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Biomedical subjects

A Kawata

Publications and source records attributed to A Kawata.

45 records · Page 3Linked to original sources

Tumor-infiltrating lymphocytes and prognosis of hepatocellular carcinoma.

Tumor-infiltrating lymphocytes (TIL) were isolated from 17 human hepatocellular carcinomas (HCC). The proliferation of TIL cultured with recombinant interleukin-2 (rIL-2) was evaluated. We also examined prognosis in relation to TIL. Successful expansion of TIL was achieved in 16 of the 17 lesions. In 10 of the 16, TIL increased more than 100-fold. Cytotoxicity to the allogeneic HCC cell line, HC-4, was demonstrated in all 13 TIL cultures tested. Maximum cytotoxicity was noted two to four weeks after culture. No statistical difference was observed either with respect to prognosis based upon growth rate or the cytotoxicity demonstrated in vitro. The initial number of TIL per unit weight of tumor was, however, significantly greater in the group for which the prognosis was good (19.0 +/- 5.1 x 10(6) vs. 5.6 +/- 1.6 x 10(6), P < 0.05). It would appear that greater lymphocytic tumor infiltration is a prognostic marker.

Aged↗

Role of fibronectin in the inhibitory effect of TGF-beta on choline acetyltransferase activity in co-cultures of spinal cord neurons and myotubes.

We have recently shown that the enhanced expression of choline acetyltransferase (ChAT) activity in co-cultures of spinal cord motoneurons and muscle cells was blocked by transforming growth factor-beta (TGF-beta) (Dev. Brain Res., 57, 129-137, 1990). This study was performed to investigate the role of fibronectin in this effect. TGF-beta increased fibronectin level about 2-fold in extracellular matrix of spinal cord cells and skeletal myotubes in culture. Addition of a synthetic polypeptide that competitively inhibits fibronectin binding to its cell surface receptor recovered the TGF-beta-induced suppression of ChAT activity in co-cultures. The polypeptide did not affect ChAT activity in cultures of spinal cord cells alone or in co-cultures without TGF-beta. These results indicate that TGF-beta inhibits the stimulation of ChAT activity in spinal cord neurons in co-culture through a change in the composition and/or amount of fibronectin in the extracellular matrix at neuromuscular contacts.

Animals↗

[Adopted immunochemotherapy using IL-2 and spleen LAK cell--randomized study].

Thirty patients with hepatocellular carcinoma who underwent hepatic resection during the recent 2 years in our department were randomized. We derived LAK cells from the autologous spleen removed during operation. The cultivation of LAK cells were done with IL-2. Adriamycin 20mg/body was injected into hepatic artery via subcutaneous implanted reservoir on the 8th postoperative day. In group A, 1.0-7.6 x 10(9) LAK cells were injected i.a on day, 10, 14, and 21 after operation. IL-2 of 5 x 10(5) JU were also injected i.a. during 3 weeks. Group B patients were treated only by adriamycin. High fever was seen in all patients belonged to group A. Twelve patients in each group were evaluable. Recurrence rate 8.3% in group A was significantly lower than 50% in group B. In experimental study, accumulation of 111In-oxine labelled LAK cells in mouse 3LL lung cancer was augmented in splenectomized ones. Adopted immunotherapy by spleen LAK-cells may be effective and safe treatment to preventing recurrence of hepatocellular carcinoma after hepatectomy.

Animals↗

Inhibition by transforming growth factor beta of choline acetyltransferase stimulation in a co-culture of spinal cord and muscle cells from mice.

Choline acetyltransferase (CAT) activity increased 11-fold in co-cultures of spinal cord and muscle cells from fetal mice relative to cultures of spinal cord cells alone. The addition of transforming growth factor-beta (TGF-beta) to the medium at 30 pM throughout the culture period inhibited the increase of CAT activity in the co-cultures, but did not affect the activity in cultures of spinal cord cells alone. TGF-beta did not inhibit glutamic acid decarboxylase activity in the co-cultures. Other growth factors such as epidermal growth factor, fibroblast growth factor and beta-NGF had little or no effect on CAT activity. TGF-beta markedly inhibited the fusion of myoblasts to myotubes and the expression of marker enzymes for muscle differentiation. When TGF-beta was included during muscle culture and removed before inoculation with spinal cord cells, myoblasts did not subsequently form myotubes. CAT activity in the spinal cord cells, however, markedly increased in co-cultures with the undifferentiated myoblasts. When TGF-beta was added to the co-cultures after myotube formation was complete, the increase in CAT activity was inhibited according to the length of TGF-beta treatment. These results suggest that TGF-beta inhibits the muscle-induced stimulation of CAT activity by inhibiting the production, secretion and/or action of trophic factors from muscle.

Acetylcholinesterase↗

[Two siblings of distal hereditary motor neuropathy with choroideremia].

Two brothers, 31 and 25 years of age, with distal hereditary motor neuropathy (distal HMN) and choroideremia are reported. Their parents were second cousins. During the first decade, their visual acuity gradually diminished with night blindness, accompanied by weakness of the legs. From the third decade, they noticed weakness of the hands. The neurological signs of both cases could be summarized as follows: bilateral pes cavus, Charcot-Marie-Tooth type distal atrophy and weakness of the four limbs, no sensory deficit, hyperreflexia in the upper limbs and knees, absent ankle jerks and plantar reflexes, and severe visual impairment due to choroideremia. In addition to these signs, the younger patient showed nystagmus and limb kinetic ataxia suggesting cerebellar involvement. Muscle biopsies and EMG studies revealed chronic neurogenic changes. MCV's in the median nerves were normal, but the extensor digitorum brevis muscles were totally denervated. SCV's, the amplitude of sensory action potentials and sural nerve biopsies were normal. In both patients, elevated CSF protein without pleocytosis and high level of serum IgA & E were demonstrated. Associations of choroideremia and abnormal laboratory findings as noted in our cases have not been so far reported in distal HMN, but we suppose these disorders may be genetically related.

Adult↗

Modification of lymphokine-activated killer cell accumulation into tumor sites by chemotherapy, local irradiation, or splenectomy.

The effects of chemotherapy or local irradiation on lymphokine-activated killer (LAK) cell accumulation into tumor sites were investigated. Lymphokine-activated killer cells labeled with 111In-oxine were injected into the caudal vein of C57BL/6 mice that had been previously transplanted with 3LL cancer. An adoptive transfer of LAK cells was carried out 4 days after treatments. Twenty-four hours after the transfer, tumor tissues were excised, and the accumulation of labeled LAK cells in the tumor was measured. In two different experiments, LAK cell accumulation in tumor in the nontreated group was 2.15% and 1.58% of the administered dose per gram of tissue. The accumulation in the groups of mice treated with cyclophosphamide, nimustine hydrochloride, or Adriamycin increased fourfold (7.38% dose/g, 6.61% dose/g), threefold (6.47% dose/g) and twofold (4.46% dose/g), respectively, as compared with the nontreated group. These agents induced significant tumor regression. In the group treated with bleomycin, which showed no significant effect on tumor growth, LAK cell accumulation in tumor remained unaltered (1.57% dose/g). However, the group treated with local irradiation, which induced significant tumor reduction, showed no increase in LAK cell accumulation into tumors. These results suggest that some antitumor drugs enhance LAK cell accumulation into tumor sites and that this increase is due to tumor modification by antitumor drugs.

Animals↗

Postoperative chemoimmunotherapy for the treatment of liver cancer.

A randomized study using spleen-derived lymphokine-activated killer (LAK) cells in hepatocellular carcinoma (HCC) is reported. We induced cytotoxic lymphocytes from resected spleen of HCC. The effect of recombinant interleukin-2 (rIL-2)-activated spleen cells for prevention of recurrence of HCC after hepatic resection was studied. Enough mononuclear cells could be harvested from the resected spleens. The induction of activated spleen cells was carried out by culture in fresh medium containing 1,500 JU/ml of IL-2. The cytotoxicity of the activated spleen cells maintained high levels during the culture period ranging from 3-30 days. These autologous activated spleen cells were administered to patients 2 days after the intra-arterial infusion of Adriamycin. A randomized study using these spleen LAK cells resulted in lower recurrence rates in the LAK IL-2-treated group. No severe side effects were observed. The lymphocytes derived from resected spleens were useful as the source of effector cells in clinical adoptive immunochemotherapy for HCC, because of their higher cytotoxicity and the simplicity of gaining a large amount of cells.

Aged↗