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Biomedical subjects

M Tani

Publications and source records attributed to M Tani.

At least 19 recordsLinked to original sources

[A case of insulinoma with frequent hypoglycemic attacks not showing evident hyperinsulinemia].

Confirmation of inappropriate hyperinsulinemia is an indispensable requisite for the diagnosis of insulinoma. We report here a case of insulinoma without evident hyperinsulinemia at an early stage. The patient, a 49-year-old woman, had been admitted to our hospital for the evaluation of frequent hypoglycemic attacks. At that time, plasma immunoreactive insulin (IRI) after an overnight fast ranged from 7 to 16 microU/ml. The ratio of IRI/fasting blood sugar (FBS) (Fajans index; normal range, below 0.3) was always between 0.13 and 0.28 even at hypoglycemic states. In addition, because computed tomography and arteriography of the abdomen failed to settle the diagnosis of insulinoma, the patient was discharged and followed up at our outpatient clinic for 2 years. She was admitted to our hospital at 51 years of age for the re-evaluation of hypoglycemic attacks. Laboratory examinations revealed high fasting plasma levels of IRI ranging from 20 to 29 microU/ml. Fajans index also increased to 0.47-0.89. Celiac arteriography was able to confirm the existence of insulinoma. We suggest that insulinoma should be considered in the presence of unexplained hypoglycemic attacks even when there is no evident hyperinsulinemia.

Blood Glucose

Antihypertensive and hormonal activity of MK 954 in spontaneously hypertensive rats.

MK 954 (DuP 753), a recently developed angiotensin II (Ang II) receptor antagonist, was administered orally for 2 weeks to spontaneously hypertensive (SHR) and Wistar-Kyoto rats (WKY). Whereas the basal levels of plasma Ang II were lower in SHR than in WKY, treatment with MK 954 markedly reduced blood pressure in SHR but not in WKY. Plasma renin activity, Ang I and Ang II were increased, while plasma aldosterone was decreased in both strains. These results no only indicate therapeutic efficacy of this agent in the chronic treatment of human hypertension, but also support the idea that the renin-angiotensin system plays an important role in the control of blood pressure in SHR.

Angiotensin I

Defective autologous mixed lymphocyte reaction (AMLR) and killer activity generated in the AMLR in cancer patients.

The autologous mixed lymphocyte reaction (AMLR) and the killer activity generated in the AMLR (AMLR-killer) in the spleen and the peripheral blood of patients with gastric cancer were investigated. The AMLR in cancer patients was suppressed, especially in the spleen, compared to that seen in controls. There was no correlation between AMLR activity and the stage status of the cancer. The cytotoxic activity of AMLR-killer cells against various tumor-cell lines was also suppressed in the spleen, and had a tendency to be suppressed in the peripheral blood of cancer patients. The autologous tumor-killing activity of AMLR-killer cells was developed in cancer patients with high AMLR activity, but was not induced in patients with low AMLR activity. Autotumor killing activity was decreased by the elimination of CD4+ cells, whereas the elimination of CD16+ cells resulted in a marked reduction in cytotoxicity against K562, indicating that the non-specific killer cells which lysed K562 were different from the specific killer cells that lysed autotumor cells. This suggests that AMLR activity is related to the differentiation and proliferation of lymphocytes with specific or non-specific cytotoxic activity and that this activity plays an important role in immune surveillance against tumors.

Adult

Clinical and immunological evaluation of intraoperative radiation therapy for patients with unresectable pancreatic cancer.

The clinical efficacy of intraoperative radiation therapy (IORT) and the changes of immunological parameters were investigated. Nine patients with unresectable pancreatic cancer were treated with IORT (2,500-3,500 cGy) and the changes of various immunological parameters were compared with those in 11 patients with advanced cancer who received external beam irradiation therapy (XRT), 2,500-3,500 cGy. After IORT, 71% of patients obtained pain relief, two of the nine patients showed a partial response, and the serum CA 19-9 level decreased in six patients. However, the median survival was only 210 days. Natural killer activity, lymphokine-activated killer activity, and interferon gamma-activated killer activity were not inhibited by IORT, and phytohemagglutinin-induced blastogenesis was actually augmented after IORT, whereas all these parameters were inhibited by XRT. Thus, it is suggested that IORT may augment or at least stabilize systemic antitumor immunity.

Aged

In vitro generation of activated natural killer cells and cytotoxic macrophages with lentinan.

The in vitro effect of lentinan in inducing activation of killer cells and cytotoxic macrophages has been examined. Human peripheral blood mononuclear cells were cultured with lentinan for 2, 4 and 8 days. After 4 days cytotoxicity was increased 4% by lentinan less than 1,000 ng/ml. After 8 days, it was increased 12% by 25 and 1,000 ng/ml lentinan. The phenotype of the killer cells induced by lentinan was CD2+, CD16+ and CD56+, suggesting that they were natural killer cells. Macrophages separated from the spleens of 6 patients with gastric cancer were cultured with lentinan for 7 days, and their cytotoxicity increased 19%. The optimal concentration of lentinan was from 25 to 100 ng/ml. The findings suggest that the antitumour effect of lentinan is due to the activation of killer cells in vivo, because the optimal concentration of lentinan for the induction of killer cells in vitro was equivalent to the plasma concentration obtained after clinical doses of this agent.

Antigens, Surface

Prospective and randomized clinical trial for the treatment of hepatocellular carcinoma--a comparison of lipiodol-transcatheter arterial embolization with and without adriamycin (first cooperative study). The Cooperative Study Group for Liver Cancer Treatment of Japan.

A randomized, controlled clinical trial comparing the use of lipiodol-transcatheter arterial embolization (L-TAE) in the presence versus the absence of Adriamycin (ADR) for the treatment of hepatocellular carcinoma was conducted from August 1988 through September 1989. In all, 125 Japanese hospitals participated in this study and 289 patients were entered in the trial. The patients were randomly allocated into group A (L-TAE) or group B (L-TAE + ADR) by telephone registration. There was no significant difference in background factors between group A and group B. Additional treatment, including repeated TAE or hepatic resection, was given to 189 patients. Among the four endpoints analyzed, the rate of tumor reduction and lipiodol accumulation in the tumor did not significantly differ between the two groups. The 3-year survival values for groups A and B were 33.6% and 34.9%, respectively; the difference was not significant. The serum alpha-fetoprotein level, however, decreased to a significantly greater extent in the group that received ADR than in the group that did not (P < 0.05). This result suggests that ADR has some favorable additional effect in L-TAE for the treatment of hepatocellular carcinoma.

Adult

Prospective and randomized clinical trial for the treatment of hepatocellular carcinoma--a comparison of L-TAE with Farmorubicin and L-TAE with adriamycin (second cooperative study). The Cooperative Study Group for Liver Cancer Treatment of Japan.

A randomized clinical trial comparing L-TAE with Farmorubicin (FARM) and L-TAE with Adriamycin (ADR) in the treatment of hepatocellular carcinoma was conducted from October 1989 through December 1990. In all, 192 hospitals participated in this study and 117 patients were entered. The patients were randomly allocated to group A (L-TAE+FARM) or group B (L-TAE+ADR). There was no significant intergroup difference in background factors. Additional treatment consisting of repeated TAE or surgery was given to 66 patients. Four factors were analyzed in this study: the percentage of reduction in tumor size, the change in the AFP level, lipiodol accumulation, and survival. None of these factors differed significantly between the two groups. The final evaluation of this study will be based on differences in survival after a long-term follow-up. Toxic effects manifested less frequently in group A than in group B, and the decrease in the platelet count in the peripheral blood was significantly lower in group A than in group B. These results suggest that FARM exerts a more favorable effect than does ADR in the treatment of hepatocellular carcinoma.

Adult

Radiotherapy of cholangiocarcinoma: the roles for primary and adjuvant therapies.

A total of 22 patients with cholangiocarcinoma who had been treated with external radiotherapy between 1978 and 1989 were analyzed. Of the 22 patients, 18 had cancer of the hepatic hilus (Klatskin) and 4 had intrahepatic biliary cancer; all but 2 of the subjects had advanced disease. In all, 16 patients underwent primary irradiation for unresectable tumors, 4 were subjected to adjuvant irradiation after gross tumor resection, and 2 received preoperative irradiation followed by gross tumor resection. The mean initial irradiation dose was 52.0 Gy (range, 26-78 Gy). The TDF (time-dose-fractionation) for the entire course of radiotherapy ranged from 49 to 154 (mean, 100). The median survival of all patients was 10 months, and the cumulative 1-year survival value was 37.7%. The external radiotherapy proved to be effective in the treatment of cholangiocarcinoma in terms of palliation and survival.

Adenoma, Bile Duct

The promotive effect of interleukin 4 with interleukin 2 in the proliferation of tumor-infiltrating lymphocytes from patients with malignant tumor.

In adoptive immunotherapy, the number of effector cells is one of the major factors relating to the therapeutic efficacy. We demonstrated that tumor-infiltrating lymphocytes (TILs) were stimulated to proliferate by incubation with interleukin 2 (IL-2) plus interleukin 4 (IL-4). TILs cultured with IL-2 plus IL-4 increased 3.1-fold more than TILs cultured with IL-2 alone. However, IL-4 did not alter the cytotoxic activity of TILs against autologous tumor cells and established tumor cell lines. It is suggested that IL-2 receptor is related to the mechanism of the proliferation of activated TILs cultured by combination with IL-2 and IL-4. Thus, the combination of IL-2 and IL-4 may increase the efficacy of adoptive immunotherapy using activated TILs.

Cytotoxicity, Immunologic

Enhancement of tumor cell susceptibility to lymphokine-activated killer cells by treatment with the streptococcal preparation OK432.

We investigated whether tumor cell lysis by LAK cells was augmented by treatment with OK432 in vitro. NK and LAK activity against K562 cells was not enhanced by their treatment with OK432. In contrast, the susceptibility of OK432-treated Daudi and KATO-III cells to lysis by LAK cells was enhanced. Succinate dehydrogenase activity and RNA synthesis were impaired in Daudi and KATO-III cells by treatment with OK432, and moreover the expression of HLA Class I antigen and beta 2-microglobulin was inhibited in OK432-treated KATO-III cells. Thus, it is suggested that the enhancement of the susceptibility of OK432-treated tumor cells with regard to succinate dehydrogenase activity, RNA synthesis, and HLA Class I antigen expression.

Antigens, Neoplasm

Serum hepatocyte growth factor levels in hepatectomized and nonhepatectomized surgical patients.

Serum hepatocyte growth factor levels were measured in hepatectomized and nonhepatectomized surgical patients. The levels were significantly increased and reached a maximum within 7 days after surgery in both groups, returning to preoperative levels 28 days after partial hepatectomy and 7 days after other operations. Multiple regression analysis showed that such maximal hepatocyte growth factor levels were significantly related to having liver cirrhosis and postoperative maximal serum total bilirubin and alanine aminotransferase levels and peripheral white blood cell counts in the hepatectomized group and to postoperative maximal peripheral white blood cell counts and serum C-reactive protein levels in the nonhepatectomized group. However, the levels showed no relation to the resected liver volume and increment of the remaining liver volume 28 days after partial hepatectomy. It is concluded that serum hepatocyte growth factor levels were increased after partial hepatectomy in association with hepatocellular dysfunction and necrosis and systemic inflammation. It is unlikely that the increase was related to liver regeneration.

Alanine Transaminase

Rate-dependent accessory pathway conduction due to phase 3 and phase 4 block. Antegrade and retrograde conduction properties.

Six patients who had antegrade phase 3 and phase 4 block in the accessory pathway were examined. In each patient, antegrade conduction over the accessory pathway was absent both at the sinus rate and at slower heart rates. During premature atrial stimulation a "window" of accessory pathway conduction was identified in all patients. The outer limits of the window ranged from 480 ms to 670 ms. The inner limits ranged from 410 ms to 620 ms. The durations of the window ranged from 20 ms to 160 ms. Three patients with orthodromic atrioventricular reentrant tachycardia showed preserved retrograde accessory pathway conduction. The remaining three patients had impaired retrograde accessory pathway conduction. One of the patients showed retrograde phase 4 block in the accessory pathway. In two patients, retrograde concealed conduction in the accessory pathway induced by ventricular stimulation prolonged the outer limit of the window in the antegrade accessory pathway conduction. These findings suggest that the mechanism of antegrade phase 3 and phase 4 block in the accessory pathway may be spontaneous diastolic depolarization in the accessory pathway and conduction disturbance at the ventricular and/or atrial insertion of the accessory pathway.

Adult

Losartan, a specific angiotensin II receptor antagonist, increases angiotensin I and angiotensin II release from isolated rat hind legs: evidence for locally regulated renin-angiotensin system in vascular tissue.

The effect of Losartan (10(-9) to 10(-6) M) on angiotensins I and II release was examined in isolated hind legs perfused with Krebs-Ringer solution from normal and bilaterally nephrectomized rats. Losartan increased dramatically both angiotensins I (Ang I) and II (Ang II) release in a dose-dependent fashion; the maximal percent increment in Ang I and Ang II release evoked by Losartan (10(-6) M) was about +380% and +160%, respectively, in normal rat hind legs. In nephrectomized animals, Losartan elicited a marked increase in both peptides dose-dependently. There was a highly positive correlation between the released amounts of Ang I and that of Ang II altered by Losartan in either normal (r = 0.954) or nephrectomized rats (r = 0.923). These results not only confirm the existence of a functional renin-angiotensin system in vascular tissues, but also suggest that the system is regulated by locally generated Ang II.

Angiotensin I

Effects of losartan, a nonpeptide angiotensin II receptor antagonist, on cardiac hypertrophy and the tissue angiotensin II content in spontaneously hypertensive rats.

Losartan, a recently developed nonpeptide angiotensin II (Ang II) receptor antagonist, was administered orally to 10-week-old spontaneously hypertensive rats (SHR) for 2 weeks. Cardiac weight and tissue Ang II, as well as plasma renin activity (PRA) and Ang II, were determined. Treatment with Losartan (10 mg/kg per day) lowered blood pressure markedly. Losartan reduced significantly the left ventricular weight by 11% compared with control rats. The left ventricular Ang II content was lowered by Losartan (18.6 +/- 0.9 pg/tissue; 21.9 +/- 0.9 pg/tissue, control, p less than 0.05), whereas PRA and plasma Ang II concentration were increased by the treatment. With the control and Losartan-treated animals, there was a significant positive correlation between the left ventricular weight and the tissue Ang II content (r = 0.563, p less than 0.05). These results provide evidence that cardiac tissue Ang II, rather than circulating Ang II, plays an important role in the pathophysiology of left ventricular hypertrophy of this animal model of human hypertension.

Analysis of Variance

Hypotensive activity of TCV-116, a newly developed angiotensin II receptor antagonist, in spontaneously hypertensive rats.

TCV-116, a recently developed angiotensin II (Ang II) receptor antagonist, was administered orally (1 mg/kg per day) to 10-week-old spontaneously hypertensive rats (SHR) for 2 weeks. Blood pressure and plasma components of the renin-angiotensin-aldosterone system were determined in these rats. TCV-116 produced a marked reduction in blood pressure without altering heart rate. Whereas plasma renin concentration (PRC), angiotensin I (Ang I) and angiotensin II (Ang II) all were significantly increased, plasma aldosterone was decreased by approximately 70% compared with control animals. These results not only indicate therapeutic efficacy of this agent in the chronic treatment of human hypertension, but support also the concept that the renin-angiotensin system plays an important role in the control of blood pressure in this animal model of human essential hypertension.

Angiotensin Receptor Antagonists

Immunoelectronmicroscopic differentiation of linear IgA bullous dermatosis of adults with coexistence of IgA and IgG deposition from bullous pemphigoid.

BACKGROUND: The differentiation between linear IgA bullous dermatosis (LABD) and bullous pemphigoid (BP) is sometimes difficult in patients who have both IgA and IgG deposition in a linear pattern at the basement membrane zone. OBJECTIVE: We address whether two cases of acquired subepidermal blistering disease with coexistence of IgA and IgG deposition in a linear pattern at the basement membrane zone are LABD or BP. METHODS: The two cases were investigated by immunoelectron microscopy and compared with two typical cases of LABD. RESULTS: In both cases, the deposition of IgA and IgG was ultrastructurally localized below the lamina densa in close association with anchoring fibrils, as was seen in two cases of typical LABD. CONCLUSION: These findings indicate that our two cases of acquired blistering disease with co-existence of IgA and IgG deposition are LABD, rather than BP.

Aged

In vitro augmentation of the cytotoxic activity of peripheral blood mononuclear cells and tumor-infiltrating lymphocytes by famotidine in cancer patients.

We investigated the in vitro effects of famotidine on the cytotoxic activity of peripheral blood mononuclear cells (PBMC) and tumor-infiltrating lymphocytes (TILs). The cytotoxic activity of PBMC was augmented by famotidine at a concentration of 10 ng/ml, which is equivalent to the serum level achieved by the intravenous administration of a dose of 20 mg. This response to famotidine was seen only in cancer patients. Both the cytotoxic activity and DNA synthesis of activated TILs were increased by the combination of interleukin-2 and 1 microgram/ml of famotidine. Augmentation of cytotoxic activity by famotidine occurred independently of any decrease in the population of suppressor T-cells. Thus, famotidine may have the potential to be used in adoptive immunotherapy with TILs for cancer patients.

Antigens, CD

Chemosensitivity testing of fresh human gastric cancer with highly purified tumour cells using the MTT assay.

A major problem associated with the chemosensitivity testing of fresh human tumour cells using the MTT assay is the contamination of nonmalignant cells in the tumour tissues. Highly purified fresh human gastric cancer cells could be obtained from 43 solid tumours and eight malignant ascites for the MTT assay. The success rate of the MTT assay was 87.9% (51 of the 58 cases), and the purity of tumour cells was greater than 90% after separation on Ficoll-Hypaque and Percoll discontinuous gradients in primary, or metastatic lesions, and also ascites. Cisplatin, mitomycin, and doxorubicin were more potent drugs than etoposide and 5-FU against gastric cancer cells. The chemosensitivity in differentiated cancer was equivalent to that in non-differentiated cancer. Twenty of the 51 patients with gastric cancer had evaluable lesions, and they received chemotherapy according to the results of the MTT assay using highly purified tumour cells. A clinical response was obtained in 12 of these 20 patients (response rate: 60.0%; five with complete response, seven with partial response).

Adult