[Study of mammary lymph node scintigraphy by Tc-99m labeled activated carbon microspheres].
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Biomedical subjects
Publications and source records attributed to T Saeki.
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A 69-year-old female, chiefly complaining of diarrhea, was admitted to the Toyama Medical & Pharmaceutical University Hospital. A barium enema and an endoscopic examination revealed a villous adenocarcinoma of the rectum. Computerized tomography disclosed multiple metastatic lesions in the liver. She underwent an amptatio recti and an intra-arterial cannulation of the common hepatic artery in order to administer anticancer agents. Gross findings of the resected specimen showed villous adenocarcinoma containing a small ulcerated lesion. Histologic findings of this lesion revealed a collision neoplasm containing both an adenocarcinoma and a carcinoid with no obvious transitional region between the two lesions. The type D carcinoid, determined according to Soga's histologic classification, showed positive argyrophil granules but no argentaffin granules in the cytoplasm. The electron-microscopic findings of the carcinoid revealed small electron-dense endocrine granules measuring about 150 approximately 300 nm in diameter. The woman died 4 months after this operation.
A cDNA encoding the carboxyl-terminal fragment of the human myeloperoxidase heavy chain was isolated and characterized. It was then used to determine the locations of the myeloperoxidase light and heavy chains in the polypeptide precursor. A cDNA library from poly(A)+ RNA from human leukemia HL-60 cells was constructed in pBR322 and screened by differential hybridization with enriched and depleted cDNA probes and then by hybridization with an oligonucleotide probe. A cDNA clone containing 1278 bp with an open reading frame of 474 bp and a 3' noncoding region of 804 bp was isolated. The amino acid sequence deduced from the nucleotide sequence consisted of 158 residues including a sequence of 14 amino acids known to be present in the heavy chain of the molecule. The cDNA also included a stop codon of TAG followed by a noncoding sequence that included a potential recognition site for polyadenylylation and a poly(A) tail. RNA transfer blot analysis with the cDNA probe indicated that myeloperoxidase mRNA was approximately 3.3 kb in length. In vitro translation of the mRNA selected by cDNA hybridization revealed preferential synthesis of a 74,000-Da polypeptide precursor that could be precipitated with anti-myeloperoxidase IgG. Antibodies specific for the heavy and light chains of myeloperoxidase were isolated from antiserum by affinity chromatography employing Sepharose columns covalently bound to the heavy or light chains. Antibodies specific for the light chain or the heavy chain readily precipitated the 74,000-Da precursor polypeptide. These results indicated that myeloperoxidase is synthesized as a single chain which undergoes processing into a light and heavy chain. Furthermore, the heavy chain of myeloperoxidase originates from the carboxyl terminus of the precursor polypeptide.
The effects of a clinical oral dose of elastase on aortic atheroma development were studied in 0.2% cholesterol-fed rabbits, with or without endothelial denudation, using a balloon catheter. Elastase slightly decreased the serum lipids, but there was no significant difference from the serum lipids in the control groups. However, elastase significantly reduced the surface involvement of Sudan IV-positive staining areas of the aortas in rabbits with and without endothelial injury. The effect of elastase on SMC proliferation stimulated by hypercholesterolemia (C-serum or C-plasma) was also investigated in ex vivo experiments. The cholesterol levels in the serum and plasma of the elastase group were not significantly different from those of the 0.5% cholesterol-fed control rabbits. Proliferation of aortic smooth muscle cells was stimulated in the control group, while such stimulation in the elastase group was significantly lower. Therefore, elastase may suppress the stimulation through plasma factors, hence a reduction in atheroma development would ensue.
Intratumoral administration of 5 K.E. OK-423 was given every other day for a patient with an abdominal wall recurrence of gastric cancer. After a total dose of 465 K.E. the abdominal tumor turned necrotic and its demarcation was monitored. Finally, the tumor separated and fell from the abdominal wall. Histologically, marked infiltration of neutrophils, lymphocytes, and macrophages were observed in the cancerous tissue. Clinically, local pain lessened and the serum CEA level decreased. PPD and PHA skin tests were markedly stimulated. A long term small-dose intratumoral administration of OK-432 seemed to be effective for a local recurrence of gastric cancer.
Various pharmacological properties of a new antiplatelet aggregating agent, 4-cyano-5,5-bis(4-methoxyphenyl)-4-pentenoic acid (E-5510), were examined in order to elucidate its mode of action, Firstly, the inhibitory effect on in vitro aggregation of platelets from humans and various experimental animals was studied. E-5510 inhibited human platelet aggregation induced by collagen, arachidonic acid, adenosine diphosphate (ADP), platelet activating factor (PAF) and epinephrine. Thrombin-induced platelet aggregation, which was not inhibited by acetylsalicylic acid (ASA) or the thiazole drug, 4,5-bis(4-methoxyphenyl)-2-(trifluoromethyl) thiazole, was inhibited by E-5510. E-5510 inhibited collagen-induced platelet aggregation in platelet-rich plasma (PRP) from guinea pigs, beagle dogs and monkey to the same degree as in human PRP, but its effect was weaker in rat PRP. Human platelet adhesion to a collagen-coated plastic disk and thrombin-induced adenosine triphosphate (ATP) release from human platelets were also inhibited by this compound. Next, the ex vivo anti-platelet effect of E-5510 was examined in guinea pigs and beagle dogs. E-5510 was the most potent among the tested drugs (ticlopidine, ASA, cilostazol and the thiazole drug. The anti-platelet effect of this compound appeared within 1 h and lasted more than 8 h after oral administration. The above results suggest that E-5510 may antagonize platelet activation by inhibiting phospholipase C and/or A2, which results in suppression of both phosphatidylinositol breakdown and arachidonic acid release from phospholipids, as well as by inhibiting cyclooxygenase. E-5510 exerted its anti-platelet action without affecting prostaglandin I2 production in the blood vessels. It is considered that E-5510 has a highly potent anti-platelet aggregating effect and a unique multi-site mode of action. This compound is a promising candidate as an antithrombotic drug for clinical use.
Clinical trials of 4-day subrenal capsule assay (SRC assay) were carried out. One hundred and forty-one cases were investigated in order to evaluate the clinical utility of the assay. A total evaluability rate of 81.0% and a response rate of 36.5% were obtained in the SRC assay. The overall predictive accuracy between the tumor sensitivity of the assay and the clinical response was 82.1%. The percentage inhibition of %DNA/protein content of the implanted tumor, as a new predictor of the tumor growth inhibition, also indicated a good prediction rate for the assay. Correlation between the sensitivity test and the end results after chemotherapy in cases of inoperable gastric cancer classified as stage IV was investigated, retrospectively. Comparison of the survival curves between the patients treated with sensitive agents and those with insensitive agents exhibited a significant advantage for the former (p less than 0.01). These results suggest the utility of the SRC assay for clinical use, but histological studies exhibited certain limitations of this assay due to the existence of early host rejection of the implanted tumor. The utility of the SRC assay should be finally evaluated using more histological assessments and clinical trials.
The effects of far (254 nm) and near (290-350 nm) ultraviolet (UV) light on mutations, intragenic and intergenic recombinations were compared in diploid strains of Saccharomyces cerevisiae. At equivalent survival levels there was not much difference in the induction of nonsense and missense mutations between far- and near-UV radiations. However, frameshift mutations were induced more frequently by near-UV than by far-UV radiation. Near-UV radiation induced intragenic recombination (gene conversion) as efficiently as far-UV radiation and the induced levels were similar in both radiations at equitoxic doses. A strikingly higher frequency was observed for the intergenic recombination induced by near-UV radiation than by far-UV radiation when compared at equivalent survival levels. Photoreactivation reduced the frequency only slightly in far-UV induced intergenic recombination and not at all in near-UV induction. These results indicate that near-UV damage involves strand breakage in addition to pyrimidine dimers and other lesions induced, whereas far-UV damage consists largely of photoreactivable lesions, pyrimidine dimers, and near-UV induced damage is more efficient for the induction of crossing-over.
Two cases of citrullinemia were reported. Case 1 was an one month old female. Her clinical course and findings were different from the fulminant type of neonatal citrullinemia reported in predominantly Caucasian countries. Our patient was well controlled under a low protein diet and essential amino acids till 9 months of age, but unfortunately she died of Reye's like syndrome. Case 2 was 31 year old male (at the time of death). He was admitted to our hospital because of hyperammonemia and mental retardation. By subsequent laboratory investigations he was diagnosed as having adult type of citrullinemia and died of hepatoma. Enzymological analysis revealed that argininosuccinate synthetase (ASS) activities in the liver tissues of the patients decreased to 40% (Case 1), 20% (Case 2) compared with those in control liver tissues. The other urea cycle enzyme activities were all within normal range. ASS activities in the kidney and brains of the two cases were within normal range. The kinetic constant values of ASS for three substrates in the tissues of liver and kidney were all normal. Results of immunochemical analyses indicated that citrullinemia in our patients was caused by a quantitative deficiency of ASS associated proteins of the liver and kidney tissues as to the molecular weight.
Four cases of multiple primary carcinoma of the esophagus associated with dysplasia were found among seven patients with squamous cell carcinoma of the hypopharynx and cervical esophagus at the Shikoku Cancer Center Hospital. Two minute carcinomas were observed in these cases. One of them was too small to detect clinically despite the application of esophagoscopy with the Lugol's solution spraying method. All four patients had continued to smoke and consume alcoholic beverages (regularly) (habitually). These findings suggested that total esophagectomy is applicable to patients with hypopharyngoesophageal cancer, particularly those who continue to drink and smoke regularly.
In case of breast cancer subjected to postmortem examinations, histopathological changes were observed, and the effects of treatment were analyzed. Surgically obtained specimens of 36 cases of breast cancer could be compared with their postmortem specimens: in 14 cases (38.9%), tumor cells tended to be lowly differentiated, while the cells were unchanged in 22 (61.1%). There were no cases of differentiated tumor cells. Lowly differentiated cells were common in patients resistant to treatment who died shortly. Stromal tissues were sclerotic in eight cases (22.2%), medullated in three (8.3%), and unchanged in 25 (69.4%). Long-surviving cases tended to have the involvement of sclerosis.
Interferon-beta (IFN-beta), 6 X 10 units/body, was administered intraperitoneally and intrapericardially daily to five recurrent cancer patients with malignant effusion. Two of them showed complete response with a disappearance of effusion and cytological negative. However, three patients showing a decrease in effusion and cytological negative were regarded as no change because of the short duration of the response (less than four weeks). Intracavitary administrations of IFN-beta were well tolerated, and no serious side effects were observed. Autopsies showed that all intestines with disseminated metastasis maintained organic elasticity and had neither ileus-like construction nor progressive adhesions. IFN-beta showed not only anticancer effects on malignant effusion, but protection against GI tract constriction through moderate control of the growth of connective tissue.
A technique to repair the stenosed tracheostoma following total laryngectomy is described along with a brief discussion of some of the factors causing tracheostomal stenosis. Technical details are presented, and the importance of an interruption of the line of circular scar contracture is emphasized.
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We reviewed 4 gastrectomized cases associated with chronic leukemia. Three patients had chronic myelogenous leukemia, one had hairy cell leukemia. Subtotal gastrectomy was performed in all cases; two operations were for gastric cancer and two for bleeding gastric ulcers. The spleen was removed in three patients without any trouble. There were no difficulties in managing the patients during and after surgery and their leukemia was not aggravated during these periods.