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Biomedical subjects

N Kennedy

Publications and source records attributed to N Kennedy.

At least 91 records · Page 5Linked to original sources
PubMed1982

Delimitation of a DNA sequence which confers inducibility by glucocorticoid hormones.

A chimeric long terminal repeat-thymidine kinase (LTR-tk) gene has been used to define the sequence requirements for glucocorticoid induction of gene expression. The original LTR-tk gene contains an entire mouse mammary tumor virus (MMTV) LTR preceding the tk gene. This gene can be expressed in a hormone-responsive fashion upon transfection into L tk--cells to produce a chimeric LTR-tk mRNA. Stepwise deletion of nucleotide sequences 5' of the viral RNA initiation site revealed that 202 nucleotides upstream of the viral cap site are sufficient for the hormonal regulation. Deletion of 5' sequences up to 59 nucleotides upstream of the viral cap site abolished RNA initiation in the LTR and hormonal induction.

Animals↗
PubMed1981

The endogenous proviral mouse mammary tumor virus genes of the GR mouse are not identical and only one corresponds to the exogenous virus.

The endogenous proviral copies of mouse mammary tumor virus (MMTV) were selected from a gene library of GR mouse DNA. We obtained five different lambda. MMTV recombinant clones. Four of them correspond to the 3' Eco RI fragments of the endogenous proviruses an one comprises an intact MMTV provirus with 2 to 3 kb of flanking mouse genomic DNA. Heteroduplex formation followed by S1 digestion under stringent conditions shows that there is nucleotide sequence heterology among the cloned endogenous proviral copies. Only one endogenous proviral copy, associated with the mtv-2 locus, was found to be totally homologous to the exogenous proviral DNA.

Animals↗
PubMed1981

Structure, stability, methylation, expression and glucocorticoid induction of endogenous and transfected proviral genes of mouse mammary tumor virus in mouse fibroblasts.

A sequence of mouse genomic DNA containing an endogenous mouse mammary tumor virus (MMTV) provirus, which was isolated by molecular cloning in lambda vector phage, has been reintroduced into cultured mouse L cells, using the thymidine-kinase cotransfection technique. Individual cell clones that acquired the transfected MMTV proviral DNA have been isolated. The transfected DNA remains stable in these cells and does not become methylated. It is transcribed into MMTV RNA, And the transcription is stimulated by glucocorticoid hormones.

Animals↗
PubMed1981

Hormone-responsive expression of an endogenous proviral gene of mouse mammary tumor virus after molecular cloning and gene transfer into cultured cells.

A recombinant lambda phage containing mouse mammary tumor virus (MMTV) proviral DNA was isolated from a gene library constructed from GR mouse liver DNA. Restriction enzyme analyses reveal that the cloned molecule contains a copy of one of the GR endogenous MMTV proviruses flanked on both sides by 2--3 kb of mouse genomic DNA. In this report we have examined the expression of the cloned MMTV provirus after cotransfection with the herpes thymidine kinase (TK; ATP:thymidine 5'-phosphotransferase,, EC 2.7.1.21) gene and integration into mouse LTK- cells. Nine individual TK+ transformants were selected, and all were found to contain MMTV-transfected DNA. One of the TK+ transformants was chosen for further study. Total poly(A)-containing RNA was isolated from the cells, and liquid hybridization analyses with MMTV cDNA showed that it contained 0.02% MMTV-specific RNA. The sizes of the MMTV-specific species were determined and found to correspond to the 35S and 24S mRNAs synthesized in MMTV-infected cells. Glucocorticoid hormones have been shown to increase the concentration of MMTV RNA in virus-infected cultured cells. Therefore, we tested the effect of dexamethasone on the concentration of MMTV-specific RNA in cells transfected with the MMTV proviral DNA. The amount of MMTV-specific poly(A)-containing RNA found in the cells grown in the presence of hormone was 0.17%. Therefore, dexamethasone causes an 8-fold increase in the amount of MMTV-specific RNA in mouse cells containing several copies of a cloned and transfected MMTV proviral gene.

Animals↗
PubMed1978

The differential enzyme susceptibility of bovine immunoglobulin G1 and immunoglobulin G2 to pepsin and papain.

Purified bovine immunoglobulins IgG1 and IgG2 were subjected to enzymatic degradation with pepsin and papain. Results were monitored using density gradient ultracentrifugation, acrylamide electrophosesis and immunodiffusion employing subclass- and light chain-specific antisera. The results indicated a marked enzymatic susceptibility of IgG1 to digestion with pepsin. This differential susceptibility can also be demonstrated in unfractionated bovine gamma-globulin. No striking differences between the two subclasses were observed during treatment with papain in the presence of cysteine and after 24 h, most IgG1 and IgG2 was degraded to Fc and Fab fragments. The pepsin Fc fragment generated from IgG2 was larger than that generated from IgG1 although the F(ab')2 fragments were simialr in size. These results are consistent with the hypothesis that the Fc region of IgG1 contains multiple cleavage sites for pepsin whereas IgG2 has few. Rabbits immunized with the first elution peak from a 30 h pepsin digest of bovine gamma-globulin fractionated on Sephadex G-150, responded primarily to common gamma-chain and IgG2-specific determinants. Thus, the differential susceptibility of bovine subclasses to pepsin provides a method for stimulating IgG2-specific antibodies in rabbits.

Animals↗
PubMed1977

Conjugation proteins encoded by the F sex factor.

Chimaeric plasmids carrying EcoRI fragments of the F sex factor have been used to identify proteins involved in conjugation and to assign them to tra cistrons. Most of these proteins are incorporated into the cell envelope and are individually regulated at the post-transcriptional level.

Bacterial Proteins↗
PubMed1977

Cell--cell interactions in conjugating Escherichia coli: role of traT protein in surface exclusion.

Escherichia coli cells carrying the F sex factor are poor recipients in conjugation. This phenomenon is called surface exclusion. Two F cistrons, traS and traT, are independently responsible for part of the whole mechanism. The traS gene product reduces DNA transfer within stable mating aggregates. The traT gene product, pTraT, results in a greatly reduced ability to form stable mating aggregates, and thus also leads to reduced DNA transfer within the cell population. pTraT is a 25,000-dalton protein incorporated into the cell envelope outer membrane. It is found in 29,000-84,000 copies per cell, depending on the plasmid expressing it. There is a parallel variation in recipient ability. Models for surface exclusion are discussed.

Bacterial Proteins↗
PubMedDate not supplied

Restriction fragment length polymorphism analysis of Mycobacterium tuberculosis isolated from patients with pulmonary tuberculosis in northern Tanzania.

Isolates of Mycobacterium tuberculosis from 88 patients with pulmonary tuberculosis in northern Tanzania were subjected to IS6110 restriction fragment length polymorphism (RFLP) analysis. Of 88 isolates, 73 fell into 11 groups of which 9 contained 2-5 isolates. Of 2 large homology groups one, group H (20 isolates), was isolated only from patients resident in the Kilimanjaro region, whereas 79% of isolates from other groups came from this region. A significant association (P = 0.023) was found between another group, M (24 isolates) and isolation from patients of the Masai tribe. The data from this pilot study support the idea that IS6110 RFLP analysis provides information which may be of value in the control of tuberculosis in Africa.

Adolescent↗
PubMedDate not supplied

Nutritional status and weight gain in patients with pulmonary tuberculosis in Tanzania.

We assessed nutritional status in 200 adult Tanzanian patients with smear-positive pulmonary tuberculosis before, during, and after 6 months of tuberculosis treatment; 148 patients (74%) were successfully followed for 12 months. Marked nutritional impairment was present on admission: 77% of males and 58% of females had a body mass index (BMI) below 18.5; approximately one-fifth had BMI < 16.0. The length of hospital stay and gender, rather than microbiological response, were the major determinants of weight gain during treatment. Patients infected with human immunodeficiency virus (HIV) gained more weight than uninfected patients. Most patients lost weight after completing treatment and returning home. At 12 months, 32% of male and 19% of female patients considered cured of tuberculosis had BMI < 18.5. It is concluded that patients with tuberculosis from this area of Tanzania frequently have evidence of malnutrition both before and after treatment for tuberculosis. Weight gain during therapy appeared to be an unreliable indicator of overall treatment response. However, the results also demonstrated that nutritional rehabilitation can be successfully achieved even in HIV-positive tuberculosis patients and in patients with a suboptimal response to therapy.

Adult↗
PubMedDate not supplied

Erotomania revisited: clinical course and treatment.

Erotomania is a rare disorder in which an individual has a delusional belief that a person of higher social status falls in love and makes amorous advances towards him/her. Little is known about the background, classification, treatment, or outcome of individuals with this disorder. The purpose of this study was to evaluate current criteria for diagnosing and classifying primary and secondary erotomania in addition to examining course, outcome, and impact on victims of erotomania. Semistructured interviews covering personal and family details in addition to treatment and outcome to date were performed on a series of erotomanic patients identified in a defined area. Evaluation of diagnosis used DSM-IV and other criteria. Fifteen erotomanic subjects (11 female, four male) were identified. Most were isolated, without a partner or full-time occupation. Forty percent had a first-degree relative with a psychiatric history and of those half had a first-degree relative with a mono-delusional disorder. Less than half of the objects of their affection, mainly noncelebrities, were subject to harassment. Subjects with primary erotomania and erotomania secondary to other psychiatric diagnoses were identified using DSM-IV criteria. Ellis and Mellsop's criteria were found to be useful in assessing erotomania but we could not replicate Seeman's fixed and recurrent groups. Treatment and outcome was better than expected particularly for those with primary erotomania and erotomanics with a diagnosis of bipolar affective disorder. In this series, erotomanic symptoms largely occurred in the context of other psychiatric disorders, although subjects with pure erotomanic symptoms were seen. Subjects were less dangerous and engaged in less harassment of victims than the literature suggests. Subjects were often isolated, unemployed, and with few social contacts. Strong family psychiatric histories were seen particularly with regard to mono-delusional disorders raising the possibility of genetic inheritance. An adaptation of Ellis and Mellsop's criteria was suggested for the diagnosis of primary and secondary erotomania. Response to treatment and prognosis was good, particularly for primary erotomania and erotomania secondary to bipolar affective disorder.

Adult↗
PubMedDate not supplied

Pharmacological management of obsessive-compulsive disorder: a review for clinicians.

Obsessive-compulsive disorder (OCD) has been treated pharmacologically with drugs that enhance availability of the neurotransmitter serotonin. This review summarizes the available literature on the pharmacological treatments of OCD. Numerous randomized controlled trials have attested to the efficacy of serotonin-reuptake inhibitors (SRIs) in treating this disorder, although a coherent model of serotonin dysfunction in OCD has not been established. Meta-analyses of randomized controlled trials have found better results with clomipramine than with other SRIs, but comparative studies have so far not replicated this finding. Aspects of the methodology in these studies that might explain this discrepancy are considered. Tolerability, side effects, dosing, and safety during pregnancy of the SRIs are discussed. Treatment of OCD with poor insight and of OCD comorbid with a tic disorder, augmentation strategies, and management of partial response to SRIs are reviewed. Finally, the available interventions for refractory OCD are considered.

Antipsychotic Agents↗
PubMedDate not supplied

The construction and cloning of synthetic genes coding for artificial proteins and expression studies to obtain fusion proteins.

Synthetic genes coding for artificial proteins with predefined and nutritionally valuable amino acid compositions have been constructed and cloned in bacterial plasmid vector pKK233-2. The genes were constructed from three easily interchangeable 'cassettes' encoding either essential, non-essential or branched-chain amino acid residues. A potential hairpin loop structure in the mRNA around the region of the ribosome binding site was probably the reason for blockage of translation from this vector. Two selected genes, AHB (containing one copy of each cassette) and A6 (consisting of six copies concatemerized A cassette) were cloned into pUR300, a beta-Gal fusion vector and expressed as fusion proteins beta-Gal-AHB and beta-Gal-A6.

Amino Acid Sequence↗
PubMedDate not supplied

Clinical features and serum beta 2-microglobulin levels in HIV-1 positive and negative Tanzanian patients with tuberculosis.

Serum beta 2-microglobulin (beta 2M) rises in the later stages of HIV disease and has therefore been used to monitor progression to AIDS. However, little work has been done on patients co-infected with HIV and tuberculosis. We studied clinical features and serum beta 2-M in 35 Tanzanian patients treated for pulmonary tuberculosis (9 HIV-positive, 26 HIV-negative). The provisional WHO clinical definition of AIDS for use in Africa was fulfilled by 89% of the HIV-positive and 65% of the HIV-negative patients. Median serum beta 2-M on admission was slightly higher in HIV-positive (3.17 mg/l) than in HIV-negative (2.85 mg/l) patients. Serum beta 2-M fell during treatment in 17/24 (71%) of HIV-negative and 3/7 (43%) HIV-positive patients followed up for 6 months. We conclude that serum beta 2-M is frequently raised in active tuberculosis, and is therefore an unreliable indicator of the stage of HIV disease in co-infected patients. The WHO clinical definition of AIDS also proved unreliable in patients with tuberculosis.

AIDS-Related Opportunistic Infections↗