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Biomedical subjects

H Tsuda

Publications and source records attributed to H Tsuda.

At least 307 records · Page 17Linked to original sources

Virus-associated haemophagocytic syndrome in previously healthy adults.

The clinical characteristics of 15 adult patients with virus-associated haemophagocytic syndrome (VAHS) were studied. The patients were 3 males and 12 females with a mean age of 39.5 years (range 20 to 67 years). Seven patients (mean age 48.6 years) were immunosuppressed by drugs or as a result of having malignant or autoimmune disease. Eight patients (mean age 31.6 years) had no underlying diseases. The prognosis of the patients with immunosuppression was poor, as previously reported, and 3 of them died. In younger adult patients with this syndrome who had no underlying immunosuppressive diseases, the prognosis was good even without therapy. The sera from the patients in both groups contained extremely high levels of macrophage colony-stimulating factor (M-CSF) and slightly elevated levels of tumour necrosis factor-alpha (TNF-alpha). These findings suggested that VAHS, can occur in presumably healthy adults and that VAHS can be a more benign condition than previously believed. M-CSF and TNF-alpha may play an important role in the development of the syndrome in both groups.

Adult↗

Hemolytic anemia in a patient with subacute bacterial endocarditis due to Streptococcus sanguis.

We describe a case of hemolytic anemia with subacute bacterial endocarditis due to Streptococcus sanguis. The major hematological features of the patient were a normocytic anemia with reticulocytosis, an elevation of serum lactate dehydrogenase, and a marked reduction of serum haptoglobin. All these signs of hemolytic anemia fluctuated in parallel with changes in inflammatory activity and were dramatically improved by the administration of benzylpenicillin, suggesting that the infection with S. sanguis itself was the cause of hemolytic anemia in this case.

Acute Disease↗

Transient regression in lymphocyte count in B-cell chronic lymphocytic leukemia after viral infection.

Transient regression in the lymphocyte count of a patient with B-cell chronic lymphocytic leukemia (B-CLL) after viral infection is reported. A similar event occurred under natural interferon-alpha (IFN-alpha) treatment. It was confirmed that the event was not caused by a direct cytotoxic effect of IFN-alpha by analyzing the DNA fragmentation to estimate apoptotic and necrotic cell death before and after the administration of IFN-alpha. The study also suggested that the event was not caused by a cytostatic effect of IFN-alpha.

Adult↗

Comparison between transabdominal and transvaginal ultrasonography for identifying endometrial malignancies.

Transvaginal ultrasound (TVS) is generally considered superior to transabdominal ultrasound (TAS) in the estimation of endometrial abnormalities. A disadvantage of TVS is the limited field of view. The purpose of this study is a comparison between TAS and TVS for endometrial cancer screening. Ninety-one postmenopausal women were included. They were evaluated by TAS, TVS, and endometrial tissue sampling. The mean endometrial thickness estimated by TVS was larger than that obtained by TAS (p < 0.0001). Sensitivity and specificity of TAS were 83.3 and 58.8% and of TVS 100 and 54.1%, respectively. We conclude that TVS might be superior to TAS, especially in patients with a retroflexed uterus.

Abdomen↗

The effect of Antineoplaston, a new antitumor agent on malignant brain tumors.

Antineoplaston (Ap), a new antitumor agent, was clinically tested for effects on malignant brain tumors. The materials were 3 cases of glioblastoma (G,B), 2 cases of anaplastic astrocytoma, 1 case of pontine glioma, 2 cases of metastatic brain tumor and 1 case of medulloblastoma. All patients underwent radiochemotherapy and surgical resection of the tumors except the cases of pontine glioma, metastatic brain tumor and anaplastic astrocytoma. For gliomas, radiochemotherapy was used with Hu-IFN-beta. Ap was administered at a dose of 7-10 g/day in combination with remission maintenance therapy of gliomas. Complete response was obtained in one anaplastic astrocytoma. Partial response was obtained in 2 cases, a pontine glioma and a metastatic brain tumor. No change was observed in 2 cases, an anaplastic astrocytoma and a multiple brain metastasis. Progression of the disease was observed in 4 cases, 3 glioblastomas and 1 medulloblastoma, which showed continuous increase in tumor size. The effects of Ap on malignant brain tumors were considered due to synergy, since it was administered with other drugs and acceleration of tumor cellular differentiation. Ap is useful as an approach to remission maintenance therapy for brain tumors.

Adult↗

Toxicological study on antineoplastons A-10 and AS2-1 in cancer patients.

Antineoplastons, which were firstly described by Burzynski, are naturally occurring peptides and amino acid derivatives which control neoplastic growth. We conducted a toxicological study of the Antineoplastons A-10 and AS2-1 in combination with other anticancer agents or radiation in 42 patients, 46 tumors with terminal stage cancer. Antineoplaston A-10 oral formulation and A-10 injectable formulation was administered in 14 and 25 patients respectively. The maximum daily dose was 10 g and 40 g, respectively and the longest term of administration was 610 days and 67 days, respectively. Antineoplaston AS2-1 oral formulation and AS2-1 injectable formulation was administered in 33 and 10 patients, respectively, the maximum daily dose was 12 g and 30 g, respectively, and the longest term was 1070 days and 25 days, respectively. The major adverse effects that may have been related to these agents as used in combination with other conventional chemotherapeutic agents or radiation were general weakness, myelosuppression, and liver dysfunction, but these effects were not seen when either Antineoplaston was administered alone. The minor adverse effects observed in single use of either Antineoplaston A-10 or AS2-1 were excess gas, maculopapullar rash, fingers rigidity, reduced cholesterol, reduced albumin, increased amylase, eosinophilia, increased alkaline phosphatase, headache, hypertension, palpitation, peripheral edema but these adverse effects did not limit to continuation of either agent. The evaluation of the usefulness of the Antineoplastons in combination therapy based on the imaging findings during the course of treatment revealed disappearance or measurable shrinkage of the tumor lasting more than one months as visualized by magnetic resonance imaging or computed tomography was seen in 15 tumors (32.6%). No increase in size of tumor for more than 3 months was observed in 8 (17.4%). The mean survival time of these patients was significantly longer than that in patients with tumors showing progressive increasing (17.52 + 3.31 months vs 4.80 + 0.65 months, p < 0.005). Antineoplaston A-10 and AS2-1 are less toxic than conventional chemotherapeutics and they were useful in maintenance therapy for cancer patients.

Adolescent↗

[The effects of sevoflurane on the coronary circulation in the instrumented dog with or without coronary stenosis].

The effects of sevoflurane on the coronary circulation were investigated in the instrumented dogs with or without coronary stenosis. A-V block was produced by injection of formalin into A-V node to control heart rate at 120 beats.min-1 by pacing and mean systemic blood pressure was held constant at 65 mmHg with the pressurized blood reservoir. Left anterior descending coronary artery was cannulated with stainless steel tube supplied from the femoral artery. Total coronary flow was measured with an electromagnetic flow probe and the regional myocardial blood flow was calculated using color microsphere technique. Coronary resistance was reduced with the increasing end-tidal concentrations of sevoflurane up to 1.2 MAC. An adjustable screw clamp was used to reduce the coronary flow down to 50% of control value. Inner/outer ratio of regional myocardial blood flow decreased with stenosis, but was unaffected with 1.2 MAC of sevoflurane. We concluded that 1.2 MAC of sevoflurane was not strong enough to dilate the coronary artery to produce the transmural steal phenomenon in the dog with coronary stenosis. Further investigations are needed to clarify how hemodynamic factors influence the transmural steal phenomenon in myocardium.

Anesthetics↗

Natural state of mutant p53 protein and heat shock protein 70 in breast cancer tissues.

BACKGROUND: Nuclear accumulation of p53 protein in breast cancer cells is generally accepted as a marker for the presence of p53 gene mutation and as an indicator of poor prognosis. Mutation in the p53 gene has been shown to cause conformational change in the p53 protein, which gives rise to a complex with heat shock protein 70 (hsp70). EXPERIMENTAL DESIGN: To clarify whether the p53 protein that accumulates in the nuclei of human cancer cells is bound to hsp70 in vivo, we compared the immunohistochemical localization of both p53 and hsp70 in 65 surgically resected cases of primary breast cancer. In four cases showing both nuclear accumulation of p53 protein and mutation of the p53 gene, identified by single-strand conformation polymorphism and direct sequence analysis, the presence of the p53-hsp70 complex was examined by coimmunoprecipitation assay. In 12 human cancer cell lines showing nuclear accumulation of the p53 protein, the presence of the p53-hsp70 complex was also examined by immunoprecipitation with two anti-p53 Ab after labeling with [35S]methionine. RESULTS: Among the 65 cases, p53 and hsp70 immunoreaction in cancer cell nuclei was detected immunohistochemically in 16 (25%) and 23 (35%) cases, respectively. The localizations of the two proteins were significantly correlated, but there was a discrepancy in the localization patterns in 23 cases. Although the p53-hsp70 complex was detected in all of the four cases in which the p53 mutation was identified, the expression levels of hsp70 detected by coimmunoprecipitation assay were much weaker than those of p53 protein. In all of the 12 cancer cell lines with nuclear accumulation of p53, no distinct 70-kDa bands were immunoprecipitated with the p53 protein. CONCLUSIONS: In human breast cancer tissue, only part of the pool of p53 is bound to hsp70.

Aged↗

[Postpartum parvovirus B19-associated acute pure red cell aplasia and hemophagocytic syndrome].

A 30-year-old postpartum woman was admitted to our hospital because of progressive anemia, malaise, night sweating, headache and low grade fever which began 9 days after delivery (day 0). She had normocytic hypochromic anemia accompanied with marked decrease in reticulocytes. In addition, a temporary decrease in platelets and white blood cells especially neutrophils were observed. Bone marrow smears showed an apparent decrease in erythroid cells and the presence of giant proerythroblasts (1.2%) as well as hemophagocytes (1.2%). IgM and IgG antibody against human parvovirus B19 (HPV) was detected on day 22 of the disease although negative results were obtained on day 3. The presence of the virus in the blood on admission was confirmed by dot-blot analysis. Thus, this case was diagnosed as acute pure red cell aplasia and hemophagocytic syndrome caused by HPV infection. This patient had been given iron for iron deficiency anemia before delivery and the iron deficiency was still present after the episode of the present disease although the iron metabolism data was perturbed during the disease. These findings suggest that HPV could cause acute pure red cell aplasia not only in patients with hemolytic anemia but also in patients with iron deficiency anemia or after acute bleeding. Furthermore it is suggested that pancytopenia often observed on HPV infection could be at least partly caused by hemophagocytic syndrome.

Adult↗

[Differential diagnosis of intracystic papillary tumors of the breast by examination of loss of heterozygosity on chromosome 16q].

Loss of heterozygosity on chromosome 16q region is shown to occur frequently in breast cancers regardless of difference in phenotype or extent of tumor spread, and inactivation of tumor-suppressor genes located on the region is considered to be involved in the acquisition of malignant phenotype of mammary glandular epithelial cells. Intracystic papillary carcinoma of the breast is diagnostically important entity because of the difficulty of differential diagnosis from intraductal papilloma preoperatively. Indeed, intracystic papillary carcinoma is usually of low-grade histologic atypia (Grade 1), and its well differentiated nature is biochemically supported by high estrogen-receptor and progesterone-receptor value in their tissue extract. Among intracystic papillary tumors of the breast, LOH on chromosome 16q was detected in 71% of intracystic papillary carcinoma, whereas it was absent in intraductal papilloma by both of Southern blot analysis and microsatellite polymorphism analysis mediated by polymerase chain reaction. Therefore, LOH on chromosome 16q was suggested to be helpful for differential diagnosis of intracystic papillary tumors and to be applicable to the materials of fine needle aspiration performed preoperatively.

Adenoma↗

[Cerebral blood flow and metabolism in Lafora disease].

An 18-year-old male manifesting intellectual deterioration and negative myoclonus was diagnosed as Lafora disease by the demonstration of Lafora bodies in the skin and muscle biopsy. The cortical evoked potential to electric stimulation of the median nerve at wrist showed the giant SEP, suggesting hyperexcitability of the sensory motor cortex. Cerebral blood flow, and cerebral glucose and oxygen metabolism were investigated by positron emission tomography (PET) in order to clarify the pathophysiological process in Lafora disease. The result showed diffusely decreased cortical glucose metabolic rate and cerebral blood flow, and moderately lowered oxygen metabolic rate. There was no increase in blood flow or glucose and oxygen metabolism in the sensorimotor cortex in spite of the presence of giant SEP. The ratio of the glucose to oxygen metabolism was not different from the mean value obtained from nine normal subjects. Based on these findings and review of the literature, it is unlikely that there is a significant deficit in cortical energy metabolism in patients with Lafora disease and it would be less plausible to have some enzymatic deficits in glucose metabolic process.

Adolescent↗

Analysis of the neurofibromatosis 2 gene in human breast and hepatocellular carcinomas.

The neurofibromatosis 2 gene (NF2) mapped to chromosome 22q is a recently isolated tumor suppressor gene that participates in the tumorigenesis of cells of embryonic neural crest origin. The structural similarities between the NF2 product, merlin-schwannomin, and the band 4.1 family raise the possibility that merlin may participate in a wide range of cell activities, in which the cytoskeleton latticework has important roles to play. In order to examine the significance of NF2 in general carcinogenesis, comprehensive analyses of 68 cases of breast carcinoma, which shows frequent loss of heterozygosity at chromosome 22, and 48 hepatocellular carcinomas of different histological grade were performed. No mutation was detected by the polymerase chain reaction-single-strand conformation polymorphism method for six exons of NF2 in any of the cases examined, suggesting that NF2 may be less important in the tumorigenesis of breast and liver cancers than in that of cancers originating from the neural crest.

Base Sequence↗

Eyelid metastasis from breast cancer showing marked response to chemotherapy.

A patient with recurrent breast cancer, who was diagnosed with eyelid metastasis as a part of systemic metastases and in whom systemic chemotherapy was markedly effective, is reported. A 50-year-old woman underwent a radical mastectomy for stage II breast cancer in October, 1988. Histologically, the tumor was invasive lobular carcinoma. In October, 1993, the patient consulted our hospital complaining primarily of swelling of the left eyelid and restriction of movement in the left eye. Metastasis from breast cancer was diagnosed on eyelid biopsy. On further examination, metastases were detected in the liver, bone, orbit, peritoneum and pleura. Systemic combined chemotherapy consisting of cyclophosphamide, adriamycin and 5-fluorouracil was administered intravenously at intervals of three weeks. Complete responses were obtained in the eyelid and peritoneal metastases after three courses, and in the liver metastasis after five courses. Partial responses were also observed in the bone and pleural metastases. The incidence of eyelid metastasis from breast cancer is very low, one case only having been previously reported in Japan and 34 cases abroad. Most of these cases were treated locally by surgical resection or radiotherapy, but the mean survival period was only 14 months, ranging from two months to four years. Eyelid metastasis from breast cancer should be regarded as a manifestation of systemic spread of the tumor and, in principle, treated by systemic therapy.

Antineoplastic Combined Chemotherapy Protocols↗

Pattern of gene alterations in intraductal breast neoplasms associated with histological type and grade.

To reveal any association between the histological type and grade of intraductal breast neoplasms and the manner of accumulation of gene alterations, eight types of gene alterations, i.e., loss of heterozygosity (LOH) on chromosomal arms 16p, 16q, 17p, 17q, and 18q, amplification of the c-erbB-2 and hst-1/int-2 genes, and mutation of the p53 gene, were examined by Southern blot analysis or single-strand conformation polymorphism analysis in a total of 60 cases of intraductal breast cancer and 18 nonmalignant proliferative lesions. Among the histological types and three histological grade groups of intraductal carcinomas, the gene alterations which occurred most frequently were LOH on 16q alone in non-comedo type and Grade 1, alterations of c-erbB-2, 17p, and 16q in comedo type and Grade 2, and alterations of 17q and p53 as well as those of 16q, 17p, and c-erbB-2 in Grade 3. LOH on 16q and 18q was frequent in intraductal carcinoma of the intracystic papillary type, whereas LOH on 18q alone was detected in 27% of papillomas. Among intraductal carcinomas, the mean number of gene alterations was largest in comedo type and Grade 3, whereas it was smallest in non-comedo type and Grade 1. It was possible that LOH on 18q and 16q was involved frequently in papillary tumori-genesis and acquisition of malignant phenotype, respectively, whereas most of the other gene alterations were involved in acquisition of aggressive biological properties by intraductal carcinoma cells. It was also possible that the phenotype of breast neoplasms was determined by the combination of gene alterations at a relatively early developmental stage.

Breast Neoplasms↗

Bilateral Breast Cancer in a Patient with a Strong Family History of Cancer: Analysis of p53 Germ Line Mutations.

We report a case of bilateral breast carcinoma in a patient with a strong family history, including 4 cases of breast carcinoma, 1 case of prostate carcinoma (father), 1 case of hepatocellular carcinoma (mother), 2 cases of gastric carcinoma, 1 case of lung carcinoma, and 1 case of lingual carcinoma, in second degree relatives, together with analysis of germ line p53 mutations. The patient was a 51-year-old female who had undergone mastectomy 9 years previously for an invasive ductal carcinoma of the right breast. Lymph nodes were free of metastases and the tumor had negative estrogen receptor (ER) status. Bone and lung metastases developed 18 months after surgery, and had been well controlled with chemoendocrine therapy. She subsequently underwent a modified radical mastectomy for carcinoma in the contralateral breast. This was an invasive lobular carcinoma with negative lymph node metastasis, negative p53 immunoreaction, negative c-erbB-2 protein and positive ER status. In this breast-prostate carcinoma-type cancer family there was a high incidence of breast carcinoma; the father, who had prostate carcinoma, was possibly a carrier of a breast carcinoma susceptible gene. We have however detected to p53 germ line mutations in the lymphocytes DNA of the patient and her niece. The accumulation of cancers in this family line remains to be elucidated further using other genetic markers.

Journal Article↗