectomy procedure was applied to a 61-year old and a 70-year old female patient with maxillary sinus fungal ball. Using this method, we created a much larger inferior meatal antrostomy without difficulty. The window provided us with an endoscopic view of the whole sinus and complete eradication of the lesion. Endoscopic modified medial maxillectomy is useful as a surgical procedure for maxillary sinus fungal ball and should be considered for better outcomes.

Compliance and problems with the surveillance program for HCC diagnosis.

We conducted a multicenter retrospective study for evaluating the background of and diagnostic opportunity for 651 patients with primary hepatocellular carcinoma (HCC). The etiologies were hepatitis B virus (HBV) in 20.0% of patients, hepatitis C virus (HCV) in 36.3%, and non-B non-C (NBNC) in 43.5%. The characteristics of non-alcoholic NBNC HCC patients included low frequency of liver cirrhosis and high frequency of life style-related diseases. The mean diameter of HCC was approximately 4cm. Most patients were diagnosed using ultrasonography and dynamic computed tomography (CT). However, 18.6% of patients were diagnosed using conventional contrast-enhanced CT. Compliance with the surveillance program for HCC diagnosis was 35.4% in HBV carriers and 49.2% in HCV carriers. The main causes of deviation from the program included undiagnosed HBV and HCV carriers, non-compliance with the surveillance program by physicians, and no medical care for HBV and HCV carriers. For an early diagnosis of HCC, it is essential to improve the diagnoses of HBV and HCV carriers, promote the follow-ups of HBV and HCV carriers in hospitals, re-educate physicians, and identify the risk factors of NBNC HCC.

Expression of anti-Müllerian hormone and its type II receptor in germ cells of maturing rat testis.

This work aimed to clarify the expression and roles of anti-Müllerian hormone (AMH) and its type 2 receptor (AMHR2) in seminiferous tubules of maturing rat testes. By quantitative RT-PCR, we determined the relative expressions of Amh, Amhr2, Scp1, Rsbn1, Ngfr, and Rhox5 in rat testes aged 5-49 days (d), and in germ cells and Sertoli cells isolated from 21d testes. Smad 1,5 and 8 expressions were also determined in 21d testes and isolated germ cells. Moreover, we performed in situ hybridization (ISH) of Amh and Amhr2 in 21d testes, and immunohistochemical staining (IHCS) in 10, 15 and 21d testes using antibodies of AMH and AMHR2. In 21d testes, expression of the spermatocyte specific gene, Scp1, increased but that of the round spermatid specific gene, Rsbn1, was faint. By ISH and IHCS, expressions of AMH and AMHR2 were strongly observed in spermatocytes of 21d testes, but not in spermatogonia. In 21d testes, expressions of immature Sertoli cell specific gene, Ngfr, and mature Sertoli cell specific gene, Rhox5, were observed. IHCS confirmed the presence of AMH and AMHR2 in Sertoli cells. Smad 1, 5 and 8 were highly expressed in 21d testes and isolated germ cells. These results indicate that not only immature Sertoli cells but also spermatocytes express AMH and AMHR2 in maturing testes. In this study, we first clarified that spermatocytes coexpressed AMH and AMHR2 in rats. We speculated that AMH produced by spermatocytes and Sertoli cells binds AMHR2 of spermatocytes and acts through SMADs.

Clinical Factors Associated With the Outcomes of Long-Term Middle Ear Ventilation Tube Insertion in Pediatric Patients.

BACKGROUND: Ventilation tube (VT) insertion is the most common treatment for otitis media with effusion (OME). However, OME recurrence and persistent tympanic membrane (TM) perforation after VT removal are encountered in a certain percentage of such children. METHODS: This study was performed to determine the outcomes of children who underwent long-term VT insertion. A total of 326 ears from 192 patients were analyzed. The associations among the patient age, sex, history of OME, history of repeated acute otitis media, placement duration, whether the VT had been removed intentionally or spontaneously, and the outcome (persistent TM perforation or OME recurrence) were analyzed. The outcomes of multiple VT tube insertions were also reviewed. We also analyzed whether or not local or general anesthesia was associated with the early spontaneous extrusion of the VT. RESULT: The OME recurrence and TM perforation rates were 29% (96/326 sides) and 17% (57/326 sides), respectively, for first insertions. In addition, 96 (29%) sides underwent ≥2 insertions. The shorter the duration for which the VT was retained in the middle ear, the more significant the rate of increase in OME recurrence. The OME recurrence was observed more often when VT was spontaneously removed than when intentionally removed. The rate of persistent TM perforation was significantly associated with male sex. Persistent TM perforation was not observed in patients who underwent 4 or 5 insertions. The anesthesia method did not significantly influence the timing of spontaneous extrusion of VT. CONCLUSION: The retention period of VT should be at least 2 years, and VT removal at the age of 7 might be a viable strategy. Multiple VT insertions are recommended for patients with recurrent OME. Ventilation tube under local anesthesia is an effective option for tolerable children.

Rat stem-cell leukemia gene expression increased during testis maturation.

We found that stem-cell leukemia (SCL), also known as T cell acute-lymphocytic leukemia (Tal-1) gene expression, was upregulated in the maturing rat testis. Strong expression of Tal-1 was detected in the normal maturing rat testis by Northern blotting. Western blotting revealed the protein size to be about 34 kDa. Protein expression was wide-spread in spermatocytes, spermtids and spermatogonia in accordance with the seminiferous epithelium cycle, as determined by an analysis of immunohistochemistry. Gene expression of Tal-1 regulatory gene, NKX3.1, was negatively correlated with Tal-1 expression. Human Tal-1 expression in the maturing testis as well as in bone marrow was observed, which suggests that the gene product is a novel cancer-testis antigen candidate. Taken together, TAL-1 may be involved in cell division, morphological changes, and the development of spermatogenic cells in the normal rat testis.

Expression of a novel sphingosine 1-phosphate receptor motif protein gene in maturing rat testes.

We screened a novel sphingosine 1-phosphate receptor type 5 motif-containing gene, LOC290876, from maturing rat testes by differential display. Gene expression was testis-specific, increased at week 7, and continued for 15 weeks. PCR analysis clarified two gene transcript isoforms, which were expressed at the same level in all samples detected in Northern blot. The deduced amino acid sequences of the two isoforms revealed differences in carboxyl terminal sequences. Gene and protein expression in the testes was dominant in the spermatocytes, and protein expression was localized to the nucleus. Taken together, these findings suggest that the LOC290876-encoded gene product is not involved in sphingosine signaling, but has distinct roles in the nucleus during the processes of spermatocyte maturation and meiosis producing spermatids.

Regulation of rat tetratricopeptide repeat domain 29 gene expression by follicle-stimulating hormone.

We screened the gene that encodes tetratricopeptide repeat domain 29 (Ttc29) in the maturing rat testis. Gene expression was determined by Northern blotting of 7-week-old rat testes, and a strong signal was detected close to the 18S rRNA band in addition to two weak high-molecular-weight signals. In situ hybridization revealed that Ttc29 was expressed primarily in the spermatocytes. We evaluated the effect of gonadotropin on Ttc29 expression using hypophysectomized rats. The pituitary was removed from 3-week-old rats, gonadotropin was injected at 5 weeks, and Ttc29 expression was determined at 7 weeks. Although testicular development and hyperplasia of interstitial cells were observed following chorionic gonadotropin treatment after hypophysectomy, Ttc29 expression was upregulated by treatment with follicle-stimulating hormone. Ttc29 encodes axonemal dynein, a component of sperm flagella. Taken together, these data indicate that axonemal dynein expression starts in the spermatocytes and is regulated by follicle-stimulating hormone.

Assessment of the ablated area after radiofrequency ablation by the spread of bubbles: comparison with virtual sonography with magnetic navigation.

BACKGROUND/AIMS: The purpose of this study was to investigate whether bubble images after radiofrequency ablation (RFA) can predict the ablated area. METHODOLOGY: The spread of bubbles 5 minutes after RFA were compared with the unenhanced area of virtual sonography with magnetic navigation in two RFA methods: expandable needle and cool-tip needle. RESULTS: Thirty-one hepatocellular carcinoma nodules were treated by RFA with either an expandable needle or cool-tip needle (n=14 and n=17, respectively) and examined. In the 14 nodules treated by expandable needle, bubble images (puncture direction; r=0.833, p=0.0002, perpendicular direction; r=0.803, p=0.0005) were closely correlated with the unenhanced area of virtual sonography. On the other hand, in 17 nodules treated by cool-tip needle, there was no correlation between the bubble images and virtual sonography (puncture direction; r=0.590, p=0.0127, perpendicular direction; r=0.342, p=0.180). CONCLUSIONS: The observation of bubbles with the expandable needle can accurately predict the ablated area and is helpful for assessing local control of RFA.

Expression of the centrosomal colon cancer autoantigen gene during spermatogenesis in the maturing rat testis.

We analyzed the gene and protein expression of serologically defined colon cancer antigen 8. Gene expression was upregulated in the maturing rat testis, and was localized to the spermatocytes. Protein was detected in the spermatids and at the sites of mRNA expression. Specific expression of colon cancer antigen 8 was observed in the maturing rat testis.

Late-onset circulatory dysfunction after thyroid hormone treatment in an extremely low birth weight infant.

Late-onset circulatory dysfunction (LCD) is a phenomenon specific to premature infants and is characterized by sudden onset of hyponatremia, hypotension, oliguria and non-physiological weight gain, without an obvious cause, in premature infants after stabilization of circulation and respiration. The cause of LCD is not clear, but adrenal insufficiency in premature infants is a severe syndrome because steroid replacement therapy is often essential to treat the symptoms. We report a rare case of a premature infant who developed an LCD crisis the day after thyroxine replacement therapy. The female infant was born at 25 weeks of gestational age, weighing 672 g, and appeared to have hypothyroidism, with free T4 of 0.19 ng/dl and elevated TSH levels of 26.3 microIU/ml at Day 14. She developed an LCD crisis the day after starting thyroxine treatment. She received steroid replacement therapy for 4 weeks and her adrenal function progressively recovered. She also needed thyroxine supplementation for 13 weeks, which maintained her thyroid function as euthyroid. Because she exhibited cortisol insufficiency and thyroid hormone insufficiency, the antecedent thyroid hormone replacement may be responsible for the onset of LCD. We must consider monitoring adrenal function when starting thyroxine therapy in premature infants with hypothyroxinemia.

Exposure to exogenous estrogen through intake of commercial milk produced from pregnant cows.

BACKGROUND: Modern genetically improved dairy cows continue to lactate throughout almost the entire pregnancy. Therefore, recent commercial cow's milk contains large amounts of estrogens and progesterone. With regard to the exposure of prepubertal children to exogenous estrogens, the authors are particularly concerned about commercial milk produced from pregnant cows. The purpose of the present study was therefore to examine concentrations of serum and urine sex hormones after the intake of cow milk. METHODS: Subjects were seven men, six prepubertal children, and five women. The men and children drank 600 mL/m(2) of cow milk. Urine samples were collected 1 h before the milk intake and four times every hour after intake. In men the serum samples were obtained before and 15, 30, 45, 60, 90 and 120 min after milk intake. Women drank 500 mL of cow's milk every night for 21 days beginning on the first day of the second menstruation. In three successive menstrual cycles, the day of ovulation was examined using an ovulation checker. RESULTS: After the intake of cow milk, serum estrone (E1) and progesterone concentrations significantly increased, and serum luteinizing hormone, follicle-stimulating hormone and testosterone significantly decreased in men. Urine concentrations of E1, estradiol, estriol and pregnanediol significantly increased in all adults and children. In four out of five women, ovulation occurred during the milk intake, and the timing of ovulation was similar among the three menstrual cycles. CONCLUSIONS: The present data on men and children indicate that estrogens in milk were absorbed, and gonadotropin secretion was suppressed, followed by a decrease in testosterone secretion. Sexual maturation of prepubertal children could be affected by the ordinary intake of cow milk.

Prevalence and clinical features of hearing loss caused by EYA4 variants.

Variants in the EYA4 gene are known to lead to autosomal dominant non-syndromic hereditary hearing loss, DFNA10. To date, 30 variants have been shown to be responsible for hearing loss in a diverse set of nationalities. To better understand the clinical characteristics and prevalence of DFNA10, we performed genetic screening for EYA4 mutations in a large cohort of Japanese hearing loss patients. We selected 1,336 autosomal dominant hearing loss patients among 7,408 unrelated Japanese hearing loss probands and performed targeted genome enrichment and massively parallel sequencing of 68 target genes for all patients. Clinical information of cases with mutations in EYA4 was gathered and analyzed from medical charts. Eleven novel EYA4 variants (three frameshift variants, three missense variants, two nonsense variants, one splicing variant, and two single-copy number losses) and two previously reported variants were found in 12 probands (0.90%) among the 1,336 autosomal dominant hearing loss families. The audiometric configuration of truncating variants tends to deteriorate for all frequencies, whereas that of non-truncating variants tends to show high-frequency hearing loss, suggesting a new correlation between genotype and phenotype in DFNA10. The rate of hearing loss progression caused by EYA4 variants was considered to be 0.63 dB/year, as found in this study and previous reports.

Expression of stanniocalcin-1 in gastrointestinal tracts of neonatal and mature rats.

Stanniocalcin-1 (STC-1) produced by ovaries endocrinologically targets to mammary glands and is secreted into milk during lactation. The decline of mother's serum level by STC-1 antiserum administration reduced the milk fat content and the pups' body fat content. Nevertheless, the pups' fecal fat content was increased, suggesting that milk-derived STC-1 could influence intestinal fat absorption. We investigated the STC-1 expression in rat gastrointestinal tissues using immunocytochemistry and in situ hybridization. STC-1 was widely expressed in the chief cells of gastric pits and the cells of intestinal glands. Goblet cells in the small intestine contained STC-1 protein in their mucus. The distribution shows that this peptide is secreted exocrinologically into the gastrointestinal lumen. Quantitative RT-PCR analysis revealed that the expression ratio was higher in the periods of heavy nutritional demand, such as growing and lactation. The endogenous STC-1, similar to milk-derived STC-1, may be involved in digestion and/or absorption in gastrointestinal organs.

Expression of rat sperm flagellum-movement associated protein genes under 2,3,7,8-tetrachlorodibenzo-p-dioxin treatment.

We analyzed the gene expression of sperm flagellum-movement associated proteins, namely, adenylate kinase domain containing protein (RGD1303144) and outer dense fiber protein 1. These gene expressions were up-regulated in a maturing rat testis, and RGD1303144 gene was expressed dominantly in spermatocytes. Although 2,3,7,8-tetrachlorodibenzo-p-dioxin administration reduced sperm motility, these gene expressions were not affected.

Frequency and clinical features of hearing loss caused by STRC deletions.

Sensorineural hearing loss is a common deficit and mainly occurs due to genetic factors. Recently, copy number variants (CNVs) in the STRC gene have also been recognized as a major cause of genetic hearing loss. We investigated the frequency of STRC deletions in the Japanese population and the characteristics of associated hearing loss. For CNV analysis, we employed a specialized method of Ion AmpliSeqTM sequencing, and confirmed the CNV results via custom array comparative genomic hybridization. We identified 17 probands with STRC homozygous deletions. The prevalence of STRC homozygous deletions was 1.7% in the hearing loss population overall, and 4.3% among mild-to-moderate hearing loss patients. A 2.63% carrier deletion rate was identified in both the hearing loss and the control population with normal hearing. In conclusion, our results show that STRC deletions are the second most common cause of mild-to-moderate hearing loss after the GJB2 gene, which accounts for the majority of genetic hearing loss. The phenotype of hearing loss is congenital and appears to be moderate, and is most likely to be stable without deterioration even after the age of 50. The present study highlights the importance of the STRC gene as a major cause of mild-to-moderate hearing loss.

Comprehensive analysis of syndromic hearing loss patients in Japan.

More than 400 syndromes associated with hearing loss and other symptoms have been described, corresponding to 30% of cases of hereditary hearing loss. In this study we aimed to clarify the mutation spectrum of syndromic hearing loss patients in Japan by using next-generation sequencing analysis with a multiple syndromic targeted resequencing panel (36 target genes). We analyzed single nucleotide variants, small insertions, deletions and copy number variations in the target genes. We enrolled 140 patients with any of 14 syndromes (BOR syndrome, Waardenburg syndrome, osteogenesis imperfecta, spondyloepiphyseal dysplasia congenita, Stickler syndrome, CHARGE syndrome, Jervell and Lange-Nielsen syndrome, Pendred syndrome, Klippel-Feil syndrome, Alport syndrome, Norrie disease, Treacher-Collins syndrome, Perrault syndrome and auditory neuropathy with optic atrophy) and identified the causative variants in 56% of the patients. This analysis could identify the causative variants in syndromic hearing loss patients in a short time with a high diagnostic rate. In addition, it was useful for the analysis of the cases who only partially fulfilled the diagnostic criteria.

Expression of the Ha-ras suppressor family member 5 gene in the maturing rat testis.

We analyzed the gene expression of Ha-ras suppressor family member 5 (Hrasls5), which is considered to modulate the Ha-ras signaling cascade, from maturing rat testis. Expression was detected primarily in the spermatocytes in the maturing rat testis. The Hrasls5 gene product might function as a tumor suppressor as well as in spermatogenesis, as deduced from its amino acid sequence.

WFS1 mutation screening in a large series of Japanese hearing loss patients: Massively parallel DNA sequencing-based analysis.

A heterozygous mutation in the Wolfram syndrome type 1 gene (WFS1) causes autosomal dominant nonsyndromic hereditary hearing loss, DFNA6/14/38, or Wolfram-like syndrome. To date, more than 40 different mutations have been reported to be responsible for DFNA6/14/38. In the present study, WFS1 variants were screened in a large series of Japanese hearing loss (HL) patients to clarify the prevalence and clinical characteristics of DFNA6/14/38 and Wolfram-like syndrome. Massively parallel DNA sequencing of 68 target genes was performed in 2,549 unrelated Japanese HL patients to identify genomic variations responsible for HL. The detailed clinical features in patients with WFS1 variants were collected from medical charts and analyzed. We successfully identified 13 WFS1 variants in 19 probands: eight of the 13 variants were previously reported mutations, including three mutations (p.A684V, p.K836N, and p.E864K) known to cause Wolfram-like syndrome, and five were novel mutations. Variants were detected in 15 probands (2.5%) in 602 families with presumably autosomal dominant or mitochondrial HL, and in four probands (0.7%) in 559 sporadic cases; however, no variants were detected in the other 1,388 probands with autosomal recessive or unknown family history. Among the 30 individuals possessing variants, marked variations were observed in the onset of HL as well as in the presence of progressive HL and tinnitus. Vestibular symptoms, which had been rarely reported, were present in 7 out of 30 (23%) of the affected individuals. The most prevalent audiometric configuration was low-frequency type; however, some individuals had high-frequency HL. Haplotype analysis in three mutations (p.A716T, p.K836T, and p.E864K) suggested that the mutations occurred at these mutation hot spots. The present study provided new insights into the audiovestibular phenotypes in patients with WFS1 mutations.

Maternal exposure of low dose of TCDD modulates the expression of estrogen receptor subunits of male gonads in offspring.

We have analyzed the effects of low-dose transplacental and lactational exposure of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on gene expression relating to the dioxin and sexual hormone cascade, and demonstrated the effects on testicular growth and sexual maturation in male offspring rats. TCDD (10 ng/kg) was administered to dams on Days 7 and 14 of gestation, and on Days 0, 7 and 14 after delivery. Gene expression of cytochrome P450 family 1 subfamily A polypeptide 1 (CYP1A1) in the liver of 17-day-old rats was significantly increased compared with controls. Furthermore, expression of estrogen receptors (ER)alpha and ERbeta was significantly increased at 17 and 42 days old, respectively in the testis of TCDD-administered rats compared with controls. Although testicular weight and the seminiferous tubule diameter were increased in 17-day-old rats, there was no difference in the number of germ cells between TCDD-treated and control animals. The expressions of androgen receptor and inhibin subunit genes were not significantly changed. These findings suggest that low-dose exposure of TCDD leads to unusual development of the testis by perturbation of steroid hormone homeostasis.