Stimulation of Cl(-) secretion by L-alanine oligopeptides in the mammalian large intestine.

A variety of oligopeptides are probably released within the intestinal tissue under inflammatory conditions or during peptide absorption. To examine whether some of these peptides can affect intestinal transport functions, we determined the effects of L-alanine oligopeptide on short-circuit current (I(sc)) and transmucosal conductance (G(t)) in submucosa-mucosa preparations from the mouse cecum and guinea pig distal colon in vitro in Ussing chambers. L-Alanyl-L-alanine (Ala-Ala, 10 mM) added to the serosal side increased I(sc) and G(t), giving a peak followed by a sustained phase (the peak increase in I(sc) was 45 +/-6 microA/cm(2) and the increase in G(t) was 0.55+/-0.11 mS/cm(2)). The tripeptide, L-alanyl-L-alanyl-L-alanine (Ala-Ala-Ala, 10 mM), added to the serosal side also induced increases in I(sc) and G(t) by a similar degree. On the other hand, luminal Ala-Ala, and serosal L-alanine and L-alanine (10 mM) caused significantly smaller increases in I(sc) and G(t) ( approximately 15 microA/cm(2) and approximately 0. 15 mS/cm(2), respectively). The Ala-Ala induced increase in I(sc) was partially inhibited by serosal bumetanide (0.1 mM) and mucosal 5-nitro-2-(3-phenylpropylamino)benzoic acid (0.1 mM), and largely suppressed by removing Cl(-) from the bathing solution. The increase in I(sc) was largely suppressed by serosal low Ca(2+) and tetrodotoxin, but was not affected by indomethacin. In the guinea pig distal colon, serosal Ala-Ala (10 mM) evoked a transient increase in I(sc) by 23+/-7 microA/cm(2) and an increase in G(t) by 1.2+/-0.3 mS/cm(2). These results suggest that Ala-Ala, and probably also Ala-Ala-Ala, added to the serosal side stimulated electrogenic Cl(-) secretion mainly through the activation of submucosal secretomotor neurons in the mammalian large intestine.

Non-Hodgkin's lymphoma of Waldeyer's ring as a manifestation of lymphoproliferative diseases associated with human T-cell leukemia virus type 1 in southwestern Japan.

Adult T-cell leukemia/lymphoma (ATL) usually presents with node- and/or cutaneous-based diseases, with a leukemic picture. It is not clear whether ATL initially manifests with lesions in Waldeyer's ring (WR) in an ATL-endemic area. In the present study, we examined distributions of immunophenotypes and the presence of human T-cell leukemia virus type 1 (HTLV-1) and Epstein-Barr virus (EBV) genomes in 62 cases of non-Hodgkin's lymphoma (NHL) of WR (NHL-WR) from two areas of Japan: Osaka, an ATL-nonendemic area (25 cases), and Okinawa, an ATL-endemic area (37 cases). In both areas, age ranged from 10 to 94 years (median, 64 yr), with a male-to-female ratio of 1.81:1. Twelve patients were in Stage I, 34 in Stage II, and 6 in Stage III; stage was unknown in 10. The 25 Osaka cases were B-cell type (16 diffuse immunoblastic type (DIB), 8 diffuse large cell predominantly noncleaved cell (DLNC), 1 cleaved cell (DLC)). Of the 37 Okinawa cases, 20 were B-cell type (3 DIB, 10 DLNC, 2 DLC, 5 other). The remaining 17 cases showed T-cell phenotype (4 DIB, 3 DLC, 3 diffuse large cell not otherwise specified, 7 other). There was a significant difference in the distribution of immunophenotypes between these two areas (P < .001). Combined studies of polymerase chain reaction (PCR) and in situ hybridization revealed the presence of EBV genome in 1 (4%) of 24 Osaka cases, 2 (13%) of 16 B-cell NHLs from Okinawa, and 3 (23%) of 13 T-cell NHLs from Okinawa. HTLV-1 proviral genome was found in 11 (85%) of 13 T-cell lymphomas from Okinawa but could not be detected in B-cell lymphomas from Osaka and Okinawa. Combined clinical, histologic, serologic, and PCR findings suggest that NHL-WR in an ATL-endemic area could be an initial manifestation of ATL.

Expression of alternatively spliced human T-lymphotropic virus type I pX mRNA in infected cell lines and in primary uncultured cells from patients with adult T-cell leukemia/lymphoma and healthy carriers.

Although human T-cell lymphotropic virus type I (HTLV-I) is the etiologic agent of adult T-cell leukemia/lymphoma (ATL), the role of viral gene expression in the progression to and maintenance of the leukemic state in vivo is unclear because of the inability of most previous studies to readily detect HTLV-I RNA in infected individuals. By using the reverse transcriptase-polymerase chain reaction, we detected spliced messages for the HTLV-I pX regulatory genes in primary uncultured cells from ATL patients and healthy asymptomatic carriers. In addition to the expected doubly spliced pX message, three alternatively spliced mRNAs were demonstrated (pX delta 17, pX-p21rex, and pX-orfII mRNAs, where orf = open reading frame). The same splice sites were shown in the messages from uncultured ATL cells and from the HTLV-I-producing C10/MJ cell line. Alternatively spliced pX mRNAs have the potential to code for known and putative pX gene products. Among the transcripts is a monocistronic mRNA likely to code for p21rex (pX-p21rex mRNA). Since alternative splicing of HTLV-I pX mRNA can be found in primary uncultured cells, it is likely to have a functional significance in vivo. This suggests possible roles for HTLV-I gene expression in the progression to and maintenance of ATL, as well as in the phase preceding it.

Vincristine-induced paralytic ileus: role of fiberoptic colonoscopy and prostaglandin F2 alpha.

Two cases of vincristine-induced paralytic ileus are described, with therapeutic correlation. Both patients had a roentgenographic picture of paralytic ileus showing fecal mass in the ascending colon and dilated bowel loops. One patient was successfully treated with glycerin and saline enema through a fiberoptic colonoscope placed in the ascending colon. The second patient was successfully treated with intravenous prostaglandin F2 alpha (PGF2 alpha). Enema through a fiberoptic colonoscope or the intravenous administration of PGF2 alpha may, therefore, prove useful in the treatment of vincristine-induced gastrointestinal toxicity.

[Drug-induced blood dyscrasia in Okinawa].

Forty one cases of drug-induced blood dyscrasia were seen in the last 10 years in six main hospitals in Okinawa. There were 16 males and 25 females. The average age was 53 year-old. The anticonvulsants were the most common causative drugs (12 cases), followed by the antithyroid drugs (6 cases) and Co-trimoxazole (4 cases). The granulocytopenia was the most common type of blood dyscrasia, comprising 51.0% of all cases. Phenytoin was the most common anticonvulsant (8 cases) and 6 cases received it as a prophylaxis following craniotomy. Three cases of antithyroid drug-induced granulocytopenia developed this complication after readministration of the antithyroid drugs. The intervals between the administration of causative drugs and the onset of blood dyscrasia were less than 3 months, except for alpha-methyldopa, gold, and chlorpromazine. Although 30 cases (73.0%) showed complete recovery, there were 3 fatalities (3.0%) which included bicytopenia due to sodium valproate, aplastic anemia due to Co-trimoxazole, and pure red cell aplasia due to aspirin. It is suggested from this study that drug-induced blood dyscrasia is not uncommon in Okinawa.

Listeriosis in hematological malignancies: report of two cases.

Listeriosis occurred in two patients with hematological malignancies, one with adult T-cell leukemia (ATL) (Case 1) and the other with chronic granulocytic leukemia (CGL) (Case 2). In Case 1, listeriosis was the initial manifestation of ATL, while it occurred in Case 2 after prolonged treatment with an alkylating agent and splenic irradiation. In both cases, depressed cell-mediated immunity was considered to be responsible for the listeriosis. Experience with the present two cases has indicated that listeriosis can be an initial manifestation of ATL, and the combination of an alkylating agent and splenic irradiation may increase the risk of listeriosis in patients with CGL.

Production of parathyroid hormone-related protein in adult T-cell leukemia cells.

Human parathyroid hormone-related protein (PTHrP) mRNA was detected in peripheral leukemic cells obtained from adult T-cell leukemia (ATL) patients as well as in cultured human T-cell leukemia virus type I (HTLV-I)-infected T-cell lines. In contrast, PTHrP mRNA was not detected in other types of leukemic cells. Using radioimmunoassay, immunoreactive PTHrP was also detected in the spent media of HTLV-I-infected T-cell lines. These results suggest that PTHrP plays an important role in developing the hypercalcemia frequently observed in ATL patients.

[Clinical study of spinal cord compression due to metastatic epidural tumors].

Eleven patients with spinal cord compression due to metastatic epidural tumors were analyzed. Primary tumors were Hodgkin's disease, non-Hodgkin's lymphoma, multiple myeloma (two patients each), cervical cancer, malignant melanoma, gastric cancer, lung cancer, and neuroblastoma (one patient each). It was felt that myelography is the most important diagnostic test, although CT scan and bone scan may give further diagnostic information in some patients. Six patients were treated with decompressive laminectomy and postoperative radiotherapy, and five with radiotherapy alone. Regardless of the pretreatment neurological status and the type of treatment given, the functional prognosis in our small series of patients appeared to be favorable for radiosensitive tumors such as malignant lymphoma and multiple myeloma.

Human T-cell leukemia-lymphoma virus type 1 and adult T-cell leukemia-lymphoma in Okinawa.

A serological survey for the presence of antibodies against the human T-cell leukemia virus, type 1 (HTLV-1) in patients seen at the Chubu Hospital in Okinawa was undertaken. All patients with the clinicopathological diagnosis of adult T-cell leukemia-lymphoma were positive. These cases had the characteristic features of adult T-cell leukemia-lymphoma: diffuse histology, often mixed cell or pleomorphic, and a high frequency of hypercalcemia, leukemic phase, diffuse visceral involvement, and opportunistic infections. The median survival of these patients was short, being only 18 weeks. Of the other patients with cancers screened, two of five other non-Hodgkin's lymphoma patients were positive and three of eight patients with other hematological cancers were positive. In addition, three of the four immediate family members of one adult T-cell leukemia-lymphoma case had antibodies. Of the other persons (both in- and outpatients) without hematological cancers, those under the age of 50 had a much lower antibody prevalence (4%) than those over 50 (30%). There was no significant difference in antibody prevalence between the two sexes in either the younger or older age group. These findings further document that Okinawa is an endemic area for HTLV-1. None of the 157 individuals screened for antibodies to HTLV-3 were positive, consistent with the fact that no cases of the acquired immune deficiency syndrome have been reported from Okinawa.