Mode of antitumor action of recombinant human tumor necrosis factor on the sarcoma Meth A transplanted in the mouse

The mode of antitumor action of rHu-TNF was elucidated in BALB/c mice bearing Meth A fibrosarcoma 7 days after transplantation with respect to time course, dose-response relationships and selectivity of the effects. The maximal cytotoxic effect on tumor cells revealed by inhibition of DNA synthesis and maximal lesional effect on tumor vasculature revealed by change in blood pool-size in the tissue were detected at 30 min and I h after administration of rHu-TNF, respectively. The dose-response relationship between cytotoxic and tumoricidal effects of rHu-TNF was irrespective of administration route. ED₅₀s of these antitumor effects afteri.v. administration of rHu-TNF were about 50 times as high as ED₅₀s afteri.t. administration. ED₅₀ ofi.t. given rHu-TNF for vascular effect was about 20 times as high as that for cytotoxicity while ED₅₀ ofi.v. rHu-TNF for vascular effect was only 2–3 times as high as that for cytotoxicity. The whole body autoradiographies with [¹²⁵I] HSA giveni.v. to see the blood influx into tumor tissue and [¹⁴C]thymidine given i.v. to see DNA synthesis in the whole body after administration of rHu-TNF revealed that the distribution of radioactivity was markedly changed in the tumor alone without any detectable change in other whole body tissues.In conclusion, thein vivo antitumor effect of rHu-TNF giveni.t. ori.v., appears to be exerted through the direct action on Meth A sarcoma rather than indirectly on tumor vasculature. Under present conditions, the effect of rHu-TNF in the whole body tissues seems rather selective on cells and vasculature of the tumor.     

Nematodes of the family Heligmonellidae (Trichostrongyloidea) collected from rodents of the Ryukyu archipelago and Taiwan

Six species of the family Heligmonellidae (Nematoda: Trichostrongyloidea), including 3 new species, are recorded from rodents of the subfamily Murinae in the Ryukyu Archipelago and Taiwan. Heligmonoides ikeharai n. sp. from Tokudaia osimensis muenninki on Mt. Yonaha, Okinawa Island, is characterized by extremely long spicules and hypertrophied ridges in the prevulval region. Heligmonoides taiwanensis n. sp. from Apodemus draco on Mt. Alishan, Taiwan, is distinguished from other members of the genus in having a markedly asymmetrical bursa and stout bursal rays. Heligmonoides alishanensis n. sp. from Niviventer confucianus on Mt. Alishan differs from the allied forms in lacking hypertrophied ridges at the level of the middle of the spicules and in having longer spicules and a smaller body. Nippostrongylus sp. from N. confucianus on Mt. Alishan resembles Nippostrongylus brasiliensis but is distinguishable in that the externolateral ray is almost the same length as the lateroventral ray in the left lobe, and the fused tips of the spicules are thin and straight. Heligmonoides ryukyensis from Mus caroli and Orientostrongylus tenorai from Bandicota indica are first recorded from Taiwan. Heligmonellid nematodes parasitic in wild rodents in these areas are considered to have been introduced with their hosts from the mainlands of China and Japan through land connections in the Pleistocene.     

Close linkage of MEN2A with RBP3 locus in Japanese kindreds

Summary The gene responsible for multiple endocrine neoplasia type 2A (MEN2A) has recently been assigned to the pericentromeric region of chromsome 10 in European Caucasian kindreds by linkage analysis using a DNA marker, interstitial retinol-binding protein 3 (RBP3). We have found tight linkage between the MEN2A and RBP3 loci in Japanese MEN2A kindreds. The maximum lod score is 5.19 at a recombination fraction of 0.00. This result suggests that mutation of a certain gene close to RBP3 is responsible for MEN2A irrespective of ethnic backgrounds.     

Carbon Use Efficiency and Cell Expansion of NaCl-Adapted Tobacco Cells

Carbon use efficiencies (gram cell organic dry weight accumulated per gram sugar assimilated from the medium) of unadapted and NaCl-adapted (428 millimolar) cells of tobacco (Nicotiana tabacum L. var Wisconsin 38) were determined to evaluate metabolic costs associated with growth and survival in a saline environment. No net increase in carbon costs was associated with salt adaptation. At low substrate levels, carbon use efficiencies of unadapted and NaCl-adapted cells were not appreciably different (0.495 and 0.422, respectively) and at higher substrate levels carbon use efficiency of NaCl-adapted cells was clearly higher than that of unadapted cells. These results indicate that a homeostasis of metabolic efficiency is established after cells have adapted to NaCl. Altered carbon availability does not cause the reduced cell volume that results from adaptation to NaCl. This does not preclude, however, the possibility that altered intracellular partitioning of carbon affects cell expansion.     

Two new nematodes from the Iriomote cat, Prionailurus iriomotensis, from Okinawa: Uncinaria (Uncinaria) maya n. sp. (Ancylostomatoidea) and Molineus springsmithi yayeyamanus n. subsp. (Trichostrongyloidea)

Uncinaria (Uncinaria) maya n. sp. (Nematoda: Ancylostomatidae) and Molineus springsmithi yayeyamanus n. subsp. (Nematoda: Molineidae) are described from the Iriomote cat, Prionailurus iriomotensis, on Iriomote Island, Okinawa, Japan. Uncinaria (U.) maya resembles Uncinaria (Uncinaria) felidis Maplestone, 1939, from Prionailurus bengalensis of India but is distinguished in that the body is much smaller, the ventral rays are set closely with the lateral rays, and the externolateral ray is much shorter than other laterals. Molineus springsmithi yayeyamanus differs from Molineus springsmithi springsmithi Inglis and Ogden, 1965, from Prionailurus bengalensis horsfieldi of East Nepal in that the body is much longer, whereas the esophagus is somewhat shorter and the spicules are divided more distally. Presence of the closely related nematodes in both the Iriomote cat and P. bengalensis suggests a close evolutionary relationship of the 2 hosts.     

Protein phylogeny of translation elongation factor EF-1α suggests microsporidians are extremely ancient eukaryotes

Partial regions of the mRNA encoding a major part of translation elongation factor 1 (EF-1) from a mitochondrion-lacking protozoan,Glugea plecoglossi, that belongs to microsporidians, were amplified by polymerase chain reaction (PCR) and their primary structures were analyzed. The deduced amino acid sequence was highly divergent from typical EF-1's of eukaryotes, although it clearly showed a eukaryotic feature when aligned with homologs of the three primary kingdoms. Maximum likelihood (ML) analyses on the basis of six different stochastic models of amino acid substitutions and a maximum parsimony (MP) analysis consistently suggest that among eukaryotic species being analyzed,G. plecoglossi is likely to represent the earliest offshoot of eukaryotes. Microsporidians might be the extremely ancient eukaryotes which have diverged before an occurrence of mitochondrial symbiosis. Sequence availability: The nucleotide sequence data reported here appear in the GSDB, DDBJ, EMBL, and NCBI databases with the accession number D32139     

SFA-1, a novel cellular gene induced by human T-cell leukemia virus type 1, is a member of the transmembrane 4 superfamily.

A novel cellular gene termed SFA-1 was isolated by differential hybridization of a cDNA library, using probes obtained from an adult T-cell leukemia cell line in comparison with probes obtained from normal CD4+ T cells and the MOLT-4 cell line. The mRNA of the SFA-1 gene is approximately 1.6 kb in size and encodes a protein of 253 amino acids, containing four putative transmembrane domains, a number of cysteine residues, and one potential N-glycosylation site in a major hydrophilic region between the third and fourth transmembrane domains. Expression of the SFA-1 gene was either absent or present at a low level in lymphoid cells but was up-regulated after transformation by human T-cell leukemia virus type 1 and transactivated by Tax. SFA-1 was broadly expressed in many human cell types and conserved in different species. Computer-aided comparison showed that SFA-1 had significant sequence homology and common structural features with members of the transmembrane 4 superfamily. SFA-1 antigen was detected as a 29-kDa membrane protein by immunoblotting, using anti-SFA-1 monoclonal antibody.