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Biomedical subjects

R Gallo

Publications and source records attributed to R Gallo.

At least 109 records · Page 6Linked to original sources

The challenge of valve surgery in a developing population.

Between August 1988 and October 1992, 1,052 patients underwent 1,522 valve procedures in our institution. Their mean age was 32.69 years (range 1-90). The etiology was rheumatic in 724 (68.8%), congenital in 120 (11.4%), degenerative in 99 (9.4%), infective in 58 (5.5%) and ischemic in 17 (1.6%). The mean preoperative functional class (NYHA) was 2.95 and 780 (74.1%) were in sinus rhythm. Repair was possible in 885 (58.1%) valves. The rate of repair versus replacement was 94.5% for the tricuspid, 56.2% for the mitral and 43.6% for the aortic valve. The total hospital mortality was 4.18%. For isolated mitral surgery it was 2.94%, for isolated aortic 4.12% and for isolated tricuspid 15%. Double valve surgery carried a mortality of 3% and triple valve surgery 13%. Hospital mortality for isolated mitral and isolated aortic surgery was lower for repair than for replacement (1.5% vs. 5% and 0 vs. 6.8%). The follow-up was 94.65% complete. The total incidence of embolic events was 2.93% with an actuarial freedom at 48 months of 92.71 +/- 5.35% for repair, 88.22 +/- 6.26% for replacement and 90.31 +/- 5.65% for patients with repair and replacement. Late mortality was 4.5%. The actuarial survival excluding hospital deaths was 94.89 +/- 2.10% for repair, 86.84 +/- 2.84% for replacement and 91.33 +/- 2.73% for the mixed group. The reoperation rate was higher for repair (13%) than for replacement (0.1%). This rate was highest for the rheumatic mitral patients with an age below 20 years (25.2%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Specific inhibition of human immunodeficiency virus type 1 replication by antisense oligonucleotides: an in vitro model for treatment.

We have developed a culture system, simulating in vivo conditions of human immunodeficiency virus type 1 (HIV-1) infection, to evaluate the long-term efficacy of antisense oligonucleotide treatment. Five oligonucleotide phosphorothioates (28-mers), complementary to different regions of HIV-1 RNA, blocked replication of the virus in a sequence-specific manner at 1 microM concentration. Variations in antiviral activity were seen among the different oligonucleotides, revealing an effect of target selection. Mismatched or random oligonucleotide phosphorothioates delayed, but did not completely inhibit, HIV-1 replication. In the case of inhibition by a splice-acceptor-site antisense oligodeoxynucleotide, a break-through phenomenon occurred after 25 days of treatment, suggesting the development of an "escape mutant." This result did not occur when the inhibitory oligodeoxynucleotides were complementary to the primary-sequence areas of the rev-responsive element and rev-1 genes. Sequential treatment of HIV-1-infected cells with a combination of different antisense oligonucleotides, each administered once, also prevented the development of escape mutants. Our results suggest that chemotherapy based on specifically targeted antisense-oligonucleotide phosphorothioates may be an effective method for reducing the viral burden in HIV-1-infected individuals at clinically achievable oligonucleotide concentrations.

Base Sequence↗

[HTLV-I retroviral variant in Zaire in patient with chronic neuromyelopathy. Nucleotidic sequence of the envelope gene].

The oncoretrovirus HTLV-I is the etiological agent of adult T cell leukemia (ATL) and tropical spastic paraparesis/HLTV-I associated myelopathy (TSP/HAM). In contrast to the human lentiretroviruses, HIV-I and HIV-2, the causative agents of AIDS, HTLV-I is genetically very stable. We report here the molecular characterization of the envelope gene of an HTLV-I variant present in a TSP/HAM patient from Zaïre, raising the question of its relevance to disease or the ethnic and/or geographical origin of the patient.

Base Sequence↗

Possible typhus-group infection in New York State: presentation of four suspect cases.

Epidemiologic investigations were recently conducted on four cases which were reported in New York State in 1986 and 1987, three of which were within one family. These included hospital chart reviews, case or family interviews, animal trappings, and ectoparasite surveys. Serologic tests and immunoblots were performed on blood samples obtained from these patients. All four patients had acute febrile illnesses; two required hospitalization and one died. Microimmunofluorescence test results using Rickettsia typhi and R. prowazekii antigens showed a greater than or equal to 4-fold increase in titer with paired sera from three patients. The remaining patient had a single serum titer of 4096 with both antigens. In addition, sera from all patients reacted with R. typhi in the immunoblot test and, from the three patients for whom sera were available, also with R. prowazekii. Results suggest that the four patients were exposed to the typhus-group rickettsiae or to an organism which shares a common epitope(s).

Adult↗

A study of HTLV-I and its associated risk factors in Trinidad and Tobago.

Seroprevalence of human T-lymphotropic virus type 1 (HTLV-I) among a sample of persons selected from a government register of businesses in Trinidad was 3.2% in 1,025 persons of African descent compared to 0.2% among 487 persons of Asian descent and 0% among 46 persons of European-descent. In Tobago, from a coastal village, among persons of African ancestry ascertained as part of a cardiovascular survey, the rate was 11.4%, which was significantly higher when corrected for age and race than the rate in Trinidad. The seroprevalence rate of antibodies to hepatitis A and B was also significantly elevated in Tobago compared to Trinidad. HTLV-I seroprevalence rates were higher in females than males while hepatitis A and B rates were not significantly different in the two sexes. For males, age was a significant determinant of HTLV-I seropositivity, while for females, age, markers of poor sanitation, and hepatitis B were each independently linked to HTLV-I seropositivity. The frequent occurrence of multiple infectious exposures in persons of lower socioeconomic circumstances in this tropical environment may result in immune activation that heightens susceptibility to HTLV-I infection.

Adult↗

Dependence of the linking deficiency of supercoiled minichromosomes upon nucleosome distortion.

The contribution from each nucleosome to the linking number of minichrosome DNA depends on two factors. These are the wrapping number, omega, which is the number of times the DNA wraps about the axis of the nucleosome; and the winding number, phi, which is the number of base pairs on the nucleosome divided by the helical repeat of the DNA. If the nucleosome is distorted with DNA surface contacts being preserved, phi remains unchanged. The wrapping number may still change, however, depending on the extent of the distortion. For example, if the usual cylindrical shape of the nucleosome is deformed into an ellipsoid while preserving the equatorial radius, then the wrapping number will increase. We apply these concepts to minichromosomes torsionally stressed by supercoiling with, for example, DNA gyrase. We analyze the experimental result that the maximum amount of supercoiling obtained by gyrase treatment of minichromosomes is the same as that of naked DNA. In particular, we show that this phenomenon can be explained by a relatively slight distortion of the nucleosome core while maintaining the surface contacts of the DNA on the core.

Chromosomes↗

Effect of nucleosome distortion on the linking deficiency in relaxed minichromosomes.

The wrapping of closed circular DNA on a protein surface, followed by relaxation with a topoisomerase and removal of proteins, produces a characteristic DNA linking deficiency, delta Lk. We show that the magnitude of delta Lk depends upon the surface shape, and we calculate changes in delta Lk caused by particular distortions of the protein wrapping surface. If the DNA remains attached to the surface during distortion, the DNA winding number, phi, is not altered. The change in delta Lk is then equal to the change in the surface linking number, SLk, which is a straightforward measure of the wrapping of the DNA around the surface. For left-handed wrapping, as in a nucleosome, SLk = -n, the number of times that the DNA axis winds around the axis of the protein complex. We calculate values of SLk for the helical wrapping of a constant length of DNA on protein surfaces having the shapes of cylinders and of ellipsoids and hyperboloids of revolution. If the equatorial radius of the protein is fixed, change in shape from a cylinder to a hyperboloid increases SLk, while the corresponding change to an ellipsoid reduces SLk. We apply the general results to the interpretation of experiments in which minichromosomes are relaxed with topoisomerase at various temperatures and delta Lk is determined. The result is that a distortion of the nucleosome core by at most 5% (the change in the radius at the axial extremity relative to the equator) is sufficient to explain the observed delta Lk changes.

Animals↗

Viral genomes in lymphomas of patients with Sjögren's syndrome.

The recent isolation of a new member of the herpes virus family (Human Herpes Virus-6, HHV-6) from patients with lymphoproliferative diseases prompted us to examine biopsies from six patients with primary Sjögren's Syndrome (SS) who developed non-Hodgkin's lymphoma. Five SS patients developed B-cell lymphoma and one developed a T-cell lymphoma based on immunoglobulin and T-cell antigen receptor (TCAR) gene rearrangements. In two SS patients with B-cell lymphomas, viral DNAs were detected, including: (a) Epstein-Barr Virus (EBV) DNA that exhibited an unusual pattern of restriction fragment length polymorphisms (RFLP) of the Bam M viral DNA segment; and (b) HHV-6 DNA in a second SS patient's lymphoma, with an RFLP similar to recent viral isolates from patients with other lymphoproliferative diseases. Viral DNA was not detected in the other four SS lymphoma biopsies. Also, all six biopsies were examined for presence of other viral DNAs (including CMV, HTLV, HIV and adenovirus) and were negative. Antibody titers to EBV-associated early-diffuse-antigen (EA-D), as assessed by ELISA method, and antibody titers against HHV-6, as detected by immunofluorescence and radio-immunoprecipitation assays, were markedly elevated in several SS patients with lymphoma and pseudolymphoma. These results suggest a potential role of EBV or HHV-6 in the neoplastic transformation that occurs with increased frequency in SS patients.

Antigens, Viral↗

Lymphadenopathy in HIV (HTLV-III/LAV) infected subjects: the role of virus and follicular dendritic cells.

Studies of human immunodeficiency virus (HIV) associated lymphadenopathy by histopathology and immunopathology showed conspicuous changes of follicular B-cell areas from a marked hyperplasia to complete involution. Immunohistochemistry showed a corresponding increase in follicular dendritic reticulum cells (FDRC) followed by progressive destruction of these cells during involution, concomitant with invasion of follicles by T-cells. HIV gag antigens were predominantly associated with FDRC in hyperplastic follicles and diminished during involution. Virus replication was by in situ hybridization seen predominantly in follicles, presumably reflecting productive infection of CD4+ cells and/or FDRC. It is concluded that local effects of the virus play an important role in HIV lymphadenopathy. The marked cytopathogenic effects on FDRC indicate that HIV infection with lymphadenopathy represents not only a disease of CD4+ cells but also of follicular antigen presenting cells (FDRC).

AIDS-Related Complex↗

Characteristics of the specific cell-mediated immune response in human immunodeficiency virus infection.

The human immunodeficiency virus (HIV)-specific lymphocyte proliferation response was determined for 40 persons at different stages of HIV infection. The specific response to purified HIV virion antigens from strain HTLV-IIIB was poor, occurred in only 9 of the 40 subjects, was not improved with the addition of interleukin-2, and was more frequent in symptom-free individuals (46%) than in patients with lymphadenopathy syndrome (10%). Reactivity to subcomponent p24 was better than that to whole HIV; reactivity was present in five of six infected persons and increased with the addition of exogenous interleukin-2. Reactivities to subcomponents (g)p41 and gp120 were also measured. This is the first evidence of a specific cell-mediated immune response to HIV antigen in HIV-infected persons. Monkeys immunized with purified HIV or with purified p24 displayed cellular immunoreactivity both to whole HIV and to subcomponents. In contrast to the poor reactivity to HIV antigen, the lymphocytes of the patients had good specific cell proliferation responses to cytomegalovirus and herpes simplex virus challenge and a normal response to the addition of phytohemagglutinin. The results suggest a functional defect in peripheral lymphocytes of some HIV-infected individuals on the basis of their response to whole HIV antigen and a better response to gag protein.

AIDS-Related Complex↗

A clinical-immunological evaluation of AIDS cases and related syndromes.

The clinical features of our cases demonstrated some of the already known characteristics of the variable spectrum of HIV infection. DA are the most important risk category in Italy. 10% of the ARC cases evolved into AIDS during a 12-month follow-up, on average. The most frequent OI in our AIDS cases were PCP, C. albicans esophagitis and chronic mucocutaneous ulcers. An high percentage of neurologic involvement from HIV was observed, and malignancies were encountered in AIDS (3 KS and 1 undifferentiated B lymphoma) as well as in ARC (1 Hodgkin's lymphoma). Statistically, significant worsening of the immunologic situation is evident as the disease progresses from LAS to AIDS. Activated B lymphocytes represent most of the cells of the germinal center during the hyperplastic stage of lymphadenopathy. Reversal of the T4/T8 ratio appears early during the initial stage of lymphadenopathy and is due to a decrease of CD4 and a relative increase of CD8. Also, destruction of the follicular dendritic cells is an early feature which becomes more evident as the disease advances and the lymph node evolves toward progressive involution. Activated B-lymphocyte augmentation with polyclonal Ig secretion appears to be related to T-independent B stimulation by coinfection such as CMV, EBV and HBV. The increase of cytotoxic/suppressor lymphocytes seems to be partly related to the excessive activation of B lymphocytes and partially directed to the cells infected by HIV or coated with its proteins (6,7,8,9). The destruction of follicular dendritic cells has been interpreted not only as a killer effect of the virus but also as a result of the intervention of CTL sensitized to the cells containing the virus (10,11). Their destruction may contribute to the impaired recognition of soluble antigen which is one of the main features of the immune deficiency of HIV infection (9,13,16).

AIDS-Related Complex↗

Efficacy of diltiazem in variant angina. Results of a double-blind crossover study in CCU by Holter monitoring. The possible occurrence of a withdrawal syndrome.

The short and long term efficacy of diltiazem, a calcium-entry blocker, has been evaluated in a group of ten patients with Prinzmetal's variant angina admitted to a CCU. In the short term part of the study, after a run-in period, diltiazem 60 mg tid and placebo were administered alternatively during 4 randomized 72 hour periods. Response was assessed using continuous Holter monitoring, measuring the frequency of transient ischemic attacks. During the run-in period the number of episodes/day/patient was 16.1. No episodes of transient ST segment elevation were recorded during both periods of diltiazem treatment in 3 patients and during one of the two periods in 4. For the group as a whole the number of episodes during the first placebo period was not statistically different from that during the run-in period (208 versus 161). No statistically significant difference was also found in 8 patients comparing the number of episodes during the second placebo period and the run-in period (166 versus 101). During each period of diltiazem treatment an highly significant reduction in the number of episodes was observed (43 and 5, p = .006 and p = .02). Two patients did not complete the study protocol. Both patients had a worsening of angina during the first placebo period following diltiazem treatment. One of them developed an acute myocardial infarction. The possible occurrence of a rebound phenomenon after withdrawal of diltiazem seems to be indicated, in 6 patients, by a significant increase in the number of ischemic episodes recorded during the placebo period following active treatment in respect to the number during the first placebo period (159 versus 73, p = .04).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Association of human T lymphotropic virus type III antibodies with sexual and other behaviors in a cohort of homosexual men from Boston with and without generalized lymphadenopathy.

Forty asymptomatic homosexually active men seen at a Boston community health center and 39 men with generalized lymphadenopathy were interviewed and filled out detailed epidemiologic questionnaires. Twenty percent of the asymptomatic men and 92 percent of those with lymphadenopathy had antibodies to human T lymphotropic virus type III (HTLV-III). None of the men have subsequently had the acquired immune deficiency syndrome (AIDS). Seropositivity was associated with receptive anal intercourse and oral exposure to ejaculate, a history of hepatitis B, anal gonorrhea, or intestinal parasites, but no other sexually transmitted diseases, and did not correlate with the use of recreational drugs. More of the seropositive men had multiple partners from New York City. An association with seropositivity was less evident in relation to the numbers of partners from San Francisco or Los Angeles, since the whole cohort generally had fewer contacts with partners from these cities. The data suggest that educational programs among homosexual men attempting to decrease AIDS risk should focus on decreasing the number of partners, receptive anal intercourse, oral exposure to ejaculate and other intimate rectal contact, and sexual contact with men from areas of increased HTLV-III seroprevalence.

Adult↗

Rearrangement and enhanced expression of c-myc oncogene in fresh tumor cells obtained from a patient with acute lymphoblastic leukemia.

Both enhanced and altered expressions of cellular oncogenes have recently been implicated in specific forms of human malignancy (for review: [2, 8]). The fact that certain human tumors have characteristic chromosomal translocations has led to the hypothesis that specific cellular oncogenes may be 'activated' in these genetic recombinations. In a number of human undifferentiated B-cell lymphoma (UBL) cell lines carrying the t(8:14) translocation it has been shown that the human c-myc gene is located on the region of chromosome 8 (8q24), which is translocated to the immunoglobulin heavy-chain (IHC) locus on chromosome 14 [7, 24]. We report here the molecular cloning of the recombination site between c-myc and IHC in fresh uncultured cells obtained from a patient with rapidly progressive and fatal acute lymphoblastic leukemia. The translocation was associated with an enhanced c-myc expression in the tumor cells of this patient.

Base Sequence↗

Modes of transmission and evidence for viral latency from studies of human T-cell lymphotrophic virus type I in Japanese migrant populations in Hawaii.

Human T-cell lymphotrophic virus type I (HTLV-I) seroprevalence was 20% among Hawaiian Japanese migrants (issei) and their offspring (nisei) from Okinawa compared to 35% in similarly aged men who were lifetime residents of Okinawa. A control group of migrants from a nonendemic area of Japan, Niigata, had low rates of HTLV-I antibodies, suggesting that Hawaii per se is not an endemic area for HTLV-I. Factors that were significantly associated with seropositivity in the Okinawa migrant groups were years of residence in Japan before migration (issei) and age for offspring of Okinawa migrants (nisei). Antibody titer was highest in Okinawa lifetime residents, intermediate in migrants (issei), and significantly lower in offspring of Okinawa migrants (nisei), with increasing titer observed with advancing age in the offspring of the migrant group. Based on these data, infection within the household occurring early in life appears to be a major route of HTLV-I transmission and may help to explain the curious geographic clustering of this virus in certain locales. As yet to be defined cofactors, including sexual transmission and/or environmental exposures (e.g., particularly before age 20), also may contribute to HTLV-I seropositivity. The pattern of rising seroprevalence and titer with age in the offspring of migrants who resided all of their lives in Hawaii raises the possibility that HTLV-I infection acquired early in life may become dormant and reexpressed with reactivation of latently infected T cells. The importance of this model in the process of viral leukemogenesis is supported by recent reports of adult T-cell leukemia in offspring (nisei) of Okinawa migrants.

Age Factors↗