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Biomedical subjects

S Ali

Publications and source records attributed to S Ali.

At least 145 records · Page 8Linked to original sources
PubMed1999

Growth inhibition of a human ovarian tumor by a novel paclitaxel derivative in SCID mice.

We report here the toxicity and therapeutic effects of 2'-alpha-bromohexadecanoyl paclitaxel (BrC16HT), a prodrug form of paclitaxel, in mice. Paclitaxel is the active ingredient of Taxol. The maximum tolerated dose, at a one dose per day for 5-day schedule, was 37.5 mg/kg for BrC16HT compared to 12.5 for Taxol administered IP, and was 12.5-25 mg/kg for either agent administered IV. Dose-dependent therapeutic effects were found for BrC16HT against a human ovarian tumor (OVCAR-3) grown in SCID mice. IP treatments with BrC16HT against early or established IP-implanted OVCAR-3 tumor increased mean survival times more than treatment with Taxol. Long-term survivors were found only in groups treated with BrC16HT. Intravenously administered BrC16HT was more effective than Taxol against SC OVCAR-3 tumor. Early treatment (25 mg/kg x 5) completely inhibited tumor growth through 120 days after tumor implantation. Pharmacokinetic studies suggest that BrC16HT is slowly hydrolyzed to paclitaxel and circulates longer than paclitaxel from Taxol. Thus, BrC16HT may provide sustained levels of paclitaxel, which may contribute to the increased efficacy of BrC16HT compared to Taxol.

Animals↗
PubMed1999

DNA typing and microsatellite associated sequence amplification (MASA) in detecting loss or gain of alleles.

Constant exposure of genomic DNA to a variety of damaging agents including radiations poses a major challenge for developing an experimental approach for monitoring such damages. No single approach can be used to address this issue. In the present article, we have provided examples of DNA typing and believe that various approaches may enable to uncover not only loss or gain(s) of the alleles but also reveal subtle changes in the genome. Similarly, our genome analysis of the animal systems provides a method to assess the effects of radiation on domestic animals.

Alleles↗
PubMed1998

Analysis of the evolutionarily conserved repeat motifs in the genome of the highly endangered central Indian swamp deer Cervus duvauceli branderi.

We have analyzed the genome of central Indian swamp deer Cervus duvauceli branderi, an inhabitant of the Kanha National Park, a wildlife conservatory in Central India, with a view to provide a genetic basis for their extinction. Evolutionarily conserved repeat sequence motifs (GATA)3.75, TA(GATA)4, (GACA)3.75, (TGG)6 and a set of mouse beta-actin primers were used to uncover the sequence variation within and between related species by employing techniques of hybridization and AP-PCR amplification. The oligo probe carrying the GACA and TGG repeat motifs was found to be positive with Cervus genome, whereas (GATA)3.75, TA(GATA)4 and beta-actin probes did not cross-hybridize with the same. AP-PCR amplification with (GACA)3.75, unlike the (TGG)6 primer, generated distinct bands in the range of 0. 37-2.10kb amongst different genomes including Cervus. A comparative genome analysis of other species using the AP-PCR approach with (GACA)3.75 primer revealed the phylogenetic status of Cervus duvauceli branderi. From the analysis of a very limited number of Cervus DNA samples, we observed a high level of genetic homogeneity that may be a prime reason for the extinction of this species. This study has implications in the context of conservation of this endangered Cervus duvauceli branderi species.

Actins↗
PubMed1998

Examination of the sensitivity of T cells to Fas ligation: induction of allospecific apoptosis.

BACKGROUND: Alloantigen-reactive T cells represent the major barrier to successful organ transplantation. However, it has been shown that cotransplantation of Fas ligand (FasL)-expressing cells can induce functional allograft tolerance in some model systems. In this study, the basis for this tolerance was investigated using a sensitive in vitro assay system. METHODS: T lymphocytes were activated by coculture with an allogeneic Epstein Barr virus-transformed B-cell line. Samples of the lymphocytes were taken daily and treated with agonistic anti-Fas antibodies or FasL-expressing cells. The time in culture required for development of optimal sensitivity to Fas-mediated apoptosis was assessed by Tdt-mediated nick end labeling (TUNEL) staining and the JAM assay of DNA fragmentation. After the induction of optimal apoptosis, a series of experiments was performed to assess the response of the T-cell population to antigen-specific rechallenge. RESULTS: Treatment of the allospecific lymphocyte population with anti-Fas antibodies or Fas-L-expressing cells did not induce apoptosis efficiently until between 6 and 7 days after initiation of the mixed lymphocyte culture; this time corresponded with decreases in the ambient interleukin 2 concentration and in Bcl-2 expression. In addition, induction of apoptosis by treatment with the agonistic anti-Fas antibody reduced the lymphoproliferative response of the T-cell population after antigen-specific rechallenge. CONCLUSIONS: These results give an important indication of the mechanism by which FasL-expressing third-party cells can reduce an allospecific T-cell response by an apoptotic mechanism. Furthermore, they demonstrate that apoptotic tolerance in vivo may only occur after the prolonged period of potentially graft-damaging T-cell activation required for acquisition of sensitivity to Fas-mediated apoptosis.

Antibodies↗
PubMed1998

An important role for BRCA1 in breast cancer progression is indicated by its loss in a large proportion of non-familial breast cancers.

The presence of BRCA1 protein was determined immunohistochemically in normal and benign breast biopsies, non-familial breast carcinomas and breast carcinomas from one or more individuals from 8 BRCA1 families. Strikingly, little staining was detected in breast carcinomas from BRCA1 families, regardless of the position or type of mutation, whereas strong immunostaining was observed in 28/28 of non-malignant breast biopsies. Furthermore, BRCA1 staining was reduced in non-familial breast carcinomas, since loss of nuclear BRCA1 staining was evident in 19% of non-familial breast carcinomas whilst a similar proportion (20%) showed absence of either cytoplasmic or nuclear BRCA1 staining. Statistical analysis indicates that breast cancer is characterised by a reduction in levels of nuclear BRCA1 in familial (p < 0.001) and non-familial breast cancer (p = 0.001). In non-familial breast cancer absence of nuclear BRCA1, but not cytoplasmic BRCA1, is more common in high grade breast carcinomas (p = 0.03) and in patients with evidence of lymph node involvement (p = 0.05). Correlation between the absence of BRCA1 protein with high grade is consistent with previous findings of a correlation between mutations in the BRCA1 gene and high grade. Our findings provide new evidence in support of BRCA1 as a tumour suppressor protein in non-familial breast cancer.

Adult↗
PubMed1998

The A kinase anchoring protein is required for mediating the effect of protein kinase A on ROMK1 channels.

In the present study, we have used the two-electrode voltage-clamp and patch-clamp techniques to study the effects of forskolin and cAMP on the ROMK1 channels, which are believed to be the native K+ secretory channels in the kidney. Addition of 1 microM forskolin or 100 microM 8-bromo-cAMP, within 10 min, has no significant effect on the current of ROMK1 channels expressed in Xenopus oocytes. In contrast, application of 1 microM forskolin, within 3 min, significantly increased whole-cell K+ current by 35%, when ROMK1 channels were coexpressed with the A kinase anchoring protein AKAP79, which was cloned from neuronal tissue. Two lines of evidence indicate that the effect of forskolin is mediated by a cAMP-dependent pathway: (i) Addition of 100 microM 8-bromo-cAMP mimics the effect of forskolin and (ii) the effect of forskolin and cAMP is not additive. That AKAP is required for the effect of cAMP is further supported by experiments in which addition of ATP (100 microM) and cAMP (100 microM) restored the activity of run-down ROMK1 channels in inside-out patches in oocytes that coexpressed ROMK1 and AKAP79 but not in those that expressed ROMK1 alone. Moreover, when we used RII, the regulatory subunit of type II protein kinase A, in an overlay assay, we identified a RII-binding protein in membranes obtained from the kidney cortex but not in membranes from oocytes. This suggests that the insensitivity of ROMK1 channels to forskolin and cAMP is due to the absence of AKAPs. We conclude that AKAP may be a critical component that mediates the effect of protein kinase A on the ROMK channels in the kidney.

Adenosine Triphosphate↗
PubMed1998

Triggerable liposomal fusion by enzyme cleavage of a novel peptide-lipid conjugate.

A novel peptide-lipid sensitive to enzyme cleavage was designed to generate liposomes that could be triggered to fuse by enzymatic activation. Covalent linkage of dioleoyl phosphatidylethanolamine (DOPE) to an elastase substrate, N-acetyl-ala-ala-, resulted in a cleavable peptide-lipid (N-Ac-AA-DOPE) with no intrinsic fusogenic activity. Cleavage of N-Ac-AA-DOPE and concomitant conversion to the fusogenic lipid DOPE could be detected after treatment with human leukocyte elastase or proteinase K, two proteases with similar substrate specificities. A strategy to utilize this cleavage to trigger fusogenicity was tested by modeling the fusion of liposomes containing the expected product of complete cleavage. Based on these results liposomes were designed to contain N-Ac-AA-DOPE, DOTAP, and PE in the ratio of 15/15/70. These liposomes exhibited lipid mixing with acceptor liposomes after elastase or proteinase K protease treatment. Activation of fusion, as monitored by a lipid mixing assay, appeared to be dependent on protease activity, as (1) heat inactivated enzyme did not activate liposomal fusion, and (2) the time and concentration dependence of proteinase K mediated cleavage of N-Ac-AA-DOPE correlated with membrane mixing. Liposomes could also be formulated that exhibited lipid mixing and transfer of aqueous fluorescent probe with erythrocyte ghosts. These observations demonstrate fusogenic lipids conjugated to enzyme substrates serve as triggerable fusion systems that may be useful for gene and drug delivery.

Dipeptides↗
PubMed1998

Prolactin receptor regulates Stat5 tyrosine phosphorylation and nuclear translocation by two separate pathways.

The SH2 domain containing signal transducers and activators of transcription (Stat proteins) are effector molecules downstream of cytokine receptors. Ligand/receptor engagement triggers Stat proteins tyrosine phosphorylation, dimerization, and translocation to the nucleus where they regulate gene transcription. Stat5, originally identified as a mammary gland growth factor, is an essential mediator of prolactin (PRL)-induced milk protein gene activation. Prolactin receptor (PRLR) is a member of the cytokine/growth hormone/PRL receptor superfamily. The mechanism through which PRLR modulates Stat5 tyrosine phosphorylation, nuclear translocation, and DNA binding was analyzed in HC11 cells, a mammary epithelial cell line, and 293-LA cells, a human kidney cell line stably overexpressing Jak2 kinase. We have found that in HC11 cells, Stat5 is specifically activated by PRL treatment, demonstrating that Stat5 is a physiological substrate downstream of PRLR. Furthermore, using different forms natural forms of the PRLR as well as receptor tyrosine to phenylalanine mutant forms, we determined that tyrosine phosphorylation of Stat5 is independent of PRLR phosphotyrosines. We established, however, that the C-terminal tyrosine of the PRLR Nb2 form, Tyr382, plays an essential positive role in PRLR-dependent Stat5 nuclear translocation and subsequently DNA binding. All together, our data propose a new model for activation of Stat5 through the PRLR, suggesting that Stat5 tyrosine phosphorylation and nuclear translocation are two separately regulated events.

Animals↗
PubMed1998

Cation-dependent fusogenicity of an N-acyl phosphatidylethanolamine.

N-acyl phosphatidylethanolamines (NAPEs) are natural lipid components of many organisms. N-acylation of unsaturated phosphatidylethanolamines with a saturated fatty acid converts them from non-lamellar organizing lipids into lamellar organizing, acidic lipids which can interact with cations and potentially return to non-lamellar structures. These special properties make NAPEs candidates for fusogens. We tested the fusogenicity of one of the NAPEs, N-dodecanoyl-di-oleoylphosphatidylethanolamine (N-C12-DOPE) mixed with dioleoylphosphatidylcholine (DOPC) in liposomes. Binding and fusion to erythrocyte ghosts in the presence of 3 mM Ca2+ required at least 60 mol% of N-C12-DOPE. Fusion was not observed when phosphatidylglycerol or phosphatidylserine was substituted for N-C12-DOPE, indicating specificity for properties of this lipid. Binding of N-C12-DOPE/DOPC (70:30) liposomes required 1 mM Ca2+ while 1.25 mM Ca2+ and Mg2+ were sufficient for lipid mixing and delivery of encapsulated dextrans to erythrocyte ghosts. These liposomes also bound and possibly mixed lipid with nucleated U-937 cells in a Ca2+ -and endocytosis-dependent manner. Low pH-dependent fusion with ghosts was observed in the absence of any divalent cation, indicating that fusion with U-937 cells could result after endocytosis into the acidic endosomes. The possible mechanisms for N-C12-DOPE mediated binding and fusion and the potential application of these liposomes as delivery vehicles for therapeutic agents are discussed.

Calcium↗
PubMed1998

Parentage assessment of an IVF calf from Bubalus bubalis by DNA fingerprinting.

We used two synthetic oligodeoxyribonucleotide probes, OAT18 and OMS1 comprising (TGG)6 and (GGTA)4 repeat motifs, respectively, in combination with HinfI enzyme for DNA fingerprinting of a calf born from embryo transfer technology, its surrogate mother (SM) and the sperm donor (bull). Of the two polymorphic probes, OAT18 was found to be more informative for correctly establishing the parentage status of the in-vitro fertilized (IVF) calf and demonstrated the genetic relationship of the SM with the bull. Two types of cluster analysis, SAHN clustering and neighbour joining tree, performed with similarity indices of these individuals produced by OAT18 probe were found to be different. Using the SAHN cluster method, SM was found to be genetically closer to the bull than to IVF calf, whereas using the neighbour joining method, IVF was closer to bull than SM. A similar result was obtained by SAHN clustering with OMS1 probe. The relevance of this approach for parentage control in the context of animal biotechnology is described.

Animals↗
PubMed1998

Localization and expression of the human estrogen receptor beta gene in uterine leiomyomata.

Estrogens have an important function in the natural history of uterine leiomyomata. The human estrogen receptor beta gene (ESR2) has been identified recently and mapped to 14q22-24, a region frequently rearranged in uterine leiomyomata and other benign tumors, including pulmonary chondroid hamartomas and endometrial polyps. Using fluorescence in situ hybridization and radiation hybrid mapping, we map ESR2 within 14q23-24.1, to a region approximately 2 Mb centromeric to the t(12;14) breakpoint in uterine leiomyomata, between markers D14S63 and WI-7536. Two YAC clones, 948B6 and 741H4, contain ESR2. Using RT-PCR, we show that ESR2 is expressed in uterine leiomyomata and pulmonary chondroid hamartomas as well as in normal myometrium. Lack of a direct relationship between rearrangement of 14q23-24 and ESR2 expression suggests that ESR2 is not involved with HMGIC or HMGIY in t(12;14) or t(6;14). However, because of its relatively close physical distance from the characteristic site of rearrangements in 14q23-24, a role for ESR2 in the pathobiology of these tumors warrants future consideration.

Chromosome Mapping↗
PubMed1998

False-positive defects in technetium-99m sestamibi myocardial single-photon emission tomography in healthy athletes with left ventricular hypertrophy.

Exercise ECG and myocardial single-photon emission tomography (SPET) are fundamental in the non-invasive evaluation of patients suspected of having coronary artery disease (CAD). The purpose of the present study was to investigate the influence of physiological left ventricular hypertrophy (LVH) on myocardial sestamibi SPET in healthy young and old athletes. Eighteen young male elite athletes (ten rowers, five power/weight lifters and three triathletes) and 14 well-trained elderly rowers were studied. All underwent a bicycle test as part of a 2-day sestamibi SPET protocol. Attenuation correction was not performed. The studies were evaluated visually and quantitatively analysed by the CEqual program with its reference files and with a file from a local non-athletic age-matched population. Echocardiographic LVH was an inclusion criterion in the young athletes. Exercise ECG was normal in all subjects. In at least three of the young athletes a reversible defect was observed by visual analysis. On quantitative analysis one-third of the young athletes had "significant" (>10 pixels) defects compared with both the local reference base and the CEqual reference population. Nearly all defects were found in the anterior or inferior wall. The remaining subjects, including all old rowers, had normal SPET findings. Anterior and inferior wall defects are so common in healthy athletes with physiological LVH that the specificity of myocardial SPET, in contrast to exercise ECG, seems to be too low for evaluation of chest pain in this group. The mechanism of anterior and inferior defects may be related to hot spots (papillary muscles?) in the lateral wall. The specificity of SPET is maintained in athletes without LVH.

Adult↗
PubMed1998

Acyl chain-length asymmetry alters the interfacial elastic interactions of phosphatidylcholines.

Phosphatidylcholines (PCs) with stearoyl (18:0) sn-1 chains and variable-length, saturated sn-2 acyl chains were synthesized and investigated using a Langmuir-type film balance. Surface pressure was monitored as a function of lipid molecular area at various constant temperatures between 10 degrees C and 30 degrees C. Over this temperature range, 18:0-10:0 PC displayed only liquid-expanded behavior. In contrast, di-14:0 PC displayed liquid-expanded behavior at 24 degrees C and 30 degrees C, but two-dimensional phase transitions were evident at 20 degrees C, 15 degrees C, and 10 degrees C. The average molecular area of 18:0-10:0 PC was larger than that of liquid-expanded di-14:0 PC at equivalent surface pressures, and the shapes of their liquid expanded isotherms were somewhat dissimilar. Analysis of the elastic moduli of area compressibility (Cs(-1)) as a function of molecular area revealed shallower slopes in the semilog plots of 18:0-10:0 PC compared to di-14:0 PC. At membrane-like surface pressures (e.g., 30 mN/m), 18:0-10:0 PC was 20-25% more elastic (in an in-plane sense) than di-14:0 PC. Other PCs with varying degrees of chain-length asymmetry (18:0-8:0 PC, 18:0-12:0 PC, 18:0-14:0 PC, 18:0-16:0 PC) were also investigated to determine whether the higher in-plane elasticity of fluid-phase 18:0-10:0 PC is a common feature of PCs with asymmetrical chain lengths. Two-dimensional phase transitions in 18:0-14:0 PC and 18:0-16:0 PC prevented meaningful comparison with other fluid-phase PCs at 30 mN/m. However, the Cs(-1) values for fluid-phase 18:0-8:0 PC and 18:0-12:0 PC were similar to that of 18:0-10:0 PC (85-90 mN/m). These values showed chain-length asymmetrical PCs to have 20-25% greater in-plane elasticity than fluid-phase PCs with mono- or diunsaturated acyl chains.

Elasticity↗
PubMed1998

Tuberculosis mortality in notified cases from 1989-1995 in Birmingham.

This is a retrospective descriptive study examining medical records of notified cases of tuberculosis in Birmingham, UK, who died before completion of treatment, plus notified cases identified at postmortem. During the study period, 1989-1995, there were a total of 2088 notifications of tuberculosis of which 75 (3.6%) died. This case-fatality rate is lower than that reported from earlier studies, a finding which may be due to improved ascertainment, earlier diagnosis and improved treatment in recent years. Forty-five deaths (60%) were in males and 30 (40%) in females. The median age at death was 66 y. Forty-five deaths (60%) were among the white ethnic group, 21 (28%) among persons of Indian sub-continent origin, 4 (5.3%) among Black Caribbeans and 5 (6.6%) among the other ethnic groups. Case-fatality rates were significantly higher (P < 0.01) in caucasians (9.4%) than in Asians (1.5%) and only half of this difference was explained by the age of those affected. Twenty-two (29%) cases were confirmed by a positive sputum smear and a further 23 (31%) by a positive sputum culture. Eighteen (24%) cases also had histological confirmation. Twelve (16%) cases were identified on autopsy. The case fatality rate in respiratory disease was significantly higher (RR = 1.19, P > 0.05) than in non-respiratory disease. As delay in diagnosis is likely to be the main contributing factor leading to death, a high index of suspicion of tuberculosis is needed when investigating elderly patients with general chronic illness, especially if there are prolonged respiratory symptoms. Early diagnosis will reduce mortality as the disease rapidly responds to treatment.

Black or African American↗
PubMed1998

Granulocyte collection efficiency and yield are enhanced by the use of a higher interface offset during apheresis of donors given granulocyte-colony-stimulating factor.

BACKGROUND: Trials evaluating granulocyte transfusions for therapy of febrile neutropenia demonstrated mixed clinical results, which may in part be due to the low neutrophil cell dose of the transfused components. To optimize the latter variable, the effect of various interface offset (IO) settings during apheresis on granulocyte collection efficiency (GCE) and yield was determined in normal donors given granulocyte-colony-stimulating factor (G-CSF). STUDY DESIGN AND METHODS: Seventeen donors underwent 44 granulocyte collections performed with a continuous-flow blood cell separator with hetastarch infusion after stimulation with G-CSF (5 micrograms/kg/day). Apheresis was performed alternatively using one of three IO settings: IO = 15 (Group 1, n = 16), IO = 25 (Group 2, n = 12), and IO = 35 (Group 3, n = 13). The GCE and yield and changes in donor platelet count, hematocrit (Hct), and red cell (RBC) volume of the components were compared among the three groups. RESULTS: The mean GCE was greater (p = 0.006) during apheresis at an IO setting of 35 (60 +/- 12%) than at an IO setting of 15 (40 +/- 17%). The mean granulocyte yield (x10(10) per procedure was 10.8 +/- 2.95 at an IO setting of 35 and 7.73 +/- 4.02 at an IO setting of 15 (p = 0.08). In a multivariate linear regression model, factors independently associated with granulocyte yield were the absolute granulocyte count (r = 0.73, p < 0.001) and blood volume of the donor (r = 0.54, p = 0.001) before the procedure and the use of an IO setting of 35 (r = 0.50, p = 0.002). There was no significant difference among the three groups in the decrement in donor platelet count or Hct with apheresis, although the mean RBC volume was greater in Group 3. CONCLUSION: Granulocyte apheresis at an IO setting of 35 rather than 15 resulted in a significant increase in the GCE. The use of an IO setting of 35 during apheresis was an independent factor associated with granulocyte yield in the multivariate model. Donor safety was not compromised by collecting granulocytes at the higher IO setting.

Adult↗
PubMed1998

The cellular clearance theory does not explain the post-dialytic small molecule rebound.

AIM: (a) To determine the normalized cellular clearance (Kcn) of urea, creatinine and phosphate in patients undergoing maintenance hemodialysis; (b) To identify the factors, particularly circulatory, which determine Kcn; (c) To evaluate whether intra-dialytic blood sampling can predict the size of the post-dialytic solute concentration rebound. METHODS: Kinetic modelling of urea, creatinine and phosphate, using a two-pool variable volume computer simulation, was performed on two occasions on 34 patients undergoing maintenance dialysis. The cellular clearance was determined (a) from the size of the rebound 50 min after the end of dialysis; (b) from a mid-dialytic blood sample. Conventional two-dimensional M-mode echocardiography and Doppler peripheral blood pressure measurement were performed. RESULTS: The model produced accurate measurements of rebound Kc for urea in 93% of measurements, creatinine in 49% and phosphate in 13%. The corresponding figures for mid-dialysis Kcn were 76%, 39% and 0%. The rebound Kcn was, for urea, 8.31 +/- 4.31 ml/kg/min, and for creatinine 4.07 +/- 2.98. The mid-dialysis Kcn was, for urea, 8.57 +/- 4.25 ml/kg/min, and for creatinine 5.06 +/- 3.36. High post-dialytic rebounds (and low Kcn values) were associated with erythropoietin use (p < 0.05) and occurrence of end-dialytic hypotension (p < 0.02). Patients treated with calcium antagonists had a significantly (p < 0.001) higher Kcn. There was no correlation between mid-dialysis and rebound Kcn. Circulatory indices had no influence on Kcn. CONCLUSIONS: The two-pool cellular clearance model is compatible with urea kinetics, but not creatinine or phosphate. It is therefore unlikely that it is the correct model for small molecule kinetics. The post-dialytic solute rebound may be partly an iatrogenic phenomenon and can be reduced by preventing post-dialytic hypotension and by calcium antagonist treatment, both of which improve regional blood flow. The size of the rebound cannot be predicted by intra-dialytic blood sampling.

Blood Urea Nitrogen↗
PubMed1998

Does vitamin D deficiency account for ethnic differences in tuberculosis seasonality in the UK?

OBJECTIVES: Notifications of tuberculosis in England and Wales are reported to peak in the summer season. The purpose of this study was to confirm that finding and to determine to what extent patients of Indian Subcontinent (ISC) ethnic origin contributed to the seasonality. The clinical presentation of the disease is presumed to occur some months following reactivation of the endogenous latent focus of tuberculosis infection. There arises the possibility of vitamin D deficiency producing immunological inadequacy at the end of winter and beginning of spring. PATIENTS AND METHODS: Monthly (or 4-weekly) aggregated data over 7 years were collected from the three countries of mainland Britain, England, Wales, Scotland and from the city of Birmingham in England. The notifications from Birmingham were divided into those of ISC ethnic origin and 'whites'. The presence or absence of seasonality was determined by fitting a sinusoidal curve by the technique called 'cosinor analysis'. In this method amplitude gives a measure of the extent of the seasonal variation. RESULTS: The summer peak of clinical diagnosis was confirmed in the UK series from England, Wales and Scotland. In England and Wales without Scotland a larger seasonal variation was present. Scotland, with a lower proportion of population of ISC ethnic origin, was examined separately and the results in Scotland alone failed to confirm seasonality. In the data from Birmingham, seasonality was confirmed with a greater amplitude, particularly in those over 60 years of age. The finding was influenced by those of ISC ethnic origin, seasonality not being present in the 'white' population. CONCLUSION: The results from Birmingham are very striking, but there were almost three times as many patients in the ISC ethnic group as in indigenous 'white' patients. A series with larger numbers of 'white' patients would be necessary to confirm the absence of seasonality in the 'white' population. The discussion reviews the evidence that vitamin D may have an important hormonal role in immunological defence in the prevention of tuberculosis.

Causality↗