Nasopharyngeal carcinoma (NPC) is an Epstein–Barr virus-associated disease with high prevalence in Southern Chinese. Using multiparametric flow cytometry, we identified significant expansions of circulating naïve and memory CD4+CD25high T cells in 56 NPC patients compared with healthy age- and sex-matched controls. These were regulatory T cells (Treg), as they overexpressed Foxp3 and GITR, and demonstrated enhanced suppressive activities against autologous CD4+CD25− T-cell proliferation in functional studies on five patients. Abundant intraepithelial infiltrations of Treg with very high levels of Foxp3 expression and absence of CCR7 expression were also detected in five primary tumours. Our current study is the first to demonstrate an expansion of functional Treg in the circulation of NPC patients and the presence of infiltrating Treg in the tumour microenvironment. As Treg may play an important role in suppressing antitumour immunity, our findings provide critical insights for clinical management of NPC.
nasopharyngeal carcinoma; Treg; antitumour immunity; tumour infiltrating lymphocytes
Many patients with amyotrophic lateral sclerosis (ALS) with cognitive impairment have fronto‐temporal dysfunction. Whereas in some patients with ALS the fronto‐temporal dysfunction is undoubtedly due to the degenerative process associated with the disease, in others dysfunction cannot be accounted for by an irreversible degenerative process alone, as it also appears to involve a reversible process. We hypothesised that reduced vital capacity can be a key contributor to the fronto‐temporal dysfunction observed in patients with ALS.
To investigate the association between fronto‐temporal dysfunction and reduced vital capacity in ALS.
16 consecutive patients who conformed to a diagnosis of definite or probable ALS (El escorial criteria) were grouped by vital capacity, and their clinical characteristics and cognitive functions, including disease duration, attention, executive function and memory, were measured.
Patients with a reduced vital capacity performed significantly poorer in memory retention (p = 0.028), retrieval efficacy (p = 0.003), spoken verbal fluency (p = 0.03) and spoken verbal fluency indexes (p = 0.016) than those with a normal vital capacity.
The fronto‐temporal dysfunction in ALS might be attributable to potentially reversible secondary effects associated with reduced vital capacity, as well as to the primary degenerative process.
Basal-like and triple-negative breast tumours encompass an important clinical subgroup and biomarkers that can prognostically stratify these patients are required.
Materials and methods
We investigated two breast cancer tissue microarrays for the expression of calpain-1, calpain-2 and calpastatin using immunohistochemistry. The first microarray was comprised of invasive tumours from 1371 unselected patients, and the verification microarray was comprised of invasive tumours from 387 oestrogen receptor (ER)-negative patients.
The calpain system contains a number of proteases and an endogenous inhibitor, calpastatin. Calpain activity is implicated in important cellular processes including cytoskeletal remodelling, apoptosis and survival. Our results show that the expression of calpastatin and calpain-1 are significantly associated with various clinicopathological criteria including tumour grade and ER expression. High expression of calpain-2 in basal-like or triple-negative disease was associated with adverse breast cancer-specific survival (P = 0.003 and <0.001, respectively) and was verified in an independent cohort of patients. Interestingly, those patients with basal-like or triple-negative disease with a low level of calpain-2 expression had similar breast cancer-specific survival to non-basal- or receptor- (oestrogen, progesterone or human epidermal growth factor receptor 2 (HER2)) positive disease.
Expression of the large catalytic subunit of m-calpain (calpain-2) is significantly associated with clinical outcome of patients with triple-negative and basal-like disease.
basal; breast cancer; calpain; calpastatin; triple negative
Cardiac rehabilitation is an accepted therapeutic intervention in patients after myocardial infarction or coronary revascularisation. The effects of cardiac rehabilitation programmes, whether home based or hospital based, on haemostatic indices (as reflected by fibrinogen, plasma viscosity, fibrin D‐dimer (an index of thrombogenesis), von Willebrand factor (vWf, an index of endothelial damage/dysfunction), soluble P‐selectin (an index of platelet activation)), vasomotor function (using flow‐mediated dilatation (FMD)) and ambulatory blood pressure (ABP) in patients with coronary heart disease are unknown.
81 patients (66 men, mean (SD) 59 (11) years) after myocardial infarction or coronary revascularisation were randomised to comprehensive hospital‐based (n = 40) or home‐based (n = 41) cardiac rehabilitation. Plasma levels of vWf, D‐dimer, fibrinogen, soluble P‐selectin and plasma viscosity, as well as FMD and 24‐h ABP, were measured at baseline and after 3 months of cardiac rehabilitation.
In patients who completed cardiac rehabilitation, levels of vWf, fibrinogen and D‐dimer were significantly lower and FMD improved (all p⩽0.001), whereas levels were unchanged in controls. Significant reductions were also observed in 24‐h mean systolic blood pressure, diastolic blood pressure and mean aortic pressure after completion of cardiac rehabilitation (all p<0.05). No significant differences were observed between the hospital‐based and home‐based cardiac rehabilitation programmes on these indices.
Cardiac rehabilitation improves haemostasis, endothelial function and ABP in patients with coronary heart disease, with no significant differences between home‐based and hospital‐based cardiac rehabilitation programmes. These effects may contribute to the beneficial effects of cardiac rehabilitation programmes on CV outcomes.
Pancreatic beta cell apoptosis is important in the pathogenesis and potential treatment of Type 1 diabetes. We investigated whether Humanin, a recently described survival factor for neurons, could improve the survival of beta cells and delay or treat diabetes in the NOD model. Humanin reduced apoptosis induced by serum starvation in NIT-1 cells and decreased apoptosis induced by cytokine treatment. Humanin induced Stat3 and ERK phosphorylation over a 24 hour time course. Specific inhibition of Stat3 resulted in nullifying the protective effect of Humanin. Humanin normalized glucose tolerance in diabetic NOD mice treated for 6-weeks and their pancreata revealed decreased lymphocyte infiltration and severity. In addition, Humanin delayed/prevented the onset of diabetes in NOD mice treated for 20 weeks. In summary, Humanin treatment decreases cytokine-induced apoptosis in beta cells in vitro and improved glucose tolerance and onset of diabetes in NOD mice in vivo. This indicates that Humanin may be useful for islet protection and survival in a spectrum of diabetes-related therapeutics.
Humanin; beta cell; survival; apoptosis; NOD mouse
Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease with complex genetic inheritance. Recently, single nucleotide polymorphisms (SNPs) in BANK1 and TNFSF4 have been shown to be associated with SLE in Caucasian populations, but it is not known whether they are also involved in the disease in other ethnic groups. Recent data from our genome-wide association study (GWAS) for 314 SLE cases and 920 controls collected in Hong Kong identified SNPs in and around BANK1 and TNFSF4 to be associated with SLE risk. On the basis of the results of the reported studies and our GWAS, SNPs were selected for further genotyping in 949 SLE patients (overlapping with the 314 cases in our GWAS) and non-overlapping 1042 healthy controls. We confirmed the associations of BANK1 and TNFSF4 with SLE in Chinese (BANK1, rs3733197, odds ratio (OR)=0.84, P=0.021; BANK1, rs17266594, OR=0.61, P=4.67 × 10−9; TNFSF4, rs844648, OR=1.22, P=2.47 × 10−3; TNFSF4, rs2205960, OR=1.30, P=2.41 × 10−4). Another SNP located in intron 1 of BANK1, rs4522865, was separately replicated by Sequenom in 360 cases and 360 controls and was also confirmed to be associated with SLE (OR=0.725, P=2.93 × 10−3). Logistic regression analysis showed that rs3733197 (A383T in ankyrin domain) and rs17266594 (a branch point-site SNP) from BANK1 had independent contributions towards the disease association (P=0.037 and 6.63 × 10−8, respectively). In TNFSF4, rs2205960 was associated with SLE independently from the effect of rs844648 (P=6.26 × 10−3), but not vice versa (P=0.55). These findings suggest that multiple independent genetic variants may be present within the gene locus, which exert their effects on SLE pathogenesis through different mechanisms.
SLE; BANK1; TNFSF4; Chinese; genetic association
This prospective study was conducted with the Korean Cancer Study Group to evaluate the efficacy and safety of cetuximab combined with modified FOLFOX6 (mFOLFOX6) as first-line treatment in recurrent or metastatic gastric cancer and to identify potential predictive biomarkers. Patients received cetuximab 400 mg m−2 at week 1 and 250 mg m−2 weekly thereafter until disease progression. Oxaliplatin (100 mg m−2) and leucovorin (100 mg m−2) were administered as a 2-h infusion followed by a 46-h continuous infusion of 5-fluorouracil (2400 mg m−2) every 2 weeks for a maximum of 12 cycles. Biomarkers potentially associated with efficacy were analysed. Among 38 evaluable patients, confirmed response rate (RR) was 50.0% (95% CI 34.1–65.9). Median time-to-progression (TTP) was 5.5 months (95% CI 4.5–6.5) and overall survival (OS) 9.9 months. Eleven patients having tumour EGFR expression by immunohistochemistry with low serum EGF and TGF-α levels showed a 100% RR compared to 37.0% in the remaining 27 patients (P<0.001). Moreover, ligand level increased when disease progressed in seven out of eight patients with EGFR expression and low baseline ligand level. No patient exhibited EGFR amplification or K-ras mutations. Gastric cancer patients with EGFR expression and low ligand levels had better outcomes with cetuximab/mFOLFOX6 treatment.
Cetuximab; chemotherapy; epidermal growth factor; epidermal growth factor receptor; gastric cancer; transforming growth factor-α
Objective: To test the hypothesis that an incremental shuttle walk test (ISWT) affects plasma indices of endothelial damage and dysfunction (von Willebrand factor (vWf)), platelet activation (soluble P-selectin), thrombogenesis (D-dimer), fibrinogen, and plasma viscosity more adversely in coronary artery disease (CAD) than in health. ISWT is a standardised walking test that provokes maximal performance and correlates strongly with maximum oxygen uptake.
Methods: Research indices were measured before a practice ISWT and immediately after the second ISWT in 53 patients with CAD (48 men, mean (SD) age 59 (10) years) and in 19 matched healthy controls (16 men, 61 (10) years). Data were analysed before and after ISWT.
Results: Despite no significant difference in total distance walked between patients and controls, vWf (162 (45) before v 170 (48) UI/dl after) and fibrinogen (2.9 (0.7) v 3.1 (0.7) g/l) concentrations, plasma viscosity (1.63 (0.12) v 1.71 (0.14) mPa·s), and D-dimer (0.20 (interquartile range 0.10–0.30) v 0.21 (0.12–0.31 mg/l; all p < 0.05), but not soluble P-selectin, were significantly increased after ISWT in patients with CAD, even after correction for plasma volume change. Only fibrinogen (2.5 (0.7) v 2.7 (0.7 g/l) and plasma viscosity (1.60 (0.08) v 1.64 (0.08) mPa·s; both p < 0.01) increased among controls. The increment of fibrinogen was significantly higher in patients than in controls (p = 0.035) and correlated with total walking distance (r = 0.46, p < 0.001) and peak heart rate (r = 0.28, p = 0.02). The increment of plasma viscosity rise also significantly correlated with total distance walked (r = 0.66, p < 0.001).
Conclusions: ISWT in patients with CAD appears to increase fibrinogen, vWf, and D-dimer compared with healthy controls.
incremental shuttle walk test; haemostatic markers; fibrinogen; soluble P-selectin; von Willebrand factor; coronary artery disease; exercise
Retinol-binding protein 4 (RBP4) is a recently identified adipokine that is elevated in the serum in several insulin-resistant states. We investigated the relationship between non-alcoholic fatty liver disease (NAFLD) and serum RBP4 in nondiabetic adults.
One hundred and fifty-nine nondiabetic, non-alcoholic subjects (95 males and 64 females) participated in this study. Division of subjects into a NAFLD group (n = 73; 45 males and 28 females) or a normal group (n = 86; 50 males and 36 females) was based on the presence of fatty liver disease determined by sonography.
Serum RBP4 levels in the NAFLD group were significantly higher than those in the normal group (62·8 ± 16·0 mg/l vs. 51·7 ± 14·6 mg/l, P < 0·0001). Multiple logistic regression analysis revealed that the RBP4 level was an independent factor associated with NAFLD (P = 0·0042). In addition, serum RBP4 levels were positively correlated with serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyltranspeptidase (GGT) levels. The significant association between serum RBP4 and GGT levels remained even after adjusting for age, gender, body mass index, the homeostasis model of assessment (HOMA) value and the presence of NAFLD (r = 0·3097, P = 0·0002).
Serum RBP4 levels are significantly associated with NAFLD and liver enzymes.
EWS/ATF1; MITF; melanocytes; clear cell sarcoma
Pyrazinamide (PZA) is one of the most important drugs for the treatment of Mycobacterium tuberculosis infection. However, the increasing frequency of PZA-resistant strains limits its effectiveness. In Korea, most PZA-resistant strains also exhibit both isoniazid and rifampin resistance making it essential to identify these resistant strains accurately and rapidly for effective treatment of mycobacterial infection. In this study, the characteristics and frequency of mutations of the pncA gene encoding pyrazinamidase were investigated in PZA-resistant clinical isolates from Korea. Automated DNA sequencing was used to evaluate the usefulness of DNA-based detection of PZA resistance. Among 95 PZA-resistant clinical isolates, 92 (97%) exhibited mutations potentially affecting either the production or the activity of the enzyme. Mutations were found throughout the pncA gene including the upstream region. Single nucleotide replacement appeared to be the major mutational event (69/92), although multiple substitutions as well as insertion and deletion of nucleotides were also identified. The high frequency of pncA mutations observed in this study supports the usefulness of DNA-based detection of PZA-resistant M. tuberculosis. Having verified the scattered and diverse mutational characteristics of the pncA gene, automated DNA sequencing seems to be the best strategy for rapid detection of PZA-resistant M. tuberculosis.
Anatomical lesions of hypothalamic area associated with hypodipsic hypernatremia have been reported only rarely. We report here a case of hypodipsic hypernatremia induced by a hypothalamic lesion. A 25-yr-old man, who had been treated with radiation for hypothalamic tumor 5-yr before, was admitted for evaluation of hypernatremia and hypokalemia. He never felt thirst despite the elevated plasma osmolality and usually refused to drink intentionally. Plasma arginine vasopressin (AVP) level was normal despite the severe hypernatremic hyperosmolar state and urine was not properly concentrated, while AVP secretion was rapidly induced by water deprivation and urine osmolality also progressively increased to the near maximum concentration range. All of these findings were consistent with an isolated defect in osmoregulation of thirst, which was considered as the cause of chronic hypernatremia in the patient without an absolute deficiency in AVP secretion. Hypokalemia could be induced by activation of the renin-angiotensin-aldosterone system as a result of volume depletion. However, inappropriately low values of plasma aldosterone levels despite high plasma renin activity could not induce symptomatic hypokalemia and metabolic alkalosis. The relatively low serum aldosterone levels compared with high plasma renin activity might result from hypernatremia. Hypernatremia and hypokalemia were gradually corrected by intentional water intake only.
HLA-A24 is the second most frequently expressed HLA-A type in Koreans (GF 22.8%). Four different serologic reaction patterns were observed in Korean A24 positive samples using a commercial serologic typing kit. To clarify the nature of serologic heterogeneity, thirteen A24 positive DNA samples representing the four different serologic reaction patterns were subjected to DNA sequencing analysis of the amplified HLA-A genes from each sample. Four A*24 alleles (A*2402101, A*2403, A*2408, and A*2421) were associated with the four unique serologic reaction patterns. During this study, a novel allele, A*2421, was characterized. The new sequence is similar to A*2402101, differing at codon 127 (AAA-->AAC; K-->N). By comparing putative amino acid sequences and serologic reaction patterns of A*24 allelic products identified in this study, several crucial sites for A24- and A9-specific antibody binding were predicted: 127K for A24 antibody binding, and 62E-65G and 166D-167G for A9 antibody binding. This information will be helpful for accurately assigning HLA-A24 types by serology and for predicting serologic types of new alleles.
Childhood-onset proximal spinal muscular atrophies (SMAs) are an autosomal recessive, clinically heterogeneous group of neuronopathies characterized by selective degeneration of anterior horn cells. The causative genes to be reported are survival motor neuron (SMN) and neuronal apoptosis inhibitory protein (NAIP) genes. The deletion of telomeric copy of SMN (SMN(T)) gene was observed in over 95% of SMAs. The deletion rate of NAIP gene is 20-50% according to disease severity. The objective of this article is to genetically characterize the childhood-onset spinal muscular atrophy in Koreans. Five Korean families (14 constituents containing 5 probands) with SMA were included in this study. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) were used for the deletion analysis of SMN(T). Multiplex PCR method was used for NAIP analysis. Four probands showed deletion of SMNT gene. Deletion of SMN(C) (centromeric SMN) gene was found in one proband who did not show the deletion of SMN(T) gene and in the father of one proband who showed the deletion of SMN(T) gene. The deletion of NAIP gene was not found among all the studied individuals. The extent of deletion in Koreans was smaller than that in other studied population. PCR-RFLP deletion analysis can be applied to diagnose SMA and make a prenatal diagnosis.
Myasthenia gravis is one of the typical organ specific autoimmune disease and the CD5+ B-lymphocytes are known to be associated with the secretion of autoimmune antibodies. The authors performed the study to establish an animal model of experimental autoimmune myasthenia gravis (EAMG) by immunizing the nicotinic acetylcholine receptor (AChR) and to understand CD5+ B-lymphocyte changes in peripheral blood of EAMGs. Lewis rats weighing 150-200 g were injected subcutaneously three times with 50 microg AChR purified from the electric organ of Torpedo marmorata and Freund's adjuvant. The EAMG induction was assessed by evaluating clinical manifestations. The CD5+ B-lymphocyte was double stained using monoclonal PE conjugated anti-CD5+ and FITC conjugated anti-rat CD45R antibodies and calculated using a fluorescence-activated cell sorter (FACS). In three out of ten Lewis rats injected with purified AChR, the EAMG models were established. The animals showed definite clinical weakness responded to neostigmine; they had difficulty in climbing the slope, or easily fell down from a vertical cage. The range of CD5+ B-lymphocytes of peripheral blood in the EAMG models was 10.2%-17.5%, which was higher than in controls. In conclusion, the EAMG models were successfully established and the CD5+ B-lymphocyte expression in peripheral blood increased in EAMGs. This provided indirect evidence of the autoimmune pathomechanism of human myasthenia gravis.
A cDNA clone encoding Schistosoma mansoni phosphoglycerate kinase (SmPGK) was previously identified by affinity-purified antibodies which are specific for 3-h-old schistosomula tegumental antigens. Antibodies to the recombinant SmPGK which has enzymatic activity were localized to various tissues including the tegument of the 3-h-old schistosomula and 42-day-old adult worms. In this study, we show that SmPGK is an immunogenic molecule in both natural infection in humans and experimental vaccination in animals. To understand the role that a highly conserved molecule like SmPGK played during schistosome infection, we affinity purified antibodies to SmPGK from patients with chronic schistosomiasis and demonstrated that they did not cross-react with human PGK. However, affinity-purified rabbit anti-SmPGK antibodies did show immunoreactivity to both human PGK and rabbit PGK. Thus, during natural infection antibodies that cross-react with human PGK are not produced; however, as a result of active immunization with an intact conserved molecule, such cross-reacting antibodies are produced. Immunological analysis of cyanogen bromide digests of SmPGK with monoclonal antibodies that recognize SmPGK but not human PGK identifies a B-cell epitope on a 12.2-kDa fragment represented by amino acids 61 to 174.
The HLA-DR molecule is a polymorphic membrane glycoprotein and one of the key molecules causing allograft rejection and graft-versus-host disease in organ transplantation. Serologic typing using DR specific alloantisera has long been used, but several problems have limited its application. The purpose of this study was to establish an efficient reverse-SSO typing system that detects DRB1 and DRB3/B4/B5 alleles on a single membrane. A DR typing membrane was prepared by immobilizing 21 dT-tailed sequence specific oligonucleotides (SSOs) on a nylon membrane and was used in a hybridization assay with digoxigenin-labeled PCR-amplified target DNA. The positive signals were detected on X-ray film using chemiluminescence. A comparison study with serology using DNAs from 105 unrelated individuals demonstrated that the reverse-SSO typing system was superior to serologic typing in terms of accuracy (100% vs 90.5%), simplicity, range of application, rapidity, and cost of the test. These data indicate that the reverse-SSO typing system can replace serology as a routine DR test, and will be useful in time-restricted solid organ transplantation and in selection of an unrelated marrow donor prior to bone marrow transplantation.
Primary hyperparathyroidism is a rare disease in children and is characterized by conspicuous skeletal and renal changes. A 12 year old male patient presented with symptoms of polydipsia, polyuria, general weakness, nausea, and vomiting which had begun 3 months earlier, and showed typical laboratory findings of primary hyperparathyroidism. Confirmatory diagnosis was made by elevated parathyroid hormone concentration in serum, technetium-thallium subtraction scan imaging method and histopathologic finding of chief cell hyperplasia. The laboratory findings revealed elevated levels of BUN, creatinine and decreased GFR. Kidney biopsy showed typical calcium deposits in tubules with marked tubulointerstitial infiltration. After subtotal parathyroidectomy, clinical findings improved remarkably.
We reviewed the clinical, electrophysiological, radiological, and histopathological findings in 25 patients with benign focal amyotrophy. There were 14 patients with upper limb type and 11 with lower limb type. 18 patients had unilateral involvement and 7 had bilateral involvement asymmetrically. The characteristics clinical features were sporadic occurrence, predominance in young males, nonprogressive course or initial progression for 1 to 3 years followed by stationary state, segmental distribution of muscle weakness and atrophy localized to one limb or both homologous limbs markedly asymmetrically, and absence of any definite sensory loss or central nervous system involvement. The electrophysiological, radiological, and muscle histopathological findings suggested chronic focal anterior horn cell disease. Although the prevalence of this disease is still unknown, the importance of recognition is being emphasized because of its common occurrence in our country and the benign prognosis.
The acute peripheral neuropathy as one of hypereosinophilic syndrome is known to be a rare disorder. The authors experienced a dramatic case with acute peripheral neuropathy, hypereosinophilia in peripheral blood, and the positive anti-GM1 antibodies. The serum protein electrophoresis showed a diffusely increased gamma-globulin region and the polyclonal gammopathy was found by the immunoelectropheresis. There was no evidence of inflammatory myopathy in vastus lateralis muscle. The sural nerve biopsy was compatible with vascular neuropathy, as there were a few myelin digestion chambers, mild perineuronal fibrosis, and perivascular lymphoplasmocytic infiltration with focal organizing thrombosis. The clinical response to prednisone therapy was excellent.
Arteriovenous malformations of the uterus are extremely rare and they occur either in congenital or acquired forms. The most common clinical presentation is abnormal uterine bleeding, which may be aggravated by therapeutic curettage. Because of their rare incidence and clinical importance in management of patients, we report a case of arteriovenous malformation causing serious bleeding during a hysterectomy for uterine leiomyoma. The patient was a 47-year-old multiparous woman who had a history of chronic vaginal bleeding for one year. Numerous anomalous blood vessels draining into the right and left uterine arteries were found on the anterior wall of the uterus and parametrium.
Surgical specimens from the cheek mucosa of 73 patients with white lesions were studied to determine various morphometric parameters that would help differentiate between the various types of oral mucosal white lesions that carry a risk of malignant change. Four cell types were represented: traumatic keratosis, leucoplakia, candidal leucoplakia and lichen planus, in addition to a control group of normal mucosa. The shape and size of the epithelial cells in two cell compartments, parabasal and spinous, were investigated by an interactive image analysis system (IBAS-1). The results showed an increase in the cell size in the parabasal cell compartment of all the white lesions compared with the normal mucosa. In the spinous cell compartment there was an increase in the cell size in lichen planus and traumatic keratosis; leucoplakia and candidal leucoplakia showed a slight decrease in cell size compared with the normal mucosa. Attempts to discriminate between the four groups of white lesions showed that these parameters can provide a high level of separation between lichen planus and the three other groups, but not between leucoplakia, candidal leucoplakia, and traumatic keratosis.
The size and shape of the cells in the basal cell layer of the oral epithelium in 100 specimens from oral mucosa were studied by using an interactive image analysis system (IBAS-1). Four groups of white lesions (traumatic keratosis, lichen planus, leucoplakia, and a "risk group") in addition to two control groups (normal mucosa and squamous cell carcinoma) were studied retrospectively. The results showed a progressive increase in the dimensions (area, perimeter, and maximum diameter) of the nuclei from normal mucosa through traumatic keratosis, lichen planus, leucoplakia and the "risk group" to carcinoma, with considerable differences. The nucleus in squamous cell carcinoma was twice as large as in normal mucosa. A substantial increase in the dimensions of both the cell and the nucleus was found in the "risk group." The nucleo:cytoplasmic ratio, contrary to what might have been anticipated in risk lesions, did not show considerable differences between the diagnostic groups. Furthermore, it was slightly decreased in the risk group compared with the normal mucosa. The shape factors (form PE and contour index) seemed to be less helpful in the identification of the "risk group." The size of the basal cell and its nucleus can be of diagnostic value for lesions with a high risk of malignant transformation.
Sixty-two “leukoplakias” from the cheeks of betel-nut chewers in West Malaysia were studied histologically. Ten biopsies were from non-tobacco betel-nut chewers. An amorphous von Kossa positive layer was seen on the keratin surface in 42 specimens. Tobacco did not appear essential for its formation, and it appeared to be significantly associated with parakeratosis. Its possible significance as a cuticle-like layer prolonging contact between carcinogens and the mucosa is discussed.
Parakeratosis appeared to be the most common form of cornification seen, and the mitotic activity in parakeratinized leukoplakias appeared to be significantly greater than orthokeratinized leukoplakias.
Comparison with studies on other population samples using different quids suggested that severe histological changes were more likely to be seen when tobacoo-containing quids were chewed as compared to non-tobacco-containing quids.
An attempt to correlate the histological changes seen with the clinical habit in leukoplakias from chewers using tobacco-containing quids suggested that epithelial atrophy appeared to be significantly related to the duration of the habit but not to the “intensity” of the habit.