Effects of CTG trinucleotide repeat expansion in leukocytes on quantitative muscle histopathology in myotonic dystrophy.
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Biomedical subjects
Publications and source records attributed to K Saitoh.
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To identify individual chromosomes of a frog karyotype by their fluorescence banding patterns, chromosomes were stained with actinomycin D and 4,6-diamidino-2-phenylindole (DAPI) after incorporation of BrdU during the late S-phase. The chromosomes of three Rana species which were selected for this study (R. ridibunda, R. lessonae and R. japonica) showed well-defined late replication bands. The fluorescence patterns obtained were the reverse of those produced by a 4Na-EDTA Giemsa-staining technique. Fluorescence patterns of the two water frog species (R. ridibunda and R. lessonae) were similar to each other, except for the different fluorescence of the centromeric heterochromatin, which gave extremely bright signals in R. ridibunda but no signal in R. lessonae. Experiments also showed differences between the fluorescence patterns of R. lessonae chromosome 13 in the Italian and Luxembourgian populations. These results show that the fluorescence replication banding using actinomycin D and DAPI is very effective in identifying individual frog chromosomes and detecting their structural changes.
BACKGROUND & AIMS: Germline mutations of DNA mismatch repair genes are responsible for cancer susceptibility in hereditary nonpolyposis colorectal cancer (HNPCC) kindreds. Transforming growth factor beta type II receptor (TGF-beta RII) has been found to be somatically altered in HNPCC. The aim of this study was to clarify further the role of TGF-beta RII alterations in HNPCC tumorigenesis, particularly in adenomas. METHODS: Fourteen adenoma specimens and 13 cancer specimens from 10 patients with HNPCC were screened for mutations in the short repeated sequences of the TGF-beta RII gene by polymerase chain reaction-single-strand conformation polymorphism. Mismatch repair genes, replication errors, and c-K-ras 2 were also analyzed in HNPCC tumors. RESULTS: Alterations of the TGF-beta RII gene at the short poly(A) repeat were found in 8 (57%) adenoma specimens and 11 (85%) cancer specimens. They were found at an earlier stage of adenomas. Two adenoma specimens showed two-hit inactivation of mismatch repair genes. Replication errors were detectable in 13 (93%) adenoma specimens. Mutations in c-K-ras 2 codon 12 were detected at a 50% frequency in adenoma specimens. CONCLUSIONS: These data indicate a strong association between TGF-beta RII gene alterations and adenoma-carcinoma progression in HNPCC.
We have examined the extradural space using a flexible extraduroscope in 74 patients undergoing extradural anaesthesia at the L2-3 interspace. Extraduroscopy showed that the extradural space becomes widely patent and the fatty tissue in the extradural space diminishes with increasing age. We postulate that these age-related structural changes may affect the spread of local anaesthetic in the extradural space.
To clarify the effects of the pregnant uterus on the extradural venous plexus in the supine and lateral positions, we studied magnetic resonance (MR) images of the lumbar spine in three parturients. T2-weighted axial MR images were obtained with the parturient in the supine and lateral positions. On each slice level in the same subject, the MR images were compared with the control MR images obtained before pregnancy. When the parturient lay supine, the pregnant uterus compressed the inferior vena cava and almost totally obstructed it; the extradural venous plexus was engorged. On turning the parturient into the lateral position, the inferior vena cava was free from compression, and the engorged extradural venous plexus was found to shrink to the level of the non-pregnant state.
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To clarify the anatomy of the extradural space of the thoracic spine, we have compared magnetic resonance (MR) images of the thoracic spine with those of the lumbar spine. In 20 healthy volunteers, T2-weighted axial MR images were obtained at the levels of the C7-T1, T7-8, T11-12 and L2-3 vertebrae. The posterior extradural space seen in the slice through the intervertebral disc varied in shape and size depending on the vertebral level, and the shape of the space converted from triangular to crescent-shaped on moving from the lumbar to the thoracic spine. In particular, the posterior extradural space was almost absent at the C7-T1 level, indicating that the posterior extradural fat was rudimentary or non-existent at the thoracocervical level. At this level, the dura mater seemed to be in direct contact with the ligamentum flavum. Segmentation of the posterior extradural space was commonly observed at the L2-3 and T11-12 levels; however, incomplete segmentation of the posterior extradural space was often present at the T7-8 level.
APC and transforming growth factor-beta type II receptor (TGF-beta RII) gene mutations, and microsatellite instability have been found in sporadic colorectal carcinomas. To clarify further the early alterations in colorectal carcinogenesis, we investigated these genetic changes in 23 protruding- and 24 superficial-type mucosal colorectal carcinomas. TGF-beta RII gene mutations and microsatellite instability were rarely found in these lesions. Nevertheless, APC was mutated in 16 of the 47 (34.0%) mucosal colorectal carcinomas and was significantly more frequently mutated in protruding- (I) and superficial elevated-type (IIa) (14/32, 43.8%) than in other superficial-type (IIa+IIc, IIb, IIc, and IIc+IIa) (2/ 15, 13.3%) mucosal colorectal carcinomas (P < 0.04). These results indicate that the APC gene may be involved from the beginning in the tumorigenesis of many early colorectal carcinomas, particularly of the protruding and superficial elevated types. However, there might be a distinct pathway for other superficial-type colorectal carcinomas, possibly not involving APC as an initial step of tumorigenesis.
Stereoselective syntheses of omega-(alpha-bromoketo) octanals and nonanal with oxygenated functions and formation of the corresponding eight-membered carbocyclic aldols by subsequent samarium(II)-mediated cyclization are demonstrated. Cyclooctenones deoxygenated at the C2 or C10 position in the taxane framework are prepared by dehydration of the above aldols.
To evaluate the effect of prostagrandin E1 (PGE1)-induced hypotension on cerebral blood flow (CBF) and carbon dioxide (CO2) reactivity of CBF, regional cerebral hemoglobin oxygen saturation (rSo2) was measured in non-neurosurgical patients (n = 10) under sevoflurane-anesthesia using near infrared spectroscopy. PGE1 was infused intravenously to maintain arterial pressure at a level of about 75% of the MAP (hypotensive group) under sevoflurane-anesthesia alone (normotensive group). Ventilation was controlled to adjust PaCO2 to hypocapnia (25-30 mmHg), normocapnia (35-40 mmHg) and hypercapnia (45-50 mmHg) in both normotensive and hypotensive groups. rSo2 during hypotension did not change by hypocapnia and normocapnia, but significantly increased by hypercapnia, compared with rSo2 during normotension. Significant correlations between rSo2 and PaCO2 during both normotensive and hypotensive groups were observed. Slope of the regression line of rSo2 and PaCO2 did not differ between the normotensive and hypotensive groups. When arterial oxygen content and cerebral metabolic rate of oxygen are constant, changes in rSo2 correlate with those of CBF. Therefore, CBF and CO2 reactivity of CBF that indicates autoregulation in response to changes in CO2 during hypotension were maintained as those during normotension. The results show that PGE2-induced hypotension maintains CBF and CO2 reactivity well in non-neurosurgical patients under sevoflurane anesthesia.
We developed a system for 24-hour ambulatory recording of blood oxygenation (SpO2) and electrocardiography (ECG). Using this system, we studied 10 healthy volunteers and 7 patients with chronic pulmonary diseases. The system incorporated a portable pulse oximeter (SM50) manufactured by Fukuda Denshi KK; the first and second channels were used to record ECG data and the third was used to record SpO2 data. An SpO2 sensor (Dispo-sensor D-25; Nellcor Inc.) was applied to the fourth of fifth finger. The SpO2 data (MicrO2; Siemens AG) were digitized and stored in the ambulatory recording device; the ECG was recorded simultaneously. The data were analyzed with a model DMW-9000H analyzer (Fukuda Denshi KK). A custom-designed program was also used, to remove noise errors. In the healty volunteers, SpO2 was at least 90% for the entire 24 hours. In all the patients, SpO2 fell below 90% at rest during the night or after a 15-minute walk. Transient atrial tachycardia was observed in 3 patients, and during the tachycardia the SpO2 was low. The number of extra ventricular beats divided by the total number of beats increased more in the patients than in the healthy volunteers (1.21 +/- 0.89 vs 0.6 +/- 0.3%, p < 0.05). SpO2 did not change significantly in the patients. In outpatients and in patients receiving home health care, the present system facilitates simultaneous diagnosis of respiratory failure an arrhythmias. In patients with chronic pulmonary diseases desaturation may cause transient atrial tachycardia.
The purpose of this study was to confirm the effect of premixed lidocaine for the reduction of pain during injection of propofol in adult patients. We conducted a prospective, randomized, double-blind trial on 106 patients. In the study group (n = 54), lidocaine 40 mg (2 ml of lidocaine 2%) was added to 180 mg of propofol (18 ml). In the control group (n = 52), 2 ml of normal saline was added to 180 mg of propofol. The pain on injection was rated as none, mild, moderate, or severe. Eleven patients (20.4%) in the study group experienced pain compared with 25 (48.1%) in the control group. Thirteen in the control group complained moderate or severe pain compared with only one in the study group. In conclusion, lidocaine 40 mg premixed with 180 mg propofol significantly reduces the incidence and severity of pain associated with propofol injection.
The effects of Gosha-Jinki-Gan on the urinary bladder contraction in anesthetized dogs were studied to elucidate the mode of action. The bladder contraction was induced by electrical stimulation of the left distal end of the pelvic nerve under the bilateral pelvic nerve and hypogastric nerve transections, or by the infusion of acetylcholine (200 micrograms) in to the abdominal aorta. The bladder contraction induced by pelvic nerve stimulation was significantly inhibited by 10 and 100 mg/kg of intravenous Gosha-Jinki-Gan administration. A similar phenomenon was observed by the administration of atropine sulfate (0.1 mg). The acetylcholine-induced contraction was significantly inhibited by administration of 100 mg/kg of Gosha-Jinki-Gan. These findings suggested that Gosha-Jinki-Gan inhibits the urinary bladder contraction induced by the stimulation of cholinergic nerve.
A patient suffered massive bleeding from the ruptured liver and laceration of the inferior vena cava due to traffic accident, and developed hypotension and decreased level of consciousness. The patient was transferred to our hospital for an emergency operation against intra-abdominal massive bleeding. This massive bleeding was controlled with autotransfusion using washing salvaging autotransfusion device (Cell Savor). Suspected brain ischemia was treated with intended mild hypothermia. When blood pressure decreased to 30 mmHg of systolic pressure over 7 minutes during the operation, suggesting the possible brain ischemia, mild hypothermia was maintained at 33.8 degrees C. Total bleeding volume was 16,700 ml, and total transfused volume was 10,700 ml. Of total transfused volume, 4,500 ml was washed salvaged blood using the intraoperative autotransfusion device. No neurological deficit was found during the postoperative course. The patient was discharged uneventfully on the 20th postoperative day. In conclusion, intraoperative autotransfusion with washed salvaged blood is a useful method for treatment of massive bleeding, and mild hypothermia is efficacious for protecting the brain from ischemia resulting from accidental hypotension.
Familial clustering of gastric cancer is probably caused by multifactorial processes, both environmental and genetic. In this report, the incidence of microsatellite instability (MSI) in 31 cases of gastric cancer in Japanese (33 lesions) with familial clustering (two or more gastric cancers within second-degree relatives) was compared to MSI in Japanese cases without a family of any cancer in age ( +/- 10 years)-, stage-, and histological subtype-matched case-control study. Although the difference noted was not significant, we noted a strong trend for MSI at any of up to seven loci of CA repeats to occur more frequently in the patients with a family history of gastric than in the control patients in early cancer (intramucosal and submucosal), whereas the prevalence of MSI was similar in both groups in more advanced cases, in which the tumor invaded beyond the proper muscle layer of the gastric wall. Because the contribution of a family history of gastric cancer to MSI apparently differs in early and advanced gastric cancer, interpretation of MSI in familial gastric cancer cases published previously require reevaluation in terms of stage and proper controls. An acquisition of CA repeat alterations in the early stage rather than in the late stage of gastric carcinogenesis may have in common etiological factors, at least in some cases, with the familial clustering of gastric cancer.
A 31-year-old male with true hermaphroditism and a 46, XX karyotype who underwent gonadectomy and extirpation of the internal sex organs at the age of 4 had a large stone 4 cm in diameter in the residual male vagina. He complained of pain on micturition, hematuria, and rectal pressure. Urethroscopy and retrograde urethrography disclosed an ostium of the male vagina in the prostatic urethra, and an impacted intravaginal stone. Transurethral electrohydraulic lithotripsy was performed. Extracorporeal shock wave lithotripsy and transurethral lithotripsy were performed for the residual stones. All stones and fragments were spontaneously passed. The stone was composed of calcium phosphate and ammonium acid urate.
We investigated interstitial pneumonia associated with collagen vascular disease (IP-CVD) in association with lung cancer. Seventy-three cases of IP-CVD were included in this study. Nine (12%) of the 73 cases were associated with lung cancer, one of which had double lung cancers. The histological types of the cancers were adenocarcinoma (5 cases), epidermoid carcinoma (2 cases), small cell carcinoma, large cell carcinoma and large cell neuroendocrine carcinoma (one case each). The lesions were located in the central or peripheral lung in 3 and 7 of the ten cancers, respectively. Of the seven cases diagnosed as having IP-CVD followed by lung cancer, five had stage I disease, and one each of the remaining two cases was in stage IIIA and stage IV. Six of the seven peripheral cancer lesions which were resected or autopsied could be analyzed with regard to the topographical relationship between the primary site and fibrotic lesions. Only three cancers were encased by or in close proximity to, honeycomb lung, although most of the lung cancers arose in relation to fibrotic lesions. Moreover, the acute exacerbation of IP-CVD after operation or chemotherapy without thoracic irradiation should be monitored carefully.
BACKGROUND: Mutations of the transforming growth factor-beta type II receptor gene (TGF-beta RII) have been found in several replication error-positive sporadic colorectal carcinomas and hereditary nonpolyposis colorectal carcinoma cell lines. The aim of this study was to clarify the role of TGF-beta RII in sporadic colorectal carcinogenesis. METHODS: The authors screened for mutations at simple repeated sequences in the TGF-beta RII gene by polymerase chain reaction-single strand conformation polymorphism. They also examined genomic instability, using five microsatellite DNA markers in 69 sporadic colorectal carcinomas. When the carcinomas exhibited the TGF-beta RII mutations, the authors screened further for mutations in two DNA mismatch repair genes, hMSH2 and hMLH1. RESULTS: Seven of the 69 cancers (10%) showed one or two A deletions in TGF-beta RII and resultant frameshift mutations in nucleotide positions 709-718 containing a (A) 10 repeated sequence; but none of these appeared in the corresponding normal DNA, indicating a somatic mutation. All of the seven cancers were located in the proximal colon; there were none in the distal colon (P < 0.01). On the other hand, 22 of the 69 carcinomas (32%) showed the replication error-positive phenotype. The frequency of replication errors in proximal colon carcinomas was higher than that in distal colon carcinomas (P < 0.05). All 7 cancers with TGF-beta RII mutations showed replication errors. One of them revealed a nonsense mutation at codon 413, and 1 revealed a loss of heterozygosity in hMSH2. CONCLUSIONS: These data indicate that mutations of TGF-beta RII are strongly related to proximal colon carcinomas with microsatellite instability and that the mechanism of carcinogenesis in some proximal colon carcinomas is similar to that in hereditary nonpolyposis colorectal carcinoma.