Biomedical subjects

Toshiaki Tanaka

Publications and source records attributed to Toshiaki Tanaka.

At least 73 records · Page 4Linked to original sources

PubMed2004

Clinical assessment and mutation analysis of Kallmann syndrome 1 (KAL1) and fibroblast growth factor receptor 1 (FGFR1, or KAL2) in five families and 18 sporadic patients.

We report on the clinical and molecular findings in 25 males and three females with Kallmann syndrome (KS) aged 10-53 yr. Ten males were from five families, and the remaining 15 males and three females were apparently sporadic cases. Molecular studies were performed for Kallmann syndrome 1 (KAL1) and fibroblast growth factor receptor 1 (FGFR1, also known as KAL2) by sequence analysis for all the coding exons, by PCR-based deletion analysis, and by fluorescence in situ hybridization (FISH) analysis, showing six novel and two recurrent intragenic KAL1 mutations in seven familial and four sporadic male cases and two novel intragenic FGFR1 mutations in two sporadic male cases. In addition, submicroscopic deletions at Xp22.3 involving VCX-A, STS, KAL1, and OA1 were identified in three familial cases and one sporadic male case affected by a contiguous gene syndrome. Clinical assessment in the 15 males with KAL1 mutations showed normal and borderline olfactory function in two males and right-side dominant renal lesion in seven males, in addition to variable degrees of hypogonadotropic hypogonadism (HH) in all the 15 males and olfactory dysfunction in 13 males. The two males with FGFR1 mutations had HH and anosmia and lacked other features. Clinical features in the remaining 11 cases with no demonstrable KAL1 or FGFR1 mutations included right renal aplasia in one female, cleft palate in one male, cleft palate and perceptive deafness in one male, and dental agenesis and perceptive deafness in one male, in addition to a variable extent of HH and olfactory dysfunction. The results suggest the following: 1) KAL1 mutations might be more prevalent in the Japanese patients than previously estimated in the Caucasian patients and can be associated with apparently normal olfactory function; 2) FGFR1 mutations account for approximately 10% of KS patients, as previously reported in the Caucasian patients, and can result in HH and olfactory dysfunction-only phenotype; and 3) renal aplasia, which is characteristic of KAL1 mutations, and cleft palate and dental agenesis, which are characteristic of FGFR1 mutations, can occur in patients without KAL1 and FGFR1 mutations.

Adolescent↗

PubMed2004

Protein-tyrosine phosphatase, nonreceptor type 11 mutation analysis and clinical assessment in 45 patients with Noonan syndrome.

We report on PTPN11 (protein-tyrosine phosphatase, nonreceptor type 11) mutation analysis and clinical assessment in 45 patients with Noonan syndrome. Sequence analysis was performed for all of the coding exons 1-15 of PTPN11, revealing a novel 3-bp deletion mutation and 10 recurrent missense mutations in 18 patients. Clinical assessment showed that 1) the growth pattern was similar in mutation-positive and mutation-negative patients, with no significant difference in birth length [-0.6 +/- 2.2 sd (n = 10) vs. -0.6 +/- 1.4 sd (n = 21); P = 0.95], childhood height [-2.6 +/- 1.1 sd (n = 14) vs. -2.1 +/- 1.6 sd (n = 23); P = 0.28], or target height [-0.4 +/- 0.9 sd (n = 14) vs. -0.2 +/- 0.7 sd (n = 17); P = 0.52]; 2) pulmonary valve stenosis was more frequent in mutation-positive patients than in mutation-negative patients (10 of 18 vs. 6 of 27; P = 0.02), as was atrial septal defect (10 of 18 vs. 4 of 27; P = 0.005), whereas hypertrophic cardiomyopathy was present in five mutation-negative patients only; and 3) other features were grossly similar in the prevalence between mutation-positive and mutation-negative patients, but hematological abnormalities, such as bleeding diathesis and juvenile myelomonocytic leukemia, were exclusively present in mutation-positive patients (5 of 18 vs. 0 of 27; P = 0.007). The results suggest that PTPN11 mutations account for approximately 40% of Noonan syndrome patients, as has been reported previously. Furthermore, assessment of clinical features, in conjunction with data reported previously, implies that the type of cardiovascular lesions and the occurrence of hematological abnormalities are different in mutation-positive and mutation-negative patients, whereas the remaining findings are similar in the two groups of patients.

Adolescent↗

PubMed2004

Statural growth in 31 Japanese patients with SHOX haploinsufficiency: support for a disadvantageous effect of gonadal estrogens.

Although gonadal estrogens are known to facilitate the development of skeletal lesion in SHOX haploinsufficiency, controversy exists as to whether gonadal estrogens are disadvantageous to pubertal growth. To clarify this matter, we analyzed growth pattern in 31 Japanese patients with a normal karyotype and molecularly confirmed SHOX haploinsufficiency. The mean height SD score at the diagnosis of SHOX haploinsufficiency was similar between patients identified in childhood and those identified in adulthood (-2.7 +/- 0.8 [n = 15] vs. -2.4 +/- 0.7 [n = 16], P = 0.36), and was significantly lower in patients identified by the studies for short stature than in those ascertained by the familial studies of the probands both in childhood (-3.0 +/- 0.6 [n = 11] vs. -1.8 +/- 0.5 [n = 4], P = 0.0051) and in adulthood (-3.0 +/- 0.9 [n = 5] vs. -2.2 +/- 0.5 [n = 11], P = 0.040). Analysis of longitudinal paired growth data obtained in seven females showed a significantly different mean height SD score between childhood and adulthood (-2.3 +/- 0.5 vs. -2.9 +/- 0.8, P = 0.0060). The results imply that gonadal estrogens have a deleterious effect on pubertal growth in SHOX haploinsufficiency, and that the growth disadvantage is recognizable by longitudinal rather than cross-sectional growth studies.

Adolescent↗

PubMed2004

Two cases of Allgrove syndrome with mutations in the AAAS gene.

Allgrove syndrome is a rare autosomal recessive disorder characterized by the triad of adrenal insufficiency, achalasia and alacrima. This syndrome, also known as triple A syndrome, is now known to be caused by mutations in the AAAS gene. In the present study, we report two new patients of Allgrove syndrome with mutations in the AAAS gene. Patient 1 was a 22-year-old Japanese woman, born to consanguineous parents. She was confirmed to have adrenal insufficiency at the age of 3 years and 6 months. She developed alacrima and bilateral optic nerve atrophy at the age of 8 years. She had been noticed to have dysphagia. Based on these findings, she was diagnosed as having Allgrove syndrome. Mutation analysis revealed a novel homozygous point mutation in exon 7 of her AAAS gene, changing codon 194 encoding Arg (CGA) to a stop codon (TGA) (R194X). Patient 2 was a 7-year-old Japanese boy, born to consanguineous parents. At the age of 1 year, he was noticed to be unable to produce tears. He was confirmed to have adrenal insufficiency, mental retardation and spastic diplegia at the age of 5 years and 4 months. He was tentatively diagnosed as having Allgrove syndrome, although he has never complained of dysphasia. Mutation analysis revealed a homozygous point mutation in exon 4 of his AAAS gene, changing codon 119 encoding Arg (CGA) to a stop codon (TGA) (R119X). Both of the R119X and R194X mutations are predicted to result in truncated and non-functioning ALADIN proteins, and thus the diagnosis of Allgrove syndrome was confirmed by the mutation analyses. These findings indicate that there exist significant clinical variability and mutational heterogeneities in Japanese patients with this syndrome.

Adrenal Insufficiency↗

PubMed2004

Clinical evaluation of recombinant human growth hormone in Noonan syndrome.

The objective of this study was to investigate the effect of administration of recombinant human growth hormone (hGH) in patients with Noonan syndrome. hGH was administered (0.5 IU/kg/week) to 15 patients with Noonan syndrome over a 2 year period. Average patient age prior to therapy was 7.5 +/- 2.5 (mean +/- SD) yr, the height SD score was -2.8 +/- 0.7, and the pretreatment height velocity and bone age were 4.8 +/- 1.0 cm/yr and 5.8 +/- 2.1 yr, respectively. The height velocity in the year prior to treatment, and 0-12 and 12-24 months after commencing treatment was 4.8 +/- 1.0 cm/yr, 7.0 +/- 1.2 cm/yr, and 5.5 +/- 0.6 cm/yr, respectively. The height velocity in the first year of treatment was significantly greater (P = 0.0001, n = 14) than the pretreatment value, but there was no significant difference in the second year. The height SD scores at the commencement of treatment, and after 12 and 24 months of treatment were -2.8 +/- 0.7, -2.4 +/- 0.7, and -2.2 +/- 0.5, respectively. Bone age advanced by 1.1 +/- 0.5 yr in the 12 months after commencing treatment. We conclude that the use of hGH may be beneficial in the treatment of Noonan syndrome, although further research is required.

Age Determination by Skeleton↗

PubMed2004

Novel compound heterozygous AIRE mutations in a Japanese patient with APECED.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autosomal recessive disorder defined by the presence of two of three conditions, namely, Addison's disease, hypoparathyroidism, and mucocutaneous candidiasis. APECED is caused by alteration in a single gene, named the autoimmune regulator (AIRE) gene. We report AIRE gene mutations in a Japanese female with APECED. The patient is a 22-year-old Japanese female who was diagnosed with Addison's disease, hypoparathyroidism, and mucocutaneous candidiasis at age 8 years. Sequence analysis of the AIRE gene revealed novel compound heterozygous mutations. One was 1471 delCinsTT in exon 11 (GenBank accession no. AB006682), which leads to a frameshift and premature truncation of a 502 amino acid protein. The other was a G-->A transition at IVS11+1. Her mother was heterozygous for 1471 delCinsTT and was normal homozygous for IVS11+1. We found novel compound heterozygous mutations in the AIRE gene of a Japanese female with APECED.

Addison Disease↗

PubMed2004

Adult GH deficiency in Japanese patients: effects of GH treatment in a randomised, placebo-controlled trial.

OBJECTIVE: To evaluate the influence of factors intrinsic to the Japanese population on consequences of growth hormone deficiency (GHD) and effects of GH treatment in adult Japanese hypopituitary patients with GHD. STUDY DESIGN: A 24-week, randomised, placebo-controlled, double-blind study in 64 patients in Japan, with GHD onset during adulthood (AO; n=27) or childhood (CO; n=37). Body composition measured by dual-energy X-ray absorptiometry (DXA) was evaluated centrally. Serum IGF-I, IGF binding protein-3 (IGFBP-3) and lipid levels were determined centrally. RESULTS: In contrast to Caucasian patients, there were no significant differences before treatment between AO and CO patients for body mass index (BMI), lean body mass (LBM) and fat mass (FM). Baseline BMI was >/=25 kg/m(2) for 32.8% of patients. For all patients combined, a significant increase in LBM and decrease in FM (P<0.001 for each) was seen with GH treatment. Serum IGF-I and IGFBP-3 were significantly lower at baseline in CO compared with AO patients, similar to Caucasian patients, and were increased in both onsets following GH treatment. Serum total and low-density lipoprotein (LDL)-cholesterol concentrations did not differ between AO and CO patients at baseline and were elevated compared with normal ranges. GH-induced decreases were significant compared with placebo for both total (P=0.036) and LDL-cholesterol (P=0.040). Glycosylated haemoglobin was increased with GH compared with placebo treatment (P=0.016) but remained within the upper limit of normal for all patients at endpoint. CONCLUSIONS: Adult Japanese hypopituitary patients with GHD demonstrated obesity relative to healthy Japanese subjects but the clinical presentation differed from that of Caucasian patients. GH treatment improved body composition and serum cholesterol profiles of adult Japanese hypopituitary patients with GHD.

Adult↗

PubMed2004

Clinical course in patients with percutaneous nephrostomy for hydronephrosis associated with advanced cancer.

We investigated the clinical courses of 33 patients with advanced malignancies who has undergone percutaneous nephrostomy (PNS) to clarify the efficacy and validity of PNS and evaluated the results according to the type of catheter. The pigtail, Malecot and balloon catheters were used. All the catheters were exchanged every 4 weeks, if necessary for larger ones. The site of the primary disease, preoperative performance status, duration of time spent at home after PNS construction, number of times the catheter was changed, type and size of the catheter and complications associated with PNS were compiled. The median overall survival was 3.0 months. Twenty-three patients (69.7%) were never discharged from hospital. Thirty patients died of their primary diseases. The median overall survival of patients with cancers of the upper gastrointestinal system, large bowel, urological organs and gynecologic organs were 1.5, 5.5, 3.0 and 3.0 months, respectively (p=0.0116). Eighteen patients (54.5%) experienced complications such as pyelonephritis, obstruction, dislodgement and so on. PNS is an appropriate urinary diversion for patients with hydronephrosis with advanced cancer and unilateral construction is effective for treating end-stage obstructive renal failure. However, PNS rarely improves the patient's quality of life and the risk of complications is unavoidable regardless of the type of catheter used.

Aged↗

PubMed2004

[Epidural hematoma after an epidural block in a patient with no coagulopathy].

We report a case of epidural hematoma after a single epidural block. The patient was a 67-year-old woman with sciatica and osteoarthritis of the spine. She had no coagulopathy. She underwent a single epidural block without difficulty 3 times in 5 days. She had a lumbar MRI for an examination of the spine 4 days after the final epidural block. Subacute epidural hematoma of 0.8 x 1.5 x 3.0 cm was revealed on MRI at L 3-4. She had no new neurological symptoms. MRI 1 month later revealed a resolution of the hematoma. Epidural hematoma after an epidural block might occur in an outpatient with no bleeding tendency.

Acute Disease↗

PubMed2004

[Spinal anesthesia for 12 patients receiving home oxygen therapy].

From Jan 2001 to Nov 2003, 12 patients receiving home oxygen therapy (HOT) underwent surgery under spinal anesthesia at Okayama Rosai Hospital. The basic diseases for HOT were emphysema (n=8), interstitial pneumonia (n=1), asthma (n=1) and lung cancer (n=1). Mean FEV1.0 and FVC were 0.85 l and 1.97 l, respectively. Mean PaO2 and PaCO2 were 76.5 mmHg and 45.5 mmHg, respectively, under nasal oxygen of 1.67 l x min(-1). Perioperative complications occured in 3 cases. In case 5, postoperative heart failure occured and was easily treated with diuretics. In case 8, intraoperative hypotension (systemic blood pressure less than 80 mmHg) occured. In case 12, the patient developed dyspnea because of high spinal anesthetic level of T1. She was not intubated because PaO2, PaCO2 and pH were not deteriorated. Perioperative PaO2, PaCO2 and pH were stable and there were no pulmonary or morbid complications in all cases. It is important to assess not only pulmonary function but also cardiovascular status by echocardiography and general physical status by Hugh-Jones classification in order to avoid severe complications.

Aged↗

PubMed2003

Insulinotropic action of glutamate is dependent on the inhibition of ATP-sensitive potassium channel activities in MIN 6 beta cells.

To investigate the cellular mechanism of insulinotropic effect of glutamate in pancreatic beta cells, we utilized patch-clamp technique to monitor directly the activities of ATP-sensitive potassium channels (K(ATP) channels). Dimethylglutamate (5mM), a membrane-permeable analog of glutamate, augmented the insulin release induced by the stimulatory concentrations of glucose (p<0.05-0.01). In the cell-attached configurations, dimethylglutamate reversibly and significantly suppressed the K(ATP) channel activities (p<0.01). On the other hand, no significant effect was observed when glutamate itself was applied to the inside-out patches, whereas the prompt and reversible suppression was recorded in the case of ATP (p<0.01). These results indicate that the insulinotropic action of glutamate in beta cells could be derived from the inhibition of K(ATP) channel activities, probably due to generation of messengers via intracellular metabolism such as ATP.

Adenosine Triphosphate↗

PubMed2003

Involvement of central mu-opioid system in the scratching behavior in mice, and the suppression of it by the activation of kappa-opioid system.

The role of central mu- and kappa-opioid receptors in the regulation of itch sensation was examined using pruritogen-induced mouse scratching behavior model. Intracerebroventricular administration of beta-funaltrexamine, a selective mu-opioid receptor antagonist, inhibited the scratching behavior induced by intradermal substance P, but subcutaneous administration of beta-funaltrexamine did not. Similarly, the scratching inhibitory activity of subcutaneously administered TRK-820, (-)-17-(cyclopropylmethyl)-3, 14beta-dihydroxy-4, 5alpha-epoxy-6beta-[N-methyl-trans-3-(3-furyl) acrylamido] morphinan hydrochloride, a kappa-opioid receptor agonist, was antagonized by intracerebroventricular administration of nor-binaltorphimine (10 microg/site), a kappa-opioid receptor antagonist, but was not by subcutaneous administration of nor-binaltorphimine. In addition, the scratching induced by the direct activation of central mu-opioid receptor by intracisternal morphine was significantly and dose-dependently inhibited by subcutaneous administration of TRK-820. Taken all together, it is suggested that the central mu-opioid receptors play a role in the processing of itch sensation, and the activation of central kappa-opioid receptors antagonize the central mu-opioid receptor mediated itch processing, thereby suppressing itch sensation.

Animals↗

PubMed2003

Size-exclusion chromatography of biological samples which contain extremely alkaline proteins.

An improved size-exclusion chromatography (SEC) was developed to isolate extremely basic (alkaline) proteins, such as trypsin (pI=10.5), lysozyme (pI=11), and histone (pI=10.8). Develosil 300 Diol-5 (300 x 8 mm I.D., 30 nm average pore diameter) column was used with an eluent of 0.1 M sodium phosphate, 1.5 M sodium chloride, glycerol (40%, v/v), 2-propanol (10%, v/v), and Brij-58 (1%, v/v). Under these conditions, the final apparent pH becomes to 4.0, and pH adjustment is not necessary. Column temperature and flow rate were 15 degrees C and 0.2 ml/min, respectively. This elution system is stable and reliable, and applications onto human pancreatic juice, human bile, and tissue homogenates were successfully achieved. Since this system is convenient for protein analysis, it is expected to be generally applicable to clinical and biochemical research for identifying protein components in combination with microsequencing.

Alkalies↗

PubMed2003

Optimal lymphadenectomy for squamous cell carcinoma in the thoracic esophagus: comparing the short- and long-term outcome among the four types of lymphadenectomy.

Controversy continues over the optimal extent of lymphadenectomy (regional versus three-field) for a potentially resectable squamous cell carcinoma in the thoracic esophagus. In the Consensus Conference of the International Society for Diseases of the Esophagus (ISDE), held in Munich in 1994, the types of lymphadenectomy were classified as standard, extended, total, or three-field lymphadenectomy. The objective of the present study was to determine the optimal procedure among these four types of lymphadenectomy. The mortality and morbidity rates, postoperative course, and survival rates were compared among 302 patients who underwent curative (R0) transthoracic esophagectomy with one of these four types of lymphadenectomy at Kurume University Hospital, Fukuoka, Japan, from 1986 to 1998. Three-field lymphadenectomy resulted in better survival than any other type of lymphadenectomy for patients with positive lymph node metastasis from a cancer in the upper or middle thoracic esophagus. A postoperative complication, such as recurrent laryngeal nerve paralysis, anastomotic leakage, and tracheal ischemic lesion, was significantly more common after three-field lymphadenectomy. However, the mortality rate was the same among the four procedures. Three-field lymphadenectomy was optimal for an upper or middle thoracic esophageal cancer with metastasis in the lymph node(s) based on improved long-term survival, whereas there was not a large difference in short-term and long-term outcomes after the four types of lymphadenectomy for a lower thoracic esophageal cancer.

Aged↗

PubMed2003

A successfully treated case of blunt traumatic right coronary ostium rupture.

Cardiac tamponade due to coronary artery rupture, as a consequence of blunt trauma, is a rare but usually fatal condition. We successfully obtained primary hemostasis with emergency room thoracotomy, followed by delayed definitive treatment of the ruptured right coronary artery ostium in a motor vehicle accident victim with multifocal hemorrhagic lesions. Survival of patients with the described serious trauma has not been reported, and we discuss herein our treatment strategy.

Adult↗

PubMed2003

Testicular metastasis from squamous cell carcinoma of the lung.

We present a case of squamous cell carcinoma of the testis that metastasized from lung cancer. The patient, who had received left pneumonectomy 2 years earlier for squamous cell carcinoma (SCC) of the lung, developed pulmonary metastasis, which was treated with chemotherapy. Although the recurrence regressed after treatment, the testicular tumor progressed gradually. Left radical orchiectomy was performed. Pathological examination revealed metastatic SCC. Testicular metastasis from lung cancer is a very rare disease.

Carcinoma, Squamous Cell↗

PubMed2003

Retroperitoneoscopic nephrectomy of a horseshoe kidney with renal-cell carcinoma.

A 55-year-old man had a solid tumor in the right part of a horseshoe kidney. He had previously undergone open cholecystectomy and appendectomy with panperitonitis. Retroperitoneoscopic nephrectomy was performed, with rapid recovery and good short-term results. This appears to be the first case of endoscopic surgery on a horseshoe kidney using ultrasonic shears for cancer.

Carcinoma, Renal Cell↗

PubMed2003

External beam radiation monotherapy for localized or locally advanced prostate cancer.

PURPOSE: We report the treatment results and complications of external beam radiation monotherapy for localized or locally advanced prostate cancer patients. METHODS: Fifty-four patients with T(1b-3a)N(0)(pN(0))M(0) prostate cancer were treated with external beam radiation monotherapy between 1989 and 2001 at four institutes. RESULTS: During the 4-122 month follow-up period (median: 25 months), 11 (20%) patients experienced biochemical failure, including one with simultaneous local recurrence. The 2-year actuarial biochemical control rate was 85%. Univariate analysis showed that the clinical T classification (P = 0.01), Gleason score (P = 0.006), pretreatment PSA (P = 0.02) and PSA nadir value (P = 0.01) were associated with a higher probability of biochemical failure. Multivariate analysis using the Cox proportional hazards model demonstrated that only the PSA nadir value was a strong predictor of PSA recurrence (P < 0.01). Adverse events were mild and tolerable. No severe urinary or bowel complications were observed. CONCLUSIONS: External beam radiation monotherapy is effective for clinically organ-confined prostate cancer with a low incidence of severe complications in a mean follow-up period of 2 years.

Adult↗