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Biomedical subjects

A Tokunaga

Publications and source records attributed to A Tokunaga.

At least 145 records · Page 8Linked to original sources
PubMed1989

[Fundamental and clinical aspects of adoptive immunotherapy with tumor-infiltrating lymphocytes].

Fundamental analysis was conducted on the phenotype and function of autologous tumor-infiltrating lymphocytes (TIL) in terms of their role as effector cells in specific immunotherapy for malignant tumors. Their effects were further examined in a preliminary clinical study. Analysis of the phenotype of lymphocytes which infiltrate tumor tissue and proliferate in the presence of IL-2, by using cell-surface subset markers, revealed proliferation of two types of lymphocytes: CD8-positive cytotoxic/suppressor T-cells and CD4-positive helper/suppressor inducer T-cells. In vitro cytotoxicity tests on these lymphocytes for antitumor activity showed that only CD8-positive lymphocytes had a much stronger antitumor effect on autologous tumor cells than LAK cells. In contrast, they showed no antitumor effect on autologous normal cells or homologous tumor cells of the same histological type, indicating specificity of their antitumor activity. Furthermore, in vitro treatment of tumor cells with interferon was found to increase both expression of MHC class I antigens and sensitivity to TIL cytotoxicity. In vitro of the close relationship between induction of CD8-positive TIL and expression of HLA (A, B, C) antigens in tumor tissue, the above findings suggest that the presence or absence of expression of MHC class I antigens plays an important role in the efficacy of adoptive immunotherapy with TIL. Significant antitumor activity was observed in patients given CD8-positive cells in a preliminary clinical study, the same as in in vitro assay. No patient showed serious side effects such as the pulmonary edema or body fluid retention observed in LAK therapy. Specific immunotherapy using TIL seems to be a promising modality in multidisciplinary treatment of cancer. Further developments from research on this subject are expected.

Aged↗
PubMed1989

[Combination therapy with etoposide, adriamycin and cisplatin in advanced primary and recurrent gastric cancer].

Fourteen patients with advanced gastric cancer consisting of seven primary cases and seven recurrent cases were treated with the combination of etoposide, adriamycin and cisplatin (EAP). One of the primary cases (14%) and three of the recurrent cases (43%) responded to the therapy, but a high incidence of toxicities including leukopenia, thrombocytopenia, alopecia, nausea and vomiting was observed. It is concluded that EAP therapy can be useful in the treatment of advanced gastric cancer if countermeasures to the toxicities of these drugs are considered.

Adenocarcinoma↗
PubMed1988

Simultaneous gastric cancer in monozygotic twins.

Monozygotic twins developed gastric cancers that were found almost simultaneously. A 47-year-old man complained of nausea and vomiting; an upper gastrointestinal series and endoscopy revealed advanced gastric cancer invading the serosa. Palliative subtotal gastrectomy was performed. In his asymptomatic twin a gastric polyp was detected during a screening examination, and this was observed for 2 years. After the former twin had undergone surgery, the latter twin was given a detailed endoscopic examination, and biopsy revealed gastric cancer limited to within the mucosa. Curative subtotal gastrectomy was performed. The noncancerous gastric mucosa of the former twin showed severe intestinal metaplasia, but that in the latter showed only spotty metaplasia. They had lived together for 40 years, but the former was a heavy smoker and drank alcohol, while the latter did not. These differences in taste might have contributed to the observed difference in intestinal metaplasia, which indicates chronic mucosal damage.

Adenocarcinoma↗
PubMed1988

Multiple organ failure without sepsis following surgical treatment of advanced gastric carcinoma.

Two patients, a 58-year-old male and a 41-year-old female, who had poorly differentiated adenocarcinoma with signet ring cells of the stomach, developed progressive multiple organ failure following their surgical treatment, even though they did not have any direct surgical complications. Their abdominal explorations revealed primary gastric tumors with deep infiltration and metastases to the regional lymph nodes. Their clinical courses were characterized by acute renal failure and respiratory distress associated with disseminated intravascular coagulation. Histopathological examination at autopsy revealed diffuse cortical necrosis of the kidneys and marked congestion, edema, and hemorrhage with or without alveolar fibrosis of the lungs. Fibrin thrombi in the lesions of the kidneys and lungs strongly suggested the existence of disseminated intravascular coagulation. It is likely that the widely spreading cancer cells themselves produced the subclinical background for disseminated intravascular coagulation, which appeared to play an important role in the development of the multiple organ failure.

Adenocarcinoma, Mucinous↗
PubMed1988

Superior olivary and lateral lemniscal neurons projecting to the cochlea in the guinea pig.

Efferent neurons to the cochlea in the guinea pig were observed in the superior olivary complex and ventral lateral lemniscal nuclei after injection of WGA-HRP into the cochlea via the round window. Of HRP-labeled nerve cells found in the brainstem, about 60% and 10% were located in the ipsilateral lateral superior olivary nucleus (LSO) and the contralateral ventral nucleus of the trapezoid body (VTB), respectively. A few labeled neurons were found in the ipsilateral VTB, contralateral LSO and the bilateral superior paraolivary nucleus (SPO). Seven percent and 5% of the labeled neurons were definitely observed in the ventrocaudal part of the contra- and ipsilateral ventral nucleus of the lateral lemniscus (VLL), respectively. A combination of acetylcholine esterase (AChE) histochemistry with the tracing of retrograde axonal transport of a fluorescent dye (DAPI) revealed that VLL neurons projecting to the cochlea, as well as about 85% of LSO neurons projecting to the ipsilateral cochlea, were AChE-positive.

Acetylcholinesterase↗
PubMed1988

[Two cases of obstructive jaundice due to advanced gastric cancer with marked response to the intravenous administration of cisplatinum].

Two cases of obstructive jaundice due to advanced gastric cancer were treated with intravenous administration of cisplatinum. The first case was a 46-year-old female who had undergone gastrojejunostomy 5 months earlier because of Borrmann type 3 gastric cancer. The tumor involved the head of the pancreas and a portion of the duodenum with distant intraperitoneal dissemination (S3N3P3H0). She was admitted to Shimodate Municipal Hospital on June 8 because of abdominal pain and jaundice. Her abdomen was distended with ascites, and there was a fist-sized tumor in the lower portion. CT examination revealed that the jaundice was caused by obstruction due to the main tumor. Histologically, the tumor consisted of poorly differentiated adenocarcinoma. Intravenous administration of CDDP (50 mg/body/week X 4), MMC (4 mg/body/week X 4) and FT (400 mg/body/day for 4 weeks) was carried out. After the chemotherapy, the jaundice, abdominal pain and ascites disappeared, and the abdominal tumor had markedly reduced in size which was regarded as PR. The second case was 66-year-old male who had received subtotal gastrectomy and transverse colectomy 16 months ago because of Borrmann type 3 gastric cancer. The tumor comprised well-differentiated adenocarcinoma and infiltrated to the mesentery of the transverse colon with positive lymphnodes (S3N1P1H0, stage IV). This time he was admitted to the hospital because of general fatigue and jaundice. According to CT examination, the common bile duct was obstructed by metastasized lymphnode around the pancreas. He had elevated serum level of total bilirubin (7.7 mg/gl) and CA 19-9 (23,000 U/ml). After the administration of CDDP (50 mg/body/week X 4) and MMC (4 mg/body/week X 4), his complaints disappeared and the serum total bilirubin level and CA 19-9 level returned within normal range. These data suggest that combination chemotherapy using CDDP was effective in these 2 cases.

Adenocarcinoma↗
PubMed1987

Immunohistochemical study of intracellular estradiol in human gastric cancer.

Tissues from primary human gastric cancers were examined for intracellular estradiol (E2) by using the avidin-biotin-peroxidase complex (ABC) immunohistochemical method on formalin-fixed paraffin-embedded sections. Reaction products of E2 were located only in the cytoplasm of the cancer cells, and not detected in noncancerous gastric epithelium. E2-positive tissues were found in 23 (44.2%) of 52 male patients, seven (20.6%) of 34 female patients and a total of 30 (34.9%) of 86 patients. In male patients, E2-positive cases occurred without age distinction. In female patients, however, E2 was not found in patients in older age groups, especially patients in the postmenopausal state. Microscopically, E2 was found frequently in intestinal type of cancers in male patients and in cancer with scirrhous growth pattern, in female patients. This is the first report of the demonstration of E2 in gastric cancer. The findings suggest that hormonal factors are involved in gastric cancer, and that the cancers contain endocrinic characteristics.

Adult↗
PubMed1987

Uncrossed retinal projection to the medial terminal nucleus of the accessory optic system in the hereditary unilaterally microphthalmic rat.

The uncrossed optic projection to the medial terminal nucleus of the accessory optic system was studied in adult rats with hereditary unilateral microphthalmia. The vestigial eye of the mutant completely lacks the optic nerve. After injection of HRP into the remaining eye the ipsilateral labeled fibers of the accessory optic system via the superior fasciculus distinctly covered the three terminal nuclei. No ipsilateral inferior fasciculus of the accessory optic system was labeled. Aberrant expansion of the uncrossed superior fasciculus fibers was observed in the medial terminal nucleus.

Animals↗
PubMed1987

Uncrossed retino-geniculate and retino-tectal projections in the hereditary unilaterally microphthalmic rats.

The dorsal lateral geniculate nucleus (CGLd) of the hereditary unilaterally microphthalmic rats showed a diminution of volume and an increase of neuronal density on the contralateral side of the vestigial eye without the optic nerve (about 60 and 160% of the normal, respectively; P less than 0.001). No significant changes were observed in the ipsilateral CGLd. Uncrossed retino-CGLd and -tectal projections were studied using the anterograde axonal transport of HRP in adult rats with the congenital unilateral microphthalmia. Aberrant expansions of the uncrossed retinal projection widely covered CGLd and the superficial layers of the superior colliculus (SCS). The distribution pattern of expanded uncrossed retinal pathway in the mutant was essentially similar to that of neonatally one-eyed rats.

Animals↗
PubMed1987

Induction of intestinal metaplasia in rats by N-ethyl-N'-nitro-N-nitrosoguanidine but not by sodium hydroxide.

Intestinal metaplasia (IM) in the glandular stomach of male Wistar rats induced by oral administration of N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) and/or intubation of 0.1N sodium hydroxide (NaOH) was studied as follows. Experiment I, sequential study: Rats in group I were given 100 micrograms/ml ENNG in drinking water for 12 weeks. Rats in group II were given 5 ml of 0.1N NaOH by gastric intubation once a week for 12 weeks. Group III control rats were given tap water. Rats were killed from week 1 until week 69 sequentially. IM was first found at week 26 in group I and at week 58 in groups II and III, its incidence being significantly higher in group I than in the other two groups (P less than 0.01), but without any difference between group II and group III. Experiment II, two-stage carcinogenesis: Rats in groups I and II were treated in the same way as in experiment I, while rats in group III were given 100 micrograms/ml ENNG for 12 weeks, followed by 0.1N NaOH once a week for 12 weeks intragastrically. All rats were killed at week 56. The numbers of metaplastic glands in groups I and III were higher than in group II. Gastric carcinomas were induced in all groups of rats treated with ENNG. The results of these two experiments show that IM is effectively induced by a carcinogen but is not enhanced by regeneration induced by alkaline treatment.

Aging↗
PubMed1987

Non-simultaneous primary cancers in five different organs in a case of cancer family syndrome.

Non-simultaneous primary malignant tumors in five different organs were detected in a case of cancer family syndrome, and the patient's offspring were found to have colorectal cancers during follow-up. The first cancer in the patient was found in the transverse colon at the age of 47, and partial colectomy was carried out. The second and third were cancers of the cecum and gallbladder which were found concurrently at the age of 61, and ileocecal resection and cholecystectomy were carried out simultaneously. The fourth was cancer of the urinary bladder which was found at the age of 66, and partial cystectomy with interstitial irradiation using a radon seed in the residual urinary bladder was carried out. The fifth was cancer of the stomach at the age of 72, and subtotal gastrectomy was carried out. All of the resected specimens were demonstrated to be different carcinomas histologically. The father and 5 of the 7 siblings of this patient suffered from gastrointestinal or uterine cancers. Furthermore, two daughters of this patient were affected with cancer; the younger with cancer of the descending colon at the age of 47, and the elder with cancers of the transverse colon and rectum at the age of 54. Thus, familial clustering of cancer was shown. Genetic characteristics may have contributed to the development of multiple primary cancers in this family.

Aged↗
PubMed1986

Estrogen and progesterone receptors in gastric cancer.

Cancerous tissue from 86 patients with primary gastric cancer were examined for the presence of receptors for estrogen (ER) and progesterone (PgR). ER and PgR were present in 8 (15.4%) and 5 (9.6%), respectively, of 52 male patients, 9 (26.6%) and 7 (20.6%), respectively, of 34 female patients, a total of 17 (19.8%) and 12 (14.0%), respectively. One male patient (1.9%) and 4 female patients (11.8%) had both ER and PgR, and 40 male (76.9%) and 22 female patients (64.7%) showed no ER or PgR. The binding activity ranged from 6 to 200 fmol/mg protein for estradiol and from 5 to 58 fmol/mg protein for progesterone. ER- and/or PgR-positive cases were characterized grossly as Borrmann type 4, and microscopically as diffuse type with scirrhous growth pattern. The presence of ER and/or PgR in some gastric cancers indicates the possibility that sex hormonal factors are involved in these tumors.

Adult↗
PubMed1986

[Clinical studies on the effect of imipenem/cilastatin sodium on infections in obstetrics and gynecology. Tissue concentrations and clinical effects].

Tissue transfer and clinical effects of imipenem/cilastatin sodium (MK-0787/MK-0791), a new carbapenem antibiotic, were studied and the following results were obtained. Penetrations of MK-0787 into uterine arterial blood and into pelvic dead space exudate were good. When MK-0787/MK-0791 was administered at a dose of 500 mg/500 mg by a 30-minute intravenous drip infusion, the peak level of MK-0787 in uterine arterial blood was 22.2 micrograms/ml, 30 minutes after the completion of the drip infusion. The peak level of MK-0787 in pelvic dead space exudate was 12.9 micrograms/ml at 2 hours and it dropped to 2.6 micrograms/ml at 6 hours. MK-0791 levels were similar to those of MK-0787. Penetrations of MK-0787 into tissues were also good. When MK-0787/MK-0791 was administered at a dose of 500 mg/500 mg by a 30-minute intravenous drip infusion, the level of MK-0787 was 2.2 +/- 1.1 micrograms/g in the oviduct, 2.7 +/- 2.1 micrograms/g in the ovary, 2.5 +/- 1.2 micrograms/g in the endometrium, 3.0 +/- 1.6 micrograms/g in the myometrium, 3.1 +/- 1.9 micrograms/g in the cervix uteri and 3.8 +/- 2.0 micrograms/g in the portio vaginalis at 1 hour after administration. These levels were reduced to halves, respectively, in approximately 2 hours. Four patients with intrauterine infections and 2 with vaginal stump infections were treated with MK-0787/MK-0791 at a daily dose of 1 g/1 g (500 mg/500 mg X 2). Good clinical and bacteriological responses were observed in 5 patients and causative organisms were eradicated in 2 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

[Pathological and endocrinological study of epithelial ovarian tumors in post-menopausal women].

We have studied 37 cases of ovarian epithelial tumors in post-menopausal women, histopathologically and endocrinologically. The normal values for androstenedione, estrone, estradiol and progesterone in healthy post-menopausal women were less than 83 ng/dl, 75 pg/ml, 30 pg/ml and 0.6 ng/ml, respectively. The numbers of cases, the serum values for which were higher than normal, were 9 of 16 (androstenedione), 9 of 16 (estrone), 22 of 29 (estradiol) and 14 of 20 (progesterone). The serum levels of these 4 sex hormones in cases with ovarian stromal condensation (stromal cell hyperplasia) were higher than normal in 8 of 11 (androstenedione), 8 of 11 (estrone), 17 of 19 (estradiol) and 9 of 12 (progesterone), whereas those in cases with no stromal condensation were elevated in 1 of 5, 1 of 5, 5 of 8 and 5 of 7, respectively. After complete removal of the tumors, these elevated sex hormone levels dropped to normal. After the dexamethasone suppression test, the suppression rates for cortisol, 17-OHCS and 17-KS were 4 times as great as those of DHEA-S (dehydroepiandrosterone-sulfate), estrone, estradiol and progesterone. 17 beta-estradiol was localized in hyperplastic ovarian stromal cells in all cases with stromal condensation. We concluded that many of the ovarian epithelial tumors produce these sex hormones and that hyperplastic stromal cells are the source an increased amount of serum estradiol.

Adenocarcinoma↗
PubMed1985

The organization of neurons in the nucleus of the lateral lemniscus projecting to the superior and inferior colliculi in the rat.

The topographic organization of neurons in the dorsal nucleus of the lateral lemniscus (DNLL) which project to the superior and inferior colliculi was studied using the retrograde horseradish peroxidase (HRP) and the fluorescent double labeling methods. Neurons projecting to the superior colliculus (SC) are situated in the rostral portion of the DNLL, whereas those to the inferior colliculus (IC) are found in the caudal area of this nucleus. These two portions are completely separated from each other and no neurons projecting to both the SC and the IC are observed. In the dorsolateral part of the rostral portion of the DNLL, neurons projecting to the ipsilateral SC are found, whereas neurons projecting to the contralateral SC are located in the central to medial part of the nucleus, but no neurons sending collateral axons to both sides of the SC were observed. Neurons located in the central part of the caudal area of the DNLL project to the ipsilateral IC and neurons in the lateral and medial parts project contralaterally to the IC. Some of the neurons in the caudal part of the DNLL have divergent axonal branching projecting to both sides of the IC. In the ventral nucleus of the lateral lemniscus, labeled neurons were observed only when the HRP was injected into the ipsilateral IC.

Animals↗