Decreased cytotoxic potential of fresh and recombinant interleukin 2-cultured large granular lymphocytes in childhood acute lymphoblastic leukemia

Cytotoxic potential (cytotoxic efficiency and binding affinity) of large granular lymphocytes (LGL) in childhood acute lymphoblastic leukemia (ALL) patients was calculated by Michaelis-Menten's kinetic equation. Cytotoxic efficiency (Vmax) of fresh or 3-day recombinant interleukin 2 (IL-2)-cultured LGL, not of similarly cultured T cells, in on-therapy ALL patients was decreased (31% in fresh LGL, P less than 0.05 and 28% in cultured LGL, P less than 0.01) as compared with that in controls, although the binding affinity (Km) of these cells were not decreased. The cytotoxic efficiency and the binding affinity of IL-2-cultured LGL in off-therapy ALL patients was not decreased. These data indicate that the cytotoxic potential of LGL was selectively decreased in on-therapy ALL patients due to the impairment in the post-binding cytotoxic process, not due to the decrease in the binding affinity.     

Radiotherapy and chemotherapy in stages I and II non-Hodgkin's lymphomas of Waldeyer's ring

Sixty-four patients with stages I and II non-Hodgkin's lymphomas (NHL) involving Waldeyer's ring treated between 1970 and 1987 were reviewed. Patients with stage II NHL were subdivided into stage II 1 (limited type) and stage II2 (advanced type) from the state of neck nodes. Stage II1 was defined as involvement of unilateral cervical nodes less than 4 cm in diameter as well as Waldeyer's ring involvement. Other stage II cases were classified as stage II2. All 17 patients with stage I NHL were treated with radiation therapy alone. Their diseases were well controlled, and none of them died of causes related to the lymphoma. Among 14 patients with stage II1 NHL, the 5-year survival rate for the 9 patients treated with radiation therapy alone was 87.5%. Until 1982, 19 of 21 patients with stage II2 NHL treated with radiation therapy alone or radiation therapy and adjuvant chemotherapy (VEMP or COPP) died within 5 years mainly of disseminated diseases. Since 1983, CHOP has been used as the main treatment as well as radiotherapy for the 12 stage II2 NHL patients. So far, only 3 of them relapsed and 2 of them died of causes related to the lymphoma. Only 1 of these 12 patients was T-cell lymphoma compared to 7 of 9 stage II2 patients before 1982. This suggests that patients with stage I and those with limited stage II can be safely treated with radiotherapy. Also aggressive chemotherapy as well as radiotherapy should be used for patients with advanced stage II NHL involving Waldeyer's ring.     

Determination of the minimal concentrations of contact activation factors in deficient substrate plasmas required to assess accurately factor XII, factor XI, factor IX, and high molecular weight kininogen

Using combined deficient plasmas prepared by passage of a deficient plasma over an anti-factor XI-monoclonal antibody column, we have determined the threshold concentrations of each coagulation factor of contact phase in factor-deficient substrate plasmas required to determine accurately the functional activities of factor XII, factor XI, factor IX and high molecular weight kininogen (HMWK). In order to reliably quantitate factor XI and factor IX activity levels, at least 20% factor XII and 20% factor XI, respectively, were required in the deficient substrate plasmas. In the assessment of factor XII activity, approximately 40% factor XI was required in the factor XII-deficient substrate plasma. On the other hand, only 11-12% factor XI or HMWK was required in the deficient substrate plasmas in the assessment of these two clotting factors. Our data emphasize that deficiencies of other clotting factors may reduce the apparent activity of the clotting factor in question if their concentration is rate-limiting in the clotting assay.     

Hyperactive phagocytosis by circulating neutrophils and monocytes in Chèdiak-Higashi syndrome

Phagocytic capacity of circulating neutrophils and monocytes was studied by electron micrsocopy in 2 children with Chèdiak-Higashi syndrome (CHS). Apparent phagocytosis of autologous leucocytes by the CHS neutrophils and monocytes was demonstrated when they were coincubated with Staphylococcus aureus in vitro, indicating their capacity for hyperactive phagocytosis. The hyperactive phagocytic capacity of the CHS phagocytes was a cellular abnormality. CHS neutrophils and monocytes are known to be defective in Chemotaxis and bactericidal capacity, and the hyperactive phagocytic capacity is another functional abnormality of CHS phagocytes.     

Chemical modification of hitachimycin. II. Synthesis and antitumor activities of carbonate derivatives

Several carbonate derivatives of hitachimycin have been synthesized and evaluated their activities including antibacterial, cytocidal against HeLa cells and in vivo antitumor against Sarcoma 180. Some of these derivatives showed higher antitumor activity than hitachimycin. Among the derivatives, 11,15-di-O-methoxycarbonylhitachimycin (2), 11,15-di-O-ethoxycarbonylhitachimycin (3) and 15-O-methoxycarbonylhitachimycin (9) were most effective in in vivo assay.     

Continent urinary reservoir formation with transverse colon for patients with pelvic irradiation

BACKGROUND: The creation of a continent transverse colon pouch for patients who had previously received radiation therapy for cervical cancer was attempted. METHODS: Three patients underwent construction of a continent urinary reservoir. Approximately 30 cm of a transverse colon segment was isolated for constructing a pouch. A reconfigured colon segment was used in two cases as a continent valve and the appendix was used in one case. Both ureters were implanted submucosally into the pouch in two patients and a reconfigured colon was also used to reconstruct a defect of the ureter in one patient. RESULTS: All patients could catheterize the pouch easily via the cutaneous stoma without incontinence. No complications were noted. CONCLUSIONS: In the event that a urinary diversion is necessary for a patient who has previously had radiation therapy, the transverse colon pouch can be a useful method to improve the quality of life. In addition, versatility of the reconfigured colon segment enables the colon pouch to be adapted to adverse clinical situations.     

Diagnostic usefulness of a hot test in patients with mild ocular myasthenia gravis

The diagnosis of myasthenia gravis (MG) can usually be made on the basis of the characteristic clinical history and signs, improvement by the use of anticholinesterase drugs, decremental responses in repetitive nerve stimulations, and assay of anti-acetylcholine receptor (AchR) antibody titers. We, however, have difficulty to make diagnosis of ocular MG patients with mild symptoms because muscular weakness is minimal and ancillary tests are negative. In the present communication, we report clinical usefulness of a hot test to provoke ptosis by warming the eyelid in ocular MG patients with minimal fatigability. Patient 1, a 27-year-old housewife, developed drooping of the right upper eyelid in May 1985. The ptosis was absent in the morning, but became apparent and worsened later. Neurological examination carried out 3 months after the onset revealed mild right ptosis, but fatigability of the levator palpebrae superioris could not be elicited by the provocative procedures such as sustained upward gaze or repeated opening and closing of eyelids. Both Tensilon and cold tests yielded negative responses. Repetitive nerve stimulations produced no decremental responses. Titers of anti-AChR antibody and antistriational antibody were within normal limits. In order to find a possible neuro-muscular blockade, we warmed the right upper eyelid by applying hot water of about 45 degrees C in a vinyl bag for 3 minutes. The hot test worsened the right ptosis and induced mild left ptosis. Tensilon administration reversed the eyelids to the previous position. Patient 2 was a 12-year-old boy with a typical history and clinical signs of ocular MG. His symptoms remitted spontaneously without any medication 3 weeks after the onset.(ABSTRACT TRUNCATED AT 250 WORDS)     

Absence of IgD-CD27(+) memory B cell population in X-linked hyper-IgM syndrome.

The present study analyzed peripheral blood B cell populations separated by IgD and CD27 expression in six males with X-linked hyper-IgM syndrome (XHIM). Costimulation of mononuclear cells from most of the patients induced no to low levels of class switching from IgM to IgG and IgA with Staphylococcus aureus Cowan strain (SAC) plus IL-2 or anti-CD40 mAb (anti-CD40) plus IL-10. Measurable levels of IgE were secreted in some of the patients after stimulation with anti-CD40 plus IL-4. Costimulation with SAC plus IL-2 plus anti-CD40 plus IL-10 yielded secretion of significant levels of IgG in addition to IgM, but not IgA. The most striking finding was that peripheral blood B cells from all of the six patients were composed of only IgD+ CD27(-) and IgD+ CD27(+) B cells; IgD- CD27(+) memory B cells were greatly decreased. IgD+ CD27(+) B cells from an XHIM patient produced IgM predominantly. Our data indicate that the low response of IgG production in XHIM patients is due to reduced numbers of IgD- CD27(+) memory B cells. However, the IgG production can be induced by stimulation of immunoglobulin receptors and CD40 in cooperation with such cytokines as IL-2 and IL-10 in vitro.