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Biomedical subjects

Y Mishima

Publications and source records attributed to Y Mishima.

At least 199 records · Page 11Linked to original sources
PubMed1990

In situ detection of cutaneous melanoma by prompt gamma-ray spectrometry using melanoma-seeking 10B-dopa analogue.

10B1-para-boronophenylalanine (10B1-BPA), one of our boronated dopa analogues developed for thermal neutron capture therapy, has been found to have a selective affinity for malignant melanoma. We have established a method of 'in situ' detection of subcutaneous melanoma lesions, using this melanoma-seeking 10B-labeled compound. In this study, we applied an 'in situ' 10B microanalysis system via detection of the prompt gamma-ray from the 10B(n, alpha)7Li reaction triggered by irradiating the 10B-containing target with pure thermal neutrons, called prompt gamma-ray spectrometry, to hamsters bearing Greene's melanoma in subcutis and to a human patient whose occipital subcutaneous tumor was suspected of being a metastatic melanoma. In the hamsters, the time-dependent 10B dynamics showed increased 10B accumulation in melanoma, after 10B1-BPA administration, in contrast to that in non-melanoma normal skin. In the human patient, after subcutaneous injection of 10B1-BPA into perilesional sites 4 cm distant from the tumor margin, the average 10B concentration in the tumor was determined to be 24 ppm (microgram/g), in contrast to 3 ppm in skin covering the tumor and 1.1 ppm in blood, indicative of selectively high 10B1-BPA uptake by the tumor.

Aged↗
PubMed1990

Antigen dynamics in melanocytic and nevocytic melanoma oncogenesis: anti-ganglioside and anti-ras p21 antibodies as markers of tumor progression.

Based on melanoma pathogenesis, phenotypic dynamics in pigment cell tumor progression detected with 11 MoAb have been defined. Anti-melanosomal A4F11 antibody reacts with every type of pigment cell tumor tested except for a few specimens. TNKH1 and anti-K.1.2 antibodies recognize nevocytic benign to premalignant tumors. HLA-DR, A.1.43, and A.10.33 antigens are expressed in advanced melanomas. Staining with anti-ganglioside GM3 and GD3 antibodies, M2590 and 4.2, respectively, reveals that most pigment cell tumors express gangliosides GM3 and GD3. But A2B5 antibody, which detects some polysialogangliosides such as GQ1C, reacts with highly progressed melanoma cells. Anti-ras p21 antibodies, RASK-3 and RASK-4, react with malignant melanomas and their premalignant lesions. These findings suggest the following: A4F11 is a universal marker of pigment cell tumors. TNKH1 and anti-K.1.2 antibodies might not be markers of melanocytic tumors but of nevocytic benign to premalignant tumors. Melanoma cells express gangliosides GM3 and GD3 as common pigment cell antigens and synthesize aberrant polysialogangliosides. Anti-ganglioside MoAb, including A2B5, are possible markers of the level of malignancy in melanoma cells like anti-A.1.43 and anti-A.10.33 antibodies. Enhanced ras p21 expression already appears on premalignant pigment cells.

Antibodies, Monoclonal↗
PubMed1990

Protein kinase C and linoleic acid-induced inhibition of melanogenesis.

Linoleic acid has been shown to inhibit melanogenesis in cultured B16 mouse melanoma cells. We report here the possible involvement of protein kinase C (PKC) in linoleic acid-induced inhibition of melanogenesis in B16 cells. A single PKC subspecies (alpha-PKC) was detected in B16 cells. The enzyme was activated by linoleic acid in vitro. The effective concentrations at which PKC was activated (25 microM; maximum response) were consistent with those for the inhibition of melanogenesis in cell culture system. In addition, the permeable diacylglycerol 1-oleoyl-2-acetyl glycerol that activates PKC also inhibits melanogenesis at 100 microM. These results suggest that activation of PKC plays a pivotal role in the linoleic acid-induced inhibition of melanogenesis in B16 cells.

Animals↗
PubMed1990

[Therapeutic evaluation of combination therapy using C-425, human native immunoglobulin liquid preparation for i.v. administration, with antibiotics in severe infections in the field of surgery].

In a nationwide study conducted in 11 surgical institutions of C-425, a newly developed human native immunoglobulin liquid preparation for intravenous injection, was combined with conventional antibiotic treatment to investigate the efficacy and safety. A total of 47 patients with severe infections which had not symptomatically responded to 3-day or longer treatment with any antibiotics was included. Doctors in charge judged the efficacy of C-425 to be "excellent" in 3 patients, "good" in 13, "fair" in 15, and "poor" in 4. Thus, a total of 16 patients (45.7%) was judged to have responded to C-425 when the "excellent" and "good" responses were combined. The number responding was 31 (88.6%) when the "fair" cases were also included. Excluding 31 patients who did not meet the Committee's criteria, the Committee judged the efficacy of C-425 in a total of 16 patients; the efficacy was "excellent" in 2 patients, "good" in 4, "fair" in 9, and "poor" in 1. The number of responding patients was 6 (37.5%) of the 16 when the "excellent" and "good" cases were combined, and 15 (93.8%) when the "fair" cases were added. Bacteriological assessment was conducted in a total of 9 patients. Causative bacteria were eradicated in 3 patients, decreased in number in 1, replaced in 2, and persisted in 3. Thus, bacteriological efficacy was observed in 6 of the 9 patients (66.7%). Neither adverse reactions nor drug-related laboratory abnormalities were observed in the 47 patients.

Adult↗
PubMed1990

[Experimental studies on drug concentrations in the liver using intra-hepatic injection of anticancer drug in combination with temporary halting of abdominal blood flow].

In a case of CDDP of 5 mg/kg injection for 5 min via the hepatic artery of non-tumor bearing rat, we assessed the influence of concomitant aortic clamping for 5 min at the intraphrenic level, which resulted in a decrease in the portal blood flow. CDDP-Platinum concentrations in the liver of rats given CDDP injection plus aortic clamping were 20.7 +/- 1.6 micrograms/g, which was two times higher than that (10.1 +/- 1.7 micrograms/g) of rat given CDDP injection alone. This enhanced CDDP-platinum concentration remained 15, 30, and 60 min after injection, respectively 1.4, 1.4 and 2.1 times higher. On the other hand, CDDP-platinum concentrations in the kidney of rats given CDDP injection plus aortic clamping were 4.5 +/- 0.8 micrograms/g, only one tenth of that (49.7 +/- 3.4 micrograms/g) of rats given CDDP injection alone. At 15 and 30 min after injection, there was no significant difference in CDDP-platinum concentrations in the kidney between these two groups. Renal toxicity observed in the group given CDDP injection plus aortic clamping was significantly less than in the group given CDDP injection alone, while hepatic toxicity seen in the former group was the same as that in the latter one.

Animals↗
PubMed1989

Changes in serum levels of Forssman-like antibody in patients with gastric cancer.

Because Forssman antigen, one of the most well-known heteroantigens, has been noted in certain cancerous tissues, it would seem that the serum levels of the Forssman antibody of patients with these cancers would be low, owing to the absorption of the naturally occurring antibody by the Forssman antigen-containing cancerous tissues. This hypothesis was tested by researchers assessing the serum hemolysin titers of 174 patients with cancer (gastric cancer, 100; colonic cancer, 40; and other cancers, 45) and of 856 age-matched, sex-matched, and blood type-matched healthy individuals against the serum levels of sheep red blood cells. Serum levels of the hemolysin of patients with gastric cancer tend to be lower than those of patients with other types of cancer and also lower than those of age-matched and sex-matched controls. The decrease was especially prominent in patients with moderately differentiated adenocarcinoma of the stomach. Preoperative and postoperative serum samples of 40 patients with gastric cancer were analyzed therefore to determine the effect of surgically removing the cancer on the serum level of the hemolysin. The results showed that the serum levels of the hemolysin antibody increased in all 40 patients after the successful surgical removal of the cancer. However, in patients with recurrence of the cancer, the serum levels of hemolysin decreased again in 11 of 11 patients. These results indicate that the serum levels of the Forssman-like hemolysin could be used as an index of recurrence in patients with gastric cancer after surgical removal of the cancer.

Adenocarcinoma↗
PubMed1989

Immunoreactive gastrin-releasing peptide as a specific tumor marker in patients with small cell lung carcinoma.

Gastrin-releasing peptide (GRP) is now known to be a very common product of small cell lung carcinoma (SCLC). With the aim of investigating the possible role of this peptide as a tumor marker of SCLC, we have developed a sensitive radioimmunoassay system for plasma immunoreactive GRP using immune-affinity chromatography for plasma extraction. Plasma immunoreactive GRP levels in control subjects were determined by using 15 ml of plasma as the starting material (minimum concentration detectable, 0.8 pg/ml). The levels in 10 control subjects were (mean +/- SD) 1.2 +/- 0.27 pg/ml; range, 0.86-1.7 pg/ml. This assay system was applied for the clinical use by using 3 ml of plasma as the starting material (minimum concentration detectable, 4.0 pg/ml). Plasma immunoreactive GRP levels were elevated in SCLC patients at frequencies of 71% in patients with limited disease and 80% in those with extensive disease. Furthermore, a change in the level showed excellent correlation with the therapeutic response. In six patients with complete response who had had elevated levels before treatment, the levels decreased to an undetectable range when the tumor disappeared, and they remained undetectable until 1 month later, when the patients were judged to have achieved complete response. In the partial response group, plasma immunoreactive GRP levels had decreased to an undetectable level in two of three patients, when the patients achieved partial response. In four patients with progressive disease, plasma immunoreactive GRP levels were elevated at the time of the progressive disease judgment, when compared with levels before treatment. The levels in 21 patients with non-SCLC (10 with adenocarcinoma, seven with squamous cell carcinoma and four with large cell carcinoma) were not elevated. These results indicate the plasma immunoreactive GRP level as a useful tumor marker in SCLC patients. It is now believed that GRP can function as an autocrine growth factor for SCLC. The present study suggests that the possible autocrine growth factor could serve as a reliable tumor marker for cancer patients.

Adenocarcinoma↗
PubMed1989

Ehlers-Danlos syndrome complicated by eventration of the diaphragm, colonic perforation and jejunal perforation--a case report.

A case of a 61 year old woman with Ehlers-Danlos syndrome who developed recurrent gastrointestinal complications is reported herein. She has been followed by Kyoundo Hospital since 1965, when she originally underwent treatment for eventration of the diaphragm and a volvulus of the stomach at the age of 41. During the past 22 years she has experienced perforation of the colon three times and jejunal perforation once. This case was considered to be type II Ehlers-Danlos syndrome. We have found 12 other cases of Ehlers-Danlos syndrome with gastrointestinal complications in the Japanese literature. More thorough examination of Ehlers-Danlos syndrome cases may reveal more subclinical gastrointestinal abnormalities. We concluded from our experience and from the literature that when colonic perforation occurs in this syndrome, total colectomy and ileo-rectal anastomosis is reasonably indicated.

Adult↗
PubMed1989

Self washout method for defecational complaints following low anterior rectal resection.

A self washout method was performed by ten patients who had defecational complaints following an anterior resection. A commercially available colostomy washout set was used for this procedure. When the patient sat down, the cone tip of the set was pressed into the anal canal by pushing the cone with the palm of the hand. The volume of water for irrigation used was 500 to 1000 ml and the subsequent defecation time was from 20 to 50 minutes. In all cases, the frequent urge to defecate disappeared and after normal defecational function had been recovered, the self washout was able to be discontinued.

Adult↗
PubMed1989

A new method of modified radical mastectomy for breast cancer.

We have developed a new type of modified radical mastectomy, the method and clinical results of which are reported herein. In this operation, axillary dissection is performed by the following two approaches. Firstly, the axillary contents are dissected from the highest possible subclavicular point to the pectoralis minor muscle, after partially cutting the sternocostal origin of the pectoralis major muscle. The second approach is from the posterior aspect of the pectoralis minor muscle to the lateral portion of the latissimus dorsi muscle. Parasternal dissection can also be performed for stage II and IIIa cancers with a central or medial tumor. After lymph node dissection, the detached edge of the sternocostal origin of the pectoralis major muscle is resutured to cover the parasternal region. Thus, complete dissection of the axillary nodes is performed whilst preserving the pectoralis major and pectoralis minor muscles. Good clinical results were achieved with respect to radicality, cosmetic effects and function in 28 patients with stage I, II, and IIIa breast cancers who were followed up for between 5 to 8 years. This new operation may therefore be adopted for the majority of patients with Stage I, II, or IIIa cancers, unless massive infiltration into the pectoralis major muscle has occurred. Preservation of both the pectoralis major and pectoralis minor muscles results in a good cosmetic appearance, good functioning of the arm and easy reconstruction of the breast following mastectomy.

Adult↗
PubMed1989

Melanogenic regulatory factors in coated vesicles from melanoma cells.

Coated vesicles have been found to contain much higher tyrosinase and gamma-glutamyl transpeptidase activities than premelanosomes. This indicates that similar to tyrosinase, gamma-glutamyl transpeptidase, an enzyme responsible for pheomelanogenesis, is highly concentrated in coated vesicles after its maturation in Golgi associated endoplasmic reticulum (GERL). Furthermore, in the pre- and post-dopaquinone melanogenic pathway, coated vesicles convert dopachrome to colorless indole compounds more quickly than in premelanosomes because of their higher dopachrome conversion factor activity. Melanosomes have been found to exhibit indole conversion factor activity, while coated vesicles show indole blocking factor activity. In moderately tyrosinase-rich premelanosomes, the levels of dopachrome conversion factor and indole blocking factor are lower than in coated vesicles or melanosomes. High levels of indole blocking factor in coated vesicles may indicate why melanin polymer formation does not occur there in vivo despite their high tyrosinase activity.

Coated Pits, Cell-Membrane↗
PubMed1989

Repair of 254 nm ultraviolet-induced (6-4) photoproducts: monoclonal antibody recognition and differential defects in xeroderma pigmentosum complementation groups A, D, and variant.

Repair kinetics of ultraviolet (UV) light-induced (6-4) photoproducts in xeroderma pigmentosum complementation group A, D, and variant cells were studied by the enzyme-linked immunosorbent assay (ELISA) using a specific monoclonal antibody raised against (6-4) photoproducts, together with unscheduled DNA synthesis (UDS) and loss of T4 endonuclease V-susceptible sites (ESS). Group AXP35KO cells completely failed to repair both ESS (cyclobutane pyrimidine dimers) and antibody-recognizing (6-4) photoproducts until tested 24 h after irradiation, and had 2% early-time UDS. Group DXP43KO cells showed about 10% removal of both (6-4) photoproducts and ESS in 24 h, despite showing a residually higher level of 40% early-time and cumulative UDS. Thus, the results substantiated the extreme UV hypersensitivity of XP group A and D cells. However, XP52KO variant cells exhibited the normal level of UDS and ESS loss, but a slightly reduced repair of antibody-recognizing (6-4) photoproducts at 6 and 12 h after irradiation, which may account for a small UV hypersensitivity of the XP variant cells.

Antibodies, Monoclonal↗
PubMed1989

Treatment of malignant melanoma by selective thermal neutron capture therapy using melanoma-seeking compound.

As pigment cells undergo melanoma genesis, accentuated melanogenesis concurrently occurs in principle. Subsequent to the understanding of intrinsic factors controlling both processes, we found our selective melanoma neutron capture therapy (NCT) using 10B-dopa (melanin substrate) analogue, 10B1-p-boronophenylalanine (10B1-BPA), followed by 10B(n, alpha)7Li reaction, induced by essentially harmless thermal neutrons, which releases energy of 2.33 MeV to 14 mu, the diameter of melanoma cells. In vitro/in vivo radiobiological analysis revealed the highly enhanced melanoma killing effect of 10B1-BPA. Chemical and prompt gamma ray spectrometry assays of 10B accumulated within melanoma cells after 10B1-BPA administration in vitro and in vivo show high affinity, e.g., 10B melanoma/blood ratio of 11.5. After successfully eradicating melanoma transplanted into hamsters with NCT, we advanced to preclinical studies using spontaneously occurring melanoma in Duroc pig skin. We cured three melanoma cases, 4.6 to 12 cm in diameter, by single neutron capture treatment. Complete disappearance of melanoma was obtained without substantial side effects. Acute and subacute toxicity as well as pharmacodynamics of 10B1-BPA have been studied in relation to therapeutic dosage requirements. Clinical radiation dosimetry using human phantom has been carried out. Further preclinical studies using human melanoma transplanted into nude mouse have been a useful model for obtaining optimal results for each melanoma type. We recently treated the first human melanoma patient with our NCT, using essentially the method for Duroc pig melanoma, and obtained similar regression time course leading to cure.

Animals↗