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Biomedical subjects

R Cone

Publications and source records attributed to R Cone.

At least 19 recordsLinked to original sources
PubMed2001

Phase I clinical trial with HIV-1 gp160 plasmid vaccine in HIV-1-infected asymptomatic subjects.

The aim of the study was to investigate the safety of an HIV-1 gp160 plasmid vaccine. Four asymptomatic HIV-1-infected subjects with CD4+ lymphocyte counts >500/microl were injected with four times 400 microg of HIV-1 modified gp160 env and rev coding DNA vaccine at 0, 4, 10 and 28 weeks. Safety parameters, including autoimmune antibodies as well as CD4+/CD8+ cell counts and HIV-1 plasma concentrations, were monitored for 52 weeks after the first vaccine application. Follow-up data for more than 3 years are now available. The DNA vaccine proved to be safe and, specifically, did not induce anti-DNA autoimmune antibodies. Vaccination had no long-term effects on the CD4+/CD8+ lymphocyte counts, plasma HIV-1 RNA concentrations or disease progression. The present data supplement published data from Philadelphia, USA, where a dose-escalating study (30-300 microg) with the same HIV-1 DNA vaccine was performed.

AIDS Vaccines↗
PubMed1999

Randomized, placebo-controlled trial of Chinese herb therapy for HIV-1-infected individuals.

CONTEXT: Alternative medicine or complementary remedies that have not been scientifically tested are nonetheless widely used to treat chronic illnesses, particularly if curative options are limited. OBJECTIVES: To assess the effectiveness of Chinese medicinal herbs in reducing symptoms and improving the quality of life of HIV-infected persons. DESIGN: Prospective, placebo-controlled double-blind study. SETTING: University-based HIV outpatient clinic. PATIENTS: 68 HIV-infected adults with CD4 cell counts <0.5 x 10(9)/L. INTERVENTION: Participants were randomized to receive four daily doses of seven pills containing a standardized preparation of 35 Chinese herbs or placebo for 6 months. MAIN OUTCOME MEASURES: Symptoms, HIV disease progression, HIV-1 RNA plasma viral loads, CD4 and CD8 cell counts, and scores on standard questionnaires for quality of life, depression, anxiety, and coping. RESULTS: Intervention and placebo groups were equivalent at baseline regarding, respectively, previous antiretroviral therapy (74% versus 79%), median CD4 cell counts (0.20 x 10(9)/L versus 0.25 x 10(9)/L), and median HIV-1 plasma viral loads (35,612 copies/ml versus 52,027 copies/ml). At enrollment, none of the study subjects was seriously ill or depressed, and average coping and quality of life scores were in the normal range. In all, 53 (78%) participants completed the study. Patients taking Chinese herbs reported significantly more gastrointestinal disturbances (79% versus 38%; p = .003) than those receiving placebo. No therapy-related toxicities were observed. At completion of the study, no significant differences between the intervention and placebo groups were found regarding plasma viral loads, CD4 cell counts, symptoms, and psychometric parameters. HIV-1 RNA level was unchanged at study end. Among participants who were not on concomitant antiretroviral therapy, median CD4 cell counts declined by 0.05 x 10(9)/L in both the intervention and placebo groups. CONCLUSIONS: This standardized formulation of Chinese herbs for HIV-infected individuals did not improve quality of life, clinical manifestations, plasma virus loads, or CD4 cell counts. The data suggest that this formulation of Chinese herbs is not effective when administered in a Western medicine setting.

Adult↗
PubMed1997

Covalent attachment of hybridizable oligonucleotides to glass supports.

A simple, rapid, and efficient method for the covalent binding of oligonucleotides to solid glass supports was developed. Glass slides were derivatized with aminophenyl or aminopropyl silanes and 5'-succinylated target oligonucleotides were attached by carbodiimide-mediated coupling. Approximately 40 to 50% of the applied target oligonucleotides covalently bound to the derivatized glass. Hybridizations with radioactively labeled oligonucleotide probes showed that up to 90% of the attached oligonucleotides were available for hybridization. This system can conveniently be applied for studies on hybridization and detection of nucleic acids.

Base Sequence↗
PubMed1997

Frequent genital herpes simplex virus 2 shedding in immunocompetent women. Effect of acyclovir treatment.

Reactivation of herpes simplex virus type 2 (HSV-2) occurs intermittently as perceived clinically and by viral culture. We performed a series of studies to evaluate the frequency and pattern of HSV-2 reactivation using both viral isolation and HSV PCR assay. Daily samples of genital secretions were obtained from 27 HSV-2 seropositive women; a subset of subjects obtained samples while receiving oral acyclovir 400 mg PO twice a day. HSV DNA was detected in genital swab specimens on 28% of 1,410 d compared with 8.1% of days by viral isolation. 11 of 20 women had HSV DNA detected on > 20% of days, 4 on > 50%, and 2 on > 75% of days; in contrast, none of the women shed on > 21% of days by viral isolation. The daily administration of oral acyclovir promptly reduced the frequency of HSV DNA detection by a median of 80%. Within 3-4 d of discontinuing daily acyclovir, HSV DNA again appeared in the genital area. HSV-2 shedding in the genital mucosa occurs much more frequently than previously appreciated. This frequent reactivation likely plays a role in the epidemic spread of genital herpes worldwide.

Acyclovir↗
PubMed1997

Holmium YAG laser-assisted osteotomies in plastic and reconstructive surgery: a preliminary report.

An Omnipulse holmium-yttrium aluminum garnet (YAG) laser was used to assist in the harvesting of outer table or split calvarial bone grafts in cadaver skulls. Two- or 4-mm depth and 0.55-mm width holes in the outer cortex of cadaveric calvarium were formed without apparent gross periosteal or bony injury. Osteotomes were then used to shave or split calvarial grafts by connecting the 2- and 4-mm depth holes, respectively. The procedure was efficient as well as precise. We believe that this method of bone graft harvesting may have the added benefit of safety by decreasing the incidence of inadvertent dural penetration. This study will lead to further analysis of the potential use for additional bony work with the Omnipulse holmium-YAG laser.

Bone Transplantation↗
PubMed1991

Subclinical manifestations of vulvar human papillomavirus infection.

We studied the presence of human papillomavirus (HPV) DNA by in situ hybridization in 74 colposcopically defined subclinical vulvar lesions obtained from 51 patients (mean age 25 years, range 18-42 years) referred for atypical Papanicolaou smears to the Colposcopy Clinic. Serial sections of formalin-fixed, paraffin-embedded biopsy tissue were stained by routine hematoxylin and eosin stain or were separately hybridized with biotin-labeled probes of HPV types 6, 11, 16, and 18 at high stringency and with mixed HPV probes at low stringency. Histologic evidence of HPV infection (koilocytosis or dysplasia) was found in eight lesions. Overall, 10 lesions were positive by in situ hybridization with HPV DNA. Although certain colposcopic features were more strongly associated with HPV DNA than others were, we were unable to demonstrate any consistent correlation between HPV DNA positivity or specific HPV DNA types and colposcopic categories. There was little correlation between HPV DNA positivity and the histopathologic incidence of HPV infection and dysplasia. Three of the 10 hybridization-positive lesions were severely dysplastic as compared with 0 of 64 nonhybridizing lesions. In spite of this association between HPV DNA and dysplasia, HPV DNA hybridization added no additional clinically relevant information to the histopathologic findings. We emphasize the significance of careful colposcopic examination of the vulva with directed biopsies.

Adult↗
PubMed1990

Cloning and expression of human and rat D1 dopamine receptors.

The importance of the dopaminergic system in brain function has been emphasized by its association with neurological and psychiatric disorders such as Parkinson's disease and schizophrenia. On the basis of their biochemical and pharmacological characteristics, dopamine receptors are classified into D1 and D2 subtypes. As the most abundant dopamine receptor in the central nervous system, D1 receptors seem to mediate some behavioural responses, modulate activity of D2 dopamine receptors, and regulate neuron growth and differentiation. The D dopamine receptor has been cloned by low-stringency screening. We report here the cloning of human and rat D1 dopamine receptors by applying an approach based on the polymerase chain reaction. The cloned human D1 dopamine receptor has been characterized on the basis of four criteria: the deduced amino-acid sequence, which reveals that it is a G protein-coupled receptor; the tissue distribution of its messenger RNA, which is compatible with that of the D1 dopamine receptor; its pharmacological profile when transfected into COS-7 cells; and its ability to stimulate the accumulation of cyclic AMP in human 293 cells.

Amino Acid Sequence↗
PubMed1989

In utero thrombosis and neonatal gangrene in an infant of a diabetic mother.

We report an infant of a diabetic mother (IDM) with in utero brachial artery thrombosis and neonatal gangrene to illustrate that there may be an increased risk for arterial as well as venous thrombosis in IDMs. The diagnosis of brachial artery thrombosis was made by using Doppler sonography flow studies and was confirmed with autopsy. The postnatal period was complicated by aortic and mesenteric artery thrombosis, with subsequent necrotizing enterocolitis, renal infarction, and death. Gangrene of a limb presenting at birth is rare, with 32 individuals reported in the literature, including this patient. Twenty-two percent (7/32) of the infants with peripartum limb gangrene were IDMs. This implies a marked increase in arterial thrombosis in IDMs over the general population. Changes in coagulation factors have been reported in newborn IDMs with poor control of maternal diabetes. Increased clotting and decreased fibrinolysis found in diabetics may lead to arterial thrombosis in IDMs in utero and postnatally. Use of anticoagulants in at-risk infants should be considered to prevent further thrombosis postnatally. Additionally, IDMs may be at increased risk for thrombotic complications from umbilical artery catheter. In utero thrombosis of the brachial artery may be one mechanism which leads to limb reduction defects in IDMs.

Aortic Diseases↗
PubMed1989

Immortalization of primary human epithelial cells by cloned cervical carcinoma DNA containing human papillomavirus type 16 E6/E7 open reading frames.

Primary human epithelial cells were transfected with a subgenomic fragment of DNA cloned from a cervical carcinoma, containing the putative transforming genes E6 and E7 from the human papillomavirus type 16 prototype. Several immortalized cell lines were generated, all retaining tumour DNA and expressing the viral genes, suggesting that either one or both of these genes is sufficient for the immortalization of primary human genital keratinocytes.

Adult↗
PubMed1988

Nosocomial transmission of rotavirus infection.

Children admitted to the infant ward between November 30, 1983, and May 5, 1984, were sampled for rotavirus antigen at admission and at 4-day intervals during subsequent hospitalization. Rotavirus was detected in 51 of 315 infants, 24 at the initial sampling and 27 after 72 hours of hospitalization (nosocomial cases). Forty-one of the cases were symptomatic and 10 were asymptomatic. Nosocomial rotavirus was detected in 5, 13 and 24% of children in the hospital for 4 to 8, 9 to 13 and greater than 13 days, respectively. Attending physicians clinically entertained the diagnosis of rotavirus infection in 58% of community-acquired cases but in only 22% of nosocomial cases. Subgrouping of 24 of the rotavirus isolates with monoclonal antibodies indicated that two-thirds of the isolates were Subgroup II, and the remainder were a mixed subgroup, with similar prevalences in the nosocomial and community-acquired cases. Only 11 of 27 instances of nosocomial rotavirus acquisition were epidemiologically associated with a rotazyme-positive roommate and in 4 of these instances different subgroups were present in the 2 roommates. These data suggest that infected roommates appear not to be a major source for direct transmission of nosocomial rotavirus infection.

Antigens, Viral↗
PubMed1988

Diagnosis of rhabdomyosarcomas with HHF35, a monoclonal antibody directed against muscle actins.

The authors have recently developed a monoclonal antibody, HHF35, that recognizes the muscle-specific isoforms of actin. To determine its potential usefulness in the differential diagnosis of "small, round, blue cell" tumors of childhood, they immunolabeled formalinor B-5-fixed tissue sections from known cases of rhabdomyosarcoma or rhabdomyoma (30), neuroblastoma (9), retinoblastoma (2), and Ewing's sarcoma (9) with HHF35 and with antibodies to creatine kinase M, myoglobin, vimentin, and neuron-specific enolase. HHF35 reacted with 29 of 30 cases of rhabdomyosarcoma, whereas antibodies to creatine kinase M and myoglobin were positive on only 12 and 7 tumors, respectively. HHF35 did not react with any case of neuroblastoma, retinoblastoma, or Ewing's sarcoma when the antibody diluent contained 50 mM EDTA. These results indicate that HHF35 is a highly sensitive and specific marker for myogenic differentiation and that it will be useful in the differential diagnosis of rhabdomyosarcomas.

Actins↗
PubMed1986

Effects of long-term dietary manganese and copper deficiency on rat skeleton.

Experiments were designed to produce biochemical changes in both serum and bone in rats by long-term dietary deficiencies of manganese (Mn) and copper (Cu). Weanling rats were fed one of three diets: 1) normal Mn and Cu (N), 2) low Mn and Cu (L) and 3) depleted Mn and normal Cu (D). After 12 mo, serum Ca and P were significantly greater in the D rats than the N rats (134, 50 mg/L and 103, 39 mg/L, respectively). Serum and femur Mn levels were lower in D rats than in normal rats. Serum and femur Cu levels were lower in L rats than N rats. Femur Ca concentrations were significantly lower in D rats than in N rats (180 and 272 mg/g, respectively). Radiographic differences could be detected in some rats fed the L and D diets. In the two deficient groups, increased serum Ca was negatively correlated with bone Ca (r = -0.69; P less than 0.01). This biochemical association may represent alterations in regulatory control of Ca at the level of the bone (decreased mineralization) combined with an increase in bone resorption. The effect of long-term dietary deficiencies in Mn and Cu should be considered in human bone metabolism.

Animal Nutritional Physiological Phenomena↗
PubMed1984

Introduction of a selectable gene into different animal tissue by a retrovirus recombinant vector.

The potential use of retrovirus vectors to transduce foreign genetic information into cells of different tissues of an animal was explored by introducing a recombinant genome carrying the Eco gpt gene into postimplantation mouse embryos. To obviate the need for preparing concentrated virus stocks, psi 2-2-5 cells producing the replication-defective murine sarcoma virus (MSV)-gpt virus were microinjected directly into embryos. The psi 2-2-5 cells were mixed with cells producing replication-competent Moloney murine leukemia virus (Mo-MuLV) to facilitate spread of the vector. A high percentage of the manipulated embryos continued to develop without disturbance and were analyzed either prior to birth or as adults for expression of both helper and Eco gpt virus. Microinjection of as few as 10 Mo-MuLV-producing cells resulted in viremia of greater than 50% of the embryos or adults, 25%-30% of which produced MSV-gpt recombinant virus in a variety of organs including thymus, spleen, lung, kidney, and brain. The fraction of vector-producing cells, however, was 3 to 5 orders of magnitude lower than that of helper-virus-producing cells. Our results demonstrate that a selectable gene can be introduced by retroviral vectors into animals and can be expressed in a wide variety of different somatic tissues.

Animals↗
PubMed1981

Specificity of the bacteriophage PBS2 induced inhibitor of uracil-DNA glycosylase.

The purified PBS2 phage-coded inhibitor of uracil-DNA glycosylase (Ura-DNA glycosylase) from Bacillus subtilis has been tested for its ability to inhibit this enzyme isolated from other prokaryotic and from eukaryotic sources. In addition, the inhibitor has been assayed for its effect on DNA glycosylases specific for other base residues in DNA. The data indicate that Ura-DNA glycosylases from a variety of sources are equally sensitive to inhibition by the inhibitor. DNA glycosylases specific for base residues in DNA other than uracil are not inhibited by the PBS2-coded inhibitor.

Bacillus subtilis↗
PubMed1981

Isolation and characterization of nuclear ribonucleoprotein complexes from Drosophila melanogaster.

The isolation of total nuclear ribonucleoprotein particles from Drosophila melanogaster embryos, using a pH 8.0, 01 M NaCl extraction of purified nuclei, is described. When the extract is fractionated on isokinetic sucrose gradients, at least six major classes of nuclear ribonucleoprotein complexes, differing in RNA and protein content as well as sedimentation behavior, are observed. The two largest complexes are preribosomal complexes. The remaining four major classes of RNPs sediment at roughly 6S, 8S, 12S and 30S. A minor class at 17S is also observed. The 30S fraction is 200-250 A in width and appears to be analogous to the mammalian monoparticle. It is composed primarily of polypeptides at about 36 000 and 37 000 daltons, along with 1-2 kilobase RNA fragments. The 6S, 8S and 12S complexes contain a few discrete small nuclear RNAs from 80-600 bases in length, along with a small number of polypeptides, about 50 000, 52 000, 56 000 and 75 000 daltons. These novel complexes are of the order of a 100 A in width (60-120 A range).

Animals↗