Virus associated adult T-cell leukemia/lymphoma (ATLL), which includes both adult T-cell leukemia (ATL) and its non-leukemic counterpart (NLATL) was studied clinically, histologically, and immunologically. The disease usually occurred in the sixth decade in both sexes equally. The patients had a rapid clinical course with frequent leukemic changes, lymphadenopathy, hepatomegaly, and occasional skin rash. Bone marrow involvement with mild infiltration and hypercalcemia were more frequent in ATL than in NLATL. Histologically the disease was categorized as malignant lymphoma, diffuse pleomorphic type with cerebriform nuclear giant cells. The lymphoma was characterized by diffuse proliferation of tumor cells with irregular nuclear configurations, varying in size and shape, and the presence of giant cells with highly convoluted cerebriform nuclei. The giant cells seemed to be a diagnostic marker. Immunologically, the tumor cells usually possessed the surface antigens recognized by OKT 3, 4, Leu 8 and anti-Tac antibodies, indicating that they were lymphomas of helper/inducer peripheral T-cells with the receptor for interleukin 2, but they demonstrated no helper/inducer functions. The patients often died of opportunistic infections due to T-cell dysfunction caused by the disease itself and strong chemotherapy.

Antibodies, Monoclonal↗

PubMedDate not supplied

Rearrangement of human T cell receptor beta and gamma chain genes in adult T cell leukemia/lymphoma.

We studied rearrangement of human T cell receptor genes (TCR) of C beta, C gamma, V gamma and J gamma in 34 cases of adult T cell leukemia/lymphoma (ATLL), consisting of 29 cases with monoclonally integrated HTLV-I proviral DNA (ATLL-W) and five without monoclonal integration (ATLL-O), in comparison with 12 cases of other peripheral T cell lymphomas (non-ATLL). All cases of both ATLL and non-ATLL showed some rearrangement of T cell receptor genes (TCRs) of C beta, C gamma, V gamma, or J gamma. Rearrangement of TCR beta was found in 28 of 29 cases of ATLL-W, all cases of ATLL-O, and eight of 12 cases of non-ATLL. Rearrangement of TCR gamma was observed in 21 of 22 cases of ATLL-W, and in all cases of ATLL-O and non-ATLL. In TCR gamma, rearrangement of C gamma was seen in six of 20 cases of ATLL-W, none of three ATLL-O cases and three of six cases of non-ATLL. V gamma rearrangement occurred in 14 of 18 cases of ATLL-W, one of two cases of ATLL-O, and three of six cases of non-ATLL. Rearrangement of J gamma was found in 16 of 22 cases of ATLL-W, two of five ATLL-O cases, and six of seven non-ATLL cases. Rearrangement was more frequent in ATLL-W than in ATLL-O and non-ATLL. The incidence rate of rearrangement of V gamma families of V gamma 1, V gamma 2, and V gamma 3 was nearly the same in each group, except for deletion of V gamma 3, which was often observed in ATLL but was absent in non-ATLL. These results indicate the usefulness of detection of TCR and HTLV-I proviral DNA to differentiate ATLL from other T cell malignancies.

Adult↗

PubMedDate not supplied

Restriction of T cell receptor variable region in lymph nodes of adult T cell leukemia/lymphoma.

Adult T cell leukemia/lymphoma (ATLL) is a mature T cell malignancy, especially derived from the CD4 positive T cell. To characterize the T cell, we examined the representation of T cell antigen receptor variable region, using the monoclonal antibodies [beta V 5 (a), beta V 5 (b), beta V 6 (a), beta V 8 (a), beta V 12 (a), alpha V 2 (a), alpha-beta V (a)]. Clinicopathologically we classified the lymph nodes of patients with ATLL into three states (1) human T cell leukemia virus type I (HTLV-I) associated lymphadenitis, reactive state; (2) incipient ATLL, early or pre-neoplastic state; and (3) ATLL, neoplastic state. The lymph nodes of all three states were composed of unvarying CD4 positive T cells. Most of the lymph nodes with ATLL consistently presented alpha V 2 antigen, but no others. In HTLV-I associated lymphadenitis, only a few cells reacted for alpha V 2, as in non-specific lymphadenitis without ATLL features. One of three cases with incipient ATLL presented alpha V 2. The selected expression of T cell antigen receptor V region might be associated with the presence of HTLV-I encoded superantigen, similar to human immunodeficiency virus (HIV).

Adult↗

PubMedDate not supplied

Hepatosinusoidal leukaemia/lymphoma consisting of Epstein-Barr virus-containing natural killer cell leukaemia/lymphoma and T-cell lymphoma; mimicking malignant histiocytosis.

Previously diagnosed cases of hepatosinusoidal T-cell lymphoma and malignant histiocytosis (MH) may include lymphoid neoplasms of natural killer (NK) cell lineage associated with Epstein-Barr virus (EBV). Such hepatosinusoidal neoplasms were found to demonstrate hepatomegaly but not lymphadenopathy, and all were diagnosed by a liver biopsy. Sixteen adult patients diagnosed with hepatosinusoidal leukaemia/lymphoma (six NK-cell leukaemia/lymphomas [NKLLs], five instances of MH, three T-cell malignant lymphomas [T-MLs], and two adult T-cell leukaemia/lymphomas [ATLLs] were examined for EBV by in situ hybridization, then were studied immunohistochemically and subjected to a DNA analysis. Among our five patients with MH, neoplastic cells showed T-cells, but no histiocytic markers, and they were considered to have either a T-cell or NK-cell lineage. All NKLLs, MHs and T-MLs, except for ATLLs accompanied by reactive hemophagocytic histiocytes, varied in number in each case. In situ hybridization revealed the presence of EBV in the nuclei of atypical cells in all of the six lymphoid neoplasms of NK-cell lineage. Each case of MH and each T-ML which represented EBV demonstrated no definite T-cell or histiocytic markers. Patients with ATLL did not reveal EBV. In all patients with hemophagocytosis, EBV was present in the nuclei of the neoplastic lymphocytes, but not in the hemophagocytic cells. Finally, the 16 cases were reclassified into eight cases with EBV-containing NKLLs, six T-MLs, and two ATLLs. In addition, no true histiocytic neoplasms were observed. The mechanism of hemophagocytosis may be therefore the production of lymphokines (macrophage-activating factors) by neoplastic lymphocytes. EBV-associated hepatosinusoidal leukaemia/lymphoma may thus contain a lymphoid neoplasm of NK-cell lineage, which made it difficult to be distinguished from the previously designated malignant histiocytosis.

Adult↗

PubMedDate not supplied

Increased intestinal absorption of insulin in a micellar solution: water-in-oil-in-water insulin micelles.

Water-in-oil-in-water (W/O/W) insulin micelles were prepared, and the possibility of insulin absorption in a micellar form was examined. In this preparation, insulin was trapped in oil droplets of oleic acid in glyceryl-alpha-monooleate. (1) W/O/W insulin micelles were absorbed from the ligated jejunal loop of rabbits to the order of 12.3 to 58.5% of the dose given (10 mU/kg body weight) during the 3-h experimental period. (2) Alloxan diabetic rats were treated with intrajejunal administration of W/O/W insulin micelles at a dosage of either 25 or 50 mU/100 g body weight, three times daily for as long as 14 days. During treatment, a significant reduction in the daily excretion of urinary glucose was observed, concomitant with a decrease in fasting blood glucose. Quantitative estimates suggested that the effectiveness of 25 mU/100 g of intrajejunal W/O/W insulin micelles was comparable to that of regular insulin at a dosage of 1 mU/100 g i.m. These results would indicate that W/O/W insulin micelles, when given enterally, are more effective in lowering blood and urinary glucose levels than W/O/W insulin emulsions in which insulin was trapped in oil droplets of triglyceride.

Animals↗

PubMedDate not supplied

Validation of I.V. small-dose insulin infusion therapy in diabetic ketoacidosis of depancreatized dogs.

A validation of small-dose insulin infusion therapy was studied by the constant i.v. infusion of various doses of insulin into ketoacidotic depancreatized dogs. Constant insulin infusion of 5 x B, 10 X B, 30 X B and 50 X B (B = 225 microunit/kg/min) was performed for 3 h by mechanical pump. The following results were obtained: (1) plasma concentrations of immunoreactive insulin (IRI) increased proportionally to the dose of infused insulin, but the higher IRI did not result in a greater fall in plasma glucose concentration, correspondingly; the mean rate of fall in plasma glucose concentration of 5 x B was not significantly lower than that of 50 x B; beta-hydroxybutyrate and arterial pH improvements were observed in each group during the 3-h insulin infusion. These data suggested that for the improvement of diabetic ketoacidosis, the insulin infusion rate of more than 30 x B, which raised the plasma IRI levels above the physiological range, was not essential; (2) the necessity of potassium supplementation during the small-dose insulin infusion was suggested if the pre-treatment level of serum potassium was low. These results confirmed that in the absence of infection or severe acidosis small-dose insulin infusion therapy is as effective as the conventional large-dose insulin therapy.

Animals↗

PubMedDate not supplied

Fibroblast growth factor stimulates the gene expression and production of tissue inhibitor of metalloproteinase-1 in bovine granulosa cells.

The hormonal control of tissue inhibitor of metalloproteinase-1 (TIMP-1) gene expression and production by growth factors, gonadotrophins, and serum factors in cultured bovine granulosa cells (BGC) were investigated. Confluent cultures of BGC were exposed to various factors in a defined medium and levels of TIMP-1 in the conditioned medium were determined by enzyme immunoassay. Basic fibroblast growth factor (bFGF) and acidic fibroblast growth factor (aFGF) showed potent stimulation of cell proliferation and TIMP-1 production by BGC, while insulin stimulated growth but not TIMP-1 production. Basic FGF stimulated TIMP-1 production and BGC cell proliferation in a dose-dependent manner. A time course of TIMP-1 production showed substantially increased levels between 18 and 24 h in both control and bFGF-stimulated BGC cultures with bFGF-stimulated cultures having markedly higher TIMP-1 production at all time points. Consistent with the TIMP-1 production data, bFGF and aFGF increased the expression of TIMP-1 mRNA as determined by northern blot analysis, while insulin, inhibited TIMP-1 mRNA levels. These results indicate that FGF-induced TIMP-1 production by BGC may support bovine embryo development in vitro.

Animals↗

PubMedDate not supplied

Experimental study on interactions between selenium and tin in mice.

The organ distributions of tin and selenium, and their excretion into urine and feces, were determined in mice. There were four groups; (A) control, (B) Sn (5 mumol/kg/d) ip injection, (C) Se (5 mumol/kg/d) sc injection, and (D) Sn plus Se (5 mumol/kg/d, each). Animals received injections once a day for 12 consecutive days. The results were the following (1) Simultaneous injection of Sn and Se enhanced accumulation of both elements in the body, i.e., in group B, 14.1% of the total injected amount of Sn was excreted into urine and feces; in group C, 46.2% of total injected Se was excreted into urine and feces; in group D, 10.9% of total Sn and 37.5% of total Se were found in excreta. (2) Large amounts of Sn were found in bone, liver, spleen, and kidney in group B. When Se was administered jointly with Sn, the concentrations of Sn in bone and liver were suppressed, whereas those in spleen and pancreas were increased. (3) The effects of Se-injections at this dose on concentrations of Se in organs were small. (4) In plasma, chemical reduction of selenite by stannous chloride was not observed.

Animals↗

PubMedDate not supplied

The role of calcium in platelet microtubule assembly-disassembly.

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Blood Platelets↗