Role of IL-7 and KL in activating molecules controlling the G1/S transition of B precursor cells

While chemically defined conditions for culturing normal tissuehave been attained for only a few cell types, the sustainedproliferation of B precursor cells expressing lL-7 receptorand c-Kit can be supported under chemically defined conditionscontaining recombinant IL-7 and the ligand for c-Kit (KL). Tounderstand the biochemical basis of the cell cycle progressionof B precursor cells proliferating under these conditions, weinvestigated the correlation between growth factor stimulationand CDK4 activity. Consistent with our findings that IL-7 regulatesthe G transition, while KL has only a little role in this process,the kinase activity of CDK4 was related closely with IL-7 stimulationbut not KL stimulation. We investigated the mechanism underlyingCDK4 activation in the IL-7-stimulated B precursor cells. Ourresults showed that (i) CDK4 and cyclin D3 are the G₁/S regulatorsin B precursor cells; (ii) their expression levels are unchangedbetween the cells in G arrest and cycling cells; and (iii) theyare present in an associated form even when the cell cycle stageis arrested at G ¹ Thus, the regulation of the expression ofCDK4 and cyctin D3 or regulation of their assembly are not themechanisms for activating CDK4 in the B precursor cells. Onthe other hand, a number of molecules co-immunoprecipitatedwith CDK4 were enhanced in the lysate of IL-7-stimulated B precursorcells. Thus, we present a possibilIty that CDK4 activation mightbe regulated by molecules associated with the CDK4-cyclin 03complex in an IL-7-dependent manner.     

Combined chemotherapy for head and neck cancer using cisplatin, methotrexate and continuous subcutaneous infusion of peplomycin

Twenty-one patients with advanced or recurrent squamous cell carcinoma of the head and neck were treated with cisplatin, methotrexate and continuous subcutaneous infusion of peplomycin. The overall response rate was 62% (13/21) with 19% (4/21) complete response. The median duration of partial response was 2 months, while that of complete response was 3 months. Toxic effects were acceptable with no fatalities, but nephrotoxicity (33%), leukocytopenia (24%), thrombocytopenia (29%) and severe nausea and vomiting (76%) occurred. Pulmonary toxicity due to continuous subcutaneous infusion of peplomycin (15 mg/day, 4 days) was not seen.     

A case of RAEB-t treated by G-CSF showing complete remission after MST-16 treatment for subsequent reversible leukemia]

A seventy-five-year-old female with general fatigue, high fever and anemia was admitted. Her chest X-ray film revealed pneumonia. She was diagnosed as RAEB-t with the normal karyotype by peripheral blood film and bone marrow aspiration; 125 micrograms/ml of G-CSF was administered s.c. daily in order to increase neutrophil count because of the prolongation of pneumonia. Her blast cells in both peripheral blood and bone marrow showed a remarkable increase by G-CSF. After the cessation of G-CSF administration, blast cells decreased rapidly, and neutrophil count in the peripheral blood increased. Her pneumonia was then cured. After 5 months of stable hematological state, 60% of her bone marrow cells became occupied by blast cells again. So 2 consecutive courses of 14 days p.o. administration of 1,200 mg MST-16/day were tried. Three months after the first MST-16 trial, her bone marrow showed complete remission (CR) which lasted about 4 months. But she died of sepsis after the first relapse. Her bone marrow in CR still revealed several features of dyspoiesis.     

UFT in esophageal cancer: a report of two cases

We report two patients with esophageal cancer who responded to UFT. The patients were a 71-year-old female and a 61-year-old male, both of whom had recurrent disease in the esophagus or abdominal lymph nodes. They had received previous treatment consisting of radiotherapy and chemotherapy containing cisplatin, methotrexate and peplomycin. Each patient was administered UFT 400 mg/day p.o. No toxic effect was seen.     

Somatic Hypermutations in the VH Segment of Immunoglobulin Genes of CDS-positive Diffuse Large B-Cell Lymphomas

De now CDS-positive (CD5+) diffuse large B-cell lymphoma (DLBL) has recently been identified as constituting a homogeneous subgroup with distinct clinicopathologic and genotypic characteristics, but its origin remains to he elucidated. Previous studies by sequence analysis of the variable region of the immunoglobulin heavy chain (V_H) have shown that CDS⁵ B-cell malignancies such as mantle cell lymphoma (MCL) and B-cell chronic lymphocytic leukemia (B-CLL) cells represent pre-geminal center (pre-GC) stage B cells in contrast with the post-GC stage of most DLBLs, which show somatic hyper mutations in V_H genes. In the present study, we investigated the V_H sequence of de novo CD5⁺ DLBL to clarify whether CD5⁺ DLBL represents the pre-GC stage, as do other CD5⁺ B-cell malignancies, or the post-GC stage, as is typical of DLBL. All eight cases (four CDS⁴ DLBL and four CDS-negative (CD5⁻) DLBL) examined by us showed somatic hypermutatiohs in the V_H segment and two of the CD5⁻ DLBL cases showed intra-clonal diversity, suggesting that CD5⁺ DLBLs were derived from the same maturation stage as CD5⁻ DLBL, but were distinct from the other indolent CD5⁺ B-cell lymphomas of B-CLL and MCL. These data suggest that de novo CD5⁺ DLBLs do not merely lie within a continuous spectrum with B-CLL and MCL, but represent a biologically distinct variant within the diagnostic framework of diffuse large B-cell lymphoma.     

Development of tyrosine hydroxylase-like immunoreactive structures in the chick retina: three-dimensional analysis.

This study was designed to investigate the developmental profile of tyrosine hydroxylase-like immunoreactive structures in the chick retina in both frozen sections and wholemount preparations. In frozen sections, cells with tyrosine hydroxylase-like immunoreactivity were first detected in 10 to 15 cell rows from the innermost part of the inner nuclear layer on embryonic or incubation day 11. They were seen in the inner cell rows of the inner nuclear layer during later periods; by embryonic day 18, the immunoreactive cells were located 1 to 3 cell rows outward from the innermost part of the inner nuclear layer where mature immunoreactive cells mainly exist. The immunoreactive cells began to give rise to processes on embryonic day 13. The processes (possibly dendrites) gradually increased in number and intensity in sublayers 1 and 4 of the inner plexiform layer during prenatal life. Several days after hatching, an abrupt increase in immunoreactive processes was noted in sublayer 1 but not in sublayer 4. On the sixth postnatal day, retinal neural elements immunoreactive for tyrosine hydroxylase seemed to exhibit a distribution pattern similar to that of the adult chick. In wholemount retinas, immunoreactive cells were initially detected at the earliest stage of embryonic day 12 in a small circle termed "starting area" occupying the ventral part of the temporal retinal field. The closer to the "starting area," the earlier the retinal area began to express many immunoreactive cells. Thus tyrosine hydroxylase cell density in individual retinal areas, as represented by cell number per square millimeter, peaked in different developmental periods varying from embryonic day 12 to day 14. At this stage, immunoreactive cells were arranged irregularly in the retina. Thereafter, the cell density as well as total cell number gradually declined and reached a plateau around embryonic day 20 when tyrosine hydroxylase-like immunoreactive cells, like those in the mature retina, showed an even distribution throughout the retina.(ABSTRACT TRUNCATED AT 400 WORDS)