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R Smith

Publications and source records attributed to R Smith.

At least 829 records · Page 46Linked to original sources
PubMed1992

Parasite-induced changes to localized erythrocyte membrane deformability in Plasmodium falciparum cultures.

The effect of intra-erythrocyte development of the Plasmodium falciparum parasite on local deformability of human erythrocyte membranes was studied by aspiration of cells into 0.56 micron diameter pores in polycarbonate filters and examination, after fixing, with a scanning electron microscope. As the aspiration pressure increased, the erythrocyte membrane was extruded into the filter pores. The pressure dependence of the protrusion length and the minimum pressure required to produce any deformation provided measures of the membrane shear and the bending moduli, respectively. At the trophozoite and, to a greater extent, schizont stage of development, host cell membrane deformability was significantly decreased. There was no appreciable difference between uninfected and ring-infected erythrocytes.

Animals↗
PubMed1992

Longevity of expanding gases in vitrectomized eyes.

The effect of lensectomy and vitrectomy on the disappearance of intraocular gas was studied in a rabbit model. Ten rabbits underwent lensectomy and vitrectomy in one eye, and ten others underwent vitrectomy alone in one eye. The second eye of each rabbit served as a control. Equal amounts of perfluorocarbon gas, either perfluoromethane (CF4) or perfluoromethane (C2F6), was injected into both eyes of the 20 animals. After an interval corresponding to one or more half-lives of the gases had elapsed, the residual volumes of gas in the paired eyes were measured directly by an invasive method and compared. The volume of gas in the aphakic vitrectomized eye was 1.3 times greater, on average, than in the paired control eye. There was no significant difference between eyes that had undergone only vitrectomy and the control eyes. It is postulated that vascular congestion and decreased aqueous secretion caused by surgical trauma were responsible for the delay in the disappearance of gas in the eyes that underwent both lensectomy and vitrectomy.

Animals↗
PubMed1992

Reappraisal of the hypo-osmotic swelling test to improve assessment of seminal fertility status.

The hypo-osmotic swelling (HOS) test has been proposed as a useful assay for evaluation of the functional competence of the human sperm membranes. To assess this further, the HOS-test was evaluated in 187 semen samples collected from fertile men and from male patients consulting for infertility. These samples were classified as normal, oligo-, astheno- or oligoasthenozoospermic on the basis of their standard semen variables. The percentage of total sperm tail swelling and of sperm exhibiting different tail swelling patterns was recorded. In the fertile men and in the group of patients with normal semen variables, significantly more (P less than 0.001) HOS-reactive sperm were observed after hypo-osmotic treatment in comparison with those groups exhibiting abnormal semen parameters. Swelling of the sperm in a hypo-osmotic medium was highly correlated with both progressive motility (r = 0.62, P less than 0.001) and sperm viability (r = 0.65, P less than 0.001). A weak positive correlation was also observed between sperm swelling and sperm morphological features (r = 0.31, P less than 0.005) and between sperm swelling and sperm concentration (r = 0.31, P less than 0.005). No significant correlation was observed between sperm swelling and in-vitro sperm fertilizing capacity as assessed by the zona-free hamster oocyte penetration assay. However the majority of the semen samples (87.3%) showing a normal penetration rate (greater than or equal to 10%) also exhibited a 60% (or higher) reaction in the HOS-test.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

The basic protein of CNS myelin: its structure and ligand binding.

Consideration of the evidence presented in this review leads to the following conclusions: (a) Isolated MBP in aqueous solution has little ordered secondary or tertiary structure. (b) In this state, the protein can associate with a wide range of hydrophobic and amphiphilic compounds, these interactions involving limited sections of the protein. (c) The strength of binding to bilayers and the accompanying conformational changes in the protein are greatest for systems containing acidic lipids, presumably because of the involvement of ionic interactions. (d) When bound to bilayers of acidic lipids, MBP will have substantially more ordered secondary structure than it manifests in aqueous solution, and it is likely to be oligomeric (possibly hexameric). (e) MBP does affect the organization of lipid aggregates. It influences strongly the separation of bilayers in multilayers of purified lipids, and at present this must be viewed as its prime role within myelin. The greatest impediment to our understanding of MBP is the lack of an assayable biological activity. In contrast to the situation with enzymes, for example, we have no functional test for changes in protein structure or changes accompanying interactions with other molecules. Current evidence suggests that the protein has a structural role within myelin and that its own three-dimensional structure is strongly dependent on the molecules with which it is associated. If this picture is correct, studies of the isolated protein or of the protein in reconstituted lipid systems may yield, at best, a rough guide to the structure within its biological environment. Further clarification of the structure and function of MBP may have to await development of more powerful techniques for studying proteins bound to large molecular aggregates, such as lipid bilayers. The paucity of generally applicable methods is reflected in the fact that even low resolution structures are known for only a handful of intrinsic membrane proteins, and even more limited information exists for proteins associated with membrane surfaces. However, the increasing use of a combination of electron microscopy and diffraction on two-dimensional arrays of proteins formed on lipid bilayers (Henderson et al., 1990) offers the hope that it may not be too long before it will be possible to study at moderate resolution the three-dimensional structure of MBP bound to a lipid membrane.

Animals↗
PubMed1992

Psychosocial growth failure: a positive response to growth hormone and placebo.

Seven children were diagnosed as having an emotional cause for growth failure. Pretreatment growth hormone secretion profiles during sleep were analysed using PULSAR. Mean (+/- SD) growth hormone concentration was 10.9 (4.4) mU/l, mean peak 19.6 (6.7) mU/l and the peak-to-peak interval 147 (108) min. Mean (SEM) IGF-I was 1.08 (0.31). The seven children received a six-month course of recombinant growth hormone in a double-blind, crossover study using a dose of 1.2 U/kg/week (28 U/m2/week). Daily placebo injections were given for the other six-month epoch, with a one month washout period. The mean (SEM) growth velocity SD score after growth hormone administration was +4.66 (1.88) and after placebo -0.60 (0.69), each value being greater than the pretreatment value of -2.32 (0.122) (p less than 0.0001 on analysis of variance). The change in IGF-I during growth hormone treatment was not significant. No significant changes in food energy or protein intake occurred.

Age Determination by Skeleton↗
PubMed1992

Comparison of rapid methods of detection of cytomegalovirus in saliva with virus isolation in tissue culture.

Two rapid methods for the detection of cytomegalovirus (CMV) in saliva from congenitally and perinatally infected children were assessed by comparison with traditional virus isolation in tissue culture (TC). The polymerase chain reaction (PCR) was used to amplify a 300-bp segment of the CMV gB gene which was detected in ethidium bromide-stained agarose gels. A centrifugation-enhanced microtiter culture method with a monoclonal antibody for the detection of early-antigen fluorescent foci (DEAFF) was also used. Saliva specimens were collected with mouth swabs from children who were between the ages of 1 month and 14 years and who had either prenatal or perinatal CMV infection. One hundred sixty samples were tested by PCR and TC; 65 (40.6%) were found positive by TC, and 58 (36.8%) were found positive by PCR. Although four samples were found positive by PCR and negative by TC, saliva from seronegative and seropositive TC-negative adults were never found positive by PCR. One hundred fifty-two samples were tested by DEAFF and TC; 64 (42.1%) were found positive by TC, and 58 (38.2%) were found positive by DEAFF. With TC results as a standard, the sensitivity and specificity of DEAFF were, respectively, 90.6 and 97.7%. Because of the greater ease of collecting saliva than urine from newborns, both of these rapid methods merit evaluation in screening for congenital infection.

Adolescent↗
PubMed1992

A national study of psychiatrists' professional activities.

OBJECTIVE AND METHOD: A mail survey was conducted in 1988-1989 to study the professional activities of U.S. psychiatrists. Data from the 19,431 active respondents are reported. RESULTS: Nineteen percent of the psychiatrists were women, an increase from the 17% reported in 1982. The median age of the respondents was 50 years. Nearly one-third of the respondents expressed interest in each of the following areas of subspecialization: adolescent psychiatry, substance abuse, geriatrics, and consultation-liaison psychiatry. More than one-fifth reported formal fellowship training in child/adolescent psychiatry. The psychiatrists worked an average of 48 hours per week--two-thirds in direct patient care--in an average of 2.3 different settings. The proportion of psychiatrists reporting private practice as their primary work setting showed a marked decline from 53% in 1982 to 45% in 1988. There was an increase from 4% in 1982 to 11% in 1988 in those whose primary work setting was a private psychiatric hospital. The typical caseload was over 60 patients, with roughly half that number seen each week. For inpatients treated, the two most common diagnoses were affective disorders and schizophrenic disorders. In a typical week psychiatrists treated about one-half of their outpatients with individual psychotherapy; three-fifths of these were also treated with medications. The average net income for psychiatrists working 35 hours or more per week was $99,850 for men and $73,174 for women. CONCLUSIONS: Major trends evident from this study are subspecialization, medicalization, privatization, feminization, and organizational diversification.

Adult↗
PubMed1992

Experimental comparison of the effects of three treatment programs for homeless mentally ill people.

A longitudinal experimental design was used to compare the effectiveness of three community-based treatment programs serving homeless mentally ill people: traditional outpatient treatment offered by a mental health clinic, a daytime drop-in center, and a continuous treatment team program that included assertive outreach, a high staff-to-client ratio, and intensive case management. At 12-month follow-up, clients in all three treatment programs spent fewer days per month homeless, showed fewer psychiatric symptoms, and had increased income, interpersonal adjustment, and self-esteem. Clients in the continuous treatment program had more contact with their treatment program, were more satisfied with their program, spent fewer days homeless, and used more community services and resources than clients in the other two programs.

Activities of Daily Living↗
PubMed1992

A pilot study of the effect upon multiple sclerosis of the menopause, hormone replacement therapy and the menstrual cycle.

A questionnaire enquiring about changes in severity of symptoms of multiple sclerosis with the menstrual cycle, menopause and use of hormone replacement therapy was answered retrospectively by 11 premenopausal and 19 postmenopausal women. Eighty-two per cent of menopausal women reported an increase in severity premenstrually. Of the postmenopausal women 54% reported a worsening of symptoms with the menopause, and 75% of those who had tried hormone replacement therapy reported an improvement. The results of this pilot study indicate the need for further research to clarify the effects of the menopause and hormone replacement therapy upon multiple sclerosis.

Adult↗
PubMed1992

Long-term follow-up on National Cancer Institute Phase I/II study of glioblastoma multiforme treated with iododeoxyuridine and hyperfractionated irradiation.

PURPOSE: We report the results of the final phase I/II program in glioblastoma (GBM) multiforme patients using only hyperfractionated irradiation and intravenous iododeoxyuridine (IdUrd). METHODS: For a decade we investigated halogenated pyrimidine radiosensitizers in an effort to exploit the potential for differential uptake of thymidine analogs between proliferating tumor and normal brain tissues. Trials began with bromodeoxyuridine (BrdUrd) but were changed to IdUrd when the latter proved less photosensitizing. A series of dose-escalating pilot trials led to treatment at a maximum-tolerated dose (MTD) of IdUrd of 1,000 mg/m2/d for two separate 14-day courses, one during the initial radiation field and one during the cone down. The radiotherapy also evolved over time and was hyperfractionated in all cases reported. Over 5 years we accrued 45 patients into the final hyperfractionated, 1,000 mg/m2/d scheme. We report here results on only the patients with minimum follow-up of 1 year (90% had at least 2 years of follow-up) or until death. RESULTS: The results do not indicate a significant benefit for use of sensitizers, as compared with other contemporary and aggressive types of radiation treatment. The median survival has been 11 months, with a 2-year actuarial survival of 9%. As yet, there are no survivors at 3 years. Tumor biopsies at craniotomy showed relatively low sensitizer incorporation. CONCLUSION: The failure of radiosensitizers combined with radiation therapy to show major benefit may be due to patient selection but appears also to be related to the combined problems of poor drug penetration/uptake into tumor, tumor-cell heterogeneity, and a high inherent cellular radioresistance of GBM.

Adult↗
PubMed1992

Beta-endrophin immunoreactivity during human pregnancy.

The human placenta has been implicated as a source of numerous peptide hormones during pregnancy. Since the immunoassay detection of the proopiomelanocortin derived peptide beta-endorphin (beta E) in placental extracts in 1978, it has remained uncertain whether placental beta E immunoreactivity (IR) is 1) secreted into the maternal circulation and 2) opiate receptor active during pregnancy. To elucidate the nature of beta E IR in the placenta, both beta E IR and N-alpha-acetylated beta E (Ac beta E) IR were simultaneously measured in extracts of human pituitaries, placentas, and plasma by two homologous RIAs. Pituitary extracts (n = 6) contained 38 +/- 7 nmol beta E IR per g wet wt tissue (mean +/- SEM), of which only 20 +/- 4 pmol/g were Ac beta E IR. Term placental extracts (n = 19) had 201 +/- 30 fmol/g wet wt total beta E IR and 30 +/- 3 fmol/g wet wt total Ac beta E IR, which comprised 15% of total beta E IR in placental extracts. Total plasma beta E IR rose from 28 weeks gestation (8.5 +/- 0.3 fmol/mL, n = 159) to peak at labor (50 +/- 4 fmol/mL, n = 98; P < 0.01) but total Ac beta E IR was found in only four 28-week (1.7 +/- 0.9 fmol/mL) and 42 labor plasma samples (0.9 +/- 0.1 fmol/mL). Gel filtration chromatography of placental and pituitary extracts showed that while less than 1% of the beta E31-size material was acetylated in the pituitary, up to 60% of the beta E31-size material in placental extracts was acetylated. In pooled third trimester plasma extracts, however, only 4% of the beta E31-size material was acetylated. Furthermore, the ratio of beta E31:beta-lipotropin in pituitary extracts (n = 3) was 0.5; pooled plasma-0.5, and placental extracts (n = 5)-1.2. These data indicate that 1) the placenta extensively N-alpha-acetylates beta E31 destroying its opiate bioactivity while the pituitary does not; 2) beta E IR in pregnant women's plasma is similar to pituitary beta E IR, being mostly nonacetylated and similar in size to beta-lipotropin. These findings are consistent with a pituitary source for the elevated plasma beta E IR found during late pregnancy which may, in turn, be a consequence of elevated plasma concentrations of placentally secreted plasma corticotropin-releasing factor IR present during the third trimester.

Acetylation↗
PubMed1992

Lead exposure and ALS.

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Amyotrophic Lateral Sclerosis↗
PubMed1992

A quantitative assessment of lung cancer risk and occupational cadmium exposure.

We have performed a quantitative assessment of the risk of lung cancer from exposure to cadmium based on a retrospective cohort mortality study of cadmium-exposed workers. The findings were analysed using a life-table analysis to estimate standardized mortality ratios (SMRs), and various functional forms of Poisson and Cox proportionate hazards models to examine dose-response relationships. An excess mortality from lung cancer was observed for the entire cohort (SMR = 149,95% CI = 95-222). Lung cancer mortality was significantly elevated among non-hispanic workers, among those in the highest cadmium-exposure group, and among workers with 20 or more years since first exposure. A statistically significant dose-response relationship was evident in nearly all of the regression analyses. Based on our analyses, the lifetime excess lung cancer risk at the current OSHA standard for cadmium fumes of 100 micrograms/m3 is approximately 50-111 lung cancer deaths per 1000 workers exposed to cadmium for 45 years.

Adult↗
PubMed1992

Nonuniform expression of a mouse mammary tumor virus-driven int-2/Fgf-3 transgene in pregnancy-responsive breast tumors.

We have developed transgenic mice in which expression of the mouse int-2/Fgf-3 gene is regulated by a single long terminal repeat from mouse mammary tumor virus. Such mice contain and transmit a replica of the activated int-2/Fgf-3 allele present in a spontaneous mammary tumor from a BR6 mouse. Although free of infectious mouse mammary tumor virus and with a different genetic background, the transgenic mice develop pregnancy-responsive mammary epithelial proliferations that are similar to the early stages of tumorigenesis in the BR6 strain. Histological examination revealed that most of these tumors showed pronounced tubular and acinar structures, features usually associated with morphological differentiation. In some cases, the tumors were locally invasive, causing disruption of the dermis which manifested itself as local hair loss. In situ hybridization showed that patterns of transgene expression in the abnormal glands were markedly nonuniform. In contrast, mouse mammary tumor virus-induced neoplasms showed more uniform expression of int-2/Fgf-3, as did the urogenital epithelial proliferations that occur among males of this transgenic line. These data suggest that mammary tumors in virally infected animals may depend primarily on autocrine stimulation by the int-2/Fgf-3 gene product, whereas both autocrine and paracrine mechanisms may contribute to tumors and hyperplasias found in transgenic animals.

Animals↗
PubMed1992

Segregation of structural collagen genes in adolescent idiopathic scoliosis.

The etiology of idiopathic scoliosis remains unknown. The condition results in a characteristic deformity of the spine and surrounding tissues. Both Types I and II collagen are important constituents of the affected tissues, and thus defective collagens are reasonable candidates for the primary abnormality in adolescent idiopathic scoliosis (AIS). Direct analyses of the amount and solubility of collagen have revealed differences between normal individuals and those with AIS. However, these changes may be secondary to the mechanical effects of the spinal deformity. Segregation analysis was done of genetic markers linked to the structural genes encoding Types I and II collagen to test these candidate loci in four pedigrees with dominantly inherited AIS. In one pedigree, markers linked to both of the Type I collagen loci (COL1A1 and COL1A2) were found to be inherited independently of the abnormal phenotype. Two pedigrees were discordant at one of the Type I loci. The condition also segregated independently of the locus for Type II collagen (COL2A1) in three pedigrees. This is evidence against idiopathic scoliosis generally being caused by mutations in the Types I and II collagen genes.

Adolescent↗