Bovine leukemia virus-related antigens in lymphocyte cultures infected with AIDS-associated viruses.

An earlier finding that lymphocytes from African patients with the acquired immune deficiency syndrome (AIDS) react with rabbit antiserum to purified antigens of bovine leukemia virus (BLV) prompted a study of the possible cross-reactions between a BLV-infected ovine cell line and human lymphocytes inoculated with a strain of lymphadenopathy syndrome-associated virus (LAV). A solid-phase radioimmunoassay was used to detect antigenic markers of the retroviruses. Crude extracts from short-term cultures of lymphocytes infected with LAV bound rabbit antisera to the LAV glycoprotein gp13 (molecular weight 13,000) and the BLV proteins p24 and gp51, but did not bind antibodies to the p24 of human T-cell leukemia virus type I (HTLV-I). Antiserum to LAV gp13 reacted with an ovine cell line producing BLV but also weakly with virus-free ovine cells. Lymphocyte cultures from four African patients with AIDS expressed BLV-related antigens within 6 to 10 days of culture, at the moment when particle-bound reverse transcriptase was produced. BLV-related antigens were induced in lymphocyte cultures from healthy individuals by addition of filtered supernatant or irradiated cells of the original culture. The antisera to BLV used in this study may prove useful for the detection of AIDS-associated viruses in short-term cultures of lymphocytes from AIDS patients or their contacts.

Delay of tumor growth in hamsters treated with lynestrenol and effect of Staphylococcus aureus Cowan A.

The action of lynestrenol, a synthetic progesterone-like substance, was studied in Syrian golden hamsters inoculated with cells transformed by herpes simplex virus type I. Daily ip injections of 1 mg lynesterol/kg delayed tumor growth. Lynestrenol alone only slightly increased the survival of the animals. This effect was more marked when the animals were also given injections of Staphylococcus aureus Cowan A. Survivors showed an increased resistance to challenge with infected cells. Hamsters previously given injections of killed transformed cells and then challenged with living cells showed a facilitation of tumor growth. This facilitation was inhibited by lynestrenol alone or combined with S. aureus Cowan A.

Cell-mediated immune response to simian oncornavirus antigens in pregnant women.

Tritiated thymidine incorporation into lymphocytes of 118 adult women was studied in the presence of mitomycin C-treated cells prepared from cell lines continuously producing Mason-Pfizer monkey virus (MPMV), baboon C-particle virus, or simian sarcoma virus (SSV) and in the presence of control cell lines documented for the absence of oncornaviruses. At the end of pregnancy, women who had 5-9 pregnancies showed a high frequency (53%) of specific positive responses to cells with MPMV antigens. The frequencies were 15% for pregnant women with smaller numbers of pregnancies and 3% for nonpregnant women with similar numbers of previous pregnancies as in the pregnancy group. None of these nonpregnant women had lymphocytes responding to stimulation by baboon C-virus antigens, but positive responses were obtained in 20 and 16% of the pregnant groups, respectively. No correlation was found between responses to MPMV or baboon C-virus antigens. Of 48 women (35 pregnant, 13 nonpregnant) who were tested for lymphocyte responses to SSV antigens, only 2 showed a positive response. The results indicated that two distinct antigens, related to MPMV and to baboon C-virus, may be expressed during pregnancy and may then induce a transient cell-mediated response.

Comparison of the immunogenicity of hamster cells transformed by adenovirus and Herpes simplex virus.

Hamsters vaccinated with adenovirus-transformed cells, modified by acetoacetylation or concanavalin A treatment, or with small numbers of living cells were partly or completely protected against challenge with 3 times 10-6 living cells. Treatment of vaccine cells with iodoacetate, Mitomycin C, neuraminidase plus Mitomycin C did not produce efficient vaccines. Herpes simplex virus-transformed cells treated by any of these procedures did not prevent, and frequently even enhanced, the growth of the homologous living cells; enhancement was often greater in female than in male hamsters. Protective and enhancing vaccines did not induce a different level of cell-mediated immunity, as detected by lymphocytotoxicity tests, which were positive for both homologous transformed cells and nontransformed hamster cells. In contrast, specific complement-dependent cytotoxic antibodies active only on adenovirus-transformed cells were induced by the protective acetoacetylated vaccine prepared from adenovirus-transformed cells; these antibodies were not present after nonprotective vaccinations. The appearance of herpes simplex virus tumors was delayed by treatment with the immunostimulant, Levamisole, or by preimmunization with Newcastle disease virus grown in SV40-transformed cells, but not by Newcastle disease virus grown in herpes simplex virus-transformed cells. Thus, only nonspecific treatments were able to impede herpes simplex virus tumor growth, while protection against adenovirus tumor was accompanied by specific cytotoxic antibodies.

Specific non-immunoglobulin G antibodies and cell-mediated response to herpes simplex virus antigens in women with cervical carcinoma.

Non-immunoglobulin G-neutralizing antibodies to herpes simplex virus (HSV) type 2 were assayed in sera adsorbed with Staphylococcus aureus Cowan I. They were present in 8% of women with normal cervical smear and in 20, 41, and 74% of women with atypia, dysplasia, and cervical carcinoma, respectively. Lymphocytes of the patients were tested for in vitro transformation by killed HSV type 1 and HSV type 2 (HSV-2), as well as by mitomycin C-treated hamster cells transformed by HSV or other viruses or not transformed. Specific stimulation by the HSV-transformed cells occurred in 2, 22, and 40% of women with normal cervical smear, dysplasia, and carcinoma of the cervix, respectively. This frequency rose to 82% during treatment with irradiation and decreased to 0% after surgery. When HSV-2 virions were used as antigens to stimulate the lymphocytes, similar differences were found between the various groups, but they were less clear-cut, since 16% of the control women had lymphocytes responding to HSV. Non-immunoglobulin G antibodies to HSV-2 were not present in blood at the same time as cell response to HSV-2-transformed cells. There was also a negative correlation between neutralizing activities of the sera and the indices of lymphocyte stimulation, indicating a regulation between humoral and cell-mediated responses.

HIV-1 infectivity and host range modification by cathepsin D present in human vaginal secretions.

OBJECTIVE: To investigate HIV-1 infectivity in the natural environment of vaginal secretions. DESIGN: Vaginal wash samples collected from 14 healthy women were incubated in vitro with various HIV-1 strains for 10 min at 37 degrees C and then assayed for infectivity on primary lymphocyte cultures, or on CEM cells, or on CD4- ME180 cells derived from vaginal epithelium. METHODS: HIV-1 infectivity was measured by early virus growth in the various host cells tested using a quantitative p24 assay and by the Karber procedure. RESULTS: Preincubation of HIV-1(IIIB) with vaginal wash samples or 2 microg/ml cathepsin D increased the ability of the virus to grow in lymphocyte cultures. The vaginal wash effect was abolished by 5 microg/ml pepstatin A, an inhibitor of aspartyl proteases. Presence of precursor and mature forms of cathepsin D in vaginal wash was demonstrated after passage through a pepstatin A-agarose column. Median tissue culture infective doses of HIV-1(IIIB) and HIV-1(JRFL) strains were increased 14.4-fold and 18-fold, respectively, after preincubation in vaginal wash sample, and were increased by pretreatment with 2 microg/ml cathepsin D. When CD4 receptors of CEMss cells were blocked by OKT4a monoclonal antibody, the cells lost susceptibility to HIV-1 (IIIB), but supported the growth of virus pretreated with vaginal wash sample or cathepsin D. These treated viruses were able to initiate infection of CD4-ME180 epithelial cells, which were not receptive to untreated virus. ME180 cells were shown to possess the messenger of CXC-chemokine receptor-4. CONCLUSIONS: Vaginal secretions may help HIV-1 transmission to women by increasing infectivity for CD4+ cells and allowing entrance into some CD4-epithelial cells.

Lethal oxidative damage to human immunodeficiency virus by human recombinant myeloperoxidase.

Human recombinant myeloperoxidase was evaluated in a cell-free system for its inactivation properties on the replication of human immunodeficiency virus, HTLV-IIIB. In the presence of a hydrogen peroxide generating system (glucose and glucose oxidase) and sodium thiocyanate, the recombinant enzyme inhibited virus-induced syncytium formation and viral replication without causing any cytopathic effects on SupT1 reporter cells. In addition, U937 monocytoid cells, chronically infected with HIV1, were exposed to recombinant myeloperoxidase (10 U/ml) and monitored during 48 h for the accumulation of intracellular p24 viral antigen. Under these conditions, the recombinant enzyme significantly reduced intracellular viral replication without affecting cell viability.

Viral antibodies in the CSF after acute CNS infections.

Viral antibodies were measured in the cerebrospinal fluid (CSF) and serum from 25 patients having acute viral central nervous system (CNS) infections, and from 39 control patients. The results, collected two weeks after the clinical onset, revealed the presence of antibodies in nine of 13 (69%) CSF specimens from patients suffering from encephalitis of myelitis, and in only one of nine (11%) of the CSF samples of those presenting a viral meningitis infection. This difference was statistically significant and suggests that the titration of viral antibodies in the CSF can be helpful in establishing the diagnosis of viral CNS infection. Our data also suggest that localized production of antibodies occurs during the course of acute CNS infections, and that the respiratory syncytial virus can be associated with CNS infections in man.

Absence of antibodies to HIV-2/HTLV-4 in six central African nations.

We studied 1508 individuals from Zaire, Burundi, Tanzania, Zambia, Kenya, and Cameroon for antibodies to HIV-2/HTLV-4. AIDS, ARC, other disease or tumor patients and healthy people were sampled from 1984-1986. By radioimmunoprecipitation and SDS/PAGE analysis and/or Western blot we failed to find any samples with specific antibodies to HIV-2/HTLV-4 indicative of infection. In contrast, 363 of these 1508 individuals demonstrated antibodies to HIV-1/HTLV-3B by the same serologic assays. HIV-2/HTLV-4 infection appears to be quite rare in Central Africa. AIDS and related syndromes in this study were exclusively correlated with HIV-1 infection. Studies in West Africa have shown high rates of infection with HIV-2/HTLV-4 where cases of AIDS are still relatively uncommon. These results indicate that HIV-2/HTLV-4 has a distinct geographic distribution from that of HIV-1 in Africa. Further studies are necessary to better define the pathogenicity and natural history of this distinct new virus, HIV-2/HTLV-4.

Antibody and cell-mediated immunity to herpes simplex virus in psychotic depression.

The incidence and antibody titers to herpes simplex virus (HSV) were found significantly higher in patients with psychotic depression as compared to normal controls. Furthermore, the cell-mediated immunity (CMI) to HSV in psychotic depression was similar to that observed after acute HSV infection or recurrence. The results suggest therefore an association between HSV infection and psychotic depression.

Expression of retrovirus-related antigen in pregnancy. II. Cytotoxic and blocking specificities of immunoglobulins eluted from the placenta.

Immunoglobulins, mostly of the IgG class, were detected in eluates of the placenta of 75% of 50 healthy women in their first or second pregnancy, 92% of 30 women with more than two pregnancies, and 87% of 23 pre-eclamptic patients. The immunoglobulins were assayed for complement-dependent cytotoxicity on human and monkey cell-lines, as well as on the same cells chronically infected with either Mason-Pfizer Virus (M-P V) or Baboon Endogenous Virus (BeV). The frequency of cytotoxic reactions was very low, except with immunoglobulins from the pre-eclamptic placentae, where one third of the samples lysed virus-infected cells with occasional killing of virus-free cells. All placental immunoglobulins which were not cytotoxic were then assayed for blocking activity by testing whether they could compete with the action of anticellular sera of virus-free cells, or with the toxic effect of antiviral sera on virus producing cells. 64% of the immunoglobulins from normal placentae competed with antiviral antibodies while only 17% blocked the action of anticellular sera. The frequency of blocking immunoglobulins was no greater in eluates from pre-eclamptic placentae. The data indicate that the placenta possesses retrovirus antigen sites which bind blocking antibodies in normal pregnancy and complement-dependent cytotoxic antibodies in pre-eclampsia.

Expression of retrovirus-related antigen in pregnancy. I. Antigens cross-reacting with simian retroviruses in human foetal tissues and cord blood lymphocytes.

Antisera to Mason-Pfizer or Baboon Endogenous Virus possessed complement-dependent cytotoxicity for cell lines chronically infected with these viruses, with some degree of cross-reaction. When appropriately absorbed with virus-free cells, the antisera were not cytotoxic for lymphocytes of adult males but lysed lymphocytes of neonates in about half of the 30 cord blood samples tested and were also cytotoxic for one third of 26 trophoblast suspensions prepared from healthy placentae. Detection of retrovirus-related antigens was no more frequent in trophoblast from 9 pre-eclamptic placentae. These viral antigens were also demonstrated in cultures of foetal tissues, but only after a period of culture and only when the cells were treated with 5-iododeoxyuridine. The results demonstrate that retroviruses are not only expressed in vivo in the placenta but can also be induced in cultures of foetal cells. Retrovirus-related antigens also seem to be present on foetal lymphocytes.

Detection and identification of human papilloma viral DNA, types 16, 18, and 33, by a combination of polymerase chain reaction and a colorimetric solid phase capture hybridisation assay.

A colorimetric microplate hybridization assay was developed previously to simplify detection procedures of DNA fragments resulting from polymerase chain reactions (PCR). This format has now been adapted for the simultaneous detection and identification of three human papillomavirus (HPV), types 16, 18 and 33, associated frequently with cervical cancer. This post-PCR detection system uses three type-specific capture oligonucleotides linked covalently to a single microplate well and three type-specific multibiotinylated oligonucleotidic probes for detection. It therefore offers a double specificity; the first is conferred by pairs of primers, specific of each type of virus tested, and the second, by the sets of capture and detection probes which are complementary to internal regions of the amplified DNA fragments. The detection format outperformed agarose gel electrophoresis of amplified DNA products in sensitivity and specificity. The rapidity and simplicity of this hybridisation system would justify its use in routine diagnostic examination of cervical specimens (smears and biopsies).

Transitional cell carcinoma of the bladder: evaluation of the role of human papillomaviruses.

OBJECTIVES: The study evaluated the conflicting results of the role of human papillomavirus (HPV) in the development of bladder carcinoma. METHODS: We analyzed the frequency of HPV types 6, 11, 16, 18, and 33 by using polymerase chain reaction on formalin-fixed, paraffin-embedded specimens, from 75 cases of transitional cell carcinoma (TCC) of the bladder. Fifteen samples of normal urothelium adjacent to TCC (10) or from normal bladder obtained at autopsy (5) served as negative controls. RESULTS: HPV type 16 deoxyribonucleic acid (DNA) was detected in 2 (2.7%) of the 75 cases of TCC and in none of the normal urinary bladder cases. The 2 patients with HPV type 16 were immunosuppressed after undergoing renal and cardiac transplantation. CONCLUSIONS: These results strongly suggest that HPVs play a minor role in the development of TCC of the bladder in the general population, although they can act as oncogenic agents in predisposed patients, such as those who are immunosuppressed.

[Epidemiology of carcinoma of the cervix (author's transl)]. / Epidémiologie du cancer du col utérin.

In order to explain why modes of sexual life influence the incidence of cervical carcinoma, several factors have been claimed to be involved. There is no solid basis for the hypothesis that sperm may be mutagenic. By contrast, epidemiological studies showed that partners whose life is not sedentary bring back home to their wives an increased risk of cervical carcinoma. The infectious factor does not seem to be associated with syphilis but may well be represented by herpes genitalis virus (Herpes Simplex type 2 virus). Women with cervical carcinoma show a variety of immunes reactions to this virus, and these reactions are statistically less frequent in control groups. In the laboratory, mouse and hamster cells have been transformed into cancerous cells by means of herpes simplex virus type 2.

[Treatment of lithiasis of the common bile duct by endoscopic sphincterotomy and laparoscopic cholecystectomy]. / Le traitement de la lithiase de la voie biliaire principale par sphinctérotomie endoscopique et cholécystectomie laparoscopique.

This paper evaluates the treatment of common bile duct stones by endoscopic sphincterotomy (SE) and laparoscopic cholecystectomy (CL). 733 patients presenting with symptomatic cholelithiasis were operated on between March 1990 April 1993; 131 (18%) of them had a preoperative suspicion of common bile duct stones (LVBP): jaundice for 41, biliary acute pancreatitis for 27 and altered liver function tests for 63. 131 retrograde cholangiographies (CPRE) were attempted with an associated SE (113 cases) in the presence of LVBP, biliary pancreatitis, enlargement of common bile duct and appearance of forced papilla. CL was performed 24 to 48 hours later. CPRE +/- SE had no mortality; 1 patient presented a retroduodenal perforation of CBD, requiring surgery. 58 cases (44.2%) of LVBP were diagnosed, without a statistically significant difference according to the clinical pattern. In the group with altered liver function tests only alkaline phosphatase was significantly predictive of LVBP. There was no mortality or morbidity related to CL; conversion rate was 9.8%; 4 of 12 cases of conversion were related to persistence of stones in the common bile duct, without any possibility of laparoscopic extraction. Mean hospital stay was 7.4 days. Efficacy of this sequential method of treatment of LVBP was 91.3%: this method seems satisfactory, not dangerous and minimally invasive, and should be indicated for pre-operative suspected common bile duct stones.

[Laparoscopic treatment of gastroesophageal reflux using fundoplication. Midterm results]. / Traitement laparoscopique du reflux gastro-oesophagien par fundoplicature. Résultats à moyen terme.

UNLABELLED: The aim of this study was to see whether the results of surgical treatment of gastroesophageal reflux disease (GERD) by laparoscopic fundoplication were satisfactory and stable over time. PATIENTS AND METHODS: From July 1992 to September 1996, 161 patients with medical treatment-dependent GERD were operated. 17 patients were excluded from the study (conversion or immediate laparotomy). The group of 144 patients included consisted of 92 men and 52 women with a mean age of 50 (25-77 years). The preoperative work-up included endoscopy, esophageal manometry and 24-hour pH monitoring. The surgical procedures were complete fundoplication without section of the short vessels (Nissen-Rossetti: 122 cases), with section of the shorts vessels (Nissen: 18 cases), or partial fundoplication of 270 degrees (Toupet: 4 cases). The patients were reviewed clinically 3 months after the operation, with repeat manometry and pH monitoring; yearly survey was performed. RESULTS: There was no postoperative mortality. The morbidity consisted of 2 respiratory complications (1.5%) with good recovery. With a follow-up of 3 and 21 months, the dysphagia rate was 24 vs 2% of patients (p < 0.05), the rate of gas bloat syndrome was 18% vs 21% (n.s.), and the GERD recurrence 6% vs 14% (p < 0.05). The mean time to recurrence was 8 months. 2 patients were reoperated: one for incisional hernia and one for slipped-Nissen. CONCLUSION: The results of laparoscopic treatment of GERD with fundoplication procedures at 2 years follow-up showed an 86% cure rate of GERD control and 94% satisfaction rate for the patients who were investigated.

[Cancer of the cervix, papillomavirus, contraception and tobacco]. / Cancer du col utérin, virus du papillome, contraception et tabac.

This survey started in May 1989 and deals with 2,436 patients treated by 10 gynecologists from the Brussels region. In addition to routine cytological analysis in cervical smears, an additional test for Human Papilloma Virus (HPV 16, 18 and 33) was advised for these women. Gynecologists filled in a questionnaire about these patients. In cases with benign cytology, virus prevalence was 2 times greater in woman who took contraceptive pills, over at least 6 months, than in each of the other groups using either diaphragm or male condoms or no contraception, or at menopausal age. It was strange to find that viral prevalence varied according to the pill trade mark, but not according to the pill hormonal content. No confounding factor in population recruitment could be detected. In contrast to viral infection, prevalence of cancer lesions was not increased in the oral contraception group. Squamous intraepithelial lesions of Low Grade and High Grade (SIL LG and HG) were on the contrary 2 times less frequent in women taking the pill, with or without HPV infection. During follow-up of 223 women, the same HPV genotype persisted in SIL lesions but it disappeared within 4 to 8 weeks in 68% of normal cervical smears. However, beyond this period, the proportion of women with persisting virus remained nearly constant, indicating that a subgroup may be less able to mount a defence against the infection. Risk factor of cigarette smoking for SIL LG or HG was 1.6 in women with HPV and 4.0 in those with no virus. This factor was 3.3 in women with oral contraception and 4.5 in the other group.

[Outcome of surgical treatment of cancer of the stomach. Report of 330 cases]. / Risultati della terapia chirurgica del cancro dello stomaco. A proposito di 330 casi.

The study concerned 330 cases of gastric adenocarcinoma operated from January 1969 to June 1996. Clinical, histological and therapeutic features were analyzed and compared during 3 periods (Group 1: 1969-79, Group 2: 1979-88, Group 3: 1989-96). The aim was to evaluate changes and results occurred in gastric carcinoma. The median age was 65 +/- 11 year (range 25-90), the sex ratio 2. The most common location was in the lower third of the stomach and the cancer was often far advanced (71 percent of stages III and IV). Subtotal gastrectomy was replaced by total gastrectomy and large lymph node dissection was systematically performed in group 3. Curative resection rate increased from 28 to 60 percent between group 1 and group 3. Despite the more radical surgery, post-operative mortality rates decreased respectively 22%, 9%, 8% for the groups 1, 2, 3 (p < 0.01) and global morbidity remained stable while the rate of intra-abdominal infection have changed in group 3 (4.8% vs 2.7% and 2.1% in respectively groups 1 and 2; p = ns). Two year survival rates were 20% for group 1.25% for group 2 and 35% for group 3 (p < 0.01). This results can be considered as encouraging but have to be confirmed at 5 year survival.

[Retro-duodenal papillary perforation after endoscopic sphincterotomy. Role of surgical treatment by exclusion of the duodenum. Apropos of 3 cases]. / Perforation papillaire rétroduodénale après sphinctérotomie endoscopique. La place du traitement chirurgical par exclusion du duodénum. A propos de 3 cas.

Among the complications of endoscopic sphincterotomy whose rate is about 10% of cases, the retroduodenal papillary perforation represents about 1% of cases. The diagnosis lies on radiological examination which may show during the sphincterotomy the extravasation of the contrast fluid used for the retrograde cholangiography; it can be suggested by the presence of clinical signs of retroperitoneal sepsis or peritonitis. The treatment depends on the severity or peritonitis. The treatment depends on the severity of the clinical symptomatology; it is generally a medical treatment associating nasogastric aspiration and antibiotherapy, and more rarely a surgical one. There is no consensus concerning surgical modalities. We report 3 cases of retroduodenal papillary perforation treated surgical by a duodenal exclusion aiming to transform a complex fistula in a bilio-pancreatic fistula which can be more easily managed by somatostatine-like drugs.