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1.
J Cell Biol ; 85(3): 549-57, 1980 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-6248564

RESUMO

A continuous tissue culture cell line (Karpas line 120), derived from a patient with acute myeloblastic leukemia, not only demonstrates myeloblastic morphology and in vitro expression of several myeloid-specific biochemical markers but also contains Epstein-Barr virus (EBV) nuclear antigen. The present studies demonstrate EBV-genome-specific DNA within the total cellular DNA by molecular hybridization, thus establishing the presence of stable viral genome integration. The cells demonstrate complex coordinated myeloid functions including ingestion, degranulation, and respiratory burst activity. Line 120 cells show a respiratory burst (superoxide and hydrogen peroxide generation and hexosemonophosphate shunt activity) in response to soluble (phorbol myristate acetate) and particulate (latex beads) stimuli, as do normal granulocytes. They ingest complement-opsonized particles (lipopolysaccharide-oil droplets, zymosan, and bacteria), and degranulate in response to them. However, unlike normal granulocytes, the line 120 cells do not demonstrate respiratory burst activity in response to these complementopsonized particles. The dissociation between ingestion of complement-opsonized particles and activation of oxygen-dependent bactericidal activity severely impairs bacterial killing as compared with normal polymorphonuclear phagocytes.


Assuntos
Transformação Celular Viral , Herpesvirus Humano 4 , Leucemia Mieloide Aguda/fisiopatologia , Consumo de Oxigênio , Fagocitose , Animais , Atividade Bactericida do Sangue , Linhagem Celular , DNA Viral/análise , Herpesvirus Humano 4/genética , Hexosefosfatos/metabolismo , Peróxido de Hidrogênio/metabolismo , Leucemia Experimental/fisiopatologia , Superóxidos/metabolismo
2.
Science ; 216(4549): 997-9, 1982 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-7079750

RESUMO

A new human plasmacytoma cell line (Karpas 707) has been established from a myeloma patient. The cultured cells are negative for Epstein-Barr viral nuclear antigen and free of mycoplasma. They are similar to plasma cells and secrete only lambda light chains. The cells are hypodiploid and contain the Philadelphia chromosome and other abnormalities. This cell line may be suitable for the production of human monoclonal antibodies.


Assuntos
Anticorpos Monoclonais/biossíntese , Linhagem Celular , Plasmocitoma/genética , Cromossomos Humanos 21-22 e Y/ultraestrutura , Humanos , Hibridomas/imunologia , Masculino , Pessoa de Meia-Idade , Plasmocitoma/imunologia , Plasmocitoma/ultraestrutura
3.
Science ; 202(4365): 318-19, 1978 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-211588

RESUMO

The production and nature of alkaline phosphatase were studied in Epstein-Barr viral nuclear antigen-positive, surface membrane immunoglobulin negative-cell lines established from two patients, one with acute myeloid leukemia and one with acute lymphoblastic leukemia. The acute myeloid leukemia-derived cells contained myeloid alkaline phosphatase, while the acute lymphoblastic leukemia-derived cells contained lymphoid alkaline phosphatase. The presence of the myeloid-specific enzyme in a surface membrane immunoglobin--negative cell line suggests that the line is composed of myeloid precursor cells and that such cells may be susceptible to infection with Epstein-Barr virus.


Assuntos
Fosfatase Alcalina/metabolismo , Antígenos Virais , Herpesvirus Humano 4 , Isoenzimas/metabolismo , Leucemia Linfoide/enzimologia , Leucemia Mieloide Aguda/enzimologia , Antígenos Virais/análise , Núcleo Celular/imunologia , Transformação Celular Viral , Herpesvirus Humano 4/imunologia , Leucemia Linfoide/microbiologia , Leucemia Mieloide Aguda/microbiologia , Receptores de Antígenos de Linfócitos B/análise
4.
J Clin Invest ; 72(3): 1005-15, 1983 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-6411766

RESUMO

The specific roles of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in controlling human spermatogenesis are poorly understood. We studied the effect of an experimentally induced, selective LH deficiency on sperm production in normal men. After a 3-mo control period, five men received 200 mg testosterone enanthate (T) i.m./wk to suppress LH, FSH, and sperm counts. Then, while continuing T at the same dosage, human FSH (hFSH) was administered simultaneously to replace FSH activity, leaving LH activity suppressed. Four men received 100 IU hFSH s.c. daily plus T (high dosage hFSH) for 13-14 wk, while one man received 50 IU hFSH s.c. daily plus T (low dosage hFSH) for 5 mo. The effect on sperm production of the selective LH deficiency produced by hFSH plus T administration was assessed. In the four men who received the high dosage hFSH regimen, sperm counts were markedly suppressed during T administration alone (0.3+/-0.2 million/cm(3), mean+/-SE, compared with 94+/-12 million/cm(3) during the control period). Serum LH bioactivity (determined by in vitro mouse Leydig cell assay) was suppressd (140+/-7 ng/ml compared with 375+/-65 ng/ml during control period) and FSH levels (by radioimmunoassay) were reduced to undetectable levels (<25 ng/ml, compared with 98+/-21 ng/ml during control period) during T alone. With the addition of 100 IU hFSH s.c. daily to T, sperm counts increased significantly in all subjects (33+/-7 million/cm(3), P < 0.02 compared with T alone). However, no subject consistently achieved sperm counts within his control range. Sperm morphology and motility were normal in all four men and in vitro sperm penetration of hamster ova was normal in the two men tested during the hFSH-plus-T period. During high-dosage hFSH administration, serum FSH levels increased to 273+/-44 ng/ml (just above the normal range for FSH, 30-230 ng/ml). Serum LH bioactivity was not significantly changed compared with the T-alone period (147+/-9 ng/ml). After the hFSH-plus-T period, all four men continued to receive T alone after hFSH was stopped. Sperm counts were again severely suppressed (0.2+/-0.1 million/cm(3)), demonstrating the dependence of sperm production on hFSH administration. Serum T and estradiol (E(2)) levels increased two- to threefold during T administration alone compared with the control period. Both T and E(2) levels remained unchanged with the addition of hFSH to T, confirming the lack of significant LH activity in the hFSH preparation. In the one man who received low dosage hFSH treatment, sperm counts were reduced to severely oligospermic levels, serum FSH was suppressed to undetectable levels, and serum LH bioactivity was markedly lowered during the T-alone period. With the addition of 50 IU hFSH s.c. daily to T, sperm counts increased, to a mean of 11+/-3 million/cm(3). During this period, serum FSH levels increased to a mean of 105+/-11 ng/ml (slightly above this man's control range and within the normal adult range), while LH bioactivity remain suppressed. After hFSH was stopped and T alone was continued, sperm counts were again severely reduced to azoospermic levels. We conclude that FSH alone is sufficient to reinitiate sperm production in man during gonadotropin suppression induced by exogenous T administration. FSH may stimulate sperm production in this setting by increasing intratesticular T through androgenbinding protein production or by increasing the sensitivity of the spermatogenic response to the intratesticular T present during exogenous T administration.


Assuntos
Hormônio Foliculoestimulante/administração & dosagem , Hormônio Luteinizante/antagonistas & inibidores , Espermatogênese/efeitos dos fármacos , Testosterona/análogos & derivados , Adulto , Relação Dose-Resposta a Droga , Estradiol/sangue , Hormônio Foliculoestimulante/antagonistas & inibidores , Hormônio Foliculoestimulante/sangue , Humanos , Hipogonadismo/induzido quimicamente , Hormônio Luteinizante/sangue , Hormônio Luteinizante/fisiologia , Masculino , Oligospermia/induzido quimicamente , Oligospermia/fisiopatologia , Cooperação do Paciente , Contagem de Espermatozoides , Testosterona/administração & dosagem , Testosterona/efeitos adversos , Testosterona/sangue
7.
Cancer Res ; 38(10): 3340-8, 1978 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-210935

RESUMO

Fourteen continuous tissue culture cell lines derived from mouse, rat, or human granulocyte-macrophage cancers were studied for expression of spontaneous and inducible markers of differentiated cells. Five cell lines (two mouse, two rat, and one human) synthesized myeloperoxidase spontaneously, and a fifth mouse line showed biochemically inducible enzyme. Twelve lines (6 mouse, 3 rat, and 3 human) produced lysozyme (muramidase), and all had detectable beta-glucuronidase. Superoxide generation was detected in one mouse, and three human cell lines following stimulation with phorbol myristate acetate. Maturation to differentiated polymorphonuclear leukocyte or macrophage morphology was induced in 3 cell lines (2 mouse and 1 human) following culture in diffusion chambers in total-body-irradiated rats. In vitro morphological differentiation was inducible in one (mouse) cell line exposed to casein, thioglycolate, or plasma from irradiated rats or mice. These findings indicate that mammalian cell lines derived from granulocyte-macrophage cancers stably express several combinations of differentiation markers. The patterns of expression of these markers did not always correlate with the morphological stage of differentiation.


Assuntos
Granulócitos/enzimologia , Leucemia Experimental/enzimologia , Leucemia Mieloide/enzimologia , Macrófagos/enzimologia , Animais , Diferenciação Celular , Linhagem Celular , Glucuronidase/biossíntese , Granulócitos/patologia , Humanos , Leucemia Experimental/patologia , Leucemia Mieloide/patologia , Macrófagos/patologia , Camundongos , Muramidase/biossíntese , Peroxidase/biossíntese , Ratos , Superóxido Dismutase/metabolismo
8.
Leukemia ; 7(7): 1047-53, 1993 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-8391614

RESUMO

A new human T-cell non-Hodgkin lymphoma cell line of the T-cell receptor (TCR) gamma/delta lineage has been derived from the peripheral blood of a patient with a subcutaneous T-cell lymphoma in leukemic phase. The cell line (Karpas 384) initially had the same characteristics as malignant cells from the patient. Both the original tumor and the cell line failed to express any T-cell differentiation antigens other than very weak cell-surface expression of CD3 and cytoplasmic CD7; with continued growth in vitro, surface CD3 became undetectable in the presence of maintained strong cytoplasmic expression. The cell line has a complex karyotype with six abnormal chromosomes exhibiting not only t(7;14) (p13;q11.2) but also inv7(p13;q22.1), t(1;2)(q11;q35), t(2;1;14) (q35;q11-q32.1;q22.1), interstitial deletion 12(q24.1q24.3), and an unidentified marker chromosome. DNA blot analysis showed that TCR C beta and TCR J alpha-C alpha DNA sequences were in germline configuration in all restriction endonuclease digests. TCR gamma sequences showed biallelic V gamma 9-J gamma P-C gamma 1 rearrangements, the TCR gamma rearrangement detected in the majority of normal TCR gamma/delta bearing cells. Use of a range of TCR delta probes showed biallelic deletion of both J delta 1 and J delta 2, but three rearranged fragments when probed with a 3' C delta genomic probe. Similar breakpoints at 7p13 have been reported in a wide range of hematologic malignancies. Molecular cloning of the t(7;14)(p13;q11.2) translocation breakpoint in this cell line may define new DNA sequences of oncogenic potential at the 7p13 locus.


Assuntos
Linfoma de Células T , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Células Tumorais Cultivadas , Aberrações Cromossômicas/patologia , Transtornos Cromossômicos , Cromossomos Humanos Par 14 , Cromossomos Humanos Par 7 , Rearranjo Gênico da Cadeia delta dos Receptores de Antígenos dos Linfócitos T , Rearranjo Gênico da Cadeia gama dos Receptores de Antígenos dos Linfócitos T , Humanos , Imunofenotipagem , Técnicas In Vitro , Cariotipagem , Masculino , Pessoa de Meia-Idade , Translocação Genética
9.
Mol Immunol ; 33(16): 1217-22, 1996 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-9129157

RESUMO

Three murine, monoclonal antibodies, IgM 5286 F2, IgM 5297 C1, and IgG 5338 H4 were generated against Shigella dysenteriae type 1 O-specific polysaccharide (O-SP)-conjugate. They are specific for the O-SP, which is a poly-[alpha-L-rhamnopyranosyl-(1-->3)-alpha-L-rhamnopyranosyl-(1-->2)-al pha-D-galactopyranosyl-(1-->3)-2-deoxy-2-amino-N-acetyl-alpha-D-glucopyr anosyl]. The VH and VL genes of these antibodies were cloned and their sequences determined. They showed 93% homology, but were quite different to the primary sequence of IgM 3707 E9, of the same O-SP-specificity, previously reported. The fine-specificities of both IgG 5338 H4 and IgM 3707 E9 were for the same disaccharide moiety in the O-SP, while IgMs 5286 F2 and 5297 C1 showed fine-specificity for the entire repeating unit of the O-SP. Therefore, divergent sequences can confer upon antibodies similar-, or even identical-carbohydrate-epitope fine-specificity. In addition, close primary sequence-homology does not preclude differences in antibody fine-specificity.


Assuntos
Anticorpos Antibacterianos/genética , Genes de Imunoglobulinas/imunologia , Região Variável de Imunoglobulina/genética , Antígenos O/imunologia , Polissacarídeos Bacterianos/imunologia , Homologia de Sequência de Aminoácidos , Shigella dysenteriae/imunologia , Sequência de Aminoácidos , Animais , Anticorpos Antibacterianos/química , Anticorpos Monoclonais/química , Anticorpos Monoclonais/genética , Ligação Competitiva/imunologia , Sequência de Carboidratos , Cadeias Pesadas de Imunoglobulinas/química , Cadeias Pesadas de Imunoglobulinas/genética , Cadeias Leves de Imunoglobulina/química , Cadeias Leves de Imunoglobulina/genética , Região Variável de Imunoglobulina/química , Camundongos , Camundongos Endogâmicos BALB C , Dados de Sequência Molecular
10.
Mol Immunol ; 32(9): 679-82, 1995 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-7643860

RESUMO

The cDNA coding for a hybridoma anti Shigella dysenteriae type 1 antibody (3707 E9) has been cloned, and sequenced. Binding patterns with fragments of the bacterial polysaccharide antigen had already been studied in detail. The VH sequence utilizes the VH441 gene, first identified amongst beta-(1,6)galactan-binding antibodies, while the VL is closely related to the V lambda 1 gene. We found that the VL3707 E9 gene employed a VL-J combinatorial joining leading to a rare Trp-->Leu substitution at position L96.


Assuntos
Anticorpos Antibacterianos/genética , Anticorpos Monoclonais/genética , Genes de Imunoglobulinas , Região Variável de Imunoglobulina/genética , Cadeias lambda de Imunoglobulina/genética , Shigella dysenteriae/imunologia , Sequência de Aminoácidos , Animais , Sequência de Bases , Códon , Primers do DNA/química , Hibridomas , Camundongos , Dados de Sequência Molecular , Mutação Puntual
11.
AIDS ; 2(4): 255-60, 1988 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-3140831

RESUMO

Before commencing rational control programmes for AIDS in Africa it is desirable to determine the relative importance of heterosexual and various non-sexual modes of transmission. We investigated this by comparing the seroepidemiologies of AIDS, hepatitis B and syphilis at two rural hospitals in southwest Uganda. During August 1986, 3% of 357 outpatients, reflecting the age and sex composition of the general population, were anti-HIV positive. Anti-HIV seropositivity, both in the outpatients and among 36 suspected prostitutes and 14 suspected AIDS cases, was confined to individuals aged 20 or over. For men, seropositivity was associated with sexual contact with prostitutes (a risk factor for 61% of young men in the study). In the prostitute group, 25% were anti-HIV positive and 46% were positive on the Treponema pallidum haemagglutination (TPHA) test for syphilis. The risk factors for HIV, but not hepatitis B, were the same as for having a history of sexually transmitted disease (STD). However, there was, surprisingly, an association between a history of STD and seropositivity for hepatitis B virus but not for HIV infection. The geographical and age distributions of seropositivity for HIV and hepatitis B virus were also quite different. Finally, blood transfusions, scarification and exposure to mosquitoes (as assessed by a history of malaria) were not evident risk factors for either HIV or hepatitis B virus. AIDS in rural Africa seems to differ in its epidemiology from hepatitis B and appears to be spread predominantly by pre-existing patterns of heterosexual activity responsible for high rates of other sexually transmitted diseases.


PIP: AIDS in rural Africa seems to differ in its epidemiology from hepatitis B and appears to be spread predominantly by preexisting patterns of heterosexual activity responsible for high rates of other sexually transmitted diseases. The authors compared the seroepidemiologies of AIDS, hepatitis B, and syphilis at 2 rural hospitals in southwest Uganda. During August 1986, 3% of 357 outpatients, reflecting the age and sex composition of the general population, were anti-HIV positive. Anti-HIV seropositivity, both in the outpatients and among 36 suspected prostitutes and 14 suspected AIDS cases, was confined to individuals aged 20 or over. For men, seropositivity was associated with sexual contact with prostitutes (a risk factor for 61% of young men in the study). In the prostitute group, 25% were anti-HIV positive and 46% were positive on the Treponema pallidum hemagglutination (TPHA) test for syphilis. The risk factors for HIV, but not hepatitis B, were the same as for having a history of sexually transmitted disease (STD). However, there was, surprisingly, an association between a history of STD and seropositivity for hepatitis B virus but not for HIV infection. The geographical and age distributions of seropositivity for HIV and hepatitis B virus were also quite different. Finally, blood transfusions, scarification, and exposure to mosquitoes (as assessed by a history of malaria) were not evident risk factors for either HIV or hepatitis B virus.


Assuntos
Síndrome da Imunodeficiência Adquirida/transmissão , Hepatite B/epidemiologia , Sífilis/epidemiologia , Sorodiagnóstico da AIDS , Síndrome da Imunodeficiência Adquirida/diagnóstico , Síndrome da Imunodeficiência Adquirida/epidemiologia , Adolescente , Adulto , Criança , Feminino , Hepatite B/diagnóstico , Vírus da Hepatite B/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , População Rural , Infecções Sexualmente Transmissíveis/epidemiologia , Sífilis/diagnóstico , Treponema pallidum/isolamento & purificação , Uganda
12.
Endocrinology ; 119(1): 362-9, 1986 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-3522211

RESUMO

During sexual development in the male rat, serum testosterone (T) levels increase markedly at 45-60 days of age. At the time of the pubertal rise in T levels, activation of the hypothalamic-pituitary axis is difficult to demonstrate, since there is little change in serum LH levels and a decrease in serum FSH levels. We determined whether experimental maintenance of stable pubertal T levels in these animals as they passed through the normal age of puberty would allow demonstration of a major increase in serum gonadotropin levels. At 14-15 days of age, male rats were castrated and outfitted with either T-containing or empty Silastic capsules. Another group of rats was left intact and outfitted with empty capsules. At various times between 29 and 58 days of age, blood was drawn for measurement of serum LH, FSH, and T levels. In the T-implanted castrated rats, serum T levels were comparable to those in midpubertal intact rats, without significant differences among age groups. In this setting of stable T levels, serum LH and FSH were suppressed to levels at or below those in pubertal intact rats until 51 days of age, when they increased significantly into the untreated castrate range. In contrast, untreated castrate animals demonstrated markedly reduced serum T and elevated LH and FSH levels that did not change significantly throughout the entire study. In intact rats, serum T levels were stable until 58 days of age, when they increased over 2-fold; serum LH levels did not change significantly with age, and serum FSH levels decreased significantly by 54 days of age. A separate group of rats was castrated and outfitted with T-containing Silastic capsules at 21 days of age. In these animals, there were significant increases in hypothalamic LHRH, norepinephrine (NE), and dopamine levels and NE turnover rate at 56 compared to 36 days of age. We conclude that stable pubertal levels of T are able to suppress gonadotropin levels in castrated rats until the normal age of puberty, at which time LH and FSH levels increase markedly. This decrease in sensitivity of the hypothalamic-pituitary axis to T negative feedback at puberty is accompanied by increases in hypothalamic LHRH, NE, and dopamine levels and NE turnover rate. These results provide direct evidence for activation of the central nervous system-pituitary mechanism regulating gonadotropin secretion at puberty in the male rat.(ABSTRACT TRUNCATED AT 400 WORDS)


Assuntos
Gonadotropinas Hipofisárias/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Maturidade Sexual , Testosterona/metabolismo , Animais , Dopamina/análise , Implantes de Medicamento , Hormônio Liberador de Gonadotropina/análise , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Masculino , Norepinefrina/análise , Orquiectomia , Ratos , Ratos Endogâmicos , Testosterona/administração & dosagem , Testosterona/farmacologia
13.
Endocrinology ; 112(3): 788-92, 1983 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-6401622

RESUMO

Aging in the male rat is associated with a reduction in circulating testosterone levels. One possible cause of this decline is an age-related alteration of central nervous system-mediated LH secretion. To examine the effects of age on the hypothalamo-hypophyseal system, in the absence of gonadal steroid feedback, we studied the pattern of pulsatile LH secretion in castrate male Sprague-Dawley rats, aged 3 months (young), 8 months (middle-aged), and 26 months (old). All animals were castrated, and after 3 weeks, they were implanted with indwelling atrial catheters. One day later, duplicate 25 microliters blood samples were obtained at 4-min intervals for 4 h, while the animals were awake and unrestrained. Serum levels of LH, FSH, and testosterone were measured in animals before castration, and blood LH levels were measured in the postcastration, repeated sampling studies. After castration, middle-aged and old animals exhibited significantly lower mean serum LH levels, associated with a diminished amplitude of LH secretory episodes compared to young rats. In the oldest group, LH pulse frequency was significantly lower compared to middle-aged and young animals. Since the control of LH secretory episodes resides in the central nervous system, we propose that alterations in frequency of LH pulses observed in the aged, castrate male rat are the result of a diminished functional capacity of LHRH-containing neurons or of neurotransmitters that modulate their activity in the aging brain.


Assuntos
Hormônio Luteinizante/metabolismo , Envelhecimento , Animais , Castração , Feminino , Hormônio Foliculoestimulante/sangue , Hormônio Luteinizante/sangue , Masculino , Radioimunoensaio , Ratos , Ratos Endogâmicos , Testosterona/sangue
14.
J Clin Endocrinol Metab ; 62(6): 1184-92, 1986 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-3084535

RESUMO

The role of FSH in the maintenance of spermatogenesis in man is poorly understood. To determine whether normal serum levels of FSH are necessary for the maintenance of quantitatively normal spermatogenesis, we first studied the effect on sperm production of selective FSH deficiency induced by chronic administration of hCG in normal men. Then, we determined the effect of FSH replacement in some of these men. After a 3-month control period, eight normal men (aged 30-39 yr) received 5000 IU hCG, im, twice weekly for 7 months. Then while continuing the same dosage of hCG, subjects simultaneously received 200 mg testosterone enanthate (T), im, weekly for an additional 6 months. hCG administration alone resulted in partial suppression of the mean sperm concentration from 88 +/- 24 (+/-SEM) million/ml during the control period to 22 +/- 7 million/ml during the last 4 months of hCG treatment (P less than 0.001 compared to control values). With the addition of T to hCG, sperm counts remained suppressed to the same degree. Except for one man who became azoospermic while receiving hCG plus T, sperm motilities and morphologies remained normal in all subjects throughout the entire study. During both the hCG alone and hCG plus T periods, serum FSH levels were undetectable (less than 25 ng/ml), and urinary FSH levels were comparable to those in prepubertal children and hypogonadotropic hypogonadal adults. We replaced FSH activity in four of the eight men in whom prolonged selective FSH deficiency and partial suppression of sperm production were induced by hCG administration. Immediately after the period of hCG plus T administration, T was stopped in four men who continued to receive hCG alone (5000 IU, im, twice weekly) for 3 months. Then, while continuing the same dosage of hCG, these men received 100 IU human FSH, sc, daily (n = 2) or 75 IU human menopausal gonadotropin, sc, daily (n = 2) for 5-8 months. During the second period of hCG administration alone, serum FSH levels were undetectable (less than 25 ng/ml), and sperm concentrations were suppressed (34 +/- 13 million/ml) compared to the control values for these four men (125 +/- 39 million/ml; P less than 0.001). With the addition of FSH to hCG, FSH levels increased (213 +/- 72 ng/ml) and sperm concentrations rose significantly, reaching a mean of 103 +/- 30 million/ml (P less than 0.03 compared to hCG alone).(ABSTRACT TRUNCATED AT 400 WORDS)


Assuntos
Gonadotropina Coriônica/farmacologia , Hormônio Foliculoestimulante/fisiologia , Espermatogênese/efeitos dos fármacos , Adulto , Gonadotropina Coriônica/administração & dosagem , Esquema de Medicação , Estradiol/sangue , Hormônio Foliculoestimulante/deficiência , Hormônio Foliculoestimulante/farmacologia , Humanos , Masculino , Contagem de Espermatozoides/efeitos dos fármacos , Testosterona/sangue , Testosterona/farmacologia
15.
J Clin Endocrinol Metab ; 59(4): 780-4, 1984 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-6434580

RESUMO

Hirsute women may have increased serum LH levels and increased ratios of LH to FSH in serum as well as increased serum androgen levels. Glucocorticoid therapy lowers serum testosterone (T) levels in some hirsute women, but no significant effects on gonadotropin levels have been reported. Sixty hirsute women had serum T, LH, and FSH levels measured before and after acute and chronic glucocorticoid administration. Both acute and chronic treatment resulted in significant suppression of T levels. Serum LH levels significantly decreased after chronic therapy. Significant direct correlations were found between T and LH or T and the LH to FSH ratio, both before and after therapy. In 11 women with normal T levels, acute or chronic glucocorticoid treatment did not produce a significant change in LH levels or LH to FSH ratios. Women (n = 26) with elevated T levels that were suppressed more than 50% during treatment had significant decreases in their mean LH levels and LH to FSH ratios. No significant change in mean LH or LH to FSH ratio occurred in women (n = 23) with elevated T levels that were not suppressed by 50%. These results demonstrate that chronic, but not acute, glucocorticoid-induced suppression of T levels in hyperandrogenic hirsute women results in lowering of LH and LH to FSH ratios.


Assuntos
Androgênios/sangue , Hormônio Foliculoestimulante/sangue , Glucocorticoides/uso terapêutico , Hirsutismo/sangue , Hormônio Luteinizante/sangue , Adulto , Dexametasona/uso terapêutico , Feminino , Hirsutismo/tratamento farmacológico , Humanos , Prednisona/uso terapêutico , Testosterona/sangue , Fatores de Tempo
16.
J Clin Endocrinol Metab ; 57(3): 645-8, 1983 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-6683724

RESUMO

Since sex hormone-binding globulin (SHBG) levels are often elevated in sera of patients with testicular insufficiency, it is important to determine whether SHBG declines into the normal range and the extent of change in free testosterone (free T) after androgen administration. Five normal men and five patients with Klinefelter's syndrome were studied before and after the administration of testosterone enanthate (200 mg, im every 2 weeks). An additional five normal men and five patients with hypogonadotropic hypogonadism (HH) were treated with hCG (2000 U, three times a week). Three months after the administration of T or hCG, serum total and free T increased in both normal men and patients. Free T increased significantly in the Klinefelter's and HH patients from 94 +/- 20 and 14 +/- 5 pg/ml, respectively, to 271 +/- 50 and 276 +/- 41 pg/ml (P less than 0.01; P less than 0.001). The increase in the normal men treated with T or hCG was also significant (from 211 +/- 52 and 220 +/- 37 pg/ml to 390 +/- 83 and 330 +/- 90 pg/ml). SHBG fell in both the T-treated normal men (from 6.5 +/- 1.2 ng dihydrotestosterone bound/ml to 4.3 +/- 0.4; P less than 0.02) and the T-treated Klinefelter's patients (from 16.4 +/- 2 to 4.3 +/- 0.5; P less than 0.01). However, it was unchanged in the hCG-treated HH patients and rose in the hCG-treated normal men (from 6.6 +/- 0.7 to 8.6 +/- 1.0; P less than 0.05). This study demonstrates that treatment of hypogonadal men with T and hCG in the doses used increased free T levels above the basal levels for normal men. However, the effects of the increase in free T, as determined by a change in SHBG, were different depending upon the type of treatment.


Assuntos
Gonadotropina Coriônica/uso terapêutico , Hipogonadismo/sangue , Síndrome de Klinefelter/sangue , Globulina de Ligação a Hormônio Sexual/metabolismo , Testosterona/análogos & derivados , Adulto , Estradiol/sangue , Humanos , Hipogonadismo/tratamento farmacológico , Síndrome de Klinefelter/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Testosterona/sangue , Testosterona/uso terapêutico
17.
FEBS Lett ; 310(2): 171-4, 1992 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-1397268

RESUMO

Novel phosphate derivatives of the anti-HIV nucleoside analogue AZT have been prepared by phosphorochloridate chemistry. In particular, phosphates carrying ester-containing side-chains are described. These materials are designed to act as membrane-soluble pro-drugs of the bio-active free nucleotides. In vitro evaluation revealed the compounds to have a pronounced, selective antiviral activity. In several cases the phosphate derivatives are more selective in their action than the parent nucleoside AZT. In particular, this arises from the low toxicity of the phosphate pro-drugs by comparison to AZT. These data support the suggestion that the phosphate derivatives exert their biological effects via intracellular release of the nucleotide forms, and suggests that such pro-drug forms may be worthy of further study.


Assuntos
Antivirais/farmacologia , HIV-1/efeitos dos fármacos , Compostos Organofosforados/farmacologia , Zidovudina/análogos & derivados , Antivirais/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , HIV-1/fisiologia , Espectroscopia de Ressonância Magnética , Pró-Fármacos/farmacologia , Replicação Viral/efeitos dos fármacos , Zidovudina/farmacologia
18.
FEBS Lett ; 237(1-2): 128-32, 1988 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-3169233

RESUMO

The plant alkaloids castanospermine, dihydroxymethyldihydroxypyrrolidine and deoxynojirimycin have recently been shown to have potential anti-HIV activity [(1987) Proc. Natl. Acad. Sci. USA 84, 8120-8124; (1987) Nature 330, 74-77; (1987) Lancet i, 1025-1026]. They are thought to act by inhibiting alpha-glucosidase I, an enzyme involved in the processing of N-linked oligosaccharides on glycoproteins. We report here the relative efficacy of a spectrum of amino-sugar derivatives as inhibition of HIV cytopathicity. Several alpha-glucosidase inhibitors and alpha-fucosidase inhibitors were found to be active at concentrations which were non-cytotoxic.


Assuntos
Amino Açúcares/farmacologia , HIV/efeitos dos fármacos , Linhagem Celular , Replicação do DNA/efeitos dos fármacos , HIV-1/efeitos dos fármacos , HIV-1/genética , HIV-2/efeitos dos fármacos , HIV-2/genética , Humanos , Estrutura Molecular , Relação Estrutura-Atividade , Replicação Viral/efeitos dos fármacos
19.
J Immunol Methods ; 82(2): 215-24, 1985 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-3900215

RESUMO

A solid phase immunoassay utilizing avidin-biotin binding has been developed for measuring anticapsular polysaccharide antibodies. Capsular polysaccharides of Escherichia coli K1, Haemophilus influenzae type b, Staphylococcus aureus types 5 and 8, and levan from Aerobacter levanicum have been biotinylated through -OH or COOH groups with retention of antigenicity. Polysaccharides were immobilized on avidin-coated microtiter wells for use in an enzyme-linked immunosorbent assay (ELISA) to detect antibody. Two preparations of biotinylated S. aureus type 8 polysaccharide were equivalent as antigens in ELISA. Specificity was demonstrated by absorption of antisera, by competitive inhibition with purified antigens, and by reaction with specific monoclonal or myeloma antibodies. Reproducibility of the assay for H. influenzae type b and S. aureus type 8 antibody was demonstrated by replicate titrations of high and low level antisera.


Assuntos
Anticorpos Antibacterianos/análise , Ensaio de Imunoadsorção Enzimática , Polissacarídeos Bacterianos/imunologia , Especificidade de Anticorpos , Reações Antígeno-Anticorpo , Avidina , Ligação Competitiva , Biotina , Enterobacter/imunologia , Ensaio de Imunoadsorção Enzimática/instrumentação , Escherichia coli/imunologia , Haemophilus influenzae/imunologia , Staphylococcus aureus/imunologia
20.
Viral Immunol ; 6(1): 43-7, 1993.
Artigo em Inglês | MEDLINE | ID: mdl-8476507

RESUMO

Two hundred and fifty apparently healthy pregnant women attending the Obstetrics and Gynecology Clinic of the Lagos University Teaching Hospital (LUTH), Lagos, Nigeria were screened for a comparison of the prevalence of HIV seropositivity and hepatitis B surface antigenemia (HBs Ag) amongst them. The Karpas AIDS cell test for HIV seropositivity and Bioman Hepatitis test kits were used as described by the manufacturers. HIV seropositive cases were confirmed using the Western blot test. Results revealed that out of the 250 pregnant women screened, 2 (0.8%) and 11 (4.4%) were HIV-1 and HBs Ag seropositive, respectively. However, the same 2 pregnant women now constituting 2 (18.2%) of the 11 HBs Ag positive pregnant women were simultaneously HIV-1 seropositive. Antibody to HIV-2 was not recorded in all HIV seropositive cases. This is the first report on the simultaneous prevalence of HBs Ag and HIV seropositivity among apparently healthy pregnant women in Lagos, Nigeria.


PIP: 250 sperm from apparently healthy pregnant patients at the Obstetrics and Gynecology Clinic at Lagos University Teaching Hospital, Lagos, Nigeria, were tested for HIV-1 and HIV-2 and hepatitis B surface antigen (HBsAg). Sera were screened for HIV with the Karpas AIDS cell test using HIV-1 and HIV-2 isolated in Great Britain, and confirmed with the Karpas confirming test and the Western blot. Bioman Hepatek kits were used for hepatitis screening. 2 pregnant women (0.8%) tested positive for HIV-1 and none for HIV-2. 11 women (4.4%) had HBsAg in their serum, and among these, 2 were positive for both HBsAg and HIV-1. This is the first report of pregnant women with both HIV and hepatitis virus screens in Lagos.


Assuntos
Soropositividade para HIV/epidemiologia , HIV-1 , HIV-2 , Antígenos de Superfície da Hepatite B/sangue , Hepatite B/epidemiologia , Complicações Infecciosas na Gravidez/epidemiologia , Comorbidade , Feminino , Soroprevalência de HIV , HIV-1/imunologia , HIV-2/imunologia , Hepatite B/sangue , Humanos , Nigéria/epidemiologia , Gravidez , Prevalência
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