Biomedical subjects
Publications and source records attributed to K Shimokawa.
A case of gastric lipoma seen in a 57-year-old-woman was reported. UGI, endoscope, CT, MRI and EUS revealed a tumor, which showed typical findings of this disease. Above all, EUS findings correlated well with the cut surface of the operative specimen.
Types of 2-nitroimidazoles and 3-nitro-1,2,4-triazoles bearing one or two fluorine atoms on their side chains were synthesized to evaluate their physicochemical properties, radiosensitizing effects, and toxicity. The reduction potential of the compounds containing one fluorine was similar to that of misonidazole (MISO), whereas that of the difluorinated compounds was slightly higher. Both mono- and difluorinated compounds had an in vitro sensitizing activity comparable to or slightly higher than that of MISO. The fluorinated 3-nitrotriazoles were almost as efficient as the 2-nitroimidazoles with the same substituent. In vivo, some of the compounds were up to twice more efficient than MISO, whereas others were as efficient as MISO. Toxicity in terms of LD50/7 in mice was quite variable depending on the side-chain structure; the amide derivatives were less toxic than MISO, whereas the alcohol and ether derivatives were more toxic. In view of the radiosensitizing effect and toxicity in vivo, at least one compound, KU-2285 (a 2-nitroimidazole with an N1-substituent of: CH2CF2CONHCH2CH2OH) has been found to be as useful a hypoxic cell sensitizer as SR-2508.
A 37-year-old male was presented with an upper abdominal mass. A retroperitoneal bulky tumor was detected and operative biopsy revealed seminoma. The right testis was undescended and atrophic which was located at the left inguinal lesion. Pathologically, the primary tumor cells were not found in the left orchiectomied testis, but only scar and fibrosis were compatible with a burned-out testicular tumor. This patient showed partial regression by multidisciplinary therapy including combined chemotherapy with CDDP, etoposide and peplomycin, and is still on the same condition and alive for 3 years. In case of extragonadal germ cell tumor without apparent testicular involvement, it is a problem to differentiate primary extragonadal germ cell tumor from occult and burned-out testicular tumor. Testis should be examined by all means available including careful exploration.
The plasma lipoprotein(a), apo AI, apo B, and acute phase proteins, were studied in 21 patients with myocardial infarction and in 11 patients after surgery. In the both groups, C-reactive protein showed a rapid increase, and alpha 1 acid glycoprotein, alpha 1 antitrypsin and lipoprotein(a) followed by a moderate increase and restored to normal values after one month. Lipoprotein(a) increased to a maximum on day 11 in the myocardial infarction group, and on day 8 in the surgery group. Only slight changes in apolipoprotein AI and B were noted. We speculate that lipoprotein(a) is an acute phase protein that plays an important roles in recovery from trauma. Recently it was reported that the amino acid sequence of apolipoprotein(a) is partly identical to that of plasminogen. This sequence suggests that lipoprotein(a) and plasminogen are related immunochemically. We examined by immunoblotting technique whether our antibody for lipoprotein(a) is influenced by a plasminogen in plasma. By enzyme-linked immunosorbent assay, it was found that the purity of plasminogen does not influence determination of lipoprotein(a).
A microspectrophotometric analysis of the DNA content has been performed on 9 advanced recurrent gastric cancer patients with measurable lesions, who has either been treated by CDDP alone or with other chemotherapeutics during a three-year period since, 1984. Histograms of the DNA content were classified into four ploidy patterns. All of the 4 responder cases (CR, PR, MR) showed type, IV, although only one of 5 non-responder cases revealed the same typing. In one of the two CR cases the DNA ploidy pattern, which was examined before and after the therapy, changed from type IV to type II. Thus it appears that an analysis of the DNA content may be useful in evaluating the effectiveness of different chemotherapies.
Exogenously administered 5-aminolevulinic acid (ALA) inhibited the formation of bacteriochlorophyll a (Bchl a) in a dose-dependent manner in the aerobic photosynthetic bacterium, Erythrobacter sp. strain OCh 114, under dark growth conditions. The ALA concentration required for half-inhibition after 24-h growth was estimated to be about 3.0 mM. Porphyrin and Bchl precursors were not found in either the cells or the growth medium. The same inhibition was also observed with cytochrome c formation. When ALA was incubated with intact cells, a large amount of ALA was converted to an unknown metabolite. The pH optimum of the conversion was 7.8. The metabolite did not react with Ehrlich's reagent, but did so with ninhydrin, giving a yellow color. Based on analyses by several techniques including mass spectrometry, ir spectrometry, and paper electrophoresis, it was identified as 4-hydroxy-5-aminovaleric acid (HAVA). Authentic HAVA prepared from ALA was a competitive inhibitor of the enzyme, porphobilinogen synthase of Erythrobacter. The Ki value for authentic HAVA was calculated to be 2.4 mM from a Dixon plot and the HAVA concentration required for half-inhibition was 17 mM. It is concluded that in Erythrobacter cells, exogenous ALA is converted to the metabolite, HAVA, which is responsible for the inhibition of porphobilinogen synthase as well as that of Bchl a and cytochrome formation.
We have developed a new sensitive method for quantifying lipoprotein(a) (Lp(a] in human serum, using a 'sandwich' type noncompetitive enzyme-linked immunosorbent assay (ELISA). The solid-phase used was a polystyrene plate. The anti-Lp(a) antibody-enzyme conjugate was labelled by linking Fab' fragments to peroxidase (EC 1.11.1.7) by the maleimide method. The minimum detectable concentration was 0.5 ng/well. Routinely, the assay was carried out with 1,000-fold diluted serum, and Lp(a) was quantified between 4.0 and 500 mg/l. Within-run coefficients of variation (CVs) ranged from 3.5% to 10.4% and between-run CVs from 5.0% to 11.1%. Results by the ELISA were in good agreement with those by radial immunodiffusion (r = 0.955). The distribution of Lp(a) in serum from 820 healthy donors was highly skewed: mean 141.1 mg/l, medium 97.9 mg/l. In cord blood, the mean and median were 15.6 and 9.8 mg/l, respectively. This ELISA for Lp(a) has the advantages of being highly sensitive and specific, simple to perform, and does not use radioisotopes.
A 55-year-old female, in which an unresectable Borrmann II-type gastric cancer (moderately differentiated adenocarcinoma) extending from vicinity of the cardia to the lower portion of the corpus, with direct invasion into the pancreas and extensive lymph node metastases, confirmed by laparotomy, was treated postoperatively by 3 courses of chemotherapy with cisplatinum in combination with mitomycin C and 5-fluorouracil. A complete response was confirmed by roentgenography and endoscopy, and, at 4 months after the first operation, a total gastrectomy with radical lymphadenectomy was performed successfully. Cancer cells were not detectable histologically in the stomach specimen and in all the lymph nodes removed. One year and 5 months after the second operation she is well, showing no sign of recurrence.
Immunofluorescence assay using monospecific and monoclonal antibodies to the 65 K major protein of human cytomegalovirus (HCMV) was carried out to monitor the expression of this protein in infected cells. Regardless of differences in the reactivity of the monoclonal antibodies, as determined by immunoblotting and immunofluorescent staining, all stained cytoplasmic inclusion bodies localized to the site of the HCMV-induced receptor for the Fc portion of IgG, suggesting that most of the 65 K major protein of HCMV colocalizes with the HCMV-induced FcR.
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A case of renal angiomyolipoma with bone formation is reported. A 61-year-old woman was admitted to our hospital with one month history of fever. About 15 cm in diameter mass was palpated in her right lower abdomen. Plain abdominal roentgenography, ultrasonography and computed tomography showed marked calcification in the cephalic portion of the right kidney, tumors surrounding right kidney and another tumor in the right lower abdomen. All these tumors and the kidney constituted a big mass continuously, and no fatty component was demonstrated. Total excision of the mass including the kidney was performed. The mass was 30 X 24 X 10 cm in size and 3,240 g in weight. Histologically, the tumor was compatible to renal angiomyolipoma. But, radiopaque shadows which looked like calcification were disclosed to be bones, and fatty tissues were not seen so much. Therefore, the name "benign mesenchymoma" was thought to be more acceptable than angiomyolipoma in this case. Preoperative diagnosis of renal angiomyolipoma is the demonstration of fatty densities in the tumor, and the characteristic extrarenal development should also be taken into consideration. Furthermore, the bone formation of angiomyolipoma, which is very rare might be an important finding to angiomyolipoma.
Case 1. A 61-year-old male, suffering from an anorectal tumor with anal bleeding, underwent an abdominoperineal rectal amputation with an R3 lymphadenectomy. The tumor was a Stage I (H0, P0, N0, S0) malignant melanoma. Despite DAV (DTIC, ACNU, and VCR) therapy, liver metastasis was detected 1 year later and the patient died 1.5 years after the operation. Case 2. A 80-year-old female, complaining of bloody stool, was diagnosed to have an anorectal malignant melanoma. She was at Stage IV and underwent an abdominoperineal rectal amputation with an R3 lymphadenectomy. The tumor 4.5 X 2.7 X 1.2 cm in size, was diagnosed to be at Stage IV (pm, n2+). She is still alive 4 years later without having received sufficient chemotherapy.
Human cytomegalovirus-infected cell polypeptides were immunoreacted by sera of renal transplant recipients and compared with those reactive with sera of healthy adult donors by means of the Western immunoblotting technique. At least 15 polypeptides with molecular weights of 155K, 123K, 102K, 89K, 79K, 71K, 65K, 60K, 55K, 50K, 46K, 42K, 38K, 33K, and 28K were immunoreacted. Sera obtained serially from renal transplant recipients reacted with most of these polypeptides and reacted more frequently and intensely with the smaller polypeptide species such as 38K, 33K, and 28K, compared with sera of healthy seropositive adults. The implications of these findings are discussed.
The presence of HCMV-infected cells inhibits the killing of mouse tumor cells by adherent PEC in an antibody-dependent cell-mediated cytotoxicity (ADCC) test system. The effect of HCMV-infected cells on ADCC is mediated by the binding of IgG to the Fc receptors of infected cells.
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A 61 year-old male patient, diagnosed to have a malignant melanoma in the left arm in April, 1981, was treated by chemotherapy (gamma-INF and DAVP) and a left axillary lymphadenectomy. In March, 1985, he had complained of hoarseness and an early laryngeal squamous cell carcinoma was found, and was subjected to laser treatment. On May 25, 1986, during his hospitalization for treatment of a multiple metastasis of a malignant melanoma, he suddenly suffered from a gastroduodenal perforation. During an emergency operation, a third cancer, a primary mixed hepatocellular and cholangiocellular carcinoma, was discovered.
A 55-year-old woman with gastric cancer underwent laparotomy and was found to have an unresectable tumor at the MC region, characterized by S3 (invasion into the pancreas), N3, P0, H0, Borrmann-II and moderately differentiated tubular adenocarcinoma. She was then treated by combined administration of cis-dichlorodiammine platinum (CDDP), mitomycin C and 5-fluorouracil (5-FU). A complete response was confirmed by upper gastrointestinal roentgenography and endoscopy. Upon reoperation 4 months after the initial laparotomy, a successful total radical gastrectomy with R2 (partially R3) lymph node dissection was performed. Histological examination of the specimens, including the stomach and lymph nodes, revealed no cancer cells in any region.
For 3 years beginning in 1984, 14 advanced and recurrent gastric cancer cases with measurable lesions (8 unresected cases, 3 cases of recurrence, 2 cases with non-curative resection, 1 case of no operation) were treated by CDDP therapy alone or in combination with other chemotherapies. CR was obtained in 2 of the 8 non-resected cases, radical gastrectomy being feasible in these 2 cases by second-look operation. Five of the 8 cases showed PD, and in 1 case the effect was rather obscure. One of the 2 non-curative resection cases achieved PR, and the other case was MR. One of the 3 recurrent cases was NC, the remaining cases being PD. The one case given no operation showed PD. Overall effectiveness of CDDP therapy for advanced and recurrent gastric cancer cases was seen in 3 (21.4%) of the 14 cases. All of these 3 cases showing effective CDDP therapy was elevated serum CEA values before the therapy, which was markedly reduced after starting the therapy, the reduction rate being very remarkable.