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Biomedical subjects

M Fujioka

Publications and source records attributed to M Fujioka.

At least 55 records · Page 3Linked to original sources

Comparison of sperm motility test methods (except computer-assisted sperm analysis) in rats under the condition of alfa-chlorohydrin treatment--collaborative investigation.

A comparison among rat sperm motility test methods including percent of motile sperm (% Motile), scoring method (Scoring), Ishii's method, Progressive Motility Test (PMT) and Sperm Quality Analyzer (SQA), was conducted using data gathered from eleven laboratories. As a unified study design, mature male rats were orally treated daily for approximately 1 week with alpha-chlorohydrin (ACH), which is known to affect the sperm motility at the epididymis, at dose levels of 2.5, 5 and 10 mg/kg, and then subjected to more than two test methods for sperm motility in each laboratory. Scoring (4 or 5 grades), Ishii's method, PMT and SQA showed high sensitivity for the detection of the effects of ACH, which were not considered to be inferior to a computer-assisted sperm analyzer (CASA). Longer incubation time before testing was considered to contribute to detecting the effects of ACH. In particular, we realized that Scoring was a favorable method even if the demerit of poor objectivity was allowed for. Percent Motile showed lower sensitivity than other test methods. The differences in sensitivity between % Motile and other methods were considered to be based on whether the defects of progressive motion could be detected. Although % Motile cannot clearly judge whether immotile sperm are dead or alive, the value is a great help for the interpretation of the result from other methods. Based on the characters for detectability, objectivity and efficiency, the most suitable method of sperm motility should be selected according to the purpose of the toxicity study.

Animals↗

Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 22). Effects of 2- and 4-week administration of theobromine on the testis.

The effects of theobromine, a xanthine derivative, on the testis were compared between rats dosed for 2 and 4 weeks to determine whether a 2-week dosing period is long enough to detect toxicity. Theobromine was administered orally to male Sprague-Dawley rats at dose levels of 250 and 500 mg/kg for 2 weeks starting at the age of 6 or 8 weeks, and for 4 weeks from the age of 6 weeks. Histopathological examination of reproductive organs revealed toxic findings in the testis at 500 mg/kg after 2 weeks of dosing at both ages, and at 250 and 500 mg/kg after 4 weeks of dosing. The primary findings were degeneration/necrosis and desquamation of spermatids and spermatocytes, vacuolization of seminiferous tubules, and multinucleated giant cell formation. These findings were present mainly in stages I-VI and XII-XIV. From these results, it is concluded that the toxic effects of theobromine on the testis can be detected by repeated dosing for 2 weeks as well as for 4 weeks.

Administration, Oral↗

[A study on the risk factors for tuberculosis epidemics observed from the results of extraordinary health examinations].

In recent years, tuberculosis (tbc) epidemics have been increasing, and have become a social problem in Japan. This study was carried out to clarify the current risk factors on tbc epidemics. The original reports of a total of 254 tbc patients whose contacts were examined for possible tbc infection (extraordinary health examinations) during 1992-97, were investigated and compared with all new pulmonary tbc cases registered during the same period in Aichi prefecture. In addition, from registration cards in each public health center, the risk factors for 19 cases of both tbc epidemics (infecting more than 20 contacts) and microepidemics infecting 10-19 contacts were further examined. The results obtained were as follows; 1. Extraordinary health examinations were carried out in 3.2% of total pulmonary tbc cases, and were carried out at higher rates among contacts with younger patients and with those having severer tbc by radiographical (p < 0.01) and bacteriological findings (p < 0.01). 2. 11 tbc epidemics (3.4%) and 34 microepidemics (14.3%) were identified among 254 examinations over 6 years. They were frequently observed in groups with abundant bacilli discharge and long lasting cough, and also in young age groups. 3. All of the 19 cases causing epidemics or microepidemics had multiple risk factors; the main factors being late diagnosis, inadequate health managements in schools and offices and poor quality of patients' living environments. Therefore, it is necessary for public health centers to work more closely with schools and industrial circles for the prevention of tbc epidemics.

Adult↗

[Study on evaluation method of patient dose in diagnostic radiology required for introducing the guidance level: investigation of entrance surface dose of patient using direct measurement by TLD].

Using direct measurement, we investigated entrance surface doses of patients for routine radiographs in attempt to develop evaluation methods of patient dose in order to establish the guidance level in Japan. To date, patient doses have been evaluated by calculations based on radiographic conditions, or model experiments using phantoms. Their patient doses are then evaluated based on several assumptions. Direct measurement of patient dose is difficult to perform in many patients due to its time requirement, level of expertise required and difficulty in providing an explanation of the procedure to the patient. However, such direct measurement is essential since it incorporates all aspects of radiography from the radiographic equipment used, to the actual conditions of each patient without assumption. In this study, we examined the (1) need for introducing the guidance level, (2) controversial points in the calculation method for patient dose evaluation, (3) evaluation accuracy required for introducing the guidance level, and (4) necessity for a standardized method.

Guidelines as Topic↗

Acetabular labrum in hip dysplasia evaluated by radial magnetic resonance imaging.

OBJECTIVE: To numerically express morphologic conditions and signal intensity in the acetabular labrum of the weight-bearing portion of hip joints in patients with hip dysplasia. METHODS: Using a radial magnetic resonance imaging (MRI) technique, where the planes are set radially centered on the midpoint of acetabulum, and which depicts the entire acetabular rim and acetabular labrum, we investigated 60 hip joints of 35 patients with hip dysplasia. RESULTS: The acetabular labrum was larger in dysplastic hips than in normal hips, and the size increased in the posterosuperior portion. All patients had portions with signal intensity changes within the labrum and had impairment on the labrum. When osteoarthrosis due to hip dysplasia was observed, signal intensity changes increased. The changes of intensity varied among the portions observed, and were stronger in the anterosuperior portions than in the superior and posterosuperior portions. CONCLUSION: Radial MRI numerically depicts morphologic conditions of acetabular labrum; the data were usable to evaluate the size difference in acetabular labrum due to hip dysplasia and the degree of impairment.

Acetabulum↗

[Combination chemotherapy with irinotecan hydrochloride plus carboplatin for patients with advanced or recurrent colorectal cancer--a pilot study].

A pilot study was performed to evaluate the feasibility and efficacy of irinotecan hydrochloride (CPT-11) plus carboplatin (CBDCA) for treatment of advanced or recurrent colorectal cancer. Fifteen patients with colorectal cancer (nonresectable, 1; noncurative resection, 5; recurrent disease, 9) were treated with CPT-11 (40-50 mg/m2) plus CBDCA (70-100 mg/m2) once a week for 2-3 weeks followed by a one-week rest. This treatment was repeated until disease progression or severe toxic effects were found. The total dose of CPT-11 ranged from 135 to 1,214 (median, 467) mg/m2 and that of CBDCA ranged from 267 to 2,022 (median, 933) mg/m2. Adverse effects included nausea (grade 2) in 2 (13.3%) diarrhea (grade 2) in 2 (13.3%), leukopenia (grade 3) in 2 (13.3%), thrombocytopenia (grade 1) in one (6.7%), and hair falling (grade 3) in one (6.7%). The response rate of 14 evaluable patients was 14.3% (CR, 1; PR,1; NC,7; PD,5). The median survival time of all patients was 405 days from the start of chemotherapy. The survival time of patients with CR, PR, and NC (n = 9) tended to be longer than that of those with PD (n = 5) (p = 0.06). The median time to disease progression was 105 days. These results suggest that this combination chemotherapy is feasible and effective in the treatment of advanced or recurrent colorectal cancer.

Adult↗

[Anesthesia for emergency surgery in 2 extremely low birth weight infants with ileus].

Two extremely-low-birth-weight infants, weighing each 684 and 975 g at birth, underwent emergency surgery because of ileus. Our previous experience with an extremely low birth weight infant, whose hemodynamic control during the surgery had been difficult without administering extra preoperative fluid and transfusion, made us administer enough fluid and transfusion during operation although their urine output was more than 2 ml.kg-1.hr-1. We gave intravenous volume to the present 2 cases before the operations despite the level of preoperative urine output and made their hemodynamic situation more stable during surgeries. We conclude it is very important to administer some amounts of intravenous volume (approximately 8-12 ml.kg-1.hr-1) in extremely low birth weight infants for emergency surgery with ileus regardless of their preoperative urine output.

Anesthesia↗

[Clinical significance of determinations of dihydropyrimidine dehydrogenase levels in primary and hepatic lesions of colorectal cancer patients].

Dihydropyrimidine dehydrogenase (DPD) levels were determined by enzyme-linked immunosorbent assay in primary tumors and adjacent normal mucosa from 114 colorectal cancer patients, including 9 with synchronous liver metastases. The level of intratumoral DPD was 55.0 +/- 38.7 unit/mg protein (n = 114) and that of mucosal DPD was 55.0 +/- 38.7 unit/mg protein (n = 114). The ratio of intratumoral DPD to mucosal DPD was 1.8 +/- 0.8 in patients developing metachronous liver metastases (n = 7), 1.0 +/- 0.5 in patients without recurrence (n = 61), and 1.0 +/- 1.1 in patients with synchronous liver metastases (n = 31) (p = 0.01, metachronous liver metastasis group versus recurrence-free and synchronous liver metastasis groups). The levels of DPD were higher in primary lesions than in synchronous liver metastasis (n = 9, p < 0.05). These results indicate that: (1) degradation of 5-fluorouracil (5-FU) is enhanced in hepatic lesions more than in primary lesions, which is consistent with previous findings showing the therapeutic advantage of hepatic arterial infusion over intravenous infusion in relation to the treatment of 5-FU for liver metastases of colorectal cancer patients; and (2) predicting the effectiveness of hepatic arterial infusion of 5-FU for patients with metachronous liver metastases is difficult based on DPD determination of primary lesions alone.

Colorectal Neoplasms↗

Postsynaptic expression of tetanus toxin light chain blocks synaptogenesis in Drosophila.

During the development of the nervous system embryonic neurons are incorporated into neural networks that underlie behaviour. For example, during embryogenesis in Drosophila, motor neurons in every body segment are wired into the circuitry that drives the simple peristaltic locomotion of the larva. Very little is known about the way in which the necessary central synapses are formed in such a network or how their properties are controlled. One possibility is that presynaptic and postsynaptic elements form relatively independently of each other. Alternatively, there might be an interaction between presynaptic and postsynaptic neurons that allows for adjustment and plasticity in the embryonic network. Here we have addressed this issue by analysing the role of synaptic transmission in the formation of synaptic inputs onto identified motorneurons as the locomotor circuitry is assembled in the Drosophila embryo. We targeted the expression of tetanus toxin light chain (TeTxLC) to single identified neurons using the GAL4 system. TeTxLC prevents the evoked release of neurotransmitter by enzymatically cleaving the synaptic-vesicle-associated protein neuronal-Synaptobrevin (n-Syb) [1]. Unexpectedly, we found that the cells that expressed TeTxLC, which were themselves incapable of evoked release, showed a dramatic reduction in synaptic input. We detected this reduction both electrophysiologically and ultrastructurally.

Animals↗

The even-skipped locus is contained in a 16-kb chromatin domain.

The even-skipped (eve) gene of Drosophila melanogaster is a crucial member of the pair-rule class of segmentation genes. We report here the characterization of a 16-kb region sufficient for all known aspects of eve expression and the rescue of an eve null mutation. We began by examining 45 kb surrounding the eve coding sequence for DNaseI hypersensitive sites and other transcription units. We find that the previously identified eve regulatory elements, those for early stripes 2, 3, and 7 and the late element, do not generate prominent hypersensitive sites. However, strong, constitutive DNaseI hypersensitive sites flank a 16-kb region, within which one developmentally regulated site is found at the eve promoter region. P-element transformation of this 16-kb domain into eve mutants rescues them to adult viability. This 16-kb domain contains regulatory elements for all known features of eve expression: the seven major blastoderm stripes, minor stripe expression during germ band extension, and later expression in the lateral mesodermal muscle precursor cells, in the central nervous system, adjacent to the invaginating proctodeum, and in a ring around the anal pad. We have begun a preliminary dissection of the 16-kb domain into its constituent regulatory elements. Other major findings include the following: (1) There is a second element for late stripe expression adjacent to the traditional late element. (2) A stripe element 3' of the gene interacts with the late element to give rise to the minor stripes seen in the even-numbered parasegments. (3) Expression in the proctodeum and anal pad is driven by sequences both 5' and 3' of the gene. (4) Expression in different sites in the central nervous system is driven by separable elements widely dispersed throughout 8 kb 3' of the gene.

Animals↗

Crystal structure of S-adenosylhomocysteine hydrolase from rat liver.

The crystal structure of rat liver S-adenosyl-L-homocysteine hydrolase (AdoHcyase, EC 3.3.1.1) which catalyzes the reversible hydrolysis of S-adenosylhomocysteine (AdoHcy) has been determined at 2.8 A resolution. AdoHcyase from rat liver is a tetrameric enzyme with 431 amino acid residues in each identical subunit. The subunit is composed of the catalytic domain, the NAD+-binding domain, and the small C-terminal domain. Both catalytic and NAD+-binding domains are folded into an ellipsoid with a typical alpha/beta twisted open sheet structure. The C-terminal section is far from the main body of the subunit and extends into the opposite subunit. An NAD+ molecule binds to the consensus NAD+-binding cleft of the NAD+-binding domain. The peptide folding pattern of the catalytic domain is quite similar to the patterns observed in many methyltransferases. Although the crystal structure does not contain AdoHcy or its analogue, there is a well-formed AdoHcy-binding crevice in the catalytic domain. Without introducing any major structural changes, an AdoHcy molecule can be placed in the catalytic domain. In the structure described here, the catalytic and NAD+-binding domains are quite far apart from each other. Thus, the enzyme appears to have an "open" conformation in the absence of substrate. It is likely that binding of AdoHcy induces a large conformational change so as to place the ribose moiety of AdoHcy in close proximity to the nicotinamide moiety of NAD+. A catalytic mechanism of AdoHcyase has been proposed on the basis of this crystal structure. Glu155 acts as a proton acceptor from the O3'-H when the proton of C3'-H is abstracted by NAD+. His54 or Asp130 acts as a general acid-base catalyst, while Cys194 modulates the oxidation state of the bound NAD+. The polypeptide folding pattern of the catalytic domain suggests that AdoHcy molecules can travel freely to and from AdoHcyase and methyltransferases to properly regulate methyltransferase activities. We believe that the crystal structure described here can provide insight into the molecular architecture of this important regulatory enzyme.

Adenosylhomocysteinase↗

A new simple technique for performing intraoperative endoscopic resection of small-bowel polyps in patients with Peutz-Jeghers syndrome.

We describe herein a simple method for performing intraoperative endoscopic resection of small-bowel polyps associated with Peutz-Jeghers syndrome, using a corrugated anesthetic tube. A 34-year-old man with Peutz-Jeghers syndrome underwent emergency surgery for an ileo-ileo-colic intussusception. A sterile corrugated anesthetic tube was inserted into the small-bowel, proximal to the affected lesion. The small bowel was then telescoped sequentially over the tube using a pleating technique. Consequently, a colonoscope inserted through the tube was easily able to reach the duodeno-jejunal junction, and ten small-bowel polyps were removed using a wire snare and electrocauterization. All resected specimens were washed out by the instillation of saline through a nasogastric tube, then collected on gauze placed near the outlet of the tube. Our technique has the following merits: it is feasible even in emergency surgery; it prevents contamination of the surgical field; and it facilitates the easy collection of polypectomized specimens.

Adult↗

Laparoscopic gastropexy for acute gastric volvulus: a case report.

A 7-year-old girl presented with an acute gastric volvulus that was reduced with a nasogastric catheter. An anterior gastropexy was undertaken laparoscopically. The gastrocolic omentum was deficient along most of the greater curvature, which had allowed organoaxial volvulus. Two years later, gastric volvulus has not recurred. Laparoscopy is an acceptable approach for the evaluation and treatment of children with acute gastric volvulus.

Acute Disease↗

Tumor-doubling time and onset of pulmonary metastasis from adenoid cystic carcinoma of the salivary gland.

Adenoid cystic carcinoma (ACC), an uncommon malignancy in the head and neck region, invades diffusely and often metastasizes to the lung, although the growth rate is very slow. A retrospective study was conducted in 30 patients with ACC to ascertain the frequency of pulmonary metastasis, the doubling time of metastatic tumor deposits, and the time of onset for pulmonary metastasis. The following results were obtained: (1) Of 30 patients with ACC, 21 had pulmonary metastases (4 initially and 17 during observation), 7 were free of metastases but have not been observed for 5 years, and 2 were free of metastases for more than 5 years but less than 10 years after the initial treatment. The cumulative metastasis rate at 5 and 10 years for this group of patients was 70% and 100%, respectively. (2) Patients with T1 or T2 tumors that have a tubular or cribriform histopathologic pattern showed pulmonary metastases about 20 months later than those with T3 or T4 tumors and a solid pattern. However, the final metastasis rate did not differ between the 2 groups after a long period. (3) The tumor doubling time of the metastatic deposits of ACC was 86 to 1064 days with an average of 393 days, which was much longer than that of most other malignant neoplasms reported previously. (4) The time of onset of pulmonary metastasis was calculated to be much earlier (average of 227 months) before the first visit. These findings suggest that the treatment method for ACC should be chosen with the consideration that many of the patients may have occult pulmonary metastases at the time of their initial evaluation.

Carcinoma, Adenoid Cystic↗

Physical examination in valvular aortic stenosis: correlation with stenosis severity and prediction of clinical outcome.

BACKGROUND AND METHODS: The goal of this study was to examine the ability of physical examination to predict valvular aortic stenosis severity and clinical outcome in 123 initially asymptomatic subjects (mean age 63 +/- 16 years, 70% men) followed up for a mean of 2.5 +/- 1.4 years. RESULTS: Doppler aortic jet velocity correlated with systolic murmur intensity (P =.003) and timing (P =.0002), a single second heart sound (P =.01), and carotid upstroke delay (P <.0001) and amplitude (P <.0001). However, no physical examination findings had both a high sensitivity and a high specificity for the diagnosis of severe valvular obstruction. Clinical end points were reached in 56 subjects (46%), including 8 deaths and 48 valve replacements for symptom onset. Univariate predictors of outcome included carotid upstroke delay (P =.0008) and amplitude (P =.0006), systolic murmur grade (P <.0001) and peak (P =.0003), and a single second heart sound (P =.003). On multivariate Cox regression analysis, the only physical examination predictor of outcome was carotid upstroke amplitude (P =.0001). CONCLUSIONS: Although physical examination findings correlate with stenosis severity, echocardiography still is needed to exclude severe obstruction reliably when this diagnosis is suspected.

Aortic Valve Stenosis↗

Completion of meiosis is not always required for acrosome formation in HSP70-2 null mice.

Hsp70-2 is a unique member of the mouse 70-kDa heat shock protein family that is synthesized during meiosis in spermatogenic cells. Germ cells in male mice homozygous for a targeted mutation in the Hsp70-2 gene (Hsp70-2(-/-)) arrest in development and undergo apoptosis at the end of the pachytene spermatocyte stage of meiotic prophase. However, cells with a putative acrosome were present occasionally in histological sections of the testes of juvenile and adult Hsp70-2(-/-) mice. This study verified that acrosomes were present and investigated the relationship between acrosome formation and the process of meiosis. Histochemistry with the periodic acid-Schiff procedure and immunostaining with monoclonal antibody MN7 verified that acrosomes were present in Hsp70-2(-/-) mice, and electron microscopy showed that some of these cells had condensing nuclei characteristic of step 8-9 spermatids. The frequency of acrosome-containing cells in Hsp70-2(-/-) mice was less than 0.01% of that in wild-type mice. Propidium iodide staining and cytophotometry indicated that the average DNA content of nuclei in MN7-positive cells in Hsp70-2(-/-) mice was usually about twice, or occasionally the same as, that of nuclei in round spermatids of wild-type mice. Meiotic metaphase I and II chromosome spreads were observed in spermatogenic cells from Hsp70-2(-/-) mice but at a much lower frequency than in wild-type mice. These results indicate that not all pachytene spermatocytes in Hsp70-2(-/-) mice arrest in meiosis, but they may divide once or sometimes twice and begin acrosome formation and nuclear condensation. This demonstrates that some aspects of spermatid development can occur without the completion of meiosis in mice, as has been reported recently for Drosophila.

Acrosome↗