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Biomedical subjects

H Friesen

Publications and source records attributed to H Friesen.

At least 19 recordsLinked to original sources

Protection of breastfeeding in Papua New Guinea.

In Papua New Guinea the bottle-feeding of babies has been increasing, predominantly among unemployed women of low educational status. Many women are unaware of their legal right to have breaks at work for the purpose of breastfeeding, and a high proportion of workplaces have no facilities for mothers who wish to breastfeed their children. The laws on the feeding of infants should be updated and implemented, and an effort is needed to explain the benefits of breastfeeding and the rights of working mothers.

Bottle Feeding

Infant feeding practices in Papua New Guinea.

Concern about a possibly increasing prevalence of bottle-feeding led in 1995 to an Infant Feeding Survey of 1822 mothers attending urban health facilities. Infant feeding practices including feeding of colostrum, exclusive breastfeeding, weaning practices and bottle-feeding were assessed. This revealed that 28.8% of mothers had not given colostrum to their babies, that 43.5% of 3-month-old babies were exclusively breastfed, and that solids were introduced before 4 months of age in over half of the study population. Bottle-feeding was used by 20% of the study population. Feeding practices differed in women of Highlands and of Coastal origin. The findings emphasize the need to strengthen health education programmes which take into account the mothers' different cultural backgrounds. The issue of breast-feeding by mothers in paid employment needs to be addressed.

Bottle Feeding

Spe3, which encodes spermidine synthase, is required for full repression through NRE(DIT) in Saccharomyces cerevisiae.

We previously identified a transcriptional regulatory element, which we call NRE(DIT), that is required for repression of the sporulation-specific genes, DIT1 and DIT2, during vegetative growth of Saccharomyces cerevisiae. Repression through this element is dependent on the Ssn6-Tup1 corepressor. In this study, we show that SIN4 contributes to NRE(DIT)-mediated repression, suggesting that changes in chromatin structure are, at least in part, responsible for regulation of DIT gene expression. In a screen for additional genes that function in repression of DIT (FRD genes), we recovered alleles of TUP1, SSN6, SIN4, and ROX3 and identified mutations comprising eight complementation groups of FRD genes. Four of these FRD genes appeared to act specifically in NRE(DIT)mediated repression, and four appeared to be general regulators of gene expression. We cloned the gene complementing the frd3-1 phenotype and found that it was identical to SPE3, which encodes spermidine synthase. Mutant spe3 cells not only failed to support complete repression through NRE(DIT) but also had modest defects in repression of some other genes. Addition of spermidine to the medium partially restored repression to spe3 cells, indicating that spermidine may play a role in vivo as a modulator of gene expression. We suggest various mechanisms by which spermidine could act to repress gene expression.

Base Sequence

NDT80 and the meiotic recombination checkpoint regulate expression of middle sporulation-specific genes in Saccharomyces cerevisiae.

Distinct classes of sporulation-specific genes are sequentially expressed during the process of spore formation in Saccharomyces cerevisiae. The transition from expression of early meiotic genes to expression of middle sporulation-specific genes occurs at about the time that cells exit from pachytene and form the meiosis I spindle. To identify genes encoding potential regulators of middle sporulation-specific gene expression, we screened for mutants that expressed early meiotic genes but failed to express middle sporulation-specific genes. We identified mutant alleles of RPD3, SIN3, and NDT80 in this screen. Rpd3p, a histone deacetylase, and Sin3p are global modulators of gene expression. Ndt80p promotes entry into the meiotic divisions. We found that entry into the meiotic divisions was not required for activation of middle sporulation genes; these genes were efficiently expressed in a clb1 clb3 clb4 strain, which fails to enter the meiotic divisions due to reduced Clb-dependent activation of Cdc28p kinase. In contrast, middle sporulation genes were not expressed in a dmc1 strain, which fails to enter the meiotic divisions because a defect in meiotic recombination leads to a RAD17-dependent checkpoint arrest. Expression of middle sporulation genes, as well as entry into the meiotic divisions, was restored to a dmc1 strain by mutation of RAD17. Our studies also revealed that NDT80 was a temporally distinct, pre-middle sporulation gene and that its expression was reduced, but not abolished, on mutation of DMC1, RPD3, SIN3, or NDT80 itself. In summary, our data indicate that Ndt80p is required for expression of middle sporulation genes and that the activity of Ndt80p is controlled by the meiotic recombination checkpoint. Thus, middle genes are expressed only on completion of meiotic recombination and subsequent generation of an active form of Ndt80p.

Cell Cycle Proteins

An Ssn6-Tup1-dependent negative regulatory element controls sporulation-specific expression of DIT1 and DIT2 in Saccharomyces cerevisiae.

Sporulation of the yeast Saccharomyces cerevisiae is a process of cellular differentiation that occurs in MATa/MAT alpha diploid cells in response to starvation. The sporulation-specific genes DIT1 and DIT2, which are required for spore wall formation, are activated midway through the sporulation program, with maximal transcript accumulation occurring at the time of prospore enclosure. In this study, we have identified a negative regulatory element, termed NREDIT, that is located between the start sites of transcription of these divergently transcribed genes. This element, which prevents expression of the DIT1 and DIT2 genes during vegetative growth, reduces expression of a CYC1-lacZ reporter gene more than 1,000-fold and acts in an orientation- and position-independent manner. We found that the ability of NREDIT to turn of expression of the reporter gene and the chromosomal DIT1 and DIT2 genes in vegetative cells requires the Ssn6-Tup1 repression complex. Interestingly, NREDIT-mediated repression of the reporter gene is maintained during sporulation. Derepression during sporulation requires complex interactions among several cis-acting elements. These are present on an approximately 350-bp DNA fragment extending from NREDIT to the TATA box and an approximately 125-bp fragment spanning the TATA box of DIT1. Additionally, a region of NREDIT which is very similar in sequence to UASSPS4, an element that activates gene expression midway through sporulation, contributes both to vegetative repression and to sporulation-specific induction of DIT1. We propose a model to explain the requirement for multiple elements in overcoming NREDIT-mediated repression during sporulation.

Base Sequence

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Consumer Advocacy

Paediatric HIV infection.

HIV infection in children is a family disease, with social, economic and medical aspects that make it one of the most challenging diseases of our time. Knowledge about the factors involved in mother-to-child transmission and the natural history of the disease is gradually increasing although there is still much to understand. As the majority of children become infected through mother-to-child transmission, perinatally acquired infection will parallel increases in heterosexual transmission and the numbers of infected women of childbearing age. Current estimates of the rate of vertical transmission range from 14% to 39% in different studies. The relative proportion of transmission occurring in utero, peripartum or postpartum may vary in different localities and remains unclear. A study recently carried out in the USA showed that zidovudine given late in pregnancy, peripartum and in the neonatal period decreases HIV transmission from 25% to 8%. The clinical presentation of HIV infection in children depends in part on exposure to different infections. In developing countries the children usually present with nonspecific signs and symptoms, such as failure to thrive, chronic diarrhoea, cough and recurrent bacterial infections. Other common presentations include generalized lymphadenopathy, oropharyngeal candidiasis, dermatitis, enlargement of parotid glands and neurological problems, including delayed development.

Anti-HIV Agents

Assessment of HIV/AIDS knowledge, attitudes and behaviour of high school students in Papua New Guinea.

OBJECTIVE: To assess the knowledge, attitudes and behaviour of high school students (grade 10) with regard to HIV infection and AIDS. METHODS: A self-administered questionnaire survey was carried out in 21 high schools in 6 different provinces. The questionnaire was anonymous and contained questions about HIV transmission, preventive measures, attitudes towards HIV infection and a few questions about personal sexual behaviour. PRELIMINARY RESULTS: A total of 1811 students completed the questionnaire. 46% were female. The average age was 17 years. Over 98% knew what AIDS and HIV were. 97% knew that HIV was sexually transmitted, but many misconceptions existed: one-third thought that HIV was transmitted by mosquitoes, 7% that HIV-infected persons were a danger in the classroom. 72% knew that using a condom at every sexual encounter was a way of protection from HIV infection. Approximately 25% reported to have had sexual contacts, and of 15-year-old students 14% were sexually active. Although STD/AIDS education is part of the curriculum for grade 8 the principals of the majority of the schools reported that no formal teaching was done. DISCUSSION: Although the majority of students knew that HIV is sexually transmitted, basic knowledge about STDs is lacking and is not taught as part of the curriculum in most of the schools. Teaching about STDs and HIV needs to be enforced and safe sexual practices need to be discussed with the students.

Acquired Immunodeficiency Syndrome

Mutation of the SPS1-encoded protein kinase of Saccharomyces cerevisiae leads to defects in transcription and morphology during spore formation.

During sporulation of Saccharomyces cerevisiae, meiosis is followed by encapsulation of haploid nuclei within multilayered spore walls. Completion of the late events of the sporulation program requires the SPS1 gene. This developmentally regulated gene, which is expressed as cells are nearing the end of meiosis, encodes a protein with homology to serine/threonine protein kinases. The catalytic domain of Sps1 is 44% identical to the kinase domain of yeast Ste20, a protein involved in the pheromone-induced signal transduction pathway. Cells of a MATa/MAT alpha sps1/sps1 strain arrest after meiosis and fail to activate genes that are normally expressed at a late time of sporulation. The mutant cells do not form refractile spores as assessed by phase-contrast microscopy and do not display the natural fluorescence and ether resistance that is characteristic of mature spores. Examination by electron microscopy reveals, however, that prospore-like compartments form in some of the mutant cells. These immature spores lack the cross-linked surface layer that surrounds wild-type spores and are more variable in size and number than are the spores of wild-type cells. Despite their inability to complete spore formation, sps1-arrested cells are able to resume mitotic growth on transfer to rich medium, generating haploid progeny. Our results suggest that the developmentally regulated Sps1 kinase is required for normal progression of transcriptional, biochemical, and morphological events during the later portion of the sporulation program.

Amino Acid Sequence

Mutagenesis of a conserved region of the gene encoding the FLP recombinase of Saccharomyces cerevisiae. A role for arginine 191 in binding and ligation.

The FLP recombinase from the 2 microns plasmid of Saccharomyces cerevisiae contains a region from amino acid 185 to 203 that is conserved among several FLP-like proteins from different yeasts. Using site-directed mutagenesis, we have made mutations in this region of the FLP gene. Five of twelve mutations in the region yielded proteins that were unable to bind to the FLP recombination target (FRT) site. A change of arginine at position 191 to lysine resulted in a protein (FLP-R191K) that could bind to the FRT site but could not catalyze recombination. This mutant protein accumulated as a stable protein-DNA complex in which one of the two bound FLP proteins was covalently attached to the DNA. FLP-R191K was defective in strand exchange and ligation and was unable to promote protein-protein interaction with half-FRT sites. The conservation of three residues in all members of the integrase family of site-specific recombinases (His305, Arg308, Tyr343 in FLP) implies a common mechanism of recombination. The conservation of arginine 191 and the properties of the FLP-R191K mutant protein suggest that this arginine also plays an important role in the mechanism of FLP-mediated site-specific recombination.

Amino Acid Sequence

Clinical features of paediatric AIDS in Uganda.

A total of 177 children seen at two hospitals in Kampala are described who were strongly suspected of having acquired immunodeficiency syndrome (AIDS), either on clinical grounds or because they fulfilled the World Health Organization (WHO) case-definition criteria for diagnosis of paediatric AIDS. Blood was taken from the 177 children and 154 of their mothers and tested for antibody to human immunodeficiency virus (HIV) by an enzyme-linked immunoassay (ELISA). Altogether, 119 (67%) children were seropositive, but only 85 (71%) fulfilled the WHO case-definition criteria, and they were significantly older than the 34 who did not fulfil the criteria. A further 58 children were seronegative but fulfilled the WHO criteria. Of the 119 seropositive children, only 3 had a history of previous blood transfusion, but 103 (98%) of 105 mothers were HIV seropositive: consequently, their children were considered to have been infected in utero or perinatally. Thirteen (26%) of 49 mothers of seronegative children were seropositive. Eighty per cent of HIV-infected children were under 2 years of age at diagnosis and 23% died within 3 months of diagnosis. None of the parents was known to be an intravenous drug user, a prostitute or bisexual. The difficulty of accurate diagnosis of AIDS presents a major problem in Africa, as the WHO clinical case-definition criteria alone are clearly not adequate.

Acquired Immunodeficiency Syndrome

Prolactin secretion and biological activity in females with galactorrhoea and normal circulating prolactin concentrations at rest.

Prolactin secretion and biological activity have been investigated in 20 females with persistent idiopathic galactorrhoea who had normal resting serum prolactin levels at presentation. Results were compared with those in 34 normal controls. Hyperprolactinaemia, which was persistent in one and intermittent in the other, developed in two patients over an observation period of 1.5 to 8.5 years. Resting prolactin levels stayed normal in the remaining eighteen who were further investigated. Menstruation was disordered in only six of the 18, while ovulation occurred (serum progesterone greater than 20 nmol/l) in all seven patients who were studied over a 5 week period. Serum prolactin concentrations over 24 h were similar in patients and controls (24 h mean +/- SEM prolactin, 288 +/- 36 mU/l, patients, n = 7; 291 +/- 21 mU/l, controls, n = 9) as were prolactin levels estimated twice weekly for 5 weeks. Prolactin responses to thyrotrophin-releasing hormone, 200 micrograms (at 20 min, 2417 +/- 658 mU/l, patients, n = 7; 2113 +/- 424 mU/l, controls, n = 8), the dopamine antagonist, domperidone, 10 mg (at 30 min, 5949 +/- 536 mU/l, patients, n = 7; 5858 +/- 460 mU/l, controls, n = 8) and insulin-induced hypoglycaemia (at 60 min, 1441 +/- 551 mU/l, patients, n = 7; 1298 +/- 183 mU/l, controls, n = 7) were similar in patients and controls. Two different radioimmunoassays using two different antisera gave similar estimates of serum prolactin levels and prolactin bioactivity in serum was normal in an in-vitro bioassay based on the ability of prolactin to stimulate proliferation of Nb2 node rat lymphoma cells (basal bioassayable prolactin, patients 355 +/- 43 mU/l, n = 10; controls 348 +/- 64 mU/l, n = 7). Metabolic abnormalities similar to those previously noted in hyperprolactinaemia were observed in the patients' 24 h profiles. These included mild hyperglycaemia (24 h mean +/- SEM glucose, 5.47 +/- 0.08 mmol/l, patients; 5.05 +/- 0.14 mmol/l, controls; P less than 0.05) and elevations in circulating lactate, pyruvate and alanine. Blood glycerol was decreased (24 h mean +/- SEM, 0.044 +/- 0.004 versus 0.058 +/- 0.004 mmol/l, P less than 0.05). In the majority of patients with idiopathic galactorrhoea, prolactin concentrations, regulation of secretion and bioactivity in vitro are normal. The galactorrhoea and metabolic abnormalities suggest increased tissue sensitivity to the lactogenic and metabolic actions of prolactin, while ovarian cyclical function is relatively spared.

Adult

A molecular method for detecting the presence of the human Y chromosome.

The presence of the human Y chromosome can be inferred from the detection of a male-specific 3.4-Kb band generated by digestion with the restriction enzyme Hae III. However, direct visualization of this band is sometimes difficult owing to high background of DNA fragments common to both sexes, and Y chromosome length polymorphism. We have shown that the 3.4-Kb band can be detected by filter hybridization to a large DNA fragment (greater than 20 Kb) also generated by Hae III digestion. Since this large DNA fragment is easily isolated from either sex, it should prove useful to determine sex when chromosome analysis is impractical.

DNA

Inverse relationship of prolactin and rat placental lactogen during pregnancy.

Serum prolactin, progesterone and rat placental lactogen (rPL) were measured in pregnant rats following removal of various numbers of conceptuses and their placentas on Day 8 of pregnancy. Blood samples were taken during the time of the expected nocturnal surge of prolactin on Days 8 and 9, and at the same time on Days 11 and 14 of pregnancy, when the surges are normally no longer present. As the number of conceptuses present decreased, the number of days the prolactin surge was present increased. Measurement of the early form of rPL (rPL-I) by lymphoma cell bioassay revealed a proportionate decrease in serum rPL-I levels on Days 9 and 11 as the number of conceptuses was decreased. This also was true for the late form of rPL (rPL-II) when measured by RIA on Day 14 of pregnancy. Thus, as rPL levels are reduced, prolactin surges remain present for increased numbers of days. This suggests that rPL may normally be an inhibitory factor to prolactin secretion during pregnancy, and is responsible for the termination of the prolactin surges at midpregnancy.

Animals

Concentrations of placental lactogen in chronically catheterized ewes and fetuses in late pregnancy.

The concentration of ovine placental lactogen (oPL) was measured by radioimmunoassay in plasma samples from chronically catheterized ewes and their fetuses from day 110 of gestation to term (about day 145). Concentrations of oPL in the plasma of the mother and fetus were raised after surgery, and remained raised for 3--5 days after the operation. Concentrations of oPL were greatest in the fetus at days 120--124 of gestation, and then declined until delivery. Mean concentrations of oPL in the fetus in late pregnancy for single, twin and triplet pregnancies were 101 +/- 6 (S.E.M.), 100 +/- 11 and 115 +/- 59 ng/ml respectively and were not significantly different. Mean concentrations of oPL in the mother in late pregnancy for single, twin and triplet pregnancies were 718 +/- 227, 1387 +/- 160 and 1510 +/- 459 ng/ml respectively; the difference between these means was significant (P less than 0.05). Peak concentrations were noted at days 130--139 of gestation after which concentrations fell and were significantly lower on the day of delivery (P less than 0.01). Concentration of oPL in the mother showed no circadian rhythm. The mean concentrations of oPL in maternal plasma during late pregnancy was significantly correlated to the combined fetal weight at birth (r = 0.624, P less than 0.01).

Animals