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Biomedical subjects

J P Dudley

Publications and source records attributed to J P Dudley.

At least 19 recordsLinked to original sources
PubMed1996

Exogenous mouse mammary tumor virus (MMTV) infection induces endogenous MMTV sag expression.

The mouse mammary tumor virus (MMTV) superantigen (Sag) protein is involved in the transmission of milk-borne MMTV from virus-infected milk in the gut to the target mammary gland tissue. Using an RT-PCR assay for in vivo MMTV infection, BALB/c or C3H mice nursed on C3H MMTV-infected mothers showed sag mRNA expression in intestine, spleen, and thymus as early as 1 day after infection, whereas uninfected BALB/c control animals had approximately 10- to 30-fold lower sag expression. Further fractionation experiments with small intestine indicated that sag expression occurred in gut-associated lymphoid cells. Restriction enzyme digestion of PCR products indicated that the sag mRNA detected was derived from the endogenous MMTVs, and sequencing analysis confirmed that the PCR products were derived from endogenous MTv-6. Expression of C3H-specific mRNA was detectable in BALB/cfC3H or C3H tissues by RNase protection or by RT-PCR. Endogenous MMTV sag expression was low in spleen and undetectable in thymocytes of C3H MMTV-infected C57BL/6 mice, a strain resistant to C3H MMTV tumorigenesis and defective for MHC class II I-E molecules. The RT-PCR assay for sag mRNA appears to measure the Sag-induced stimulation previously predicted for milk-borne MMTV infection. Together these data suggest that exogenous MMTV sag expression is minimal, but sufficient to rapidly stimulate transcription of endogenous MMTV sag mRNA in B- and T-cells in an MHC class II I-E-dependent manner. The endogenous sag expression on maternal lymphocytes may increase the number of proliferating T-cells available for milk-borne MMTV infection.

Animals↗
PubMed1996

Major histocompatibility complex class II I-E-independent transmission of C3H mouse mammary tumor virus.

C57BL/6 mice are resistant to C3H mouse mammary tumor virus (MMTV)-induced mammary tumorigenesis and lack major histocompatibility complex class II I-E molecules that are essential for presentation of C3H superantigen to T cells. T cells are needed for transmission of milk-borne MMTV from the gut to the mammary gland. In this report, we show that infectious C3H MMTV is produced by C57BL/6 mice that nurse on C3H mothers but that virus production in the mammary gland is delayed compared with that in I-E+ mouse strains.

Animals↗
PubMed1995

Mouse mammary tumor viruses with functional superantigen genes are selected during in vivo infection.

Mouse mammary tumor virus (MMTV) encodes a superantigen that is important for viral infectivity in vivo. To determine whether superantigen function was required for infection by milk-borne MMTV, we created HYB PRO/Cla transgenic mice. These mice produced a full-length, packaged viral RNA with a frameshift mutation that caused premature termination of the superantigen protein. Young HYB PRO/Cla mice showed no deletion of their cognate V beta 14+ T cells, although they shed virus in their milk. The nontransgenic offspring of the HYB PRO/Cla mice were infected with this virus, since transgene-specific viral transcripts were detected in their mammary glands. Surprisingly, these offspring demonstrated the progressive deletion of V beta 14+ T cells characteristic of exogenous MMTV (C3H) infection. Sequence analysis demonstrated that these newly acquired viruses had reconstituted superantigen open reading frames resulting from recombination between the HYB PRO/Cla and endogenous Mtv-1 proviral RNAs. Thus, there is selection during the infection process for MMTVs with functional superantigen genes.

Amino Acid Sequence↗
PubMed1994

A longitudinal study of cytomegalovirus infection in human immunodeficiency virus type 1-seropositive homosexual men: molecular epidemiology and association with disease progression.

Cytomegalovirus (CMV) isolates from 234 asymptomatic human immunodeficiency type 1 (HIV-1)-positive men were analyzed for molecular relatedness using junctional hybridization. Of isolates shed simultaneously at two or more body sites, 36% from 22 men were different. Of 180 isolates collected from 67 men over 15 months, different strains were isolated serially from 27 men (40%), most from semen. After follow-up of 58 months (mean), the relative hazard of HIV infection progressing to AIDS was 1.8 (95% confidence interval [CI], 0.9-3.7) for men shedding the same strain of CMV and 3.0 (95% CI, 1.4-6.1) for men shedding different strains compared with men not shedding CMV in semen. The prevalence of CMV-specific IgM was higher in men shedding different versus same CMV strains (32% vs. 18%; P = .244). Thus, presence of multiple CMV strains in HIV-1-positive homosexual men is associated with progression to AIDS, possibly via activation of HIV-1-infected CD4 cells.

Cohort Studies↗
PubMed1993

The relationship between T-cell levels and CMV infection in asymptomatic HIV-1 antibody-positive homosexual men.

To investigate the relationship between cytomegalovirus (CMV) infection and progression of HIV-1 disease, a group of 234 asymptomatic, HIV-1 antibody-positive homosexual men were examined for CMV isolation and levels of CMV IgM antibodies, CMV IgG antibodies, and CD4+ and CD8+ T-lymphocytes. CMV IgG antibodies were present in 100% and CMV IgM antibodies in 22% of the men. CMV was isolated from the semen of 45% of the men. No relationship was observed between CMV IgM antibodies and CMV in semen or CD4+ levels. CD4+ cell levels were significantly lower in those from whose semen CMV was isolated. In addition, an inverse relationship was observed between the concentration of CMV in semen and CD4+ levels. We postulate that the seminal tract may be a reservoir for systemic CMV infection in HIV-infected homosexual men. Reinfection from this or other sources may result in recurrent stimulation of HIV-1 replication and lead to a further decline in CD4+ cells. Clarification of whether persistent CMV infection is secondary to HIV-1-induced immunodeficiency or, conversely, promotes a more rapid decline in immunocompetency will require follow-up studies.

AIDS-Related Opportunistic Infections↗
PubMed1992

Transgenic mouse mammary tumor virus superantigen expression prevents viral infection.

Endogenous mouse mammary tumor virus (MMTV) proviruses have recently been shown to cosegregate genetically with the minor lymphocyte-stimulating loci, also termed self-superantigens. The antigenic activity has been localized to the open reading frame (ORF) protein encoded in the long terminal repeat of MMTV. We show here that unlike their nontransgenic littermates, transgenic mice expressing high levels of an ORF protein derived from the C3H exogenous MMTV specifically delete their V beta 14+ T cells and do not become infected with this virus when it is present in their mother's milk. Thus, it appears that MMTV utilizes cells of the immune system in its infection pathway, and mice that retain endogenous MMTVs should be immune to infection by exogenous virus. These results offer possible new approaches to anti-viral therapy or immunization.

Animals↗
PubMed1992

Sequence analysis of the int-2/fgf-3 gene in aggressive human breast carcinomas.

A number of primary human breast carcinomas exhibit amplification of the chromosome 11 region containing the int-2/fgf-3 proto-oncogene, and progression of breast cancer has been correlated with int-2 amplification or with certain restriction fragment length polymorphisms (RFLPs) of the int-2 gene. Using the polymerase chain reaction (PCR), we obtained the int-2 coding sequences from six primary tumors, four of which exhibited amplification of the int-2 gene and one of which exhibited amplification of the neu gene. The majority of these tumors (five of six) were aggressive, as judged by their early recurrence, metastasis, or both. Nucleotide sequencing of PCR products revealed that previously described BamHI and PstI RFLPs of the int-2 gene, as well as a new polymorphism at position 9154, were located within the intron between the second and third exons. A seventh tumor was used to localize one of the PstI RFLPs 5 bp from the splice-acceptor site of the third exon. However, none of the tumor DNAs analyzed showed differences in the int-2 protein coding regions when compared with normal placenta DNA. These results imply that aggressive human breast cancers encode an unaltered form of the int-2 protein.

Base Sequence↗
PubMed1992

Otolaryngologic manifestations of the mucopolysaccharidoses.

A retrospective review of 45 children with mucopolysaccharidoses was performed to determine the frequency of complications related to the head and neck. In this series, every patient had at least one complication involving the head and neck region, and in over half, operative intervention by the otolaryngologist was required. Upper airway obstruction occurred in 17 (38%) and necessitated a tracheostomy in 7 (16%). Cervical spine instability occurred in 8 (18%), making airway management difficult. Recurrent respiratory infections occurred in 17 (38%), and chronic recurrent middle ear effusions were noted in 33 (73%). This review demonstrates that children afflicted with the mucopolysaccharidoses frequently have otolaryngologic-related complications that are common throughout their life span and often the primary management issue in their continuing care. The otolaryngologic management of these patients is outlined based on the results of this study and review of the relevant literature.

Adolescent↗
PubMed1991

Psychosocial predictors of gay men's AIDS risk-reduction behavior.

Used psychosocial variables derived from the health belief model (Rosenstock, 1974), Bandura's (1986) self-efficacy framework, and protection motivation theory (Rogers, 1984) to predict self-reported AIDS risk-reduction behaviors in a sample of 389 homosexual men who participated in the Multicenter AIDS Cohort Study in Los Angeles and who knew their HIV antibody status. Hierarchical multiple regression analyses showed that self-efficacy, perceived risk, response efficacy, and prior sexual behavior accounted for approximately 70% of the variance in the total number of sexual partners and the number of anonymous partners over a 6-month interval, controlling for demographic variables, HIV antibody status, and presence of a primary partner. A logistic regression analysis showed that barriers to change predicted increased unprotected anal receptive intercourse over a 6-month interval, controlling for prior behavior. The relation of health beliefs to risk-reduction behavior was substantially different for HIV-seropositive men without primary partners than for other groups of gay men. Implications for interventions are discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1991

The endogenous Mtv-8 provirus resides within the V kappa locus.

The endogenous Mtv-8 provirus previously has been mapped within approximately 0.52 centimorgan from several V kappa markers on mouse chromosome 6. Using Southern blotting and DNA from a recombinant backcross mouse from the C57BL/6 (Mtv-8 positive) and C58 (Mtv-8 negative) strains, Mtv-8 was localized to the same side of the crossover point as immunoglobulin kappa (Ig kappa)-V24 but on the opposite side of the crossover from Ig kappa-V10 and Ig kappa-V21. Molecular cloning and characterization of cellular DNA adjacent to Mtv-8 revealed a functional V kappa 9 gene approximately 4.6 kb downstream and in the same transcriptional orientation as the provirus. These data suggest that Mtv-8 is within the centromere-proximal portion of the V kappa locus.

Animals↗
PubMed1990

Analysis of the int-1, int-2, c-myc, and neu oncogenes in human breast carcinomas.

We have examined the DNA obtained from 100 primary breast carcinomas for oncogene markers which might have predictive value for poor prognosis. Ninety-six of the tumors were analyzed for the presence of restriction fragment length polymorphisms (RFLPs) previously identified in the int-2 gene. An 8.4-kilobase BamHI fragment and a 3.9-kilobase PstI fragment specific for the int-2 gene, in the absence of other restriction fragments, was found in 17 of 50 (34%) lymph node-negative patients and in 27 of 44 (61%) lymph node-positive patients. This combination of int-2 RFLPs (8.4/3.9) was found in a significantly different proportion (P = 0.02) of patients with greater than 3 positive lymph nodes compared to patients with fewer positive lymph nodes, suggesting that these RFLPs may be valuable for distinguishing among node-negative patients for chemotherapy. In contrast, the observed low frequency of int-1, int-2, neu, and c-myc amplification limited their usefulness as clinical predictors of disease recurrence.

Breast Neoplasms↗
PubMed1990

Enterococcus faecalis and otitis media with effusion. How to treat.

Although microorganisms are cultured in only one out of 3 middle ear effusions, viable and non-viable bacteria are presumed to be responsible in part for otitis media with effusion (OME). Because of this association, antibiotics in sublethal, bacteriostatic, or bacteriocidal concentrations are frequently used as non-surgical therapy for OME. Antibiotic treatment is predicated on the assumption that microorganisms responsible for OME are the same ones which produce acute otitis media. This may not always be the case. Enterococcus faecalis (formerly known as beta-hemolytic group D Streptococcus) was isolated in pure culture from 3 middle ears of two patients with OME. The significance of the isolation of this bacteria, an enteric organism which is infrequently found in upper respiratory tracts, is its lack of susceptibility to the usually prescribed oral antibiotics. In each of the children, failure to respond to antibiotics led to tympanocentesis and culture followed by middle ear drainage with insertion of middle ear ventilating tubes. Unless intravenous antibiotics are used, surgical drainage should be the procedure of choice when E. faecalis is found in the middle ear.

Child, Preschool↗
PubMed1990

Negative regulation in correct tissue-specific expression of mouse mammary tumor virus in transgenic mice.

Mouse mammary tumor virus (MMTV) is an endogenous murine retrovirus that is expressed in the epithelial cells of the mammary and salivary glands, lungs, kidneys, and seminal vesicles and in the lymphoid cells of the spleen and thymus. Several studies have shown that the long terminal repeat (LTR) of this virus can direct the expression of reporter genes to the same tissues in transgenic mice. To determine whether multiple regulatory elements within the LTR are involved in this tissue-specific expression, we have established lines of transgenic mice containing transgenes that have deletions in the MMTV LTR. Deletions of all LTR sequences upstream of -364 or of LTR sequences from -165 to -665 both result in the expression of linked reporter genes such as the simian virus 40 early region or the bacterial enzyme chloramphenicol acetyltransferase in novel sites, such as the heart, brain, and skeletal muscle; expression of endogenous MMTV and transgenes containing the full-length LTR is not detected in these organs. Negative regulation appears to involve more than one region, since deletion of sequences between either -201 and -471 or -201 and -344, as well as sequences upstream of -364, results in inappropriate expression in heart, brain, and skeletal muscle. Therefore, a negative regulatory element(s) in the MMTV LTR can suppress transcription from the viral promoter in several different organs. This represents the first example of generalized negative regulatory elements that act in many different tissues in transgenic mice to prevent inappropriate expression of a gene.

Animals↗
PubMed1990

Malignant hyperthermia in the otolaryngologic patient: prospective anesthetic and surgical management of eight children.

Malignant hyperthermia (MH) is a rare genetic myopathy whose hallmark is rise in body temperature. This hypermetabolic state is triggered by inhalational anesthetics and/or depolarizing muscle relaxants such as succinylcholine. Even the use of dantrolene may not be protective against the hypermetabolic crisis. Eight patients at risk for MH undergoing tonsillectomy, adenoidectomy, and/or myringotomy with ventilation tube insertion were anesthetized with nitrous oxide, barbiturates, opiates, tranquilizers, and nondepolarizing muscle relaxants without dantrolene and without complication. Cardiac monitoring and rectal temperatures were followed. In order to provide additional evidence, all eight patients had vastus lateralis muscle biopsies with subsequent caffeine-halothane contracture studies performed. The contracture study showed positive results in seven of eight patients studied, indicating MH-susceptible muscle. No anesthetic or operative complications were encountered. This study demonstrates that patients at risk of developing MH crisis can have otolaryngologic procedures performed relatively safely while undergoing appropriately selected anesthesia.

Adenoidectomy↗
PubMed1989

Lymphomas with acquired mouse mammary tumor virus proviruses resemble distinct prethymic and intrathymic phenotypes defined in vivo.

A number of murine T cell lymphomas expressing the T cell Ag Thy-1 contain acquired mouse mammary tumor (MMTV) proviruses. These lymphomas all express detectable levels of MMTV RNA, yet the majority of the tumors fail to produce MMTV particles. To determine if the ability of lymphomas to produce MMTV is a reflection of the differentiation state of the tumor, we examined eight lymphomas for expression of surface B and T cell Ag as well as for rearrangements and expression of TCR genes. All tumors could be grouped into three categories observed in vivo, including early lymphoid, nonmature intrathymic T cells, and immature intrathymic T cells. Cell lines corresponding to all three phenotypes produced MMTV particles, suggesting that production of virus is not linked to the differentiation state of lymphoid cells. These studies highlight the potential advantage of studying T cell lymphomas vs mixed primary populations or T cell hybridomas for evaluation of both phenotypic and molecular markers in clonal T cells.

Animals↗
PubMed1989

Emergency ear, nose, and throat procedures.

This comprehensive article reviews some of the most common injuries to the ear, nose, and throat, and in addition reviews the relative anatomy of this area of the body. Particular attention is paid to the treatment of the patient with epistaxis, a common presentation to the Emergency Department.

Abscess↗
PubMed1989

Seroconversion, sexual activity, and condom use among 2915 HIV seronegative men followed for up to 2 years.

A cohort of 2915 HIV-1-seronegative men from the four centers of the Multicenter AIDS Cohort Study (MACS) was followed at 6 month intervals for 24 months to identify men who developed antibodies to HIV-1. Two hundred thirty-two men (8%) seroconverted. The highest attack rate was among men who reported practicing both receptive and insertive anal-genital intercourse. The attack rate among men who reported practicing receptive but not insertive intercourse was 3.6 times higher than among men practicing insertive intercourse although those practicing insertive only reported 38% more different partners. Only two men seroconverted who reported not practicing analgenital intercourse in the 12 month prior to the first antibody-positive visit. Because men were followed every 6 months, one of these men could have been infected within 6 months of the actual development of HIV-1 antibodies. The seroconversion rate was significantly lower among men who reported using condoms with all their partners. The results of this study (a) reaffirm that receptive anal-genital intercourse is the major route of infection among homosexual men of HIV-1, (b) suggest that there is a low risk of HIV-1 infection to the insertive partner in anal-genital intercourse, (c) suggest that infection may rarely occur through sexual activities other than anal-genital intercourse, (d) provide evidence that condoms as currently used by men in the MACS provide significant but not complete protection against HIV-1 infection, and (e) suggest that the number of men in the homosexual community engaging in high-risk behavior is declining.

Bisexuality↗