RESUMO
We present a study on the optical losses of Fabry-Pérot cavities subject to realistic transverse mirror misalignment. We consider mirrors of the two most prevalent surface forms: idealised spherical depressions, and Gaussian profiles generated by laser ablation. We first describe the mode mixing phenomena seen in the spherical mirror case and compare to the frequently-used clipping model, observing close agreement in the predicted diffraction loss, but with the addition of protective mode mixing at transverse degeneracies. We then discuss the Gaussian mirror case, detailing how the varying surface curvature across the mirror leads to complex variations in round trip loss and mode profile. In light of the severe mode distortion and strongly elevated loss predicted for many cavity lengths and transverse alignments when using Gaussian mirrors, we suggest that the consequences of mirror surface profile are carefully considered when designing cavity experiments.
RESUMO
The inhibition of 3H-thymidine incorporation into the DNA of mitogen-stimulated lymphocytes from patients with chronic lymphocytic leukaemia by chlorambucil was measured in vitro and the results related to clinical drug resistance. The assay proved to be both sensitive and specific showing a clear separation of those patients with responsive disease from those with disease resistant to treatment. There was evidence of primary drug resistance in untreated patients. In almost all patients who received treatment this led to increasing resistance to chlorambucil in vitro. The assay is predictive of clinical responsiveness and provides a potential means whereby new therapeutic agents and treatment modifiers may be investigated.
Assuntos
Clorambucila/farmacologia , DNA de Neoplasias/biossíntese , Leucemia Linfocítica Crônica de Células B/metabolismo , Linfócitos/metabolismo , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Contagem de Leucócitos/efeitos dos fármacos , Ativação Linfocitária , Masculino , Timidina/farmacocinéticaRESUMO
Vasospasm of the vertebrobasilar system was induced in seven dogs by the intracisternal injection of autologous blood. Somatosensory and brain stem auditory evoked potentials were recorded before and after the induction of angiographically confirmed vasospasm. Additionally, somatosensory evoked potentials were monitored during graded hypotension to 40 mm Hg. There was no significant alteration in the evoked potentials by vasospasm or hypotension. Detailed clinical examination and postmortem histopathological studies did not demonstrate any focal neurological deficit or infarction attributable to vasospasm. Previous studies have noted close correlations between decreased cerebral blood flow and evoked potential alterations. Induced hypotension to a mean arterial pressure of 40 mm Hg in the presence of documented vasospasm was not sufficient to cause evoked potential changes, focal neurological deficit, or pathological evidence of infarction in the canine model.
Assuntos
Potenciais Somatossensoriais Evocados , Hipotensão/fisiopatologia , Ataque Isquêmico Transitório/fisiopatologia , Animais , Pressão Sanguínea , Infarto Cerebral/fisiopatologia , Modelos Animais de Doenças , Cães , Ataque Isquêmico Transitório/patologia , Monitorização Fisiológica , Tempo de Reação/fisiologiaRESUMO
Serum methionine and valine have been assayed microbiologically in 31 patients anaesthetized with and in 13 controls anaesthetized without nitrous oxide. Isoleucine has been similarly assayed in five cases and three controls. The preinduction levels of both methionine and valine were considerably below those of semifasting healthy adults. Serum methionine fell significantly in both groups as did valine and isoleucine in the controls. These findings are attributed to dietary restriction before and during the operation. Serum valine was significantly elevated in patients anaesthetized with nitrous oxide but only in those anaesthetized for 3 h or longer. Isoleucine also was elevated in two of the five cases exposed to nitrous oxide. Reasons are given for attributing these elevated levels to the direct action of nitrous oxide. Valine is entirely and isoleucine is partly catabolized along the adenosylcobalamin dependent propionyl-CoA-succinyl-CoA pathway. It is concluded that their elevated levels are caused by the inactivation of adenosylcobalamin by nitrous oxide thereby inducing the methylmalonyl mutase block in this pathway. It is suggested also that the relief of this block by adenosylcobalamin in pernicious anaemia could provide a possible metabolic basis for the well recognized early subjective improvement encountered in this disease following vitamin B12 therapy.
Assuntos
Anestesia , Isoleucina/sangue , Metionina/sangue , Valina/sangue , Adolescente , Adulto , Idoso , Anestesia/efeitos adversos , Cobamidas/antagonistas & inibidores , Feminino , Humanos , Masculino , Metilmalonil-CoA Mutase/metabolismo , Pessoa de Meia-Idade , Óxido Nitroso/efeitos adversosRESUMO
The serum "uracil+uridine" level, expressed as uracil, has been measured in 21 cases of vitamin B12 deficiency, in which the serum folate was normal, and compared with the level in 97 normal subjects. The level in the vitamin B12 deficient group (11.9 mumol/1). was significantly lower than in the controls (15.7 mumol/1., P less than 0.005). Nine of the former were complicated by stystemic illness but the clinical and haematological features in the remaining 12 were consistent with the diagnosis of pernicious anaemia in relapse. The serum uracil level in this group was even lower (10.21 mumol/1., P less than 0.01). This finding is unexpected in view of the generally accepted indirect role of vitamine B12 in the methylation of deoxyuridine monophosphate to deoxythymidine monophosphate. Reasons are given for not accepting these results as reflecting the main biochemical lesion in vitamin B12 deficiency. Although they do not give direct support to an impairment in the methylation of deoxyuridine monophosphate, they do not exclude it as they test only one possible metabolic pathway and moreover they could represent the result of more than one action of vitamin B12 on uracil metabolism. They do show, however, that some aspect of uracil metabolism other than methylation is affected in vitamin B12 deficiency in man.
Assuntos
Anemia Perniciosa/sangue , Uracila/sangue , Uridina/sangue , Anemia Perniciosa/complicações , Humanos , Vitamina B 12/sangue , Deficiência de Vitamina B 12/sangue , Deficiência de Vitamina B 12/complicaçõesRESUMO
The serum "uracil+uridine" levels, expressed as uracil, have been measured in 10 cases of pernicious anaemia both before and after treatment, and compared with the levels in 97 normal subjects. The mean pre-treamtent value (8.82 mumol/1., range 6.0-12.0 mumol/1.) differed significantly from that of the normal controls (15.7 mumol/1., range 5.7-40.5 mumol/1., t = 8.8, P less than 0.001). This confirms the low serum uracil level previously reported in pernicious anaemia relapse. The level rose progressively after treatment, reaching a maximum on the fourth day (mean 17.85 mumol/1., range 9.3-23.4 mumol/1.). This was not significantly different from the mean of the normal control group. The difference between the pre- and post-treatment levels was significant on days 3,4 and 5 (P less than 0.005, P less than 0.001 and P less than 0.005 respectively) and the rise preceded the reticulocyte response by 24 h. A further case was treated with pysiological doses of vitamin B12 (2 mug daily for 6 d) and a similar rise in the serum uracil level noted. These results are not explained by any of the known functions of vitamin B12. They are, however, similar to the changes in the serum methionine levels previously reported in pernicious anaemia. The latter were readily explained by the known action of vitamin B12 on "de novo" methionine synthesis and it is suggested that the synthesis of uracil, like that of methionine, might be influenced by vitamin B12 in man.
Assuntos
Anemia Perniciosa/tratamento farmacológico , Uracila/sangue , Uridina/sangue , Vitamina B 12/uso terapêutico , Relação Dose-Resposta a Droga , Humanos , Fatores de TempoAssuntos
Uracila/sangue , Uridina/sangue , Adolescente , Adulto , Fatores Etários , Idoso , Bioensaio , Criança , Pré-Escolar , DNA/biossíntese , Humanos , Lactente , Recém-Nascido , Lactococcus lactis , Pessoa de Meia-IdadeRESUMO
A microbiological method for the assay of uracil is described. The growth of the test organism is supported by uracil and also by uridine but not by uridylic acid. The method therefore measures uracil and uridine together. The ;uracil + uridine' level, expressed as uracil, has been measured in blood from 144 normal subjects ranging in age from cord blood to the eighth decade. The mean level of 22 mu mol/l (0.25 mg%) in cord blood decreases to 15 mumol/l (0.17 mg%) in adults over the age of 20. There is no difference between the sexes. Uracil is of interest because (a) it is a constituent base of RNA, (b) it is the precursor of two of the bases thymine and cytosine that enter into the composition of DNA, and (c) under certain circumstances it has mutagenic properties. The last is dependent upon the existence of two tautomeric forms of uracil, the common keto form which pairs normally with adenine and the rare enol form which pairs with guanine. A mistake in base pairing which allows uracil in its enol form to enter the DNA molecule and pair with guanine can result in a G = C --> A = T base transition in the DNA molecule. The molecular mechanism involved as well as the possible bearing on somatic mutation are discussed.
Assuntos
Uracila/sangue , Uridina/sangue , Fatores Etários , Técnicas Bacteriológicas , Sequência de Bases , Bioensaio , Meios de Cultura , Feminino , Humanos , Cinética , Lactococcus lactis/metabolismo , Masculino , Mutagênicos , Fatores Sexuais , Uracila/análogos & derivados , Uridina Monofosfato/sangueRESUMO
A microbiological method for the assay of valine, leucine, and methionine in serum is described and its accuracy and reproducibility are assessed. Under the conditions specified the L-isomers only of the three amino acids are measured. The serum levels of the three amino acids in 60 normal subjects are presented.