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Biomedical subjects

M Harris

Publications and source records attributed to M Harris.

At least 181 records · Page 10Linked to original sources

Child abuse reports in families with sudden infant death syndrome.

This study investigates the relation between sudden infant death syndrome (SIDS) cases and reports to public child protection service (CPS) agencies of suspected child abuse or neglect prior to the sudden deaths. SIDS data were collected from the Ventura County Medical Examiner's death investigation records of 1981 through 1995. Names of deceased infants, their parents, and any other caretakers who might have been with the infant near the time of death were submitted to the county CPS, where they were referenced for reports of abuse or neglect. A control population of non-SIDS infants and their caretakers were checked in a similar manner. The 150 infants from the control group were compared with 157 SIDS infants; no significant statistical difference was found between groups in the incidence or type of CPS referrals. These findings suggest that screening CPS records for previous referrals is an ineffective method by which to detect infanticides misdiagnosed as SIDS and may cast unwarranted suspicion on otherwise typical SIDS cases.

California↗

Psychosocial factors associated with depression: a study of socially disadvantaged women with young children.

This study aims to use valid measures to a) estimate the prevalence of depressive disorder and b) identify psychosocial factors associated with depression in a sample of socially disadvantaged women with children. One hundred ninety-three women, recruited through a doorknock of public housing estates completed an interview that included the Diagnostic Interview Schedule to identify cases of depression and the Mannheim Interview for Social Support. The women also completed self-report questionnaires assessing psychological morbidity, life events, perceptions of intimate relationships, and personality factors. The 6-month prevalence of major depression was 17% and the lifetime prevalence 29%. Major depression was associated with perceptions of low parental care during childhood and low care from current partner, vulnerable personality style, increased reporting of life events, and an unsatisfactory social support network.

Adolescent↗

In situ hybridisation and immunocytochemical localisation of osteolytic cytokines and adhesion molecules in ameloblastomas.

Ameloblastomas produce interleukin-1-like activity that could explain some part of their osteolytic capability. However, the cellular source of this osteolytic activity is unknown. In the present study, cytokines with known inflammatory and osteolytic activity, i.e., interleukin-1 (IL-1), tumour necrosis factor (TNF), and interleukin-6 (IL-6), have been localised by immunocytochemistry and in situ hybridisation. The cellular adhesion receptors ICAM-1, E-selectin and VCAM-1 have also been immunolocalised. Immunocytochemistry demonstrated that all seven specimens showed positive staining for IL-1alpha and IL-6 with these cytokines being located in the stellate reticulum-like cells and vascular endothelium. Very faint staining for IL-1beta was seen in four of seven specimens. No reaction was seen for TNF-alpha. All specimens demonstrated E-selectin staining in the vascular endothelium and ICAM-1 and VCAM-1 staining in the stellate reticulum-like cells and the endothelium. In situ hybridisation for the cytokines showed the presence of mRNA of both IL-1alpha and IL-6 in the stellate reticulum-like cells. Faint staining for IL-1beta was also seen. No staining was seen for TNF. These findings show that ameloblastomas synthesize two bone-modulating cytokines, IL-1alpha and IL-6, and that these are synthesized mainly by the stellate reticulum-like cells. These tumours also contain a proportion of activated blood vessels in which endothelial cells express the cellular adhesion receptors ICAM-1, E-selectin and VCAM-1.

Ameloblastoma↗

Virion incorporation of human immunodeficiency virus type 1 Nef is mediated by a bipartite membrane-targeting signal: analysis of its role in enhancement of viral infectivity.

The nef gene of primate immunodeficiency viruses is essential for high-titer virus replication and AIDS pathogenesis in vivo. In tissue culture, Nef is not required for human immunodeficiency virus (HIV) infection but enhances viral infectivity. We and others have shown that Nef is incorporated into HIV-1 particles and cleaved by the viral proteinase. To determine the signal for Nef incorporation and to analyze whether virion-associated Nef is responsible for enhancement of infectivity, we generated a panel of nef mutants and analyzed them for virion incorporation of Nef and for their relative infectivities. We report that N-terminal truncations of Nef abolished its incorporation into HIV particles. Incorporation was reconstituted by targeting the respective proteins to the plasma membrane by using a heterologous signal. Mutational analysis revealed that both myristoylation and an N-terminal cluster of basic amino acids were required for virion incorporation and for plasma membrane targeting of Nef. Grafting the N-terminal anchor domain of Nef onto the green fluorescent protein led to membrane targeting and virion incorporation of the resulting fusion protein. These results indicate that Nef incorporation into HIV-1 particles is mediated by plasma membrane targeting via an N-terminal bipartite signal which is reminiscent of a Src homology region 4. Virion incorporation of Nef correlated with enhanced infectivity of the respective viruses in a single-round replication assay. However, the phenotypes of HIV mutants with reduced Nef incorporation only partly correlated with their ability to replicate in primary lymphocytes, indicating that additional or different mechanisms may be involved in this system.

Amino Acid Sequence↗

Genetic and environmental contributions to the association between quantitative ultrasound and bone mineral density measurements: a twin study.

This study was designed to assess the relative contributions of genetic and environmental factors to the variation and covariation of quantitative ultrasound (QUS) measurements and their relationships to bone mineral density (BMD). Forty-nine monozygotic (MZ) and 44 dizygotic (DZ) female twins between 20 and 83 years of age (53 +/- 13 years, mean +/- SD) were studied. Digital (phalangeal) QUS (speed of sound [SOS]) and calcaneal QUS (broadband ultrasound attenuation [BUA] and velocity of sound [VOS]) were measured using a DBM Sonic 1200 ultrasound densitometer and a CUBA ultrasound densitometer, respectively. Femoral neck (FN), lumbar spine (LS), and total body (TB) BMD were measured using dual-energy X-ray absorptiometry. Familial resemblance and hence heritability (proportion of variance of a trait attributable to genetic factors) were assessed by analysis of variance, univariate, and multivariate model-fitting genetic analyses. In both QUS and BMD parameters, MZ twins were more alike than DZ pairs. Estimates of heritability for age- and weight-adjusted BUA, VOS, and SOS were 0.74, 0.55, and 0.82, respectively. Corresponding indices of heritability for LS, FN, and TB BMD were 0.79, 0.77, and 0.82, respectively. In cross-sectional analysis, both BUA and SOS, but not VOS, were independently associated with BMD measurements. However, analysis based on intrapair differences suggested that only BUA was related to BMD. Bivariate genetic analysis indicated that the genetic correlations between BUA and BMD ranged between 0.43 and 0.51 (p < 0.001), whereas the environmental correlations ranged between 0.20 and 0.28 (p < 0.01). While the genetic correlations within QUS and BMD measurements were significant, factor analysis indicates that common genes affect BMD at different sites. Also, individual QUS measurements appear to be influenced by some common sets of genes rather than by environmental factors. Significant environmental correlations were only found for BMD measurements and ranged between 0.50 and 0.65 (p < 0.001). These data suggest that QUS and BMD measurements are highly heritable traits. While it appears that there is a common set of genes influencing both QUS and BMD measurements, specific genes yet to be identified appear to have greater effects than that of shared genes in each trait.

Absorptiometry, Photon↗

Isolation of proteins from subacrosomal region of spermatozoa from a marsupial, the tammar wallaby (Macropus eugenii).

Recent studies indicate that subacrosomal proteins are necessary for the attachment of the acrosome onto the nucleus during sperm formation, and for the stability of the nuclear membrane during fertilization. For the first time, subacrosomal proteins have been isolated from a marsupial species, the tammar wallaby (Macropus eugenii), using a method developed in our laboratory. Whole ejaculated spermatozoa were fractionated into head and tail sections by ultrasonication to extract subacrosomal proteins. The heads (> 95% purity) were then isolated from tail sections using centrifugation with a three-step discontinuous sucrose gradient (35, 68 and 75% (w/v). The heads were treated with 0.1% (v/v) Triton X-100 which stripped off the acrosome, but not the subacrosomal proteins, from the head. The proteins were finally extracted by 100 mmol NaOH l-1. Four prominent subacrosomal polypeptides, with molecular masses of 45, 38, 33 and 29 kDa, were recognized from the SDS-PAGE gel. The localization of these polypeptides (particularly the 45 kDa polypeptide) was confirmed by fluorescent and immunogold labelling with polyclonal antibodies raised in mice against the obtained polypeptides. In wallaby testes, the 45 kDa polypeptide was detected as early as at the step 3 spermatid and was mainly associated with the membrane of the newly formed acrosome vesicle. This polypeptide was also found on the acrosomal membrane of all older spermatids. The 45 kDa polypeptide was found on the acrosomal region of the spermatozoa collected from the caput, corpus and cauda of the epididymis. The similarity of the sperm anatomy of the tammar wallaby with that of other marsupials, such as the brushtail possum, implies that this procedure could be applied effectively to other marsupial species with minor modification.

Animals↗

Evaluation of a dental floss containing soluble pyrophosphate on calculus formation using a short-term clinical model.

This clinical study compared the effect of a dental floss containing 0.25 mg tetrasodium pyrophosphate per cm and a placebo floss on supragingival calculus formation using a 6-week, partial-mouth toothshield model. The six lower anterior teeth were scaled and polished before each 2-week period (i.e., pre-trial, washout, trial). During both the pre-trial and trial periods, subjects brushed twice daily with a non-tartar control dentifrice, while a toothshield protected the six test teeth from brushing. After rinsing with water and removing the shield, they flossed the test teeth. All subjects used placebo floss during the pre-trial period in order to determine the baseline Volpe-Manhold Index (VMI) calculus formation scores, which were used to balance groups for the trial period. During the trial period, one group used the placebo floss, while the second group used the pyrophosphate floss. The final results demonstrated that the pyrophosphate floss significantly inhibited calculus formation between teeth (mesial-distal scores) by 21%, and on labial surfaces by 37% relative to the placebo floss.

Adult↗

Development of oculomotor functioning in preadolescence, adolescence, and adulthood.

We examined developmental differences in smooth pursuit eye tracking proficiency in a large sample of preadolescent, adolescent, and adult males. Smooth pursuit was quantified using general measures of oculomotor functioning and by examining the frequency and dynamic characteristics of specific saccadic events. Examination of age effects using general measures indicated that, by late adolescence, the smooth pursuit system reached adult levels of functioning. No significant differences were found between the adolescent and adult groups on most global measures. However, both groups had better eye tracking than the preadolescent group, suggesting that during preadolescence the oculomotor system is still developing and is not yet capable of optimal performance. Examination of the frequency and dynamic characteristics of the saccadic events yielded additional information regarding the nature of the smooth pursuit eye tracking differences of the three age groups.

Adolescent↗

Laboratory evaluation of the reach tooth & gum care toothbrush and three additional manual toothbrushes for subgingival access.

A new laboratory procedure has been developed to evaluate subgingival access efficacy (SAE) of toothbrush bristles using clinical toothbrushing motions and pressure-sensitive paper placed around simulated tooth shapes and gingival tissues under wet brushing conditions. Subgingival access is determined by measuring the maximum distance of the bristle marks from the brushing stroke on the pressure-sensitive paper under the simulated gingival tissues. Four manual toothbrushes (Reach Tooth & Gum Care, Colgate Total Design, Mentadent and Oral-B Advantage) with differing designs, bristle feathering or outside row dimensions were evaluated. Each toothbrush design was evaluated for 28 assessments on anterior and posterior tooth shapes. On overall assessments for subgingival access, the Reach Tooth & Gum Care toothbrush was significantly (p < 0.05-0.001) superior to the other three commercially available toothbrushes tested.

Analysis of Variance↗

Role of viral load in heterosexual transmission of human immunodeficiency virus type 1 by blood transfusion recipients. Transfusion Safety Study Group.

Eighteen transfusion recipients infected with human immunodeficiency virus type 1 (HIV-1) were followed prospectively with their 19 long-term sexual partners from 1986 to 1993 in California, Florida, and New York. Follow-up included clinical, behavioral, immunologic, serologic, and virologic evaluations. Two partners were already infected when seen 18 and 34 months after sexual contact began following the infectious transfusion. Four of 17 initially seronegative partners seroconverted during 23 person-years of observation. The recipient's clinical status, mononuclear cell subset variations, and time trend in CD4+ counts had no association with transmission. Individual plasma HIV-1 ribonucleic acid (RNA) loads were stable during observation, and sexual transmission was not attributable to an upward trend or transient burst in viremia. However, recipients who transmitted HIV-1 to their sexual partners had higher mean viral RNA levels than did nontransmitting recipients (4.3 vs. 3.6 log10 copies/ml; p = 0.05). Although this series was small, the prospective observations suggest that viral load was the only characteristic in the recipient that contributed to heterosexual infectiousness.

Acquired Immunodeficiency Syndrome↗

DNA-protein cross-links produced by various chemicals in cultured human lymphoma cells.

Chemicals such as cis-platinum, formaldehyde, chromate, copper, and certain arsenic compounds have been shown to produce DNA-protein cross-links in human in vitro cell systems at high doses, such as those in the cytotoxic range. Thus far there have only been a limited number of other chemicals evaluated for their ability to produce cross-links. The purpose of the work described here was to evaluate whether select industrial chemicals can form DNA-protein cross-links in human cells in vitro. We evaluated acetaldehyde, acrolein, diepoxybutane, paraformaldehyde, 2-furaldehyde, propionaldehyde, chloroacetaldehyde, sodium arsenite, and a deodorant tablet [Mega Blue; hazardous component listed as tris(hydroxymethyl)nitromethane]. Short- and long-term cytotoxicity was evaluated and used to select appropriate doses for in vitro testing. DNA-protein cross-linking was evaluated at no fewer than three doses and two cell lysate washing temperatures (45 and 65 degrees C) in Epstein-Barr virus (EBV) human Burkitt's lymphoma cells. The two washing temperatures were used to assess the heat stability of the DNA-protein cross-link, 2-Furaldehyde, acetaldehyde, and propionaldehyde produced statistically significant increases in DNA-protein cross-links at washing temperatures of 45 degrees C, but not 65 degrees C, and at or above concentrations of 5, 17.5, and 75 mM, respectively. Acrolein, diepoxybutane, paraformaldehyde, and Mega Blue produced statistically significant increases in DNA-protein cross-links washed at 45 and 65 degrees C at or above concentrations of 0.15 mM, 12.5 mM, 0.003%, and 0.1%, respectively. Sodium arsenite and chloroacetaldehyde did not produce significantly increased DNA-protein cross-links at either temperature nor at any dose tested. Excluding paraformaldehyde and 2-furaldehyde treatments, significant increases in DNA-protein cross-links were observed only at doses that resulted in complete cell death within 4 d following dosing. This work demonstrates that DNA-protein cross-links can be formed in vitro following exposure to a variety of industrial compounds and that most cross-links are formed at cytotoxic concentrations.

Acetaldehyde↗

Increased low-level chromosome 21 mosaicism in older individuals with Down syndrome.

During a study of the familial aggregation of Down syndrome (DS) and Alzheimer disease (AD), we observed an increase in mosaicism for disomy 21 in older individuals with DS. In a total of 213 DS subjects who were studied cytogenetically, only 1 of 121 (0.8%) under age 45 exhibited mosaicism, while 14 of 92 (15.2%) who were age 45 or older had mosaicism. Mosaicism in this report connotes "low-level" mosaicism, where all 15 individuals exhibited a modal chromosome number of 47 (i.e., trisomy 21), and at least two cells lacked one of the three chromosomes 21. The occurrence of aneuploidy for chromosomes 15, 17, and X increased with age, and an inverse correlation between chromosome loss and size was also observed. Because older individuals had not been karyotyped at birth, it was not possible to determine whether our observations were due to either increased survival of mosaic individuals or accumulation of disomy 21 cells via increased chromosome loss with aging of the trisomy 21 individual. Using a modeling approach involving life table methods, we obtained results that suggested acquired mosaicism as the predominant mechanism to explain our findings. These results support the hypothesis that as individuals with DS age, there is an increased loss of chromosome 21.

Adolescent↗

Developmental regulation of angiotensin type 1 and 2 receptor gene expression and heart growth.

Little is known regarding the developmental regulation of the cardiac angiotensin type 1 (AT1) and type 2 (AT2) receptor genes or their role in normal cardiac growth. Regulation of AT1 and AT2 receptor genes were examined using total and poly A + RNA isolated from whole Sprague-Dawley rat hearts. AT1 mRNA levels were 3.5-fold higher in the 19-day-old fetal heart compared to the 90-day-old adult as detected with 2 or 5 microg of poly A + RNA. AT2 mRNA was only detectable with 20 microg of poly A + RNA. AT2 mRNA levels were highest in the 19-day-old fetal heart with no detectable message in the 90-day-old adult heart. Qualitative PCR for AT2 mRNA also could not detect AT2 mRNA in the adult heart. Treatment with the AT1 receptor antagonist losartan for 3 weeks in the 21-day-old rat or for 4 days in the 38-day-old rat resulted in a significant decrease in heart/body weight in both groups and body weight in the 3-week treatment group. AT2 blockade for 4 days with PD123319 or beta-receptor blockade with propranolol for 3 weeks did not alter heart/body weights. Losartan treatment also resulted in a three-fold increase in cardiac AT1 mRNA levels in both the 4-day and 3-week treatment groups compared to controls. We conclude that Ang II, acting primarily, if not exclusively via the AT1 receptor plays a significant role in the regulation of normal cardiac growth in the young rat.

Angiotensin Receptor Antagonists↗

Evidence that resistance to osmotic stress is mediated by gene amplification.

The mechanism for resistance to osmotic stress in V79 Chinese hamster cells is unknown. Previous experiments have provided little or no support for mechanisms based on gene mutation or stable changes in gene expression. An alternative explanation, based on gene amplification is offered in the present study. The evidence comes from experiments with PALA, which is N(Phosphonoacetyl)L-aspartate. Since no other mechanism than gene amplification is known for resistance to PALA, PALA resistance can be used as a reporter for gene amplification in other systems if cross-resistance occurs. Clonal lines resistant to hypertonic NaCl or to hypertonic mannitol were cross-resistant in dose-response tests with graded PALA. PALA resistant lines were also obtained by direct exposure of sensitive stock V79 cells to appropriate levels of PALA. In subsequent tests these lines were found to be refractory to osmotic stress when exposed to hypertonic NaCl or hypertonic mannitol. These results suggest that PALA and osmotic stress act as inductors as well as selective agents. The induction of gene amplification is not confined to the system under selection, but occurs at other points in the genome. It is this more general induction that explains cross-resistance between two otherwise unrelated characteristics.

Animals↗