Profile of T-cell lymphomas in Ibadan, Nigeria.
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Adult↗
Biomedical subjects
J O Thomas
Publications and source records attributed to J O Thomas.
Malignant lymphoma in western province of Saudi Arabia.
A review of all malignant lymphomas seen at the King Khalid National Guard Hospital, Jeddah, Saudi Arabia between January 1985 and June 1993 was done. There were 106 cases of non-Hodgkin's lymphoma with a male: female ratio of 2.1:1. Low grade, intermediate grade and high grade lymphomas constituted 17.9%, 36.8% and 28.7% respectively. A comparatively lower frequency of follicular lymphomas (5.6%) was noted, compared to the Western literature. Of the few cases immunophenotyped, T-cell and B-cell tumours make up 29% and 71%, respectively.
Adolescent↗
Thyroid cancers in Ibadan, Nigeria.
Recent reviews of thyroid malignancies indicate an increasing incidence with suggestions that incidence and regional variation in histological types may be related to socioeconomic and environmental factors. We studied 137 cases of thyroid cancer occurring in the University College Hospital, Ibadan over a 20-year period (1965-1984), consisting of 45 males and 92 females. The ages ranged from 8-85 years with a mean age of 40 years. Papillary carcinoma constituted 45.3% cases, whilst follicular carcinoma made up 44.5% with a frequency ratio of 1:1. Seven cases (5%) of medullary carcinoma were seen and these had a male/female ratio of 1.3:1 with an average age of occurrence of 34 years. In contrast to previous studies from this environment, there is a suggestion of an increasing trend in the incidence of papillary carcinoma in our centre. The significance of changing socio-economic and environmental factors in the region are highlighted.
Adolescent↗
Bladder carcinoma in Ibadan Nigeria: a changing trend?
A review of cases of bladder carcinoma in Ibadan, Nigeria between 1979-1989 suggest a changing trend with a rise in the frequency of transitional cell carcinoma (49.9%) relative to squamous cell carcinoma (SCC). Earlier reports from Ibadan indicated a preponderance of SCC. However, similar to other reports, SCC is more frequent amongst those aged 50 years and below (45.5%) compared to TCC (18%). This frequency has often been related to schistosomal infestation. Though the possibility of age-related factors are considered, the significance of changing environmental and socio-economic factors are highlighted. Whilst better public enlightenment and health education, may help in lowering the intensity of schistosomal infestation, increasing urbanization and industrialization may be increasing environmental factors that predispose to transitional (urothelial) cell carcinoma of the bladder.
Adult↗
Primary testicular causes of infertility. Do environmental and socio-cultural factors have a role?
A review of 81 cases of testicular biopsies, done as part of the routine investigation for oligospermia or azoospermia amongst otherwise healthy Saudi males, was carried out at the King Khalid National Guard Hospital, Jeddah. The results showed that 42% of cases had normal seminiferous tubules with adequate spermatogenesis. When compared with similar series from the literature, the Saudi population had a higher rate, 27.2%, of Sertoli-cell-only syndrome, compared to a range of 7.9-15% from other series. Hypospermatogenesis, maturation arrest and diffuse tubular atrophy with interstitial fibrosis made up 3.7, 8.6 and 16.0% respectively. The significance of environmental factors, socio-cultural habits and consanguineous marriages as possible influencing factors are highlighted.
Adult↗
Histopathology of lymphadenopathy in a tropical country.
A review of 1153 lymph node biopsies received at the Pathology Department of the University College Hospital (UCH), Ibadan within a five year period was done. Analysis showed that 427 of the lymph nodes (37%) had normal or non-specific reactive changes, 27.7% showed granulomatous inflammation and 35.5% showed malignancy, lymphoid or metastatic tumours. Tuberculosis was the single most common granulomatous inflammatory condition constituting 94.5% of the granulomatous inflammatory lesions. Tuberculosis was also the commonest cause of lymph node enlargement in childhood (0-14 years) whilst malignant condition was the commonest above forty five years of age.
Adolescent↗
DNA looping by the HMG-box domains of HMG1 and modulation of DNA binding by the acidic C-terminal domain.
We have compared HMG1 with the product of tryptic removal of its acidic C-terminal domain termed HMG3, which contains two 'HMG-box' DNA-binding domains. (i) HMG3 has a higher affinity for DNA than HMG1. (ii) Both HMG1 and HMG3 supercoil circular DNA in the presence of topoisomerase I. Supercoiling by HMG3 is the same at approximately 50 mM and approximately 150 mM ionic strength, as is its affinity for DNA, whereas supercoiling by HMG1 is less at 150 mM than at 50 mM ionic strength although its affinity for DNA is unchanged, showing that the acidic C-terminal tail represses supercoiling at the higher ionic strength. (iii) Electron microscopy shows that HMG3 at a low protein:DNA input ratio (1:1 w/w; r = 1), and HMG1 at a 6-fold higher ratio, cause looping of relaxed circular DNA at 150 mM ionic strength. Oligomeric protein 'beads' are apparent at the bases of the loops and at cross-overs of DNA duplexes. (iv) HMG3 at high input ratios (r = 6), but not HMG1, causes DNA compaction without distortion of the B-form. The two HMG-box domains of HMG1 are thus capable of manipulating DNA by looping, compaction and changes in topology. The acidic C-tail down-regulates these effects by modulation of the DNA-binding properties.
Animals↗
Structure of the HMG box motif in the B-domain of HMG1.
The conserved, abundant chromosomal protein HMG1 consists of two highly homologous, folded, basic DNA-binding domains, each of approximately 80 amino acid residues, and an acidic C-terminal tail. Each folded domain represents an 'HMG box', a sequence motif recently recognized in certain sequence-specific DNA-binding proteins and which also occurs in abundant HMG1-like proteins that bind to DNA without sequence specificity. The HMG box is defined by a set of highly conserved residues (most distinctively aromatic and basic) and appears to define a novel DNA-binding structural motif. We have expressed the HMG box region of the B-domain of rat HMG1 (residues 88-164 of the intact protein) in Escherichia coli and we describe here the determination of its structure by 2D 1H-NMR spectroscopy. There are three alpha-helices (residues 13-29, 34-48 and 50-74), which together account for approximately 75% of the total residues and contain many of the conserved basic and aromatic residues. Strikingly, the molecule is L-shaped, the angle of approximately 80 degrees between the two arms being defined by a cluster of conserved, predominantly aromatic, residues. The distinctive shape of the HMG box motif, which is distinct from hitherto characterized DNA-binding motifs, may be significant in relation to its recognition of four-way DNA junctions.
Amino Acid Sequence↗
Hepatobiliary changes in Nigerians with sickle cell anaemia.
The histology of a liver specimen from the autopsy of each of 58 sickle cell anaemia patients aged 3-45 years was examined. Sinusoidal distension (present in all specimens), haemosiderosis and erythrophagocytosis (56), portal triaditis (47), cholestasis (24), focal necrosis and fibrosis (23), and extra-medullary erythropoiesis (3) were observed. The livers from the older patients (30-45 years) showed severe haemosiderosis, chronic inflammation, pigment stones and fatty change.
Adolescent↗
Chromatin structure of the beta-globin chromosomal domain in adult chicken erythrocytes.
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Animals↗
Triage of patients with abnormal cervical smears in the absence of colposcopy.
In a group of 246 patients with dyskaryotic cervical smears, 144 had 4-quadrant punch biopsies (4Q), while 102 had Lugol's iodine applied to the cervix before punch biopsies were taken from abnormally stained areas (ISD) to determine whether the latter will improve the chances of taking biopsies from areas of cervical intraepithelial neoplasia (CIN). In the ISD group, 66 (64.7%) of the patients had histological confirmation of CIN compared to 56 (38.9%) of those in the 4Q group. Follow-up smears in patients with benign histological findings revealed dyskaryosis in 54.7% and 25% in the 4Q and ISD groups respectively, which is suggestive of a higher false-negative rate in the 4Q group. It is suggested that where facilities for colposcopically-directed biopsy of the cervix is unavailable, patients with abnormal smears should have Lugol's iodine applied before punch cervical biopsies are taken.
Biopsy, Needle↗
Kidney histology and clinical correlates in malignant hypertension.
In this clinico-pathologic study, post-mortem kidney material from 30 cases with malignant hypertension (MHT) defined as severe hypertension with bilateral retinal haemorrhages and exudates (grade III retinopathy) with (grade IV retinopathy) or without papilloedema, were studied. Mucoid intimal proliferation (MIP) in interlobular artery and ischaemic collapse of the glomerular tufts occurred in all cases, whereas fibrinoid necrosis (FN) was seen in only 24 (80%) of the cases. FN was not correlated nor associated with sex, age, blood pressure, retinopathy or serum creatinine. Tubular atrophy and interstitial fibrosis occurred in 24 (80%) and correlated best (rS = 0.8, p < 0.05) with serum creatinine in comparison to glomerular sclerosis (rS = 0.6, p = n.s), fibrinoid necrosis (rS = 0.49, p = n.s) and epithelial crescents (rS = 0.43, p = n.s). This study provides histologic evidence of lack of difference between grades III and IV retinopathy, shows MIP as the more characteristic vascular lesion in MHT and also, good correlation between renal function and tubulointerstitial involvement.
Adolescent↗
A cytoplasmic chaperonin that catalyzes beta-actin folding.
We have isolated a cytoplasmic chaperonin based on its ability to catalyze the folding of denatured beta-actin. The cytoplasmic chaperonin is organized as a multisubunit toroid and requires Mg2+ and ATP for activity. The folding reaction proceeds via the rapid ATP-independent formation of a binary complex, followed by a slower ATP-dependent release of the native product. Electron microscopic observations reveal a striking structural change that occurs upon addition of Mg2+ and ATP. The eukaryotic cytoplasm thus contains a chaperonin that is functionally analagous to its prokaryotic, mitochondrial, and chloroplastic counterparts.
Actins↗
Cooperative binding of the globular domains of histones H1 and H5 to DNA.
In view of the likely role of H1-H1 interactions in the stabilization of chromatin higher order structure, we have asked whether interactions can occur between the globular domains of the histone molecules. We have studied the properties of the isolated globular domains of H1 and the variant H5 (GH1 and GH5) and we have shown (by sedimentation analysis, electron microscopy, chemical cross-linking and nucleoprotein gel electrophoresis) that although GH1 shows no, and GH5 little if any, tendency to self-associate in dilute solution, they bind highly cooperatively to DNA. The resulting complexes appear to contain essentially continuous arrays of globular domains bridging 'tramlines' of DNA, similar to those formed with intact H1, presumably reflecting the ability of the globular domain to bind more than one DNA segment, as it is likely to do in the nucleosome. Additional (thicker) complexes are also formed with GH5, probably resulting from association of the primary complexes, possibly with binding of additional GH5. The highly cooperative nature of the binding, in close apposition, of GH1 and GH5 to DNA is fully compatible with the involvement of interactions between the globular domains of H1 and its variants in chromatin folding.
Animals↗
Mammalian mitochondrial chaperonin 60 functions as a single toroidal ring.
Chaperonins are thought to participate in the process of protein folding in bacteria and in eukaryotic mitochondria and chloroplasts. While some chaperonins are relatively well characterized, the structures of the mammalian chaperonins are unknown. We have expressed a mammalian mitochondrial chaperonin 60 in Escherichia coli and purified the recombinant protein to homogeneity. Structural and biochemical analyses of this protein establish a single toroidal structure of seven subunits, in contrast to the homologous bacterial, fungal, and plant chaperonin 60s, which have double toroidal structures comprising two layers of seven identical subjects each. The recombinant mammalian chaperonin 60, together with the mammalian chaperonin 10 (but not with bacterial chaperonin 10), facilitates the formation of catalytically active ribulose-bisphosphate carboxylase from an unfolded state in the presence of K+ and MgATP. Analysis of the partial reactions involved in this in vitro reconstitution reveals that the single toroid of chaperonin 60 can form stable complexes with both unfolded or partially folded [35S]ribulose-bisphosphate carboxylase and mitochondrial (but not bacterial) chaperonin 10 in the presence of MgATP. We conclude that the minimal functional unit of chaperonin 60 is a single hepatmeric toroid.
Adenosine Triphosphate↗
Intracellular distribution of a nuclear localization signal binding protein.
The transport of proteins into the nucleus requires the recognition of a nuclear localization signal sequence. Several proteins that interact with these sequences have been identified, including one of about 66 kDa. We have prepared antibodies that recognize the 66-kDa nuclear localization signal binding protein (NLSBP) and inhibit nuclear localization in vitro. By immunofluorescence, it is seen that the NLSBP is predominantly cytoplasmic and is distributed peripherally around the nucleus and the microtubule organizing center. There is also a weak punctate staining of the surface of the nucleus. Methanol-fixed cells can also be stained directly with fluorescently labeled karyophilic proteins. These stains reveal the same cytoplasmic structures as anti-NLSBP. The expression of the NLSBP is growth dependent. When cells grown to confluence are examined, the cytoplasmic staining is greatly reduced, leaving the punctate nuclear staining as the predominant feature. In serum-starved cells, very little staining of either the cytoplasm or the nucleus can be seen. Upon simulation by the addition of serum, the original cytoplasmic and nuclear envelope staining is restored. Cells grown in the presence of colchicine or taxol have an altered NLSBP distribution but apparently normal cytoplasmic nuclear transport.
Amino Acid Sequence↗
Sociocultural habits and urological malignancies in Ibadan, Nigeria.
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Cultural Characteristics↗
The transport of proteins into the nucleus requires the 70-kilodalton heat shock protein or its cytosolic cognate.
The 70-kDa heat shock protein hsp70 and its constitutively expressed cognate, hsc70, are abundant proteins implicated in a number of cellular processes. When a permeabilized cell system for examining the transport of proteins into the nucleus is depleted of hsc70 and hsp70, either by affinity chromatography on ATP-agarose or with antibodies against these proteins, nuclear transport activity is lost. Full activity is restored by the addition of HeLa proteins that bind to ATP-agarose. hsc70 and hsp70 are the active factors, since activity is also fully restored by the addition of either recombinant hsc70 or hsp70 which has been bacterially expressed and highly purified. The restoration of activity is saturable. The transport system requires other cytosolic factors as well, including at least one protein that is sensitive to inactivation by N-ethylmaleimide, but neither hsc70 nor hsp70 is the sensitive protein.
Adenosine Triphosphate↗