Search PubMed⌕ Search

Biomedical subjects

M Shiraishi

Publications and source records attributed to M Shiraishi.

At least 73 records · Page 4Linked to original sources

Radiation-associated ischemic coloproctitis: report of two cases.

Radiation-associated ischemic coloproctitis is a rare clinical entity caused by vascular insufficiency to the rectosigmoid colon. It most commonly occurs after radiotherapy for gynecological cancer. We present herein the cases of two patients who developed radiation-associated coloproctitis with transmural necrosis and eventual perforation. Perforation of the rectosigmoid colon occurred 3.5 years after radiotherapy in case 1, a 46-year-old woman, and presented as a well-defined small area of transmural necrosis. Conversely, in case 2, a 55-year-old woman, it occurred 1.5 years after radiotherapy, and presented as segmental, diffuse transmural necrosis. The lesion in case 1 had been caused by intramural vascular obliteration due to marked fibrosis of the bowel wall, while that in case 2 had been caused by occlusion of the mesenteric artery with thrombosis. Both patients underwent Hartmann's resection without rectal excision, and survived the perforative event.

Colon, Sigmoid↗

Microsatellite instability in double cancers of the esophagus and head and neck.

It is generally accepted that patients with squamous cancers of the esophagus are known to have a high risk of concomitant head and neck cancer. However, there have been only a few reports describing microsatellite instability (MSI) in patients with both esophageal squamous cell carcinoma and head and neck cancers. To evaluate the role of genetic instability in carcinogenesis in such patients, we analyzed six microsatellite loci in 21 tumors from 10 patients who had developed primary cancers of both the esophagus and the head and neck. MSI was detected in 6 out of 10 patients. In five patients with double cancer, MSI was observed at the same microsatellite loci in both the esophageal and the head and neck tumors obtained from the same individuals. These data suggest that such patients may have the same underlying defect in the mismatch repair system, providing insight into possible mechanisms for field carcinogenesis.

Carcinoma, Squamous Cell↗

Radiation-associated rectal cancer: report of four cases.

BACKGROUND/AIMS: Radiation-associated rectal cancer is a remarkable clinical entity. We demonstrate 4 patients (mean age 68 years, range 63-74) who had undergone pelvic radiotherapy for cervical cancer. We indicate some characteristics of radiation-associated rectal cancer. RESULTS: Two patients had received intracavitary and external pelvic radiotherapy, while the remaining 2 had external pelvic radiotherapy following hysterectomy. The mean total radiation dose was 63 Gy, though radiation dose information was not available for 1 patient. Colorectal cancer developed at a mean time of 20.7 years (range 11-30) after radiation therapy. All patients presented with chronic radiation colitis, and 3 demonstrated abnormal tumor markers. Colonoscopy revealed an ulcerative, localized well-differentiated adenocarcinoma of the rectosigmoid colon in 1 patient, and diffusely infiltrating cancers of the lower rectum, one signet-ring cell carcinoma and two mucinous carcinomas in the remaining 3. One case was stage I, 2 were stage IIIa, and the remaining case was stage IV. Three patients underwent abdominoperineal resection. The remaining patient was felt to be inoperable. The colorectal wall demonstrated the changes of chronic radiation injury. Two patients died within a short time because of their advanced cancers. CONCLUSION: Radiation-associated rectal cancer has a tendency to be diagnosed in the advanced stage and to have a poor prognosis. A literature review and our case report suggest that since there are no reliable clinical or laboratory indicators of the presence of a curable colorectal cancer in the setting of chronic radiation proctocolitis, surveillance with a colonoscope should be done 10 years after irradiation in patients with previous pelvic radiotherapy.

Aged↗

[Thromboxane A2 antagonist--discovery of seratrodast].

We were interested in RCS (rabbit aorta contracting substance) and SRS-A (slow reacting substance of anaphylaxis) and their involvement in human bronchial asthma. When we started our anti-asthmatic drug research in the 1970's. We synthesized a lot of chemical compounds and eventually discovered that AA-861 inhibited the generation of SRS-A from the lung tissue of actively sensitized guinea pigs. AA-861 was found to be a potent 5-lipoxygenase inhibitor. This compound reduced experimental allergic asthma in guinea pigs, but it is easily metabolized in the body. More recently, we found a novel compound, AA-2414 (seratrodast), which is not metabolized in the body. AA-2414 proved to be not a 5-lipoxygenase inhibitor, but a thromboxane A2 (TXA2) receptor antagonist. Seratrodast is the first receptor antagonist that is being developed as an anti-asthmatic drug. Seratrodast inhibits both immediate-, late asthmatic responses in guinea pigs, and also reduces airway hyperresponsiveness in dogs. The anti-asthmatic action of seratrodast in animal models indicates that the drug should be of use in the treatment of human asthmatics. In clinical studies, seratrodast showed a marked effect to improve clinical parameters in bronchial asthma. It is also reported that seratrodast is free from harmful aftereffects. Clinical trials are under way in the US.

Animals↗

Alteration of mosaic methylation of the repeat unit of the human ribosomal RNA genes in lung cancer.

We have investigated the methylation status of the repeat unit of the human ribosomal RNA genes in lung cancer. Using a Southern blot analysis approach we have determined that the non-transcribed region of these genes was generally heavily methylated, while the transcribed region was not methylated in either tumor or normal DNA. Our study also revealed that, in one tumor, the boundary of mosaic methylation of the repeat unit was not distinct. In the same tumor, both the non-transcribed ribosomal spacer region and the L1 interspersed repeat sequences became partially demethylated. In tumor cells, the methylation status of DNA can be altered, but the methylation of subtelomeric repeats was found to be maintained. These results suggest that the mosaic methylation of the repeat unit is not necessarily maintained in tumor DNA, while subtelomeric repeats escape tumor-specific wave of demethylation.

Blotting, Southern↗

Tight interaction between densely methylated DNA fragments and the methyl-CpG binding domain of the rat MeCP2 protein attached to a solid support.

In a previous report we have found that a number of short DNA fragments methylated at CpG sequences bound more tightly to a methyl-CpG binding column than DNA fragments having a larger number of methyl-CpG sequences. The column consists of a polypeptide comprising the DNA binding domain of the rat MeCP2 protein attached to a solid support. In the present study, we have investigated the features of short DNA fragments which bind tightly to a methyl-CpG binding column. Tight binding was observed when the DNA fragment had a high density of methyl-CpG sequences. Many of these fragments, derived from human genomic DNA, contained Alu repeated sequences supporting the previous observation that the highly-abundant Alu sequences are highly methylated. Our results suggest that methyl-CpG density is an important factor in the interaction between DNA fragments and the DNA binding domain of MeCP2 attached to a solid support.

Animals↗

Anesthetic management for pheochromocytoma resection using spinal cord stimulation and intravenous nicardipine--a case report.

We have used spinal cord stimulation (SCS), diazepam and nitrous oxide for maintenance of general anesthesia. Blood pressure was maintained by bolus administration of nicardipine for the removal of pheochromocytoma. Both SCS and nicardipine reduced systemic vascular resistance and SCS increased cardiac output. However, neither SCS nor nicardipine could inhibit the release of norepinephrine. SCS proved to be useful as one of anesthetic technique during the removal of pheochromocytoma, and also in the management of postoperative pain and the prevention of complications.

Adrenal Gland Neoplasms↗

[Lung volume reduction surgery for pulmonary emphysema].

Surgical treatment for pulmonary emphysema has received renewed attention, because many studies have demonstrated improvements in dyspnea and pulmonary function. After lung volume reduction surgery (LVRS) for carefully selected advanced pulmonary emphysema, pulmonary functional impairments, such as expiratory flow limitation, increase in lung volume, decrease in lung elastic recoil, impaired gas exchange are improved. Improvements of dynamic hyperinflation, respiratory muscle function and exercise tolerance were also demonstrated after LVRS for pulmonary emphysema. Finally these functional effects may improve symptom and prognosis of pulmonary emphysema with better quality of life. Although the basic mechanism responsible for the improvements are not well known yet, physiological mechanisms which brought improvement after surgical treatment for pulmonary emphysema should be further investigated.

Exercise Tolerance↗

[An autopsied case of subacute progressive dementia with flactuated disturbance of consciousness, myoclonus and periodic synchronous discharges on EEGs].

We present an autopsied case which developed progressive dementia at the age of 45. EEGs showed periodic synchronous discharges (PSD) when he showed fluctuated cloudy consciousness with myoclonus. Cerebrospinal fluid examination showed mild to moderate increase in protein and monocytes for duration of illness, but antivirotics and antibiotics were not effective. He was not apallic even at the terminal stage when computed tomography (CT) revealed marked cerebral atrophy, and died of pneumonia 27 months after onset. He was clinically diagnosed as having Creutzfeldt-Jakob disease (CJD) because of subacute progressive dementia, myoclonus and PSD. Neuropathological examination revealed marked brain atrophy with severe neuronal loss and gliosis in the cerebral cortex and subcortical nuclei, although no spongiform degeneration was found. Senile plaques, neurofibrillaly tangles, argyrophilic glial inclusions and glial nodules were not detected. Prion protein immunoreactivity was negative. Therefore, this case can not be neuropathologically diagnosed as having CJD, Alzheimer's disease, non-Alzheimer-type degenerative dementias or any encephalitis. This case might have suffered from an unknown new disease.

Brain↗

The isolation of CpG islands from human chromosomal regions 11q13 and Xp22 by segregation of partlymelted molecules.

We isolated fragments containing parts of CpG islands from human chromosomal regions chosen for expected differences in gene density by segregation of partly melted molecules. Restriction fragments of P1 bacteriophage clones covering a region of 11q13 and those of cosmid clones derived from Xp22 were recovered from bands in denaturing gradient gels that were retained following prolonged exposure to electric field. Forty-five independent fragments derived from 11q13 and five from Xp22 were isolated. Nucleotide sequence analysis revealed that 11 of the 45 fragments from 11q13 contained CpG islands including four derived from known genes in 11q13. None of the five fragments derived from Xp22 resembled CpG islands. The number of CpG island fragments obtained was consistent with the expectation based on the number of Not I restriction endonuclease sites present at these regions. Adjustment of parameters in our quasi-theoretical approach to the rate of fragment dissociation improves the discrimination between retention and non-retention. The results support probable identification of CpG island fragments by their reduced rate of strand dissociation when retarded in a denaturing gradient gel.

Base Sequence↗

Detection of DNA abnormalities by arbitrarily primed PCR fingerprinting: allelic losses in chromosome 10q in lung cancers.

DNA fingerprinting using arbitrarily primed PCR (AP-PCR) is useful for detecting cancer-specific DNA aberrations without targeting any particular genes or knowing any nucleotide sequences in advance. AP-PCR fingerprinting is an efficient method for finding loss of anonymous chromosomal regions in cancers. We analyzed DNA from 44 human non-small cell lung cancers by fingerprinting using a single primer and found a loss of signal intensity in a DNA fragment amplified from chromosome 10 (fragment F) in 15 tumors. The detailed location of the fragment F locus on chromosome 10q was determined by PCR-based analysis of radiation hybrid panels using a sequence-tagged site established for the fragment. In 12 of the 15 tumors, loss of the signal detected by AP-PCR fingerprinting was in agreement with the results obtained by analysis of allelic imbalances using 7 polymorphic CA-microsatellite DNA markers for loci around the fragment F locus (p=0.0009). We conclude that a hitherto unknown suppressor gene for lung cancer resides at 10q in the vicinity of fragment F.

Alleles↗

Identification of histamine-production-increasing factor produced by stimulated RBL-2H3 rat basophilic leukemia cells as granulocyte-macrophage colony-stimulating factor.

When RBL-2H3 rat basophilic leukemia cells were stimulated by antigen or the Ca2+ ionophore A23187, the activity to increase histamine production by rat bone marrow cells in the conditioned medium increased time-dependently. To characterize the histamine-production-increasing factor (HPIF) produced by RBL-2H3 cells, the conditioned medium was collected 8 h after stimulation by A23187, and the factor was purified by three-step chromatography, the specific activity being increased by 9000-fold. The partial amino acid sequence of the peptide obtained by S. aureus V8 protease digestion was identical to the internal amino acid sequence of rat granulocyte-macrophage colony-stimulating factor (GM-CSF). In addition, GM-CSF mRNA levels in RBL-2H3 cells were increased by A23187 with a peak at 4 h. Furthermore, recombinant rat GM-CSF increased histamine production by rat bone marrow cells. These findings suggested that HPIF produced by the stimulated RBL-2H3 cells is GM-CSF. Possible significant roles of HPIF at the late phase of allergic inflammation are discussed.

Amino Acid Sequence↗

NMR study of the interaction between the B domain of staphylococcal protein A and the Fc portion of immunoglobulin G.

The solution structure of the B domain of staphylococcal protein A (FB) complexed with the Fc fragment of immunoglobulin G (IgG) is reported. A previous NMR analysis has shown that in solution FB is composed of a bundle of three alpha-helices, helix I, helix II, and helix III [Gouda, H., Torigoe, H., Saito, A., Sato, M., Arata, Y., and Shimada, I. (1992) Biochemistry 31, 9665-9672]. In contrast, the crystal structure of FB in the FB-Fc complex lacks helix III. Uniformly 15N- and 15N/13C-labeled FB were prepared, and the backbone 13C resonances were assigned. The spectral data obtained in the present study indicated that in solution all three helices including helix III are preserved in the FB-Fc complex. The mode of interaction of FB with the Fc fragment was discussed on the basis of the combined data of hydrogen-deuterium exchange experiments and 1H-15N correlation spectroscopy. It was concluded that a contiguous surface shaped by F14, Y15, E16, L18, and H19 in helix I, and N29, Q33, L35, and K36 in helix II is responsible for the binding.

Amino Acid Sequence↗

Morphologic and mucin histochemical analysis of transitional zones in advanced ulcerated colorectal carcinomas: potential prognostic indicators.

BACKGROUND AND OBJECTIVES: The transitional zone, which is normal-appearing mucosa that surrounds a primary colorectal carcinoma, has characteristic histologic features, and an increased amount of sialomucin in the transitional zone have been associated with a poorer prognosis. To clarify the prognostic effects of changes in the transitional zone we studied the transitional zone in cancers of the colon and rectum. METHODS: A total of 105 specimens resected for advanced colorectal carcinoma were studied to identify the effectiveness of evaluating morphologic types (polypoid or nonpolypoid growth type) and mucin expression (sulfomucin or sialomucin type) of the transitional zone as a prognostic indicator. RESULTS AND CONCLUSIONS: Nonpolypoid carcinomas were likely to have invaded the deeper layers and lymphatic vessels and go on to develop advanced disease. Sulfomucin-type tumors were predominantly found in the right side colon and followed a relatively favorable course. Our results indicate that the morphologic and mucin components of the transitional zone may be prognostic indicators for advanced colorectal carcinoma.

Adult↗

Successful gene transfer to the porcine liver in vivo with an adenoviral vector.

In vivo gene transfer to the porcine liver was tested with adenoviral vector to achieve molecular biological graft modulation. In adult female pigs immunosuppressed with cyclophosphamide, cyclosporine, and prednisolone, the liver was surgically isolated and flushed out with cold lactate Ringer solution (4 degrees C), by means of a pump-controlled bypass of the portal vein and the inferior vena cava in Groups A and D. In Group A (n = 4), 2 x 1011 pfu of the adenoviral vectors (pAdexCALacZ) were injected through the left hepatic artery during cold ischemia. In Group (n = 4), 2 x 1011 pfu of adenovirus vectors were injected through the auricular vein in a one-shot manner without a laparotomy. In Group C (n = 4), 2 x 1011 pfu/ml of adenoviral vectors were injected through the hepatic artery in a one-shot manner, without a surgical isolation of the liver. Group D (n = 4) animals received the same protocol as Group A except for the fact that they did not receive the immunosuppressive regimen. In a polymerase chain reaction, a transfected LacZ sequence was detected until POD 28 in Group A, but not in the other groups. In 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-gal) staining, only the Group A animals revealed apparent staining predominantly in the portal area at POD 2, which then continued to be recognized until POD 28. The in situ perfusion of the liver combined with immunosuppression is thought to provide an ideal environment for the liver-directed adenovirus-mediated gene transfer to the porcine liver, by enabling a long contact with a high titer of the adenoviral vector.

Adenoviridae↗

Radiation enterocolitis: overview of the past 15 years.

From April 1980 to April 1995 a total of 54 patients (53 women, 1 man) were hospitalized in our department for the surgical treatment of radiation enterocolitis. Two surgical protocols were applied for these patients: intestinal decompression procedures alone (intestinal bypass, colostomy, or both; n = 18) or an intestinal resection in addition to decompression (n = 36). The clinical factors contributing to survival after irradiation were retrospectively reviewed by a multiple variate proportional hazards model. As a result, patients treated with decompression procedures alone had an 11 times higher risk for death than those treated with the addition of intestinal resection. In the former group, 5 of 18 patients died of bleeding from the remaining intestine after operation. We concluded that surgical resection of the diseased intestine is a useful procedure for treating radiation enterocolitis to reduce intestinal bleeding from the irradiated intestine.

Adult↗