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PubMed2005

REM sleep behavior disorder and REM sleep without atonia in patients with progressive supranuclear palsy.

STUDY OBJECTIVE: To compare sleep characteristics, rapid eye movement (REM) sleep without atonia, and REM sleep behavior disorder (RBD) in patients with progressive supranuclear palsy (tauopathy), patients with Parkinson's disease (a synucleinopathy), and control subjects. DESIGN: Sleep interview, overnight polysomnography, and Multiple Sleep Latency Tests. PATIENTS: Forty-five age- and sex-matched patients with probable progressive supranuclear palsy, (n=15, aged 68 +/- 8 years, 7 men), patients with Parkinson disease (n=15), and control subjects (n=15). SETTINGS: Tertiary-care academic hospital. INTERVENTION: N/A. RESULTS: Compared to the 2 other groups, patients with progressive supranuclear palsy had a longer duration of wakefulness after sleep onset and twice as much sleep fragmentation and percentage of stage 1 sleep but had similar apnea-hypopnea indexes, periodic leg movements indexes, and mean daytime sleep latencies. REM sleep percentage was as low in patients with progressive supranuclear palsy (8% +/- 6% of total sleep time) as in patients with Parkinson disease (10% +/- 4%), versus 20% +/- 6% in controls (analysis of variance, P < .0001). Interestingly, patients with progressive supranuclear palsy had percentages of REM sleep without atonia (chin muscle activity: 33% +/- 36% of REM sleep) similar to those of patients with Parkinson disease (28% +/- 35%) and dramatically higher than those of controls (0.5% +/- 1%, analysis of variance, P = .008). Four (27%) patients with progressive supranuclear palsy had more than 50% REM sleep without atonia (as did a similar number of patients with Parkinson disease), and 2 of them (13%, vs 20% of patients with Parkinson disease) had clinical RBD. The four patients with progressive supranuclear palsy with excessive daytime sleepiness slept longer at night than the 11 patients with progressive supranuclear palsy who were alert (442 +/- 14 minutes vs 312 +/- 74 minutes, student t tests, P = .004), suggesting a primary nonnarcoleptic hypersomnia. CONCLUSION: REM sleep without atonia and RBD were as frequent in patients with progressive supranuclear palsy as in patients with Parkinson disease. It suggests that the downstream cause of parkinsonism, rather than its primary neuropathology (synucleinopathy vs tauopathy), is a key factor for REM sleep behavior disorder.

Aged↗
PubMed1998

HPV, histologic grade and age. Risk factors for the progression of cervical intraepithelial neoplasia.

OBJECTIVE: To evaluate the clinical significance of human papillomavirus (HPV) type, grade of cervical intraepithelial neoplasia (CIN) and age on the progression of CIN. STUDY DESIGN: Clinical follow-up data, histopathologic diagnosis, polymerase chain reaction (PCR) and HPV DNA typing were available on 194 patients, 119 with CIN 2/moderate dysplasia and 75 with CIN 3/severe dysplasia. RESULTS: HPV 16 was observed most frequently (47.0%) in progressed CIN, while HPV-negative cases (57.7%) were most frequently regressed. HPV positivity (P = .0466), especially HPV 16 positivity (P = .0104), was significantly more frequent than HPV negativity in the progression group. The rate of CIN progression was higher with HPV (50.5%) than without HPV (35.4%). Of the CIN cases with HPV 16, 56.5% progressed, while 30.8% of the CIN cases with HPV 6 and/or 11 and 35.4% of the CIN cases without HPV progressed. The probability of progression was 1.87-fold higher in the HPV-positive group than that in the HPV-negative group (P = .03). Multiple logistic regression analysis revealed that HPV (odds ratio 2.23, P = .0103) and grade of the lesion (odds ratio 3.30, P = .0002) in the initial biopsy strongly and independently correlated with progression of CIN. CONCLUSION: HPV status and histologic grade are independent predictive risk factors for progression and may be useful in the management of CIN.

Adult↗
PubMedDate not supplied

Metastasis-Associated genes and metastatic tumor progression.

The morbidity in most cancer patients is not due to their primary cancers; it is due to metastatic disease. Thus understanding the progression of tumors to the metastatic state and the changes that take place in highly malignant cells are important in the development of new therapeutic approaches to diagnose, prognostically assess and treat highly progressive malignancies. Changes in the expression of certain genes or alterations of gene structures and encoded products can result in benign tumor cells progressing to the invasive and metastatic states. This has been shown in the laboratory by transferring dominantly acting oncogenes into susceptible cells and then testing the malignant properties of these cells in vivo. Usually such rapid qualitative changes in malignant state occur only rarely; the natural progression of tumor cells to the invasive or metastatic state occurs through a slow stepwise process of change. Tumor progression, in some instances, can be reversible, involving changes in dominantly acting oncogenes or tumor suppressor genes. The natural progression of tumors to highly malignant states also involves their ability to circumvent host microenvironmental controls that regulate cellular growth and diversity. Quantitative changes in gene expression rather than qualitative changes in gene structure are important in microenvironmental effects on progression. One of the important mechanisms of cellular regulation in epithelial tissues, such as breast epithelium, appears to be mediated by intercellular junctional communication. Changes in gene expression can result in loss of junctional communication, followed by cellular diversification and progression. Highly malignant tumor cells that have slowly evolved in vivo with only a few qualitative changes in gene structure have probably undergone extensive cycles of diversification and have multiple quantitative differences in gene expression. Some of these genes are related to metastasis. For example, we have identified a novel gene called mta1 (rat) or MTA1 (human) that appears to be involved in mammary cell motility and growth regulation. This may be an example of a gene that regulates highly malignant cellular phenotypes. When coupled with other cellular changes, such as loss of intercellular communication, specific changes in gene expression may result in cellular diversification and tumor progression.

Animals↗
PubMed1993

Profiles of language impairment in primary progressive aphasia.

OBJECTIVE: The profile of language impairment in patients with primary progressive aphasia in comparison with the language impairment in patients with Alzheimer's disease and after stroke. DESIGN: The Western Aphasia Battery and the Mattis Dementia Rating Scale evaluated the language and cognitive impairment. Follow-up studies were done 1 to 5 years after the initial testing in seven of 10 patients with primary progressive aphasia, and a postmortem examination of the brain was done in two patients. SETTING: All 10 patients with primary progressive aphasia were previously healthy, community-dwelling persons when first tested. PATIENTS AND OTHER PARTICIPANTS: All patients with primary progressive aphasia reported at least a 2-year history of slowly progressive aphasia without other signs of global dementia. The initial Western Aphasia Battery results of the 10 patients with primary progressive aphasia were compared with those of a sample of 10 patients with probable Alzheimer's disease and with those of a sample of 10 patients with aphasia due to a left hemispheric stroke. Both reference samples were matched for age and sex; the sample with stroke-caused aphasia was additionally matched for the aphasia type. RESULTS: Expressive language disability with reduced speech fluency and anomia but preserved language comprehension and nonverbal cognition were typical features in early stages of primary progressive aphasia. Spontaneous speech was significantly more impaired in patients with primary progressive aphasia in comparison with those with aphasia after left hemisphere stroke and with language impairment in patients with Alzheimer's disease. Follow-up examinations revealed continuous, often rapid deterioration of language impairment. The neuropathological examination showed Alzheimer's disease in one patient and Pick's disease in the other. CONCLUSION: The profile of aphasia suggests that primary progressive aphasia tends to affect anterior parts of the language-dominant cortex first.

Aged↗
PubMed2005

The relationship between cartilage loss on magnetic resonance imaging and radiographic progression in men and women with knee osteoarthritis.

OBJECTIVE: To determine the relationship between radiographic progression of joint space narrowing and cartilage loss on magnetic resonance imaging (MRI) in patients with symptomatic knee osteoarthritis (OA), and to investigate the location of MRI-based cartilage loss in the knee and its relation to radiographic progression. METHODS: Two hundred twenty-four men and women (mean age 66 years) were studied. Radiographs and MRI of the more symptomatic knee were obtained at baseline and at 15- and 30-month followup. Radiographs of the knee (with weight-bearing) were read for joint space narrowing (scale 0-3), with progression defined as any worsening in score. We used a semiquantitative method to score cartilage morphology in all 5 regions of the tibiofemoral joint, and defined cartilage loss as an increase in score (scale 0-4) at any region. We examined the relationship between progression of joint space narrowing on radiographic images and cartilage loss on MRI, using a generalized estimating equation proportional odds logistic regression, adjusted for baseline cartilage score, age, body mass index, and sex. The medial and lateral compartments were analyzed separately. RESULTS: In the medial compartment, 104 knees (46%) had cartilage loss detected by MRI. The adjusted odds ratio was 3.7 (95% confidence interval 2.2-6.3) for radiographic progression being predictive of cartilage loss on MRI. However, there was still a substantial proportion of knees (80 of 189 [42%]) with cartilage loss visible on MRI when no radiographic progression was apparent. Cartilage loss occurred frequently in the central regions of the femur and tibia as well as the posterior femur region, but radiographic progression was less likely to be observed when posterior femur regions showed cartilage loss. Radiographic progression appeared specific (91%) but not sensitive (23%) for cartilage loss. Overall findings were similar for the lateral compartment. CONCLUSION: While our results provide longitudinal evidence that radiographic progression of joint space narrowing is predictive of cartilage loss assessed on MRI, radiography is not a sensitive measure, and if used alone, will miss a substantial proportion of knees with cartilage loss.

Aged↗
PubMed1994

Progressive B-cell chronic lymphocytic leukaemia frequently exhibits aberrant p53 expression.

We have analysed the p53 status in non-progressive and progressive chronic B-cell leukemia (B-CLL) by ELISA, immunoprecipitation, FACS and cDNA sequencing in relation to in vitro proliferation in response to Staphylococcus aureus strain Cowan I (SAC) and IL-2. In FACS, cells from progressive leukaemia were found to over-express p53 with a conformation recognized by PAB240. In a PAb240-based ELISA, 60% of progressive B-CLL were positive. DNA sequencing of p53 exons 5 to 9 revealed a codon 179 His to Gln change in one of the ELISA-positive, progressive B-CLL but failed to reveal any mutations in 4 other ELISA-positive, progressive B-CLL. Among progressive B-CLL populations, 10/14 responded by proliferation in vitro to SAC/IL-2. In non-progressive cells, low levels of p53 were found by FACS, none was positive in the PAb240 ELISA and only one case showed a weak proliferative response to SAC/IL-2. Low p53 expression was also seen in different types of normal B cells, resting and activated, and in EBV-transformed B-cell lines, in contrast to the high expression observed in Burkitt lymphoma cell lines with verified p53 mutations. We conclude that progressive B-CLL is characterized by aberrant p53 expression which may be a significant prognostic factor.

Adult↗
PubMed1995

c-jun and multistage carcinogenesis: association of overexpression of introduced c-jun with progression toward a neoplastic endpoint in mouse JB6 cells sensitive to tumor promoter-induced transformation.

Tumor promoters such as 12-O-tetradecanoylphorbol-13-acetate (TPA) and epidermal growth factor (EGF) induce neoplastic transformation, elevated c-jun protein expression, and activator protein-1 (AP-1)-dependent gene expression in JB6 mouse epidermal cells sensitive to tumor promoters (clone 415a P+ cells). In contrast, JB6 cells resistant to tumor promoter-induced transformation (clone 307b P- cells) exhibit a greatly reduced TPA or EGF inducible c-jun expression and AP-1 activity. We have recently shown that induced AP-1 is necessary for tumor promoter-induced transformation of P+ cells because introduction of a dominant negative c-jun mutant into P+ cells inhibits both AP-1 dependent transactivation and the transformation response to tumor promoter. The intent of the investigation presented here was to test the hypothesis that elevation of AP-1 activity is sufficient to cause progression to the P+ phenotype in P- cells or to the transformed phenotype in P+ cells. Clonally derived P+ and P- recipient cells transfected with a human c-jun expression construct and overexpressing c-jun protein were tested for progression by assaying for constitutive or inducible anchorage independent phenotype and nude-mouse tumorigenicity. Overexpression of c-jun did not produce progression in P- cells but did increase the probability of progression in P+ cells (two of five transfectant cell lines progressed to the tumor phenotype). In addition, c-jun overexpression did not increase AP-1 activity in any of the P-/c-jun transfectants or in the two of five P+/c-jun transfectants that acquired the transformed phenotype. The P+/c-jun transfectants that showed elevated AP-1 activity did not progress to the tumor phenotype, demonstrating that an increase in AP-1 activity is insufficient for this progression. Since P(+)-to-tumor phenotype progression occurred in cells overexpressing c-jun but not AP-1, we propose that P(+)-to-transformed phenotype progression is c-jun dependent and AP-1 independent.

Animals↗
PubMed1999

Problems in designing and recruiting to therapeutic trials in primary progressive multiple sclerosis.

Patients with primary progressive multiple sclerosis have atypical clinical and magnetic resonance imaging (MRI) characteristics which present unique problems in designing and recruiting to therapeutic trials. The first randomised controlled therapeutic trial specifically for primary progressive multiple sclerosis is now underway. Although only an exploratory phase II study, it has provided further insight into difficulties in diagnosis, classification and choice of clinical and MRI outcome measures. Patients with primary progressive multiple sclerosis have a wide differential diagnosis and do not readily conform to the Poser criteria. They may therefore present diagnostic uncertainty, particularly as their classification often relies on a retrospective history. This was highlighted during the recruitment to this study of interferon-beta1a. Of the 138 patients referred with a definite diagnosis of primary progressive multiple sclerosis only 50 were enrolled in the study. Of the 88 patients not included, 50% either did not have primary progressive multiple sclerosis, or the diagnosis was not secure. Outcome measures pose particular problems. Clinically the focus must be on progression, and the measure should be both responsive and reliable. In relation to MRI, the currently recommended measures for therapeutic trials in relapsing/remitting and secondary progressive multiple sclerosis show little change in primary progressive multiple sclerosis, and therefore more pathologically specific MRI measures are required. Strict clinical guidelines and further developments in clinical and MRI measures are required to facilitate future therapeutic trials in primary progressive multiple sclerosis.

Brain↗
PubMed1985

Prognostic significance of progression of coronary artery disease.

Angiographically documented coronary artery disease (CAD) can progress. Although progression itself is frequently recognized in patients who have undergone repeat cardiac catheterization, its prognostic significance remains unclear. To evaluate the influence of progression on survival, 313 patients with CAD who underwent catheterization twice (39 +/- 25 months apart) were followed for 3 to 129 months (mean 41 +/- 30) after the second angiogram. At the time of the second angiogram, 21, 91, 113 and 88 patients had 0-, 1-, 2- and 3-vessel CAD, respectively. The mean ejection fraction (EF) of the group was 55 +/- 13%. Progression was noted in 139 patients (44%). Of the 313 patients, 33 died and 39 had acute myocardial infarction (AMI) during follow-up. Four-year survival was estimated at 94% and 83% in the nonprogression and progression groups, respectively. Progression was predictive of survival by (univariate) long-rank test (p less than 0.01), but only EF (p less than 0.001), number of diseased vessels (p less than 0.01) and percent stenosis in the left main coronary artery (p less than 0.05) were independently significant by (multivariate) Cox regression analysis. Four-year survival without AMI was 89% and 73% in the nonprogression and progression groups, respectively. Progression was related to survival without AMI (p less than 0.001) by log-rank test. Cox regression analysis provided 3 independent predictors of survival without AMI: number of diseased vessels (p less than 0.01), progression (p less than 0.01), relative risk = 2.28) and EF (p less than 0.01). Results were similar when analyzing only the 39 AMIs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1976

The cardiac conduction system in progressive systemic sclerosis. Clinical and pathologic features of 35 patients.

Progressive systemic sclerosis may be associated with focal myocardial fibrosis. Electrocardiographic abnormalities including conduction block are common in progressive systemic sclerosis but whether they are due to direct destruction of the specialized conduction tissue of the heart is uncertain. The conduction systems of 35 patients with progressive systemic sclerosis were studied. Of these 35 patients, 17 (50 per cent) had myocardial fibrosis of the type seen in progressive systemic sclerosis. In 10 of the 17, it was severe. Sinus node fibrosis was present in 13 patients and was nearly as frequent in those with as in those without the progressive systemic sclerosis myocardial lesion. Overlying pericarditis may have contributed to the fibrotic changes within the sinoatrial nodes in seven of the 13 patients. The atrioventricular node and main His bundles were normal. However, fibrotic changes were found in the proximal bundle systems in six patients. In three of the six, severe myocardial progressive systemic sclerosis was present, two had focal fibrous atrophy of the left bundle, and one had complete interruption of the right bundle. In only the latter patient was this reflected in the electrocardiogram which showed a right bundle branch block. Three patients without progressive systemic sclerosis myocardial lesions also had fibrous atrophy of a portion of the proximal left bundle branch, and in one the electrocardiogram showed an isolated left anterior hemiblock. Thus, morphologic abnormalities within the conduction system in our patients are difficult to attribute to progressive systemic sclerosis per se. Furthermore, although conduction abnormalities were more frequent in patients with myocardial disease, specific conduction system disease was not the cause in most patients. As has been noted in ischemic heart disease, the conduction system appears to be relatively spared from the myocardial changes of progressive systemic sclerosis, and the high incidence of conduction disturbances in this condition may be a consequence, rather, of damage to working myocardium.

Adolescent↗
PubMed2004

Aortic stiffness and diameter predict progressive aortic dilatation in patients with Marfan syndrome.

AIM: Patients with Marfan syndrome may develop dissection due to progressive dilatation in the entire aorta, which is not always predictable by mere anatomic assessment of the aortic diameter, especially of the descending aorta. The aim of this study was to identify the predictive value of aortic stiffness on the occurrence of dissection and progressive aortic dilatation. METHODS AND RESULTS: In 78 non-operated patients with Marfan syndrome (mean age 31+/-8 years, mean aortic root diameter 43+/-6 mm, range 31-55 mm) aortic stiffness and diameters were assessed by magnetic resonance imaging (MRI) at multiple levels. After a median follow-up of 71 months (25-75%: 68-72 months) a second MRI was performed and the incidence of aortic dissection and progressive aortic dilatation, defined as mean aortic diameter increase >1 mm/year was determined. During follow-up, 4 (5%) of 78 patients developed an aortic dissection (1 type A, 2 type B, and 1 infra-renal dissection). Twenty (26%) of the 78 patients had progressive aortic root dilatation. There were 5 (6%) patients with progressive descending thoracic aortic dilatation and 6 (7%) with progressive abdominal aortic dilatation. Multivariate logistic regression analysis revealed that local distensibility was an independent predictor of progressive thoracic descending aortic dilatation (OR=4.14, 95% CI, 1.02-16.7). For progressive aortic root and abdominal aortic dilatation local initial diameter appeared to be the major predictor (OR=1.37, 95% CI, 1.16-1.62; OR=1.36, 95% CI, 1.09-1.69, respectively). CONCLUSION: In patients with Marfan syndrome both aortic diameter and aortic distensibility are independent predictors of progressive aortic dilatation. For optimal risk assessment and monitoring of patients with Marfan syndrome, both aortic stiffness and diameter should be assessed at least annually.

Adolescent↗
PubMedDate not supplied

Cytolipotoxicity-induced involution of the female reproductive tract following expression of obese (ob/ob) and diabetes (db/db) genotype mutations: progressive, hyperlipidemic transformation into adipocytic tissues.

Both diabetes (db/db) and obese (ob/ob) single gene mutations induce a progressive, hyperglycemic-hyperinsulinemic endometabolic environment which promotes hypercytolipidemic, utero-ovarian involution in C57BL/KsJ mice. The progressive expression of the induced diabetes-obesity syndrome (DOS) results in female reproductive sterility and eventual organoatrophy. In order to define the intra-cytoplasmic alterations induced by the progressive cytolipidemia on cellular vitality, utero-ovarian tissue samples were collected from both control (+/?) and littermate-matched ob/ob or db/db C57BL/KsJ mice at either 4 weeks (initial-onset DOS phase), 8 weeks (progressive, overt DOS phase), or 16 weeks (chronic-DOS phase) of age for cytolipid distribution analysis. All db/db and ob/ob mutant groups exhibited phenotypic obesity and systemic hyperglycemia-hyperinsulinemia relative to age-matched littermate +/? groups. In all db/db and ob/ob age groups, a progressive hypercytolipidemia was noted relative to +/? groups. When analyzed for lipid channeling, a progressive perinuclear mapping pattern of cytolipid distribution was noted. The primary locus of initial db/db and ob/ob cytolipid deposition was localized to the baso-polar regions in endometrial epithelia samples, or to the interstitium-thecal layer border of ovarian follicular compartments, during the initial-onset DOS phase. Progressively, intra-cytoplasmic lipid mobilization promoted a consistent perinuclear channeling of lipid vacuoles, ultimately isolating nuclear loci from the peripherally displaced cytoplasmic organelles within uterine epithelial layers. In db/db and ob/ob ovarian tissue samples, a progressive, gradient-related lipid infiltration of interstitial, thecal and, ultimately, granulosa cell layers promoted an enhanced rate of follicular-lipidemic atresia relative to +/? groups. In each tissue layer, the cytolipidemia promoted a dramatic perinuclear lipid-isolation barrier from intra-cytoplasmic organelle domains. With age-related exacerbation of the DOS syndrome, cytoplasmic nuclear-organelle displacement and lipoisolation resulted in cellular atresia, promoting the eventual utero-ovarian organoatrophy which characterized the chronic-DOS phase in db/db and ob/ob C57BL/KsJ mutants. These results indicate that the cytoinvolution associated with reproductive tract atrophy in these genetically mutant, diabetic-obese models is promoted by the disruption of the normal cytoarchitecture of utero-ovarian tissue layers induced by the progressive lipid sequestration, accumulation and ultimate isolation-induced disruption of intra-cellular organelle compartmentalization.

Adipose Tissue↗
PubMed1997

Progression of ischaemic stroke and excitotoxic aminoacids.

BACKGROUND: Mechanisms involved in progression of stroke are little understood. Studies in animals have shown an association between neuronal death mediated by excitatory aminoacids and deterioration in focal cerebral ischaemia. We looked for an association between concentrations of glutamate and glycine in plasma and cerebrospinal fluid (CSF) and early progression in a prospective study of 128 patients with acute ischaemic stroke. METHODS: Of 556 consecutive admissions to our emergency unit, 128 eligible patients with ischaemic stroke were included in our study. Blood and CSF samples were taken within the first 24 h from stroke onset when cerebral oedema had been excluded on a previous cranial computed tomography. Ischaemic stroke was judged to be in progression if the Canadian stroke scale score (1.5 = maximum neurological deficit, 10 = no deficit) fell by 1 or more points during the first 48 h after inclusion. Glutamate and glycine concentrations in plasma and CSF were measured by high-performance liquid chromatography. The effect of plasma and CSF glutamate concentrations on progression was analysed by logistic regression. FINDINGS: 43 (33.6%) patients had progressing ischaemic stroke. Concentrations of glutamate and glycine in plasma and CSF were higher in patients with progressing stroke than in those with stable cerebral infarcts (p < 0.0001). There was a significant linear correlation between CSF and plasma concentrations of glutamate (r = 0.79, p < 0.001). The positive predictive value of a plasma glutamate concentration of more than 200 mumol/L for progression of ischaemic stroke was 97% (95% CI 85-100). Glutamate concentrations of more than 200 mumol/L in plasma and of more than 8.2 mumol/L in CSF were independently and significantly associated with progression of neurological deficit (26.1 [6.9-98.6] and 40.9 [7.6-220], respectively). INTERPRETATION: Early neurological progression of acute ischaemic stroke is associated with high concentrations of glutamate in blood and CSF. Measurement of plasma glutamate may be useful for the early detection of those patients with acute stroke who will deteriorate during 48 h after onset.

Aged↗
PubMed2000

Autologous stem cell transplantation in progressive multiple sclerosis--an interim analysis of efficacy.

Based on the good results of experimental transplantation in animal models of multiple sclerosis and of other autoimmune diseases, we have treated 24 patients suffering from chronic progressive multiple sclerosis with high-dose chemotherapy (BEAM regimen) followed by autologous blood stem cell rescue and antithymocyte globulin. Blood stem cells were mobilised with cyclophosphamide at 4g/m2 and G- (or GM-) CSF. In 9 cases, additional CD34+ cell-selection of the graft was performed. Here we update previously published results of this novel treatment, mainly with regard to clinical efficacy, as the median follow-up time has reached 40 months (range, 21-51). Infections were the principal toxicity early after the procedure, with death of a patient from aspergillosis 65 days post stem cell infusion. No serious late events occurred apart from a case of autoimmune thyroiditis that developed 11 months after transplant in a patient who had received a CD34+ cell-depleted graft. Mild and transient neurotoxicity was observed in 10 patients (42%), most probably associated with fever and infections. Eighteen patients (18/23; 78%) responded to the treatment, i.e., they were improved or stabilized, while five patients progressed, of which 4 had primary progressive disease. Of those improved or stabilised (18), 9 patients have maintained stable condition whereas 9 developed relapses or they slowly resumed progression, although their disability scores have not gotten worse than they were before transplantation. The probability of progression-free survival (compared to entry status) at 3 years is 92% for patients with secondary progressive disease and 39% for the primary progressive type. CD34+ cell-selection did not seem to yield better results except for a delay in progression or in relapse after transplantation. These results appear better than those achieved by any other treatment of progressive multiple sclerosis, including beta-interferon, but they need to be confirmed by other open or controlled studies in view of the well-known difficulty of judging objectively the effect of a treatment in patients with this disease.

Adult↗
PubMed2006

Insulin delays the progression of Drosophila cells through G2/M by activating the dTOR/dRaptor complex.

In Drosophila and mammals, insulin signalling can increase growth, progression through G1/S, cell size and tissue size. Here, we analyse the way insulin affects cell size and cell-cycle progression in two haemocyte-derived Drosophila cell lines. Surprisingly, we find that although insulin increases cell size, it slows the rate at which these cells increase in number. By using BrdU pulse-chase to label S-phase cells and follow their progression through the cell cycle, we show that insulin delays progression through G2/M, thereby slowing cell division. The ability of insulin to slow progression through G2/M is independent of its ability to stimulate progression through G1/S, so is not a consequence of feedback by the cell-cycle machinery to maintain cell-cycle length. Insulin's effects on progression through G2/M are mediated by dTOR/dRaptor signalling. Partially inhibiting dTOR/dRaptor signalling by dsRNAi or mild rapamycin treatment can increase cell number in cultured haemocytes and the Drosophila wing, respectively. Thus, insulin signalling can influence cell number depending on a balance between its ability to accelerate progression through G1/S and delay progression through G2/M.

Animals↗
PubMed2005

Relation between the axial length and lenticular progressive myopia.

PURPOSE: To investigate the possible risk factors associated with lenticular progressive myopia and to compare the differences between patients with lenticular progressive myopias and senile cataracts. METHODS: We retrospectively reviewed cases that had been diagnosed as lenticular progressive myopia with a discrete nuclear sclerotic cataract and progressive myopic changes in one hospital from January 1998 to February 2003. A total of 47 eyes of 35 patients were enrolled in this study. In all, 32 eyes of 29 cases of common senile cataract receiving cataract extraction surgery during the study period were randomly chosen (every four cases in time sequence within a 2-month period by two ophthalmologists' clinic in 2002) as the control group. We compared the preoperative refraction status, keratometry (K-values) and axial lengths between these two groups. The possible ocular or systemic associating diseases were also investigated in the study group. RESULTS: In the lenticular progressive myopia group, the mean age at surgery (52.9+/-9.2 years) is younger than that in the senile cataract group (68.1+/-7.3 years). The mean axial length in the study group (25.68+/-1.93 mm) is statistically significant longer than that in the control group (22.97+/-0.83 mm) (P<0.0001). Besides, patients with lenticular progressive myopia had significantly lower mean K-values (43.25+/-1.42 diopters) than patients with senile cataracts (44.25+/-1.28 diopters) (P<0.01). There were no other ocular or systemic diseases closely associated with lenticular progressive myopia. CONCLUSIONS: Patients with nuclear cataract combined with lenticular progressive myopia have longer axial length than patients with senile cataract. The longer axial length may be one of the important risk factors predisposing to lenticular progressive myopia.

Adult↗
PubMed2003

Time to progression is dependent on the expression of the tumour suppressor PTEN in ovarian cancer patients.

BACKGROUND: Quantitative analyses of PTEN expression of ovarian cancer tissues were performed in this study. PTEN expression was investigated in terms of each patient's progression-free interval to indicate the role of PTEN in the generation of platinum refractory tumours. MATERIALS AND METHODS: The study group comprised 20 ovarian cancer patients from whom fresh frozen tissues of both the primary tumour and specimens of progressive disease were available. The PTEN protein and phosphorylation of the downstream effector protein kinase B (PKB) were quantified by Western blot analyses and subsequent densitometry. Data were analyzed for individual PTEN variation with respect to the clinical course as defined by the progression-free interval. RESULTS: Applying the usual clinical criteria for platinum-sensitivity after progression, seven patients were considered platinum-sensitive whereas 13 patients had suffered a progression within 12 months after the chemotherapy. In 5/7 (71%) cases with prolonged time to progression, an increase in PTEN was observed. Decline of PTEN expression occurred in 9/13 (69%) patients with poor outcome. PTEN expression corresponds inversely to PKB phosphorylation in 14/20 (70%) tissues investigated. CONCLUSIONS: The data suggest that decreased PTEN expression accompanies the progression of ovarian cancer. Declining PTEN expression results in a shortened relapse-free interval, whereas an increase of PTEN prolongs the time to progression. However, as far as recurrence occurs, PTEN is not the only mechanism to suppress tumour progression in ovarian cancer.

Adult↗
PubMed2000

Natural course of progression of liver fibrosis in Japanese patients with chronic liver disease type C--a study of 527 patients at one establishment.

Patients with chronic hepatitis C infection show a gradual progression of fibrosis to liver cirrhosis and hepatocellular carcinoma (HCC). We studied whether the progression of liver fibrosis differed among Japanese subjects who were infected with different hepatitis C virus (HCV) genotypes. In 527 patients we examined whether there was a relationship between gender, age, history of blood transfusion, interval between date of blood transfusion and date of liver biopsy or date of diagnosis of HCC, serum alanine aminotransferase level, platelet count or HCV genotype, with the extent of liver fibrosis, classified into four stages (F1-F4). Moreover, we compared the mean rate of liver fibrosis progression per year in patients with each HCV genotype. Patients who had a higher fibrosis score tended to be older, have a lower platelet count and a longer interval since blood transfusion than those who had a lower fibrosis score. The mean rate of liver fibrosis progression was 0.12 +/- 0.15 stages per year after the blood transfusion. However, the progression rate of liver fibrosis in patients who had received a blood transfusion when they were > or = 30 years of age was 0.19 +/- 0.22, while the progression rate of liver fibrosis in the patients who had received a blood transfusion when they were < 30 years was 0.09 +/- 0.09. In conclusion, chronic hepatitis C is a progressive disease, and patients with genotype 1b, 2a and 2b have a similar rate of progression of liver fibrosis. Particular attention should be paid to patients who are infected with HCV when > or = 30 years of age, because intrahepatic fibrosis rapidly progresses in these patients.

Adult↗