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Biomedical subjects

T Sakano

Publications and source records attributed to T Sakano.

At least 91 records · Page 5Linked to original sources

LPF-induced T cell colony formation: effect of PMA and interleukin-2, and surface marker analysis.

We demonstrated that a primary exposure to the lymphocytosis promoting factor (LPF) of Bordetella pertussis-induced T cell colony formation. Colony formation was observed when mononuclear cells (MNC) were cultured at concentrations of more than 1 X 10(6)/ml, and reached a peak on day 8. However, the number of colonies generated with LPF was about one-third induced with phytohaemagglutinin (PHA). Removal of monocytes from MNC or T cells resulted in the failure of colony formation, but colony growth could be restored by the addition of monocytes or B enriched cells, indicating that they were required for the optimal colony growth induced by LPF. In the absence of accessory cells, optimal colony growth from monocyte depleted T cells could be obtained when an appropriate concentration of phorbol myristate acetate (PMA) or interleukin-2 (IL-2) was added in the cultures with LPF. PMA did not enhance LPF-induced colony formation in the cultures containing a sufficient amount of exogeneous IL-2. These findings suggest that IL-2 is essential to LPF-induced colony formation. Surface marker analysis showed that most of LPF-induced colony cells were T cells. The percentages of T4+ and T gamma cells of LPF-induced colony cells were more, and T8+ cells less, than those of PHA-induced colony cells. Ia1, T9 and Tac antigens were detected on many colony cells induced by LPF or PHA. These results indicate that the phenotype of LPF-induced colony cells differs from those of PHA, but the sequential antigen expression on lymphocytes triggered by IL-2 might be similar in both LPF- and PHA-induced colony formation.

Antigens, Surface↗

Regulation of reticulum cell sarcoma tumor growth in SJL/J mice by a serum inhibitor affecting T-cell proliferation.

The reticulum cell sarcoma (RCS) tumor in SJL/J mice has been shown to stimulate a strong syngeneic proliferative response. A unique characteristic of the RCS tumor is that it requires host T-cells for growth. Consequently, factors that inhibit host T-cell proliferation may have a profound effect on tumor cell growth in vivo. This report investigates the relationship between a serum inhibitor of T-cell proliferation and tumor growth. Inhibition was measured in an interleukin 2-dependent proliferation of the CTLL-2 line. Sera from mice with RCS transplantable lines or from mice with spontaneous tumors were much less inhibitory than were sera from normal syngeneic SJL/J mice or from allogeneic mice. The inhibitory activity appears to follow a circadian rhythm, because serum derived in the morning was more inhibitory than was serum derived in the evening. Serum from female mice was less inhibitory than serum from male mice. In contrast to male mice, serum from 35-week-old female mice was as inhibitory as was that from young (8- to 12-week-old) mice. The mechanism of serum inhibition in tumor-bearing mice was examined. The serum was tested for the presence of interleukin 2 which could decrease inhibitory activity, and no interleukin was found. Furthermore, absorption of the serum with CTLL-2 cells did not enhance the inhibitory effect to the level of normal mouse serum. These results suggest that tumor growth in vivo coincides with less serum inhibitor, providing an adequate T-cell response requisite for tumor growth. This corroborates the notion of RCS-host T-cell interaction necessary for tumor growth which is in part regulated by a serum inhibitor.

Animals↗

Non-H-2-linked control of in vivo growth of SJL/J-derived reticulum cell sarcoma in recombinant inbred strains between BALB/cKe and SJL/J mice.

This report investigated the growth of reticulum cell sarcoma (RCS) in several congenic and recombinant inbred strains between BALB/cKe female (H-2d) and SJL/J male (H-2s) mice. SJA20 mice congenic with SJL/J except at the Igh locus supported RCS growth. Recombinant mice of the H-2d haplotype did not support RCS growth. However, recombinant inbred mice of the H-2s haplotype varied in their susceptibility to permit RCS growth in vivo. These results supported the role of non-H-2 gene(s) controlling the growth of RCS. Since the recombinant strains of mice exhibited different immunologic characteristics and since RCS tumor growth depended on the ability of the mice to develop a strong antitumor proliferative response, the findings reported here suggested that non-H-2 genes control the magnitude of the syngeneic proliferative response and consequently regulate RCS growth in vivo.

Animals↗

[Phase I trial of 4'-O-tetrahydropyranyl-doxorubicin (THP)--a multi-institutional cooperative study].

A phase I trial of a new anthracycline derivative, 4'-O-tetrahydropyranyldoxorubicin (THP), was conducted in 54 patients with various advanced solid tumors and malignant lymphomas. Starting dose was 5 mg/m2 i.v. and dose escalations were made by a modified Fibonacci search scheme. There were 40 evaluable courses. The dose-limiting toxic effect was leukopenia which was dose-related and reversible. The maximum tolerated dose for a single i.v. injection was estimated to be 55 mg/m2. The median nadir day for leukopenia was day 12 with recovery occurring 13 days (median) after reaching the nadir. Thrombocytopenia was less commonly observed than leukopenia. Other toxic effects were mild gastrointestinal disturbances, fever and general malaise. Ventricular extrasystole was observed in a case of pancreatic cancer who received 5 mg/m2 of the drug. There were no cases with alopecia, or with hepatic or renal dysfunction. With regard to objective tumor response, CR was observed in 2 cases with NHL, and MR in 2 cases with lung cancer, and 1 case each with breast cancer and NHL. Response occurred at a dose of more than 35 mg/m2. The recommended dose schedule for phase II trial is 35-45 mg/m2 by single i.v. injection at 3-4-week intervals.

Aged↗

Second primary malignancies in lymphoma patients.

We evaluated the occurrence and the type of second malignancies among 74 patients with Hodgkin's disease (HD) and 407 patients with non-Hodgkin's lymphoma (NHL) who were treated at the National Cancer Center Hospital for more than one year. Fifteen patients developed a second malignancy. In 10 of these patients the second cancer was gastric cancer, but no cases of acute nonlymphocytic leukemia were encountered. The observed number of second cancers in females among the HD patients was significantly (p less than 0.005) greater than the expected incidence based upon the number of age-adjusted person-years both for all cancers and for stomach cancer. However, no significant differences between males and females in the NHL patients were found. Furthermore, no significant differences were seen in any of the groups between the observed and expected numbers of second malignancies according to the treatment.

Adult↗

[The significance of reinduction chemotherapy with adriamycin for relapsed non-Hodgkin's lymphoma of Waldeyer's ring].

Of those patients with localized (CS I-II) non-Hodgkin's lymphoma of Waldeyer's ring who were treated with radiotherapy or radiotherapy plus chemotherapy and who suffered relapses at the National Cancer Center Hospital over the past 22 years, 24 cases were analyzed on the basis of their response rate and duration of remission with reinduction chemotherapy, and survival time after recurrence. The group [ADM (+)], treated with regimens including adriamycin, was compared with the group [ADM (-)] treated with regimens excluding adriamycin. Complete response was seen in 9 out of 11 cases (81.8%) and in 8 out of 13 cases (61.5%) for the ADM (+) group and the ADM (-) group, respectively (p greater than 0.1). The period of complete response of the ADM (+) and ADM (-) groups was compared using the logrank method. The prognosis of the former was significantly (p less than 0.01) better than that of the latter and the median duration of remission was 30 months and 7 months, respectively. When the survival after recurrence of the ADM (+) and ADM (-) groups was compared, the median survival time was 38 months for the ADM (+) group and 12 months for the ADM (-) group, but no significant difference was observed between the two groups (0.05 less than p less than 0.1).

Adult↗

Pituitary abnormalities detected by high resolution computed tomography with thin slices in primary hypothyroidism and Turner syndrome.

Pituitary hyperplasia, microadenoma or an empty sella was detected in three children with primary hypothyroidism and three with Turner syndrome with the use of high resolution contrast-enhanced computed tomography (CT) with thin slices. Hyperplasia or microadenoma of the pituitary gland frequently occurs secondary to primary hypothyroidism and gonadal dysgenesis, and recognition of these results may eliminate unnecessary surgery in favor of hormone replacement therapy. High resolution contrast-enhanced CT, especially coronal CT, with thin slices is very helpful in demonstrating these pituitary abnormalities.

Adenoma↗

Diarrhea in neonatal piglets caused by K99+ST+ enterotoxigenic Escherichia coli.

Enterotoxigenic Escherichia coli strains were isolated from the feces of 34.4% of 64 diarrheaic neonatal piglets on seven farms. Of a total of 518 isolates, 86 (16.6%) were enterotoxigenic and grouped into four phenotypes: K99+ST+ (K99 pilus antigen and heat-stable enterotoxin producing, 36 strains), ST+ (37 strains), K88+LT+ (K88 pilus antigen and heat-labile enterotoxin producing, 11 strains), and K88+ST+ (2 strains). K99+ST+ and ST+ isolates showed multiple drug resistance and most of those (58.3% and 56.8%, respectively) belonged to O serogroup 101. A K99+ST+ isolate proved to be capable of inducing diarrhea and death in hysterectomy-produced colostrum-deprived piglets when orally inoculated.

Animals↗

The mitogenic effect of the lymphocytosis promoting factor from Bordetella pertussis on human T gamma and non-T gamma cells.

We studied the effect of lymphocytosis promoting factor (LPF), derived from the supernatant fluid of a culture of phase I Bordetella pertussis strain Tohama, on human lymphocyte proliferation. LPF was a potent mitogen for human mononuclear cells, specifically T cells. LPF failed to induce cytoplasmic immunoglobulin production by B cells. Removal of the monocytes from the T cell fraction diminished responses to LPF, but the response could be restored completely by the addition of 5.0% monocytes. These results suggest that LPF-induced cell proliferation is at least partially dependent on monocytes. In contrast to PHA, LPF stimulated T gamma cells to a greater extent than non-T gamma cells, but the magnitude of the T gamma or non-T gamma cell response was less than that of T cells, indicating that synergistic interactions between T gamma and non-T gamma cells are required for maximal response.

Bacterial Toxins↗

Comparison of phorbol myristate acetate and phytohaemagglutinin as stimulators of in vitro T lymphocyte colony formation of human peripheral blood lymphocytes. I. Surface markers of colony cells.

Human T lymphocyte colonies were grown in methylcellulose semi-solid cultures in the presence of phytohaemagglutinin (PHA) and/or phorbol myristate acetate (PMA). Surface marker analysis showed lower percentages of OKT3- and OKT4-positive cells in PMA-induced colonies than those in PHA-induced colonies. The percentage of OKIa1-positive cells in PMA-induced colonies was approximately twice that in PHA-induced colonies. The percentage of OKT9-positive cells in PMA-induced colonies was significantly lower than that in PHA-induced colonies. These data suggest that the subsets of PMA-induced colony cells express a more immature phenotype than that of PHA-induced colony cells and that, among PMA-induced colony cells, there are fewer T cells in the proliferative status at the time tested. When 3 X 10(5)/ml monocyte-depleted T cells, at which concentration of seeded cells neither PHA nor PMA could induce colony growth, were cultured in the presence of both PHA and PMA, T cell colony growth was observed. In T cell colonies induced by a combination of PHA and PMA, the percentages of OKT3-, OKT4- and OKT8-positive cells were different from those in colonies induced by either PHA or PMA alone. These results suggest that PMA acts not only as a substitute for monocytes and/or interleukin-1, but may directly affect lymphocyte proliferation induced by a combination of PHA and PMA.

Antibodies, Monoclonal↗

Favorable effect of dimethyl sulfoxide on secondary amyloidosis in juvenile rheumatoid arthritis.

A girl with secondary amyloidosis as a complication of juvenile rheumatoid arthritis was administered dimethyl sulfoxide by topical application to the skin. Her gastrointestinal symptoms and massive proteinuria improved. Decreased left ventricular function and creatinine clearance also improved remarkably. The favorable effect of dimethyl sulfoxide in this single patient deserves further study in a controlled trial.

Adolescent↗

Immunogenicity and safety of an attenuated Bordetella bronchiseptica vaccine in pigs.

The immunogenicity and safety of an attenuated Bordetella bronchiseptica vaccine for swine atrophic rhinitis (AR) was evaluated in 22 hysterectomy-produced, colostrum-deprived pigs and 18 conventional pigs. None of 8 pigs inoculated at 7 days of age intranasally with greater than or equal to 3 X 10(5) colony-forming units (CFU) of vaccinal strain/pig and 2 of 5 pigs inoculated at 7 days of age intranasally with 3 X 10(4) CFU of the vaccinal strain/pig developed AR after intranasal challenge exposure with a virulent strain at postinoculation week (PIW) 3. The remaining 3 vaccinated pigs and 4 nonvaccinated pigs developed AR. Thirteen pigs were inoculated intranasally with 3 X 10(6) to 3 X 10(9) CFU of the vaccinal strain at 7 days of age. At PIW 12, the pigs were killed and necropsied. None of the pigs had clinical signs of AR and/or pneumonia. Virulence was studied by transmission of vaccinal strain through 3 serial growing passages on the nasal mucosa of a litter of hysterectomy-produced colostrum-deprived pigs. Inoculum (nasal swab samples from 2 pigs 4 days after inoculation with 10(8) CFU of vaccinal strain at 5 days of age) was inoculated into the nasal cavity of 2 nonvaccinated pigs. This procedure was repeated 3 times. After the 1st passage, the vaccinal strain was recovered on postinoculation day 4, but after postinoculation day 4, the vaccinal strain was not recovered until the end of the 3rd passage. Turbinate atrophy or pneumonia was not recognized in these inoculated pigs. The vaccinal strain provided immunogenicity without ill effects.

Animals↗

Complete deficiency of adenine phosphoribosyltransferase: a report of three cases and immunologic and phagocytic investigations.

The levels of adenine phosphoribosyltransferase (APRT:EC 2.4.2.7) were determined in red blood cells (RBCs), peripheral mononuclear cells (MNCs), and polymorphonuclear leukocytes (PMNLs) from normal controls and from two families with APRT deficiency. No APRT activity was demonstrated in MNCs and PMNLs of patients with complete deficiency of RBC-APRT. APRT deficiency occurs not only in RBCs but also in MNCs and PMNLs. Immunologic and phagocytic examinations showed normal hemogram and serum immunoglobulin levels, and normal E-rosette forming cells and surface immunoglobulin-bearing cells. Lymphocyte blastogenesis in response to phytohemagglutinin and lymphocyte differentiation to cytoplasmic immunoglobulin-producing cells induced by pokeweed mitogen were normal. No major defects were apparent in natural killer activity. Phagocytic functions were normal as tested by bactericidal activity, O2-consumption, chemotaxis, and chemiluminescence response.

Adenine Phosphoribosyltransferase↗

Effects of tunicamycin and various monosaccharides on phytohaemagglutinin-induced autorosette formation.

The structural characteristics of autologous red blood cell (ARBC) receptors on human peripheral blood lymphocytes (PBL) induced by phytohaemagglutinin (PHA) were examined. Tunicamycin, which is known to be a blocker of the protein glycosylation of N-glycosidic type glycoprotein, significantly inhibited the production of ARBC receptors. When trypsinized PBL were cultured in the presence of tunicamycin, the inhibitory effect was enhanced. When several monosaccharides were added to the mixture of ARBC and PBL pre-treated with PHA for 24 h, D-mannose caused the most inhibition, and galactose and D-fucose also caused significant inhibition. These data suggest that N-glycosidic type glycoproteins play an important role in binding sites to ARBC on PBL surface membranes and that more than one type of glycose may be involved.

Adult↗

Levels of vitamin D-metabolites in a case of acro-osteolysis syndrome.

On the initial examinations of a 17-year-old boy with acro-osteolysis syndrome, the levels of serum 25-hydroxycholecalciferol (25OHD) were low, whereas serum levels of 1,25-dihydroxycholecalciferol (1,25(OH)2D) were normal. Administration of 1 alpha-hydroxycholecalciferol (1OHD) failed to improve the osteoporosis, although the serum 25OHD level rose to normal. It is unlikely that impaired bone remodeling due to abnormal vitamin D-metabolism was a primary defect in our patient.

Adolescent↗