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Biomedical subjects

M H Klein

Publications and source records attributed to M H Klein.

At least 19 recordsLinked to original sources
PubMed2001

Maternity leave, women's employment, and marital incompatibility.

This research investigated the relationship between the length of women's maternity leave and marital incompatibility, in the context of other variables including the woman's employment, her dissatisfaction with the division of household labor, and her sense of role overload. Length of leave, work hours, and family salience were associated with several forms of dissatisfaction, which in turn predicted role overload. Role overload predicted increased marital incompatibility for experienced mothers but did not for first-time mothers, for whom discrepancies between preferred and actual child care were more important. Length of maternity leave showed significant interactions with other variables, supporting the hypothesis that a short leave is a risk factor that, when combined with another risk factor, contributes to personal and marital distress.

Adult↗
PubMed2001

Timing of initial exposure to maternal major depression and children's mental health symptoms in kindergarten.

BACKGROUND: Little is known about the influence on child mental health symptoms of the timing of initial exposure to maternal major depression or whether the timing is associated with 'pure' or co-occurring internalising and externalising symptoms. AIMS: To address these issues, while also taking account of child gender and family socio-economic status. METHOD: In a prospective community-based study, 421 kindergarten teachers rated children's symptoms. Previous assessments of maternal major depression indicated whether children were first exposed during infancy, in the toddler/pre-school period, or never. RESULTS: Exposure during infancy was associated with high internalising symptoms, especially when co-occurring with high externalising symptoms. Initial exposure in the toddler/pre-school years increased the risk of 'pure' externalising symptoms among girls. CONCLUSIONS: The association of child mental health symptoms with the timing of initial exposure to maternal depression highlights the need for effective prevention and intervention strategies addressed to the developmental issues of each period.

Adolescent↗
PubMed2001

Self-concept correlates of the personality disorders.

This study investigated the extent to which the DSM personality disorder dimensions are associated with discrete patterns of self-concept. Participants were 366 men and women who were receiving mental health services and who completed the Wisconsin Personality Disorders Inventory to assess the personality disorders and Benjamin's INTREX questionnaire to describe their "typical" self-concepts. Although there was some overlap between categories, most were associated with fairly distinct patterns of self-concept. The disorders also clustered together in meaningful ways along the major axes of Benjamin's interpersonal model of the self-concept.

Adolescent↗
PubMed2001

Predictors, prodromes and incidence of postpartum depression.

The purpose of this study was to determine the incidence of clinically significant depression occurring between 1 and 4 months postpartum and to investigate whether somatic complaints, subsyndromal depressive symptoms, or birth-related concerns among non-depressed women at 1 month were predictive of postpartum depression. This is a prospective cohort study of 465 women from the Wisconsin Maternity Leave and Health Project (WMLHP). Women who were not depressed at 1 month postpartum were reassessed 3 months later for depression occurring at any time in the interval between 1 and 4 months postpartum. Depression was defined as either meeting the criteria for major depression on the National Institute of Mental Health (NIMH) Diagnostic interview Schedule (DIS) or scoring above 15 on the Center for Epidemiologic Studies Depression Scale (CES-D). Physical symptoms were assessed by an adapted Health Responses Scale. Other measures were developed specifically for the WMLHP. Of 465 women, 27 (5.8%) became clinically depressed between 1 and 4 months postpartum. In a logistic regression analysis, four variables (maternal age, depression during pregnancy, thoughts of death and dying at 1 month postpartum, and difficulty falling asleep at 1 month postpartum) were predictive of depression at 4 months postpartum. Breast-feeding, mode of delivery, family income, parity and mother's education did not predict depression. The existence of subsyndromal depressive symptoms, particularly thoughts of death and dying, may represent a prodromal phase of depression and should alert clinicians to the possibility of future postpartum depression. Women with a history of depression during pregnancy should be monitored for signs of postpartum depression for a minimum of 4 months. Obstetricians are in a unique position during the postpartum check-up to screen women for these predictors of future postpartum depression and possibly to avert the development of a clinically significant depressive episode.

Adult↗
PubMed2000

The IgA/IgM receptor expressed on a murine B cell lymphoma is poly-Ig receptor.

T560, a mouse B lymphoma that originated in gut-associated lymphoid tissue, expresses receptors that bind dimeric IgA and IgM in a mutually inhibitory manner but have little affinity for monomeric IgA. Evidence presented in this paper indicates that the receptor is poly-Ig receptor (pIgR) known in humans and domestic cattle to bind both IgA and IgM. The evidence includes the demonstration that binding of IgM is J chain dependent, and that pIg-precipitated receptor has an appropriate Mr of 116-120 kDa and can be detected on immunoblots with specific rabbit anti-mouse pIgR. Overlapping RT-PCR performed using template mRNA from T560 cells and oligonucleotide primer pairs designed from the published sequence of mouse liver pIgR indicate that T560 cells express mRNA virtually identical with that of the epithelial cell pIgR throughout its external, transmembrane, and intracytoplasmic coding regions. Studies using mutant IgAs suggest that the Calpha2 domain of dimeric IgA is not involved in high-affinity binding to the T560 pIgR. Inasmuch as this mouse B cell pIgR binds IgM better than IgA, it is similar to human pIgR and differs from rat, mouse, and rabbit epithelial cell pIgRs that bind IgA but not IgM. Possible explanations for this difference are discussed. All clones of T560 contain some cells that spontaneously secrete both IgG2a and IgA, but all of the IgA recoverable from the medium and from cell lysates is monomeric; it cannot be converted to secretory IgA by T560 cells.

Amino Acid Sequence↗
PubMed1999

Disruption of the mycobacterial cell entry gene of Mycobacterium bovis BCG results in a mutant that exhibits a reduced invasiveness for epithelial cells.

Mycobacteria belonging to the Mycobacterium tuberculosis complex have the ability to invade and replicate in non-phagocytic cells, an event that requires the presence of bacterial surface components capable of triggering a cell response and the subsequent internalization of the microorganism. In this study, we report the sequencing of the mycobacterial cell entry gene (mce) of Mycobacterium bovis bacillus Calmette-Guérin (BCG) and the generation and characterization of a mutant BCG strain with an inactivated mce gene, by homologous recombination with double cross-over. This mutant strain does not express the mycobacterial cell entry protein (Mce) and exhibits a reduced ability to invade the non-phagocytic epithelial cell line HeLa as compared to wild-type BCG.

Cloning, Molecular↗
PubMed1999

Engineering of noninfectious HIV-1-like particles containing mutant gp41 glycoproteins as vaccine candidates that allow vaccinees to be distinguished from HIV-1 infectees.

Many AIDS vaccine candidates under development may elicit immune responses similar to those observed in and used to screen human immunodeficiency virus type 1 (HIV-1)-infected individuals. Therefore, it is important to develop vaccine candidates that incorporate antigenic markers and allow vaccinees to be distinguished from HIV-1 infectees. To this end, we introduced a series of mutations into and in the vicinity of the major immunodominant region (MIR) of gp41 (residues 598-609), a domain recognized by almost all HIV-1 infectees, and evaluated whether HIV-1-like particles incorporating such mutant glycoproteins could be expressed in mammalian cells. Results indicated that although up to three consecutive amino acids could be replaced within MIR without significantly affecting particle formation or gp160 processing, deletions within MIR impaired envelope processing. Replacement of HIV-1 MIR by part or most of the corresponding domain from other lentiviruses markedly decreased or abolished gp160 processing. Synthetic peptides corresponding to a mutated MIR incorporating three amino acid replacements were not recognized by a panel of sera from HIV-1 infectees, suggesting that HIV-1-like particles with this type of mutation represent potential candidate vaccines that could allow vaccinees to be distinguished from HIV-1 infectees.

AIDS Vaccines↗
PubMed1999

Derivation and prediction of temperamental types among preschoolers.

The number and nature of temperamental types in 488 children aged 3 years 6 months was examined on the basis of a broad set of temperamental characteristics, including positive and negative emotionality and the attentional and behavioral control domains. Configural frequency analysis methods showed clear support for two temperament types: controlled-nonexpressive and noncontrolled-expressive. These types showed meaningful differences against external criteria related to a wide range of problem behaviors from the emotional, social, and attentional domains. The reports of problem behaviors were obtained contemporaneously from fathers and caregivers. These findings replicated a year later when children were aged 4 years 6 months. Furthermore, the findings showed that infant and toddler-age temperamental characteristics differentiated these preschool-aged types. The authors discuss the implications of the results for a categorical view of temperament-personality.

Attention↗
PubMed1998

Modifications of HIV-1 retrovirus-like particles to enhance safety and immunogenicity.

HIV-1 retrovirus-like particles can be produced in VERO cells that have been transfected with an expression construct encoding HIV-1 structural proteins. The particles are entirely non-infectious although structurally they resemble infectious virus particles. This makes them a promising candidate for use as an HIV-1 vaccine. In order to ensure their safety and enhance their immunogenicity, the retrovirus-like particles were modified in a number of ways. A large deletion in the HIV-1 pol gene has eliminated reverse transcriptase and integrase activities. Deletion of RNA packaging signals in the RNA untranslated leader sequence and in Gag reduced packaged RNA to 5% of that in HIV-1 virus. Replacement of the existing HIV-1LAI envelope protein with that of HIV-1MN has ensured that immune responses to the particles are relevant to those against the majority of HIV-1 clade B isolates. In addition to these changes in particle composition, yields of the modified particles were increased using a superior method of inducing the expression construct promoter, and an effective scheme for particle purification was developed. Immunization of non-human primates demonstrated that the particles were capable of generating anti-HIV-1 neutralizing antibodies. The technological refinements reported here will permit retrovirus-like particles to be tested safely in humans, and the change in envelope proteins should allow a more realistic evaluation of the immunogenicity of these particles. Experience gained in engineering these refinements will greatly facilitate other modifications that may be required to achieve maximum efficacy as a vaccine against HIV-1.

AIDS Vaccines↗
PubMed1998

Recollections of parental behaviour, adult attachment and mental health: mediating and moderating effects.

BACKGROUND: Attachment theory posits links between early experiences with parents, adult relationships and adult mental health, but does not specify whether these are independent, mediating, or moderating effects. METHODS: Associations of parent's behaviour on the Parental Bonding Instrument, adult attachment styles and three dimensions of mental health were investigated in a large sample of women and men. RESULTS: Men and women with secure styles recalled higher levels of care from both parents than those with fearful styles. Maternal and paternal control were more consistent predictors of increased distress for men than for women. Fearful and preoccupied adult styles were associated with higher levels of distress in both men and women. While adult styles had few mediating effects on the association of parental behaviour and mental health, interactions between the fearful style and parental variables suggested that this form of insecurity sometimes accentuated the impact of high parental care or low paternal control on mental health in both men and women; among women, however, the secure style seemed to buffer somewhat the negative effect of high parental control. CONCLUSION: Although the amount of variance explained by either parental behaviour or adult styles was modest, patterns of moderating effects of adult styles on associations between parental behaviour and mental health suggested that both continuity and discontinuity principles can be applied to understanding these links.

Adult↗
PubMed1998

The Haemophilus influenzae HtrA protein is a protective antigen.

The htrA gene from two strains of nontypeable Haemophilus influenzae has been cloned and sequenced, and the encoded approximately 46-kDa HtrA proteins were found to be highly conserved. H. influenzae HtrA has approximately 55% identity with the Escherichia coli and Salmonella typhimurium HtrA stress response proteins, and expression of the H. influenzae htrA gene was inducible by high temperature. Recombinant HtrA (rHtrA) was expressed from E. coli, and the purified protein was found to have serine protease activity. rHtrA was found to be very immunogenic and partially protective in both the passive infant rat model of bacteremia and the active chinchilla model of otitis media. Immunoblot analysis indicated that HtrA is antigenically conserved in encapsulated and nontypeable H. influenzae species. Site-directed mutagenesis was performed on the htrA gene to ablate the endogenous serine protease activity of wild-type HtrA, and it was found that eight of nine recombinant mutant proteins had no measurable residual proteolytic activity. Two mutant proteins were tested in the animal protection models, and one, H91A, was found to be partially protective in both models. H91A HtrA may be a good candidate antigen for a vaccine against invasive H. influenzae type b disease and otitis media and is currently in phase I clinical trials.

Amino Acid Sequence↗
PubMed1998

Nasopharyngeal colonization with nontypeable Haemophilus influenzae in chinchillas.

Colonization of the nasopharynx by a middle ear pathogen is the first step in the development of otitis media in humans. The establishment of an animal model of nasopharyngeal colonization would therefore be of great utility in assessing the potential protective ability of candidate vaccine antigens (especially adhesins) against otitis media. A chinchilla nasopharyngeal colonization model for nontypeable Haemophilus influenzae (NTHI) was developed with antibiotic-resistant strains. This model does not require coinfection with a virus. There was no significant difference in the efficiency of NTHI colonization between adult (1- to 2-year-old) and young (2- to 3-month-old) animals. However, the incidence of middle ear infection following nasopharyngeal colonization was significantly higher in young animals (83 to 89%) than in adult chinchillas (10 to 30%). Chinchillas that had recovered either from a previous middle ear infection caused by NTHI or from an infection by intranasal inoculation with NTHI were completely protected against nasopharyngeal colonization with a homologous strain and were found to be the best positive controls in protection studies. Systemic immunization of chinchillas with inactivated whole-cell preparations significantly protected animals not only against homologous NTHI colonization but also partially against heterologous NTHI infection. In all protected animals, significant serum anti-P6 and anti-HMW antibody responses were observed. The outer membrane P6 and high-molecular-weight (HMW) proteins appear to be promising candidate vaccine antigens to prevent nasopharyngeal colonization and middle ear infection caused by NTHI.

Age Factors↗
PubMed1998

A 20-kilodalton N-terminal fragment of the D15 protein contains a protective epitope(s) against Haemophilus influenzae type a and type b.

A conserved 80-kDa minor outer membrane protein, D15, of Haemophilus influenzae has been shown to be a protective antigen in laboratory animals against H. influenzae type a (Hia) or type b (Hib) infection. To localize the protective B-cell epitope(s) within the D15 protein and to further explore the possibility of using synthetic peptides as vaccine antigens, a 20-kDa N-terminal fragment of D15 protein (truncated D15 [tD15]) was expressed as a fusion protein with glutathione S-transferase in Escherichia coli. The tD15 moiety was cleaved from glutathione S-transferase by using thrombin and purified to homogeneity. The purified soluble tD15 appeared to contain immunodominant protective epitope(s) against Hia and Hib, since rabbit antisera directed against tD15 were capable of protecting infant rats from Hia or Hib bacteremia. The ease of purification of soluble tD15, therefore, makes it a better candidate antigen than the full-length recombinant D15 which is produced as inclusion bodies in E. coli. Furthermore, both the purified tD15 fragment and a mixture of tD15-derived peptides spanning amino acid residues 93 to 209 of the mature D15 protein were capable of inhibiting the protection against Hib conferred on infant rats by rabbit anti-tD15 antiserum, indicating that the protective epitopes of D15 may not be conformational. However, the administration of pooled rabbit immune sera raised against the same panel of peptides failed to protect infant rats from Hib infection.

Amino Acid Sequence↗
PubMed1998

Cloning and expression of the Moraxella catarrhalis lactoferrin receptor genes.

The lactoferrin receptor genes from two strains of Moraxella catarrhalis have been cloned and sequenced. The lfr genes are arranged as lbpB followed by lbpA, a gene arrangement found in lactoferrin and transferrin receptor operons from several bacterial species. In addition, a third open reading frame, orf3, is located one nucleotide downstream of lbpA. The deduced lactoferrin binding protein A (LbpA) sequences from the two strains were found to be 99% identical, the LbpB sequences were 92% identical, and the ORF3 proteins were 98% identical. The lbpB gene was PCR amplified and sequenced from a third strain of M. catarrhalis, and the encoded protein was found to be 77% identical and 84% similar to the other LbpB proteins. Recombinant LbpA and LbpB proteins were expressed from Escherichia coli, and antisera raised to the purified proteins were used to assess antigenic conservation in a panel of M. catarrhalis strains. The recombinant proteins were tested for the ability to bind human lactoferrin following gel electrophoresis and electroblotting, and rLbpB, but not rLbpA, was found to bind lactoferrin. Bactericidal antibody activity was measured, and while the anti-rLbpA antiserum was not bactericidal, the anti-rLbpB antisera were found to be weakly bactericidal. Thus, LbpB may have potential as a vaccine candidate.

Amino Acid Sequence↗
PubMed1998

The transferrin binding protein B of Moraxella catarrhalis elicits bactericidal antibodies and is a potential vaccine antigen.

The transferrin binding protein genes (tbpA and tbpB) from two strains of Moraxella catarrhalis have been cloned and sequenced. The genomic organization of the M. catarrhalis transferrin binding protein genes is unique among known bacteria in that tbpA precedes tbpB and there is a third gene located between them. The deduced sequences of the M. catarrhalis TbpA proteins from two strains were 98% identical, while those of the TbpB proteins from the same strains were 63% identical and 70% similar. The third gene, tentatively called orf3, encodes a protein of approximately 58 kDa that is 98% identical between the two strains. The tbpB genes from four additional strains of M. catarrhalis were cloned and sequenced, and two potential families of TbpB proteins were identified based on sequence similarities. Recombinant TbpA (rTbpA), rTbpB, and rORF3 proteins were expressed in Escherichia coli and purified. rTbpB was shown to retain its ability to bind human transferrin after transfer to a membrane, but neither rTbpA nor rORF3 did. Monospecific anti-rTbpA and anti-rTbpB antibodies were generated and used for immunoblot analysis, which demonstrated that epitopes of M. catarrhalis TbpA and TbpB were antigenically conserved and that there was constitutive expression of the tbp genes. In the absence of an appropriate animal model, anti-rTbpA and anti-rTbpB antibodies were tested for their bactericidal activities. The anti-rTbpA antiserum was not bactericidal, but anti-rTbpB antisera were found to kill heterologous strains within the same family. Thus, if bactericidal ability is clinically relevant, a vaccine comprising multiple rTbpB antigens may protect against M. catarrhalis disease.

Amino Acid Sequence↗