Biomedical subjects
Publications and source records attributed to M Sakurai.
A 2-year-old boy developed acute myositis associated with rotavirus gastroenteritis. He had remarkable swelling and subcutaneous edema, mostly in the legs, 4 days after the onset of gastroenteritis. Marked elevation of creatine kinase was observed while serum albumin, immunoglobulin, and complement were decreased.
BACKGROUND: The bacterial pathogens commonly responsible for diarrhea in children under the age of 5 in Zambia were identified and the most effective methods of diagnosis of such infections in laboratories with limited resources, such as those in developing countries, are recommended. METHODS: Stool samples were collected from children under the age of 5 years who visited the Diarrhoea Training Unit (DTU) of Zambia University Teaching Hospital in Lusaka, Zambia, between May 1992 and May 1993. A total of 639 children were evaluated for the presence of bacterial infection using standard culture media. The prevalence of bacterial pathogens was compared with that reported from other developing countries. RESULTS: Pathogenic strains of Escherichia coli were isolated from 95 (14.9%) children, Shigella species from 65 (10.2%) children, and Vibrio cholerae from 21 (3.3%) children. The presence of visible blood in the feces was an early indicator of the presence of shigellosis. CONCLUSIONS: E. coli, Shigella species and Vibrio cholerae were the major causes of bacterial diarrhea in the Zambian children studied. Research is required to determine the prevalence of such enteropathogenic strains. The use of adequate diagnostic procedures is indispensable to appropriate management. The recommendations have been prepared as a manual for the identification of enteropathogenic bacteria to be used in laboratories with limited resources, such as in developing countries.
PURPOSE: To test the feasibility of a system for intermittent irradiation synchronized with respiratory motion in a clinical setting. MATERIALS AND METHODS: A newly developed gate pulse controller that starts and stops irradiation at a chosen phase of the respiratory cycle by controlling a linear accelerator was used in six patients with lung cancer. A laser displacement sensor was used for the detection of respiratory motion. Three patients underwent radiation therapy during the cycles between 50% expiration and 50% inspiration (step 1), and three patients underwent radiation therapy during the cycles between 70% expiration and 30% inspiration (step 2). RESULTS: The system functioned well; irradiation was verified with portal verification radiography in all six patients. The range of the tumor position during synchronized irradiation was detectable with fast portal localization radiography. The treatment times for steps 1 and 2 were 1.38-1.71 and 2.03-2.18 times longer, respectively, than those for conventional irradiation. CONCLUSION: Synchronized irradiation with the authors' system allowed convenient and reliable reduction of the target volume. Further study is needed to standardize the system for clinical use.
BACKGROUND AND PURPOSE: Some neuronal subpopulations are especially vulnerable to ischemic injury. In the spinal cord, large motor neurons are vulnerable to ischemia and are selectively lost after transient ischemia. However, the mechanisms of the neuronal loss have been uncertain. We hypothesized that spinal motor neurons might be lost by apoptosis and investigated a possible mechanism of neuronal death by detection of double-strand breaks in genomic DNA and immunohistochemical analysis for caspases, ie, interleukin-1beta converting enzyme (ICE), Nedd-2, and CPP32. METHODS: We used a rabbit spinal cord ischemia model created with a balloon catheter. The spinal cord was removed at 8 hours, 1, 2, or 7 days after 15 minutes of transient ischemia, and histological changes were studied with hematoxylin-eosin staining. To detect double-strand breaks in DNA, a staining with terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick end labeling (TUNEL) was performed. Furthermore, expression of ICE, Nedd-2, and CPP32 was investigated by Western blotting and immunohistochemical analysis. RESULTS: Motor neurons were selectively lost at 7 days after transient ischemia. TUNEL study demonstrated that no cells were positively labeled until 1 day after ischemia, but nuclei of some motor neurons were positively labeled at 2 days. Western blot analysis revealed no immunoreactivity for ICE and slight immunoreactivities for Nedd-2 and CPP32 in the sham-operated spinal cords. However, immunoreactivity became apparent at 8 hours after transient ischemia, decreased at 1 day, and returned to baseline level at 2 days. Immunohistochemical analysis demonstrated that motor neurons were responsible for induction of those caspases. CONCLUSIONS: Double-strand breaks in genomic DNA and induction of three caspases were demonstrated. These results indicate that motor neuron death in the spinal cord after transient ischemia is profoundly associated with activation of apoptotic processes.
Reduction of septal mass by inducing septal infarction using catheter techniques is a new therapy for hypertrophic obstructive cardiomyopathy (HOCM). We report a case of severe HOCM that was dramatically improved by this non-surgical treatment. A 60-year-old woman with HOCM had suffered dyspnea (NYHA class III) with syncopal attack despite medical treatment. Left heart catheterization showed a resting pressure gradient across the left ventricular outflow tract of 156 mmHg. Two proximal septal branches of the anterior descending coronary artery were catheterized with a balloon catheter by the usual percutaneous coronary angioplasty techniques and were completely blocked by injection of absolute alcohol. The pressure gradient decreased to 26 mmHg after the procedure. Symptoms were markedly improved (NYHA class I) without any medical treatment. The reduced pressure gradient was maintained at the 3-month follow-up catheterization (36 mmHg). Further long-term follow-up is needed, but this treatment would seem to to be a promising technique for reducing pressure gradient in symptomatic patients with HOCM.
The expression and fate of exogenous DNA (lacZ gene), introduced into the gonads of chimaeric embryos and chickens that had been produced by transfer of primordial germ cells (PGCs) transfected in vitro, were examined. PGCs obtained from embryonic blood were transfected in vitro by lipofection and transferred to the partially sterilized recipient embryos. Expression of the lacZ gene was observed in the gonads of chimaeric embryos incubated for 3 days after the PGC injection (71.2%, 37/52). Introduction of the lacZ gene into the gonads of chimaeric embryos was confirmed by PCR analysis. The percentage of embryos with gonads positive for the lacZ gene was 95% (38/40) after 3 days of incubation after the PGC injection. The lacZ gene, however, appeared to persist episomally but was gradually lost during embryonic development. After 17 days of incubation after the PGC injection, the lacZ gene was detected in only 14.3% (3/21) of the embryos examined. Although the lacZ gene was detected in the gonads of two hatched chicks (11.1%), it was not detected in the gonads of chimaeric chickens at sexual maturity. Offspring derived from the lipofected PGCs were obtained from the chimaeric chickens at frequencies of 12.1-69.9% in males and 71.6-97.6% in females. The technique developed in the present work could be used to test the expression of exogenous DNA in the gonads of early chicken embryos and should facilitate the production of transgenic chickens.
Trigonocephaly involves premature fusion of both the metopic suture and the sutures in the skull base. Surgical treatment by opening of the prematurely fused metopic suture and expansion of the anterior cranial base by creating "neosutures" was used to treat three children with trigonocephaly. The combination of lateral canthal advancement and radical forehead remodeling achieved excellent results. These procedures can also prevent the development of midface hypoplasia such as hypotelorism. The two younger patients, aged 0 and 6 months, achieved rapid bone growth in the defects and normalization of intercanthal and interpupillary distances. The older patient, aged 8 years, retained some skull defects at follow-up. The optimal age for surgery is 3-6 months, which allows good cosmetic results and minimizes visual repercussions with relatively low perioperative risks.
Acute ischemic stroke involving the entire vascular distribution of a carotid or middle cerebral artery can cause massive cerebral edema. This study evaluated external decompression for the treatment of massive stroke and analyzed possible prognostic factors. Twenty-four patients with acute massive cerebral infarction, which had progressed to tentorial herniation and impending death, underwent external decompression after medical therapy failed to achieve an effective response. The neurological outcome 2 months after surgery using the Glasgow Outcome Scale was severe disability in 14 patients, vegetative state in two, and death in eight. The overall mortality was 33%. Various characteristics (age, sex, etiology, side of hemispheric infarction, pupillary asymmetry, Japan Coma Scale, distribution of infarction, hemorrhagic infarction, midline shift, tentorial herniation) were evaluated to determine the factors associated with high mortality after surgical intervention. There was no statistically significant relationship between any variable and mortality. Mortality was especially high in the patients with preoperative consciousness level of 200, anterior, middle, and posterior cerebral artery territory infarction, and stage III of tentorial herniation. Postoperatively, all patients with severe disability returned to a clear level of consciousness. Six patients with dominant hemisphere stroke had some measure of communicative skills in spite of aphasia. External decompression is a life-saving treatment for patients with massive cerebral infarction and can provide a reasonable quality of life even for those with dominant hemisphere strokes. Decompressive surgery should be considered and performed as soon as possible if computed tomography demonstrates signs of descending tentorial herniation.
We report a case of a 20-year-old Japanese female with recurrent anaplastic large cell lymphoma (ALCL) associated with Sjögren's syndrome (SjS). She was first diagnosed to have ALCL presenting with axillary lymphadenopathy, which within a month underwent spontaneous remission, at the age of 12 years. Eight years later she developed left inguinal lymphadenopathy with clinical overt sicca symptoms associated with elevated serum IgG, interleukin (IL)-1beta and IL-6 levels. Lymph node biopsy was now diagnostic of ALCL characterized by large pleomorphic CD30+ blast cells with the specific chromosomal abnormality, t(2;5)(p23;q35). In contrast to this the salivary gland and renal biopsy revealed infiltration of small lymphocytes, morphologically and cytogenetically distinct from the ALCL cells. Interestingly, SjS symptomatology correlated with disease activity of ALCL and based on an association with elevated IgG and IL-6 levels, suggesting that the concurrence of these two diseases could be more than coincidental. To the best of our knowledge, this is the first reported case of ALCL presenting concurrently with SjS.
It has been reported that aclarubicin inhibits etoposide (VP-16) induced cytotoxicity in human lung cancer cell lines (1, 2). However, it still remains unclear how aclarubicin (ACR) inhibits etoposide-induced cytotoxicity. We report here that the combination of ACR and VP-16 showed antagonistic cytotoxic effect in P388 murine leukemic cells. DNA unwinding assay showed that 1000 ng/ml ACR significantly reduced VP-16 induced early DNA double strand(ds) breaks compared to that of VP-16 alone at a concentration of 10 microM. However, ACR did not inhibit VP-16 induced early DNA double strand breaks at a concentration of 100 ng/ml, a clinically achievable concentration. Furthermore, DNA repair occurred within two hours after removing VP-16 even if ACR was co-cultured at concentrations of 100 and 1000 ng/ml. DNA agarose gel electrophoresis and detection of sub-G1 fraction by flowcytometer showed that 100 ng/ml of ACR inhibited VP-16 induced DNA ladder formation and formation of sub-G1 fraction. Radioactive precursor incorporation studies showed that VP-16 inhibited DNA synthesis rather than RNA synthesis. On the other hand, ACR selectively inhibited RNA synthesis at a concentration of 100 ng/ml. The VP-16 induced increment of [3H]-L-leucine uptake was canceled by addition of 100 ng/ml of ACR. These data suggest that ACR inhibited VP-16 induced apoptosis by the inhibition of RNA synthesis along with protein synthesis, but not early DNA double strand breaks and DNA repair at a concentration of 100 ng/ml in P388 murine leukemic cells.
We report a simultaneously operated case of a 68-year-old man with lung cancer accompanied with aortic arch aneurysm. Preoperative staging CT for lung cancer incidentally demonstrated another lesion in the para-aortic arch area, which was suspected to be rather a pleural or intrapulmonary lesion by enhanced CT and MRI. However, this lesion was intraoperatively diagnosed as a cystic small sized-aneurysm. After a left upper lobectomy with lymph node dissection for lung adenocarcinoma (T2N0) was performed, this aneurysm was tightly wrapped using PTFE felt during the course of one operation. The difficulty of peroperative diagnosis by CT and MRI for small sized-aneurysm is discussed, and surgical stragety for lung cancer accompanied with such an aortic aneurysm is also commented.
Changes in the expression of intracellular interleukin-2 (IL-2), interleukin-4 (IL-4), interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha in newborn and adult lymphocytes induced by herpes simplex virus (HSV)-1 were examined. Cord blood mononuclear cells (CBMC) or adult peripheral blood mononuclear cells (PBMC) were infected with HSV-1 and cultured with phorbol 2-myristate 13-acetate (PMA) plus ionomycin in the presence of monensin for 4 hr. Surface antigen and intracellular cytokines were stained simultaneously and analyzed by flow cytometry. The percentage of cells that expressed IL-2, IFN-gamma, and TNF-alpha was significantly increased in HSV-1-infected CD3+, CD4+, CD8+, CD45RA+, and CD45RO+ lymphocytes compared with uninfected lymphocytes from adult PBMC. The percentage of cells that expressed IL-2 and TNF-alpha was increased significantly in HSV-1-infected CD3+, CD4+, CD8+, and CD45RA+ lymphocytes compared with uninfected lymphocytes from CBMC. IFN-gamma was under the detectable level in HSV-1-infected and uninfected lymphocytes from CBMC. Intracellular IL-4 was not detected in HSV-1 or in uninfected lymphocytes from PBMC and CBMC. These results demonstrate that HSV-1 enhances intracellular levels of IL-2, IFN-gamma, and TNF-alpha in adult lymphocytes and defective IFN-gamma production in cord blood.
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BACKGROUND: In 1982, the Fourth International Workshop on Chromosomes in Leukemia reviewed data prospectively collected on 716 patients with acute myeloid leukemia (AML) diagnosed between 1980 and 1982. The present study examined the extended follow-up on these patients. METHODS: The analyses included cytogenetic and clinical data, with a median follow-up of 14.7 years, from 54 patients with treatment-associated AML and 628 with de novo AML. Of these patients, 291 received induction therapy that would be considered standard by today's criteria; no patient received high-dose cytarabine (HiDAC) intensification. RESULTS: Among the patients with treatment-associated AML, the only long-term survivor in retrospect appears to have had de novo AML. Among the patients with de novo AML, achievement of complete remission and survival varied significantly based on cytogenetic classification among all 628 patients as well as among those who did and did not receive standard induction therapy. The remission rate and survival were significantly better with standard induction therapy for patients with t(15;17) and normal cytogenetics. Multivariate analyses showed that karyotype was an independent predictor of survival for all patients and those receiving standard induction therapy. Only 8.9% of patients were alive 5 years following diagnosis, but 5 years of continuous remission was synonymous with cure. Even among 5-year survivors who had suffered a previous relapse, 41% appeared to be cured. Survival among patients in continuous remission for > or = 10 years varied significantly by cytogenetic classification. In the absence of HiDAC intensification, no complete responders with t(8;21) and only 7% with normal cytogenetics survived continuously 10 years disease free. CONCLUSIONS: Cure of AML following specific therapies must be evaluated in the context of cytogenetics. A meta-analysis incorporating cytogenetic data is indicated for patients with > or = 10 years of follow-up.
We previously reported that invasive squamous cell carcinomas of the uterine cervix are of monoclonal composition. In the current study, we extended our previous work to determine the clonal composition of cases of high-grade squamous intra-epithelial lesion (HSIL). Clonal analysis targeting the HUMARA locus was performed on cervical tissue from 9 cases, 8 showing heterozygosity at the HUMARA locus and being, therefore, informative for clonality analysis. Uterine cervices were cut into 12 blocks, fixed with formalin and embedded in paraffin, and DNA was extracted from targeted lesions of each block. A total of 30 samples of cervical intra-epithelial neoplasia 3 (CIN3) (14 samples of carcinoma in situ and 16 samples of severe dysplasia) and 1 sample of CIN2 (moderate dysplasia) were analyzed. Monoclonal composition of the lesions was demonstrated in 30/30 cases of CIN3. Polyclonal composition was seen in the single case of CIN2. In 6 uterine cervices, in which dysplastic lesions were present in more than 3 blocks, the pattern of X-chromosome inactivation was the same in all lesions, suggesting that these individual lesions were derived from a single cell, with intraepithelial extension within the cervical mucosa. By contrast, one uterus contained 2 discontinuous dysplastic foci with different patterns of X-chromosome inactivation, indicating that the 2 lesions developed independently from each other. Our results demonstrate that (i) lesions of CIN3 (severe dysplasia and carcinoma in situ) are composed of a clonal neoplastic population of cells and (ii) most cases of HSIL are unifocal in origin.
BACKGROUND: Intimal lesions observed in the coronary arteries (CAs) of patients who have suffered episodes of Kawasaki disease (KD) raise concern about the premature development of arteriosclerosis. Accordingly, we investigated endothelial function in the epicardial and resistance CAs after KD during long-term observation. METHODS AND RESULTS: We assessed the responses of left epicardial and resistance CAs to serial intracoronary infusions of acetylcholine (final concentrations, 0.1 and 1 micromol/L) and nitroglycerin in subjects by using quantitative angiography and a Doppler flow wire system. Three age-matched groups were evaluated: 8 control subjects (group 1), 10 KD patients with normal left CA from the onset (group 2), and 8 KD patients with a persistent or regressed aneurysm in the left anterior descending CA (LAD) (group 3). Acetylcholine (1 micromol/L) changed the LAD area to 114.0+/-2.6%, 72.7+/-3.9% (P<.05 versus group 1), and 88.9+/-4.3% (P<.05 versus groups 1 and 2) of baseline in groups 1, 2, and 3, respectively, with a similar degree of increased coronary blood flow in each group. Nitroglycerin increased the LAD area to 143.5+/-7.7%, 132.3+/-1.9%, and 120.8+/-5.6% (P<.05 versus group 1), respectively. CONCLUSIONS: Results demonstrate a persistent endothelial dysfunction in the epicardial but not resistance CAs in patients after KD and enhanced stiffness of persistent or regressed aneurysms. The concern over early arteriosclerosis warrants the surveillance of KD patients from childhood to adulthood.
BACKGROUND: Endothelium-dependent nitric oxide-mediated vasodilation is impaired in rats with pulmonary hypertension (PH) induced by chronic hypoxia or by monocrotaline injection. We therefore investigated whether the prolonged administration of the nitric oxide precursor L-arginine would alleviate PH in both rat models. METHODS AND RESULTS: Fifty-nine rats were exposed to hypobaric hypoxia (380 mm Hg, 10 days) or room air and injected intraperitoneally with L-arginine (500 mg/kg), D-arginine (500 mg/kg), or saline once daily from day -3 to day 10. An additional 38 rats injected subcutaneously with monocrotaline (60 mg/kg) or saline were treated similarly with L-arginine or saline from day -3 to day 17. At the end of the experiment, awake mean pulmonary arterial pressure was determined. The heart was dissected to weigh the right ventricle, and the lungs were obtained for vascular morphometric analysis. Hypoxic rats developed PH (30.8+/-0.7 versus 19.2+/-0.4 mm Hg in controls; P<.05) and right ventricular hypertrophy. Their pulmonary arterial wall thickness and the proportion of muscular arteries in the peripheral arteries increased. L-Arginine but not D-arginine reduced PH (24.8+/-0.7 mm Hg; P<.05), right ventricular hypertrophy, and pulmonary vascular disease. Monocrotaline rats developed PH (34.9+/-2.1 versus 18.8+/-1.2 mm Hg in controls; P<.05), right ventricular hypertrophy, and pulmonary vascular disease. Again, L-arginine reduced PH (24.3+/-1.7 mm Hg; P<.05), right ventricular hypertrophy, and pulmonary vascular disease. CONCLUSIONS: We conclude that L-arginine ameliorated the changes associated with PH in rats, perhaps by modifying the endogenous nitric oxide production.