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Simultaneous determination of maternal and fetal plasma 11-deoxycorticosterone (DOC), corticosterone (B), 18-hydroxycorticosterone (18OH-B) and aldosterone (ALDO) in normal and toxemic pregnancies was performed by utilizing a newly developed radioimmunoassay. The mean levels of plasma DOC and ALDO in normal term pregnancy were significantly higher than those of nonpregnant women. Comparing the mean levels of umbilical arterial plasma to those in maternal plasma at delivery, DOC and ALDO were consistently higher in the former, while B was higher in the latter, and 18OH-B was largely unchanged. However, no umbilical arteriovenous gradient was found in any corticosteroid measured. In toxemia of pregnancy, the corticosteroid levels in the maternal plasma were lower than those in normal pregnancies, and in umbilical arterial plasma, B was significantly higher and 18OH-B and ALDO remained almost the same as those in normal pregnancy. Thus, it appears that ALDO synthesis in mother in normal term pregnancy was enhanced but in toxemia of pregnancy it was suppressed, while in the fetus, it was enhanced not only in normal pregnancy but also in toxemia of pregnancy.

Since the isolation of an HIV-2-related virus from captive macaques (SIVMAC), the origin of human immunodeficiency viruses, a much debated subject, has been attributed to monkeys. The sequence of SIVAGM, which is derived from a naturally infected African green monkey, shows equal relatedness to HIV-1 and HIV-2, suggesting that the derivation of these viruses from SIVAGM is unlikely. Recent sequence analysis of SIV from a captive sooty mangabey (SIVMAC), however, shows its close relatedness to HIV-2 and SIVMAC, indicating a possible origin of HIV-2 and SIVMAC from SIVSM (refs 4, 7, 9). We report here the sequence of a novel simian lentivirus, SIVMND, isolated from a wild-caught mandrill in Africa. It is distinct from the three other main groups, HIV-1, HIV-2/SIVMAC/SIVSM and SIVAGM, and therefore represents a fourth main group of primate lentiviruses. Phylogenetic analysis indicates that these four main virus groups might have diverged from a common ancestor at about the same time, long before the spread of AIDS in humans.

Recently, the authors determined the partial sequence of simian immunodeficiency virus (SIV) from the mandrill (SIVMND) and found SIVMND to be a new member of the HIV/SIV group, equidistant from other members, including SIVAGM. Experimentally, the African green monkey and cynomolgus monkey could be infected with SIVAGM and the cottontop tamarin with SIVMND. However, no clinical sign of an AIDS-like disease was observed in these monkeys.

Tumor cells of feline leukemia were examined for structural abnormality and expression of the myc gene. Four of 12 spontaneous leukemia cases showed structural abnormalities of the myc gene detected by Southern blotting analysis. Of these 4 cases, one (Case 1) showed a DNA rearrangement in the 5' portion of the c-myc locus associated with integration of feline leukemia virus (FeLV) genome. Another case had a newly inserted myc gene which was transduced by FeLV. In the 2 other cases, no relation of abnormalities of the myc gene to FeLV was detected. One case of experimental leukemia induced by inoculation of a cell line, FT-1, established from Case 1 showed a c-myc gene rearrangement similar to that observed in Case 1. Expression of myc RNA was examined in 3 leukemia T-cell lines, FT-1, FL74 and F422, by Northern blotting analysis. A high level of myc transcript was detected in all 3 cell lines. The size of myc RNAs in FT-1 and FL74 was the same as that of normal myc RNA, while in F422 which had myc-containing FeLV (myc-FelV), the full genome and spliced form of myc-FeLV viral RNA were detected.

A 57-year-old male was admitted to our hospital with bloody sputum, whose right lung had been resected for squamous cell carcinoma of the lung three and a half years ago. Tomographic examinations and chest CT films showed the presence of tracheal tumor. Histological examinations of the biopsy specimen obtained from tracheal tumor, using bronchofiberscopy, identified squamous cell carcinoma. Trachea was resected in the length of six cartilages and end to end anastomosis was performed. Though lung cancer and tracheal cancer were same histological type, clinical findings confirmed that this case was double primary cancer. Postoperative course was uneventful except for minor leakage of anastomosis site.

Proviral integration of a simian retrovirus highly homologous to human T-cell leukemia virus type I was examined in cellular DNAs extracted from primary peripheral blood lymphocytes of 31 adult African green monkeys (Cercopithecus aethiops) that were seropositive for simian T-cell leukemia virus type I (STLV-I). Among these monkeys, one case with overt leukemia, showing pleomorphic leukemia cells similar to those in human adult T-cell leukemia (ATL), and five cases in a preleukemic state of ATL-like disease were found. Judging from the integration site of the provirus genome, primary lymphocytes of these leukemic or preleukemic cases contained monoclonally proliferated STLV-I-infected cells, whereas lymphocytes of other seropositive monkeys without hematological abnormalities were polyclonal, and those of seronegative monkeys did not contain the provirus. The restriction patterns with PstI ans SstI of most STLV-I proviruses were identical to those of the previous isolate from this species, but in three monkeys there was a deletion of one PstI site. From the correlation of the development of simian ATL-like disease with the monoclonal integration of the STLV-I provirus genome, it should be indicated that STLV-I has similar leukemogenicity to human T-cell leukemia virus type I, and so STLV-I infection in African green monkeys will be useful as an animal model of human ATL.

Macrophages and fibroblasts are major components of the postsurgical repair process. In order to understand more fully the interaction between these two cell types, we studied the modulation by macrophages of the incorporation of [3H]thymidine into postsurgical fibroblasts recovered from the site of peritoneal injury. Peritoneal exudate cells (PEC):(greater than 95% macrophages) were collected from rabbits 4 and 7 days after resection and reanastomosis of the small intestine. PEC were suspended in Medium 199 (M-199) with 3% fetal calf serum (FCS) and incubated for 48 hr. Fibroblasts were obtained from rabbits that underwent abrasion of the parietal peritoneum 7 days previously, and were cultured for 7 days in M-199 with 3% FCS. Fibroblasts were then replated and incubated with macrophage-spent medium. Incorporation of [3H]thymidine into fibroblasts was significantly suppressed after 24 hr of incubation with macrophage-spent media compared to the incorporation by fibroblasts incubated with fresh medium (control). This suppression was most profound when fibroblasts were incubated with resident (nonsurgical) macrophage-spent medium. The incorporation of thymidine by macrophage-spent media groups then increased rapidly and reached control levels at 48 hr of incubation. After 54 hr of incubation, the incorporation of thymidine by fibroblasts incubated with media from postsurgical macrophages was significantly higher than that of control. Morphological changes in fibroblasts also appeared as the culture with macrophage-spent media progressed. Initially, fibroblasts were shaped like pine needles, but after 7 days of culture, fibroblasts assumed a spherical shape. Round-shaped fibroblasts returned to the original morphology (pine needle shape) after incubation for 48 hr with macrophage-spent medium.(ABSTRACT TRUNCATED AT 250 WORDS)

Genetic variability in human immunodeficiency virus type 1 (HIV-1) has been studied extensively, but the total nucleotide sequence of the HIV-2 genome has been reported only in two strains. For phylogenetic analyses of HIV, the genetic variability of HIV-2 should be investigated. This paper reports the complete nucleotide sequence of an HIV-2 isolate from Ghana, HIV-2[GH-1]. This virus showed approximately 85% homology in overall nucleotide sequence with HIV-2ROD. The amino acid sequence of the gag and pol proteins of HIV-2[GH-1] showed 90% homology with those of HIV-2ROD, but its env gene and central regions were highly variable (more than 20% divergence in amino acids), indicating the presence of extensive genetic heterogeneity in HIV-2. However, the sequences with specific functions were relatively well conserved in these HIV-2 isolates.

We investigated the effect of myocardial preservation and preoperative stroke work index (SWI) and left ventricular end-diastolic pressure (LVEDP) upon the early postsurgical kinetics of left ventricular function in thirty-four patients after prosthetic cardiac valve replacement. They received both-sided cardiac catheterization and measurement of cardiac output by dye dilution method in a standard fashion. Myocardial temperature was measured simultaneously and consecutively during aortic cross-clamping period (greater than 70 min) on open heart surgery. Thereafter, each postsurgical left ventricular function was estimated at three, six, twenty-four and forty-eight hours after weaning from cadiopulmonary bypass (CPB) by using Swan-Ganz catheter. SWI0 X 1000/AnI was used as an improved index of postsurgical cardiac function, because it was incorporated with the preoperative left ventricular stroke work index (SWI0) and anoxic index (AnI), which was the integral of myocardial temperature during aortic cross-clamping period. Otherwise, we regarded LVEDP as an estimate of preoperative cardiac function. So we compared them with the early postsurgical left ventricular SWI, respectively. As a result, the relation between SWI0 and the postsurgical SWI (SWI24 and SWI48) showed positive correlations with correlation coefficients 0.52 and 0.70, and the relation between AnI and the early postsurgical SWI (SWI3 and SWI6) showed negative correlations with correlation coefficients -0.56 and -0.52. While the relation between SWI0 X 1000/AnI and postsurgical SWI (from SWI0 to SWI48) showed positive correlations with correlation coefficients decreasing from 0.76 to 0.57. LVEDP showed negative correlations to SWI0 and SWI48 with correlation coefficients -0.48 and -0.45.(ABSTRACT TRUNCATED AT 250 WORDS)

Some wild African green monkeys are known to be naturally infected with a retrovirus related to human immunodeficiency virus (HIV) without having any apparent symptoms of an AIDS-like disease. This simian immunodeficiency virus, designated SIVAGM, may be helpful in clarifying the evolution and pathogenicity of HIV. Some virus strains that were previously reported to be isolated from African green monkeys were shown to be laboratory contaminations of SIVMAC (SIV from a rhesus macaque) Here we report the complete DNA sequence of authentic SIVAGM, which was isolated from a naturally infected African green monkey of Kenyan origin. Comparison of the genome of SIVAGM with those of known HIV/SIVs indicates that the virus is a new simian lentivirus that is approximately equally distantly related to HIV-1 and HIV-2 in contrast to SIVMAC, which is much closer to HIV-2 than to HIV-1 (refs 5, 9).

The deposition and lysis of fibrin are important processes in normal peritoneal healing. Since macrophages secrete a neutral plasminogen activator, we studied the production of plasminogen-dependent, fibrinolytic activity by postsurgical macrophages. Peritoneal exudate macrophages were collected from rabbits after resection and reanastomosis of their ileum. Intracellular plasminogen activator (PA) activity of resident (nonsurgical) macrophages was 8.4 +/- 1.8 milli-Plough units (mPU)/10(6) cells. Postsurgical Day 1 macrophages had significantly less activity (0.33 +/- 0.056 mPU/10(6) cells) compared to resident cells. Thereafter, the PA activity gradually increased and reached control levels by Postsurgical Day 7. The PA activity secreted by postsurgical macrophages into serum-free medium after 48 hr of culture was also determined. Conditioned medium from macrophages collected on Postoperative Days 1-5 exhibited less PA activity than buffer controls. PA activity was detected after acid treatment of the conditioned medium to remove acid-labile inhibitors. The activities of PA in acid-treated conditioned medium increased gradually and reached nonsurgical levels by Postsurgical Day 7. In spent medium from macrophages collected on Postsurgical Days 1-3, high levels of urokinase inhibitory activities were secreted; production gradually decreased during the later postoperative period. This inhibitory activity of macrophage-conditioned medium on urokinase-like PA activity was partially diminished by acidification of the media. These results support the hypothesis that macrophages in the postsurgical exudate may play an important role in the fibrinolytic process during peritoneal wound healing, perhaps through production and secretion of plasminogen activator as well as acid-labile and resistant protease inhibitors.

The purpose of this study was to determine the proliferative activity of tissue repair fibroblasts recovered directly from injured peritoneum at various times after surgery and to test the mitogenic response of tissue repair cells (TRC) to growth factors. Rabbits underwent bilateral peritoneal abrasion (5 X 5 cm) with sterile gauze until punctate bleeding developed. Postsurgical (Days 2, 5, 7, and 10) tissue repair cells were recovered from the injured peritoneum by scraping with a scalpel blade. Although tissue repair cells consisted of a mixed cell type after 4 days in culture, recovered cells were essentially fibroblasts. These TRC were then pulsed with [3H]thymidine after 4 days in culture. The incorporation of thymidine into Postsurgical Day 5 TRC increased significantly compared to that of Day 2 TRC (P less than 0.05). Incorporation then decreased with time following surgery. Fibroblast growth factor (FGF) and epidermal growth factor (EGF) stimulated the incorporation of thymidine into TRC. However, the response of Postsurgical Day 7 and 10 TRCs to 1 microgram/ml EGF was significantly greater than those of Postsurgical Day 2 and 5 TRCs (Day 2 TRC, 166 +/- 7.4; Day 10 TRC, 420 +/- 96% of control cells without EGF, P less than 0.05). Platelet-derived growth factor (PDGF, 10 ng/ml) also stimulated the incorporation of thymidine into Day 10 TRCs, but this stimulatory activity (129.9 +/- 8.5% of control) was less than EGF or FGF. IL-1 alpha and IL-2 did not stimulate the incorporation of thymidine into TRC at a concentration of 100 pg/ml, but these cytokines did stimulate protein synthesis by TRC.(ABSTRACT TRUNCATED AT 250 WORDS)

This report describes the isolation and characterization of a retrovirus of the HIV-2 group from a Ghanaian AIDS patient which has different restriction patterns from previously reported HIV-2 viruses. The virus was morphologically very similar to HIV-1 and HIV-2, and had Mg2+-dependent reverse transcriptase. Like previous HIV isolates, it induced severe cytopathic effects in CD4-positive human lymphoid cell lines. Its major proteins were shown to be gp110, p66, p55, p41, gp32, p30 and p26 by Western blot analysis. In dot-blot hybridization experiments, the virus hybridized with a HIV-2 DNA probe, but not with HIV-1 and SIVagm probes in stringent conditions. These data indicate that this Ghanaian virus is a HIV-2 group virus. However, in a Southern blot hybridization experiment, the restriction patterns of this virus, designated HIV-2 [GH-1], were quite different from those of previously reported HIV-2 viruses from West Africa isolated at the Pasteur Institute.

Penicillin-binding protein 5 in Pseudomonas aeruginosa had moderately penicillin-sensitive D-alanine carboxypeptidase activity. As in Escherichia coli, a defect in this enzyme activity was not lethal.

The purpose of this study was to determine the patterns of [14C]proline and [14C]glucosamine incorporation by tissue repair cells (TRC) as modulated by postsurgical macrophages. Rabbits underwent a midline laparotomy followed by resection (2.0 cm) and reanastomosis of their ileum. Another group of rabbits underwent peritoneal wall abrasion with sterile gauze until punctate bleeding developed. Postoperative (1-28 days) exudate cells (PEC) were recovered from the peritoneal cavity after reanastomosis, and (TRC) were obtained directly from the injured peritoneal surface after abrasion. Since the postsurgical exudate was composed mainly of macrophages, we examined the effect of postsurgical macrophage-spent media on the incorporation of [14C]proline, [14C]glucosamine, and [3H]thymidine by TRC. After 7 days of culture, Postsurgical Day 7 TRC were incubated with spent media from postsurgical PEC (greater than 90% macrophages). When TRC were cultured with macrophage-spent media, the number of TRC increased significantly compared to that of fresh medium-treated controls. The incorporation of [3H]thymidine by TRC was also enhanced by macrophage-spent media. The incorporation of [14C]proline and [14C]glucosamine by TRC was also enhanced when incubated with macrophage-spent medium. However, when data were expressed on a per cell basis, incorporation of [14C]proline and [14C]glucosamine by TRC cultured with macrophage-spent media was the same or less than that by cells incubated with fresh medium. These data suggest that the increase in incorporation of glucosamine and proline into connective tissue protein by postsurgical repair cells may be directly modulated by macrophages recruited in response to surgical injury and that this increase is due to the fibroproliferative effect of postsurgical macrophages.

In order to characterize further the metabolic activity of postsurgical macrophages, we examined their potential to produce superoxide anion (O2-) in response to phorbol myristate acetate. Rabbits underwent resection and reanastomosis of their ileum after which peritoneal exudative cells (PEC) were collected at various times after surgery. Macrophages were isolated from the PEC with a discontinuous Percoll gradient. Thereafter, O2- release by these cells in response to phorbol myristate acetate (PMA) was determined by cytochrome c reduction. Macrophages recovered on postsurgical Days 3-7 expressed three- to fourfold greater O2- release than resident (nonsurgical) macrophages (P less than 0.001). In a time-course study of O2- release, maximum release occurred at 6 hr postsurgery, dropped to half of peak levels by Day 1, increased to peak levels again on Day 4, and remained increased until Day 7. The ability of macrophages to release O2- than gradually decreased, reaching control levels by Day 13. These data suggest that resident peritoneal macrophages are rapidly primed to produce enhanced amounts of superoxide anion in response to appropriate stimuli after surgery, and that macrophages subsequently recruited into the peritoneal cavity as a result of surgical trauma may also be primed for enhanced O2- release as they differentiate into modulator macrophages for tissue repair.

Infection with a simian retrovirus (STLV-I) closely related to human T-lymphotropic virus type I (HTLV-I) was investigated in non-human primates living in their native countries in Africa and Asia. Serum antibodies cross-reacting with HTLV-I antigens were detected in 85 of 567 non-human primates of 30 species. Seropositive animals were found among African green monkeys, olive baboons, Sykes' monkeys, mandrills and patas monkeys in several countries in Africa, and cynomolgus monkeys, Celebes macaques and siamangs in Indonesia. The frequency of seropositivity was much higher in adult than in young African green monkeys, cynomolgus monkeys and Celebes macaques. STLV-Is were isolated by establishing II lines of virus-producing lymphoid cells in the presence of interleukin-2 from 5 species of seropositive non-human primates, i.e. the African green monkey, Sykes' monkey, Celebes macaque, cynomolgus monkey and siamang. All these cell lines had T-cell markers and Tac antigen, and the cell lines from the African green monkey and Sykes' monkeys were Leu2a+ while those from other species were Leu3a+. These cell lines expressed viral antigens reacting with human sera from adult T-cell leukemia (ATL) patients and monoclonal antibodies (MAbs) against p19 and p24 of HTLV-I core proteins, and produced virus particles having RNA-dependent DNA polymerase activity. Cellular DNAs from these cell lines contained provirus sequences homologous to HTLV-I, shown by Southern blot hybridization. The restriction patterns of these provirus genomes were different from those of HTLV-I and were also dissimilar in the different species.

SM-1652 (sodium 7-[D(-)-alpha-(4-hydroxy-6-methylpyridine-3-carboxamido)-alpha-(4-hydroxyphenyl)acetamido]-3-[(1-methyl-1H-tetrazol-5-yl) thiomethyl]-3-cephem-4-carboxylate) is a new semisynthetic cephalosporin derivative with a broad spectrum of antibacterial activity. Its in vitro activity against gram-positive bacteria was comparable to that of cefazolin. SM-1652 exceeded cefazolin in potency and broadness of antibacterial activity against such Enterobacteriaceae as indole-positive Proteus spp., Enterobacter cloacae, and Serratia marcescens. A remarkable feature of the spectrum of SM-1652 is its high activity against Pseudomonadaceae. Against 200 clinical isolates of Pseudomonas aeruginosa, SM-1652 was significantly more active than cefoperazone, cefotaxime, and sulbenicillin and as active as cefsulodin. The activities of SM-1652 against Pseudomonas maltophilia and Pseudomonas cepacia were superior to those of cefoperazone, cefotaxime, cefsulodin, sulbenicillin, and gentamicin. SM-1652 was relatively stable to hydrolysis with plasmid-mediated penicillinases and cephalosporinases produced by gram-negative bacteria.

Two isolates of human T-cell leukemia virus type I (HTLV-I) were obtained from lymphocyte cultures of a healthy carrier in Gabon and another in Ghana. Their proviruses were analyzed by Southern blot hybridization and compared with prototypical HTLV-I isolated in Japan and the United States. The provirus genomes of both strains were highly homologous to the prototype HTLV-I along the whole viral genome. The restriction endonuclease sites of the Ghanian isolate were almost identical with those of the prototype HTLV-I, but 10 of 26 sites of the Gabonese isolate were different from those of the prototype. Furthermore, the restriction map of the Gabonese isolate resembled those of a simian T-cell leukemia virus (STLV-I) isolated from a chimpanzee from Sierra Leone and a variant of HTLV-I from Zaire (HTLV-Ib) more closely than those of any other known HTLV-I. These results indicated the existence of some unique strains of HTLV-I transmitted among African people, and the importance of clarifying the origin and transmission of HTLV group viruses.