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Biomedical subjects

M Samuel

Publications and source records attributed to M Samuel.

At least 19 recordsLinked to original sources
PubMed1992

Transcriptional inhibition of the bacteriophage T7 early promoter region by oligonucleotide triple helix formation.

We have identified a purine-rich triplex binding sequence overlapping a -35 transcriptional early promoter region of the bacteriophage T7. Triplex-forming oligonucleotide designed to bind this target was annealed to T7 templates and introduced into in vitro transcription systems under conditions favoring specific initiation from this promoter. These templates demonstrated significant transcriptional inhibition relative to naked genomic templates and templates mixed with non-triplex-forming oligonucleotide. It is suggested that triplex formation along this target interferes with transcriptional initiation, and this mechanism may hold potential to disrupt bacteriophage T7 early transcription in vivo.

Bacteriophage T7↗
PubMed1992

A simple and rapid method to study the association of the contact proteins of blood coagulation.

Native and reduced SDS polyacrylamide gel electrophoresis on the automated PhastSystem (Pharmacia) were used to demonstrate protein-protein binding interactions and structural changes during proteolytic activations of the proteins involved in contact activation. The "mobility shift" assay in native gels has been used to visualize the kinetics of activation of factor XII by dextran sulfate as well as the formation of kallikrein-cleaved high molecular weight kininogen. It shows the formation of prekallikrein-high molecular weight kininogen complexes and factor XII-dextran sulfate complex for the first time in gels. The use of automation makes this procedure fast and reproducible using nanogram amounts of protein in relatively short time.

Amino Acid Sequence↗
PubMed1992

Human factor XII (Hageman factor) autoactivation by dextran sulfate. Circular dichroism, fluorescence, and ultraviolet difference spectroscopic studies.

The first event leading to the activation of the plasma kallikrein-kinin system is the surface-dependent conversion of factor XII to an active enzyme. Factor XII autoactivation was investigated using dextran sulfate as a soluble activating surface, and the significance of aggregation and the nature of the conformational change were examined by ultraviolet difference spectroscopy, fluorescence and circular dichroism. Results indicate that DS500 (500-kDa dextran sulfate) induces aggregation of factor XII. Analysis of the binding data suggests that 165-192 factor XII molecules can bind to one DS500 chain, while a 1:1 stoichiometry is observed with 5-kDa dextran sulfate. The interaction of factor XII and dextran sulfate is a biphasic process. It is initiated by a fast contraction of the molecule upon binding, as revealed by an apparent increase in organized secondary structures, and then followed by a slow relaxation process during cleavage and subsequent activation. Overall, the results are consistent with a model in which factor XII undergoes conformational changes upon binding to the activating surface. The rapidity of autoactivation in the presence of DS500, as opposed to 5-kDa dextran sulfate, implies that aggregation provides a special mechanism whereby proteolytic cleavage is accomplished efficiently when factor XII molecules are bound side by side on the DS500 molecule.

Circular Dichroism↗
PubMed1992

Progression to AIDS in HIV-infected homosexual and bisexual men with hairy leukoplakia and oral candidiasis.

OBJECTIVE: This study was designed to assess the significance of HIV-related oral lesions in predicting the rate of progression to AIDS. DESIGN: Cohorts were investigated prospectively, and oral examinations were performed by clinicians trained in the diagnosis of oral lesions. SETTING: We studied three existing cohorts of homosexual and bisexual men in San Francisco, California, USA. PARTICIPANTS: Of the HIV-infected men who received standardized oral examinations (n = 791), 603 were eligible for analysis of baseline examinations and 448 for analysis of follow-up examinations. MAIN OUTCOME MEASURES: We determined time from presence of oral lesion at baseline or follow-up examination, or from participant self-reported history of the lesion, to diagnosis of AIDS. RESULTS: Using proportional hazard regression and stratifying by CD4 lymphocyte count at the time of baseline oral examination, we found that the rate of development of AIDS was increased among men with hairy leukoplakia [relative hazard, 1.8; 95% confidence interval (CI), 1.2-2.7], oral candidiasis (relative hazard, 7.3; 95% CI, 3.1-17.3), and both lesions (relative hazard, 3.1; 95% CI, 1.6-6.1) compared with men with normal findings. On follow-up examination, stratifying for CD4 count, the rate of progression to AIDS was similar for those with hairy leukoplakia compared with those with oral candidiasis. The progression rate from oral candidiasis to AIDS was faster from presence on baseline examination than from presence on follow-up examination or from self-reported history of the lesion. CONCLUSION: The presence of oral candidiasis and/or hairy leukoplakia on baseline examination confers independent prognostic information and should be incorporated into HIV-staging schemes.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Smooth muscle myosin isoform distribution and myosin ATPase in hypertrophied urinary bladder.

Hypertrophy of the urinary bladder was produced in rabbit by partial ligation of the urethra. Electrophoresis of the bladder smooth muscle myosin on highly porous (3.5-7% gradient) SDS-polyacrylamide gel revealed two heavy chain isoforms, SM-1 and SM-2 with approximate molecular weights of 204,000 and 200,000, respectively. The ratio of the SM-2 to SM-1 heavy chain is 3:1 for myosin isolated from normal bladder smooth muscle, and this ratio changes to about 1:1 in hypertrophied bladder. Despite a change in the ratio of SM-2 to SM-1, the myosin ATPase and the actin-activated ATPase activities are not altered in response to hypertrophy.

Animals↗
PubMed1991

Mechanism for the inhibition of acto-heavy meromyosin ATPase by the actin/calmodulin binding domain of caldesmon.

Caldesmon, an actin/calmodulin binding protein, inhibits acto-heavy meromyosin (HMM) ATPase, while it increases the binding of HMM to actin, presumably mediated through an interaction between the myosin subfragment 2 region of HMM and caldesmon, which is bound to actin. In order to study the mechanism for the inhibition of acto-HM ATPase, we utilized the chymotryptic fragment of caldesmon (38-kDa fragment), which possesses the actin/calmodulin binding region but lacks the myosin binding portion. The 38-kDa fragment inhibits the actin-activated HMM ATPase to the same extent as does the intact caldesmon molecule. In the absence of tropomyosin, the 38-kDa fragment decreased the KATPase and Kbinding without any effect on the Vmax. However, when the actin filament contained bound tropomyosin, the caldesmon fragment caused a 2-3-fold decrease in the Vmax, in addition to lowering the KATPase and the Kbinding. The 38-kDa fragment-induced inhibition is partially reversed by calmodulin at a 10:1 molar ratio to caldesmon fragment; the reversal was more remarkable in 100 mM ionic strength at 37 degrees C than in 20 or 50 mM at 25 degrees C. Results from these experiments demonstrate that the 38-kDa domain of caldesmon fragment of myosin head to actin; however, when the actin filament contains bound tropomyosin, caldesmon fragment affects not only the binding of HMM to/actin but also the catalytic step in the ATPase cycle. The interaction between the 38-kDa domain of caldesmon and tropomyosin-actin is likely to play a role in the regulation of actomyosin ATPase and contraction in smooth muscle.

Actins↗
PubMed1991

Intellectual, social and nutritional status of children in an Ethiopian orphanage.

Children at the Jimma community orphanage between the ages of 5 and 14 years were given a battery of tests to assess their intellectual, social, and nutritional well-being relative to a group of family-reared controls. On two tests of intellectual ability, the Ravens Progressive Matrices and the Conservation test, the orphanage children performed as well as the family children. Children who entered the orphanage at an early age scored higher than those who entered later. On social-emotional measures of self-esteem, the orphanage children scored higher than or similar to the controls. However, in terms of their relationships with adults, the orphanage children reported fewer interactions and weaker attachments to adults. This was largely determined by the higher child: adult ratio in the orphanage than in family homes. Also, the orphanage children were more likely to be stunted but not more likely to be wasted than the family children. The former was attributed to the malnutrition experienced by children before they entered the orphanage, which in many cases was during the 1984 famine. Stunting was associated with lower Ravens scores. The generally favourable status of the orphanage children can largely be attributed to the noninstitutional orphanage rather than to their preorphanage family life. This raises disturbing questions about family life under conditions of economic stress.

Child↗
PubMed1991

The prevalence of oral lesions in HIV-infected homosexual and bisexual men: three San Francisco epidemiological cohorts.

To establish the prevalence of HIV-related oral lesions, we performed oral examinations of members of three San Francisco epidemiological cohorts of homosexual and bisexual men over a 3-year period. Hairy leukoplakia, pseudomembranous and erythematous candidiasis, angular cheilitis, Kaposi's sarcoma, and oral ulcers were more common in HIV-infected subjects than in HIV-negative subjects. Among HIV-infected individuals, hairy leukoplakia was the most common lesion [20.4%, 95% confidence interval (CI) 17.5-23.3%] and pseudomembranous candidiasis was the next most common (5.8%, 95% CI 4.1-7.5%). Hairy leukoplakia, pseudomembranous candidiasis, angular cheilitis and Kaposi's sarcoma were significantly more common in patients with lower CD4 lymphocyte counts (P less than 0.05). The prevalence of erythematous candidiasis and Kaposi's sarcoma increased during the 3-year period. Careful oral examinations may identify infected patients and provide suggestive information concerning their immune status.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Population-based estimates of zidovudine and aerosol pentamidine use in San Francisco: 1987-1989.

From the San Francisco Men's Health Study (SFMHS) and the San Francisco General Hospital Cohort we derived partially population-based estimates of zidovudine (ZDV) use in San Francisco from 1987 to 1989. Data from the SFMHS alone were used to make estimates of aerosol pentamidine (AP) use in 1989. From 1987 to 1989, zidovudine use increased from 36 to 68% in participants with AIDS. In participants with symptomatic HIV infection without AIDS and in those with less than 200 CD4 cells, ZDV use increased initially but then leveled off (from 6 to 25% and 24 to 55%, respectively). Zidovudine use with more than 500 CD4 cells increased from 0.5 to 4%. In 1989 AP use with less than 200 CD4 cells was 42% and with AIDS was 44%. Whereas 50% of participants with AIDS and less than 200 CD4 were using both ZDV and AP, only 14% of those without AIDS but with less than 200 CD4 cells were using both. Surprisingly few members of these cohorts are using therapies proven effective in reducing the morbidity and mortality of HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Effects of phosphorylation, magnesium, and filament assembly on actin-activated ATPase of pig urinary bladder myosin.

The relationship between the light-chain phosphorylation and the actin-activated ATPase activity of pig urinary bladder myosin was either linear or nonlinear depending on the free Mg2+ concentration. Varying the free [Mg2+] in the presence of 50 mM ionic strength (I) had a biphasic effect on the actin-activated ATPase. In 100 mM I, the activity increased on raising the free [Mg2+]. The activity of the phosphorylated myosin was 3-23-fold higher than that of the unphosphorylated myosin at all concentrations of free Mg2+, pH, and temperature used in this study. The increase in the turbidity and sedimentability of both phosphorylated and unphosphorylated myosins on raising the free [Mg2+] was associated with a rise in the actin-activated ATPase activity. However, myosin light-chain phosphorylation still had a remarkable effect on the actin activation. The myosin polymers formed under these conditions were sedimented by centrifugation. Experiments performed with myosin polymers formed in mixtures of unphosphorylated and phosphorylated myosins showed that the presence of phosphorylated myosin in these mixtures had a slight effect on the sedimentation of the unphosphorylated myosin but it had no effect on the actin-activated ATP hydrolysis. Electron microscopy showed that the unphosphorylated myosin formed unorganized aggregates while phosphorylated myosin molecules assembled into bipolar filaments with tapered ends. These data show that although the unphosphorylated and phosphorylated myosins have the same level of sedimentability and turbidity, the filament assembly present only with the phosphorylated myosin can be associated with the maximal actin activation of Mg-ATPase.

Actins↗
PubMed1989

Absence of DNA damage-mediated induction of human methyltransferase specific for precarcinogenic O6-methylguanine.

The ability of cultured normal human fetal liver and kidney epithelial cells to repair the premutagenic and precarcinogenic O6-methylguanine (O6-MeGua) DNA adduct was determined by directly monitoring its loss in cellular DNA and quantitating the number of O6-MeGua-DNA-methyltransferase (O6-MT) molecules per cell. Following treatment of the epithelial cells with the direct acting carcinogen N-methyl-N-nitrosourea (MNU), the loss of the O6-MeGua adduct was biphasic, exhibiting a half-life of 2.0 and 1.5 h in the liver and kidney cells, respectively. The activity of O6-MT in the liver and kidney epithelial cells in culture was 0.19 pmol/mg protein or 18,500 molecules/cell. The activity of O6-MT was maintained throughout the life of the cultures, i.e., 20 subpassages or 50 cumulative population doublings for the liver and kidney. In order to ascertain whether human fetal epithelial cells exhibit an induction of O6-MT, the cell cultures were treated with single and multiple conditioning doses of N-methyl-N-nitro-N-nitroso-guanidine (MNNG) or gamma-irradiated and assayed for the amount of O6-MT. A 1 h exposure of cells to 2, 4, and 8 microM MNNG resulted in an 80-100% decrease of the initial O6-MT activity which was restored to the constitutive levels within 48 and 72 h post-treatment. Rat hepatoma cells, used as a positive control, increased their levels of O6-MT to 2.8-fold the constitutive levels following treatment with MNNG. Treatment of the human liver and kidney epithelial cells with chronic low doses of MNNG exhibited O6-MT levels identical to untreated cells. The O6-MT activity in epithelial cells remained unaffected upon pre-irradiation with 1.2 or 2.5 Gy of gamma-irradiation.

Animals↗
PubMed1989

Endometrial adenocarcinoma histologic subtypes: clinical and pathologic profile.

All cases of endometrial adenocarcinoma treated at the Geisinger Medical Center from January 1970 to June 1980 were retrospectively reviewed in an attempt to elucidate the clinical and pathologic profiles of the various histologic subtypes. Complete clinical and pathologic data was available in 418 cases of stage I endometrial adenocarcinoma. The frequency of the histologic subtypes were adenocarcinoma 66%, adenoacanthoma 16%, adenosquamous 5%, papillary 8%, clear cell 3%, and secretory 2%. Absolute 5-year survival was adenocarcinoma 88%, adenoacanthoma 91%, adenosquamous 62%, papillary 63% (P less than 0.01), clear cell 43% (P less than 0.001), and secretory 89%. When comparing the clinical and pathologic profile of the various histologic subtypes, adenosquamous (52%, P less than 0.001) and clear cell (43%, P less than 0.05) were associated with the highest percentage of grade 3 differentiation. Adenosquamous (38%, P less than 0.05) and clear cell (36%) also had the highest percentage of deep myometrial invasion. Papillary subtype (46%, P less than 0.05) was associated with the highest percentage of nulliparity. There was no difference among the subtypes when comparing menopausal status, exogenous estrogen, obesity, hypertension, diabetes, or uterine size. In summary, (1) adenocarcinoma and adenoacanthoma are the most frequent subtypes; (2) adenosquamous, papillary, and clear cell have decreased 5-year survival; (3) the decreased 5-year survival in adenosquamous and clear cell subtypes appears to be associated with increased grade 3 differentiation and deep myometrial invasion while the poor prognosis associated with papillary subtype was not related to grade or myometrial invasion.

Adenocarcinoma↗
PubMed1989

DNA photoreactivating enzyme from human tissues.

Photoreactivating enzyme activity has been quantitated in human fetal skin, kidney, lung, liver, brain and intestine, and in neonatal human foreskin. In all the tissues examined there were at least two activities: one nominally greater than 10,000 Da, and one nominally less than 10,000 Da. Both can photolyze pyrimidine dimers in DNA using only light of wavelengths greater than 320 nm, thus excluding tryptophan-mediated dimer splitting as an important mechanism for these activities. The activities are inactivated by digestion with trypsin or pronase, and decreased partially or totally by heating to 65 degrees C. The activities from all six tissues, as well as that from neonatal foreskin, act catalytically in dimer photolysis. The properties of macromolecular size, heat lability, protease sensitivity and catalytic pyrimidine dimer photolysis by a non-tryptophan-mediated mechanism correspond to those of a true photoreactivating enzyme.

Deoxyribodipyrimidine Photo-Lyase↗
PubMed1988

[The prevention of AIDS among young people].

In the first section of the article, the authors consider the epidemiological data available in Switzerland mid-june 1988, concerning persons between 15 to 24, either already suffering from AIDS or HIV-positive. These data are compared with those from Europe and the United States. In a second section, the authors analyse the attitude and behaviors of young people with respect to sexuality in general and to AIDS. In a third section, they survey different AIDS prevention programs and methods, namely campaigns through schools, the mass media and youth associations. The role of health and medical profession is also considered. Alternative strategies are presented: travelling exhibitions, mobile disco, street work, adoption of adolescent go-betweens etc. The article concludes that prevention should extend beyond the information: youth discussion dialogue and participation is essential.

Acquired Immunodeficiency Syndrome↗
PubMed1988

The San Francisco Men's Health Study: continued decline in HIV seroconversion rates among homosexual/bisexual men.

The incidence of infection by the human immunodeficiency virus (HIV) has been monitored since 1984 in an area probability sample of homosexual/bisexual men drawn from a six-kilometer square area of San Francisco where the epidemic of acquired immunodeficiency syndrome (AIDS) has been most severe. Annualized HIV seroconversion rates in previously uninfected cohort members have declined by 88 per cent from 5.9 per cent during the first six months of 1985 to 0.7 per cent during the last six months of 1987. Concurrent declines of approximately 80 per cent in the prevalence of sexual behaviors associated with HIV transmission were also observed in the sample.

AIDS Serodiagnosis↗