Prognostic significance of cytochemical analysis of leukemic M2 blasts

Cytochemical analysis of leukemic blasts from 46 patients with acute myeloblastic M2 leukemia (according to the FAB classification) was performed before and after cytostatic therapy, and compared with findings obtained in 20 age- and sex-matched control subjects. Cytochemical findings for myeloperoxidase (MPO), Sudan black B, acid phosphatase and alpha-naphthyl-acetate esterase (ANAE) were related to the achievement of the first complete remission (CR),i.e. data were compared after the patients had been divided into CR and non-CR groups. The analysis clearly showed that a high proportion of myeloperoxidase- and, to a lesser extent, Sudan black B-positive blasts before treatment may have constituted a significantly unfavourable prognostic factor.     

The renal cortical lymphatic system in the rat,hamster, and rabbit

Rat, hamster, and rabbit renal cortical lymphatics were examined by light and electron microscopy. Rat and hamster kidneys possessed both intra- and interlobular lymphatics that were structurally similar at the light microscopic level. Ultrastructural examination of the hamster lymphatic endothelium, however, revealed an unusual arrangement of cytoplasmic extensions not seen in the other two species. The intralobular lymphatics were related primarily to tubules, afferent arterioles, and renal corpuscles and were consistent with lymph formation from both plasma filtrate and tubular reabsorbate. Interlobular lymphatics were seen in connective tissue associated with the interlobular blood vessels. Rabbit cortex contained only interlobular lymphatics. Cross-sectional area, maximum diameter, volume density, and profile density were determined by stereological measurements using a computer-based image analyzer. The morphological data from the rat were used, in combination with published values for lymph flow, to calculate the rate of lymph formation per unit area of endothelium in lymphatics of the renal cortex. Among kidneys fixed by retrograde perfusion, the cortical lymphatic system was most extensive in maximum diameter, volume density, and profile density. It was smallest in the rabbit and intermediate in the rat. Lower volume and profile density were found for rat kidneys fixed by the dripping technique. It was concluded that: (1) tubular reabsorbate probably contributes to renal lymph in the rat and hamster, but not in the rabbit; (2) significant differences exist in the extent of the renal lymphatic systems among the three species, with the hamster kidney having the richest network and the rabbit the poorest; (3) the method of fixation influences the measured size and density of renal cortical lymphatics; and (4) the estimated rate of lymph formation in the kidney of the rat is roughly comparable to that in the dog.     

HnRNP CBP35-CBP67 interaction during stress response and ageing

Previous studies have demonstrated the existence of nuclear carbohydrate binding proteins in a variety of mammalian cells with molecular masses of 35 000, 67 000, and 70 000 (CBP35, CBP67, and CBP70), which are associated with nuclear ribonucleoprotein (RNP) complexes. CBP35 consists of two domains, an aminoterminal portion that is homologous to certain regions of proteins of the heterogeneous nuclear RNP complex, and a carboxyl-terminal portion homologous to β-galactoside-specific lectins. CBP35 it has been proposed, like the glucose-specific lectin, CBP67, to guide RNP complexes through the nuclear pore. Here we show that the exposure of mature rats to stress induces an increase in nuclear CBP35 bound to CBP67 and retained on immobilized glucose. Nuclear extracts from the livers of old rats displayed no detectable stress response. This CBP35·CBP67 association detected in rat liver is considered with respect to the CBP35·CBP70 association recently observed in HL60 cell nuclear extracts.     

Proangiogenic cytokines (bFGF and VEGF) in BALF from two different lung segments examined by high resolution computed tomography (HRCT) in patients with sarcoidosis

The aim of the study was to evaluate the concentrations of bFGF and VEGF in double BAL (2 x 120 ml) from two different lung segments: (s.A) from upper lobe with the most and (s.B) from lower lobe with the least extensive involvement estimated by high resolution computed tomography (HRCT). Examined group consisted of 28 sarcoid patients with homogeneous, regular distribution of nodular opacities in conventional chest X-ray (14 F, 14 M aged 19-54). Eleven healthy volunteers served as controls. In patients with sarcoidosis we observed the significantly higher levels (p < 0.01) of bFGF (1.79 pg/ml, 1.48 pg/ml) and VEGF (107.5 pg/ml, 109.7 pg/ml) in BAL from s.A and s.B respectively in comparison with BAL from lung segments Abis and Bbis in control group (bFGF: 0.75 pg/ml, 0.47 pg/ml and VEGF: 33.7 pg/ml, 43.9 pg/ml respectively). bFGF in BAL from s.A in active sarcoidosis was higher than in s.A and s.B in non-active sarcoidosis. Concentrations of bFGF in BAL from both s.A and s.B correlated positively with CD4/CD8 ratio and absolute number of lymphocytes, CD4 cells and lymphocytes HLA-DR estimated in BAL from these lung segments. We conclude that bFGF and VEGF may be involved in sarcoidosis pathogenesis and bFGF may be useful in estimation of sarcoidosis activity.     

Interactions between imidazoline compounds and sulphonylureas in the regulation of insulin secretion

1. Imidazoline α₂-antagonist drugs such as efaroxan have been shown to increase the insulin secretory response to sulphonylureas from rat pancreatic B-cells. We have investigated whether this reflects binding to an islet imidazoline receptor or whether α₂-adrenoceptor antagonism is involved.
2. Administration of (±)-efaroxan or glibenclamide to Wistar rats was associated with a transient increase in plasma insulin. When both drugs were administered together, the resultant increase in insulin levels was much greater than that obtained with either drug alone.
3. Use of the resolved enantiomers of efaroxan revealed that the ability of the compound to enhance the insulin secretory response to glibenclamide resided only in the α₂-selective-(+)-enantiomer; the imidazoline receptor-selective-(−)-enantiomer was ineffective.
4. In vitro, (+)-efaroxan increased the insulin secretory response to glibenclamide in rat freshly isolated and cultured islets of Langerhans, whereas (−)-efaroxan was inactive. By contrast, (+)-efaroxan did not potentiate glucose-induced insulin secretion but (−)-efaroxan induced a marked increase in insulin secretion from islets incubated in the presence of 6 mM glucose.
5. Incubation of rat islets under conditions designed to minimize the extent of α₂-adrenoceptor signalling (by receptor blockade with phenoxybenzamine; receptor down-regulation or treatment with pertussis toxin) abolished the capacity of (+)-and (±)-efaroxan to enhance the insulin secretory response to glibenclamide. However, these manoeuvres did not alter the ability of (±)-efaroxan to potentiate glucose-induced insulin secretion.
6. The results indicate that the enantiomers of efaroxan exert differential effects on insulin secretion which may result from binding to effector sites having opposite stereoselectivity. Binding of (−)-efaroxan (presumably to imidazoline receptors) results in potentiation of glucose-induced insulin secretion, whereas interaction of (+)-efaroxan with a second site leads to selective enhancement of sulphonylurea-induced insulin release.

     

Role of the notochord in the development of cephalic structures in normal and anencephalic human fetuses

Summary Normal and anencephalic human conceptuses were analysed histologically to investigate the role of differentiation of the intracranial notochord and its relation to the formation of the basichondrocranium. We have examined 16 normal embryos and fetuses and 4 anencephalic fetuses. Each developmental stage of formation of the normal basichondrocranium presented specific morphological changes during the course of notochord depletion. In contrast with normal specimens, anencephalic fetuses presented malformations of the basichondrocranium which were always related to an abnormal position of the notochord. Macroscopical differences between craniorachischisis and cranioschisis in fetuses with anencephaly correlated with the existence of two histologically different degrees of malformation. In fetuses with craniorachischisis we found severe disturbances in the shape, position and ossification of the basichondrocranium and in the course of the intracranial notochord. In fetuses with cranioschisis the described disturbances of the basichondrocranium and intracranial notochord were mild. In addition, marked differences in affection of the central nervous system and the hypophysis were observed. These findings suggest different periods of dysmorphogenesis. Our results underline the importance of the chordal mesoderm in the differentiation for the formation of cephalic structures in Man.     

Intracranial dural empyema

Intracranial dural empyema is a neurosurgical emergency with potentially devastating complications. The prognosis is adversely affected by delay in diagnosis. Modern imaging techniques, especially contrast enhanced CT and MRI, have improved the speed and accuracy of radiological diagnosis of this condition, with an associated reduction in mortality. Despite this, there may still be a delay in diagnosis, partly owing to the subtlety of early radiological signs, especially on unenhanced CT. We present cases that illustrate some of the radiological manifestations, complications and potential pitfalls in diagnosis.     

Cluster analysis of diffusion tensor magnetic resonance images in human head injury

OBJECTIVE: Issues surrounding the nature of the edema associated with traumatic brain injury in humans, and its evolution in the acute phase, remain unresolved. This study aimed to characterize the topographical nature of the pathophysiological changes in human traumatic brain injury with diffusion tensor magnetic resonance imaging. METHODS: Multislice diffusion-weighted magnetic resonance imaging data were acquired from five patients undergoing elective ventilation for management of traumatic focal contusion or hematomas. The diffusion tensor and the T2-weighted intensity were then computed for every voxel in the image data set for each patient. The topographical distribution of abnormalities in the trace of the diffusion tensor and T2-weighted images were characterized by cluster analysis. RESULTS: In four patients with technically satisfactory data, a narrow band of tissue was observed in the periphery of focal lesions, which was characterized by selective reduction in the trace of the diffusion tensor, without any associated increase in the T2-weighted signal intensity. CONCLUSION: This change is interpreted as indicating either a partial redistribution of water from the extra- to intracellular compartment, or a reduction in the diffusivity of water in the intracellular or cytosolic environment. These diffusion and T2-weighted characteristics are also found in early ischemic change, hence, such regions may represent potentially salvageable tissue at risk of permanent damage. The study illustrates the advantage of using information contained within the diffusion tensor in addition to more conventional imaging sequences.     

Carbonic anhydrase IX expression predicts outcome of interleukin 2 therapy for renal cancer.

PURPOSE: Renal cancer response to interleukin 2 (IL-2) therapy and patient survival has been correlated with tumor histology and carbonic anhydrase IX (CAIX) expression. In an effort to confirm and expand these observations, we examined CAIX expression in pathology specimens from renal cancer patients who had previously received IL-2 therapy. EXPERIMENTAL DESIGN: Paraffin-embedded tissue sections of renal cancer were immunostained with the MN-75 monoclonal antibody to CAIX and expression levels were correlated with histologic findings and clinical outcome. RESULTS: Tissue specimens were obtained from 66 patients; 27 of whom (41%) had responded to IL-2-based therapy. Fifty-eight specimens were assessed as clear cell, with 56, 33, and 4 having alveolar, granular, and papillary features, respectively. Twenty-four (36%), 31 (47%), and 11 (17%) were classified into good, intermediate, and poor prognosis groups according to the Upton pathology model. Forty-one specimens (62%) had high CAIX expression. Twenty-one of 27 (78%) responding patients had high CAIX expressing tumors compared with 20 of 39 (51%) nonresponders (odds ratio, 3.3; P = 0.04). Median survival was prolonged (P = 0.04) and survival >5 years was only seen in high CAIX expressers. In patients with intermediate pathologic prognosis, all nine responders had high CAIX expression versus 11 of 22 nonresponders. A resultant group with good pathologic prognosis alone or with intermediate pathologic prognosis and high CAIX contained 26 of 27 (96%) responders compared with 18 of 39 (46%) nonresponders (odds ratio, 30; P < 0.01) and exhibited longer median survival (P < 0.01). CONCLUSIONS: CAIX expression seems to be an important predictor of outcome in renal cell carcinoma patients receiving IL-2-based therapy and may enhance prognostic information obtained from pathology specimens.     

HbA1c‐based diabetes diagnosis among patients with glucokinase mutation (GCK‐MODY) is affected by a genetic variant of glucose‐6‐phosphatase (G6PC2)

Aims Genetic variation at the rs560887 locus of the glucose‐6‐phosphatase, catalytic 2 gene (G6PC2) is known to affect regulation of fasting glycaemia. We determined the rs560887 genotype of patients with monogenic diabetes and glucokinase gene mutations (GCK‐MODY) and correlated the genotypes with HbA_1c levels. Methods Patients from families with GCK‐MODY were recruited from two large cohorts from Poland (n = 128) and the Czech Republic (n = 154). Genotypes at the rs560887 polymorphic site in G6PC2 were examined using real‐time quantitative polymerase chain reaction. The effect of rs560887 genotype on age at diagnosis of GCK‐MODY and initial HbA_1c levels were evaluated separately within both cohorts. Following that, a meta‐analysis of rs560887 genotype–HbA_1c associations of both Polish and Czech cohorts was performed to confirm homogeneity of findings and validate cohort‐specific results. Results GG homozygosity at rs560887 was associated with marginally elevated HbA_1c levels (P = 0.07 in both cohorts). The effects observed in both groups were very homogeneous (Q = 0.18; P = 0.68). Meta‐analysis showed that GG homozygosity at rs560887 was associated with mean HbA_1c levels higher by 2.4 mmol/mol (0.24%), 95% CI 0.5–4.4 mmol/mol (0.05–0.44%) than in individuals with other genotypes. Additionally, meta‐analysis of both cohorts showed that GG homozygous individuals had higher odds of reaching the 48 mmol/mol (6.5%) diagnostic threshold of diabetes; (odds ratio 1.90; 95% CI 1.07–3.36; P = 0.03). No such effects were observed for age at diagnosis of diabetes. Conclusions Variation at the rs560887 locus of G6PC2 is associated with worse glycated haemoglobin levels in individuals with GCK mutations; GG homozygotes are more likely to meet diagnostic criteria for diabetes based on HbA_1c level.