Heterogeneity of neurons reprogrammed from spinal cord astrocytes by the proneural factors Ascl1 and Neurogenin2.

Astrocytes are a viable source for generating new neurons via direct conversion. However, little is known about the neurogenic cascades triggered in astrocytes from different regions of the CNS. Here, we examine the transcriptome induced by the proneural factors Ascl1 and Neurog2 in spinal cord-derived astrocytes in vitro. Each factor initially elicits different neurogenic programs that later converge to a V2 interneuron-like state. Intriguingly, patch sequencing (patch-seq) shows no overall correlation between functional properties and the transcriptome of the heterogenous induced neurons, except for K-channels. For example, some neurons with fully mature electrophysiological properties still express astrocyte genes, thus calling for careful molecular and functional analysis. Comparing the transcriptomes of spinal cord- and cerebral-cortex-derived astrocytes reveals profound differences, including developmental patterning cues maintained in vitro. These relate to the distinct neuronal identity elicited by Ascl1 and Neurog2 reflecting their developmental functions in subtype specification of the respective CNS region.

Diagnostic value of the nuclear matrix protein 22 test and urine cytology in upper tract urothelial tumors.

OBJECTIVE: To investigate the diagnostic value of the nuclear matrix protein 22 (NMP22) test in comparison to urine cytology for the detection of upper tract urothelial carcinoma. PATIENTS AND METHODS: Patients with transitional cell carcinoma of the upper urinary tract (n = 34) and patients with renal calculosis (n = 25) were included in this study. Voided urine samples and separated catheter urine specimens were assayed for NMP22 and cytological examination. RESULTS: The sensitivity of the NMP22 test in separated and voided urine was 73.2 and 70.5%, respectively, compared to 64.7 and 58.8% of urine cytology. The specificity of the NMP22 test in separated and voided urine was 88 and 92%, respectively, compared to 96 and 96% of urine cytology. The combination of separated and voided urine is the best method because the sensitivity is 79.41% and specificity 88%. There is a high agreement of the NMP22 test in voided and separated urine (kappa = 0.795, p < 0.01), indicating that the voided urine is adequate for diagnosis. CONCLUSIONS: The NMP22 test has higher sensitivity but lower specificity than cytology. The combination of these two tests could be a very useful diagnostic method for detection of upper urothelial tumors.

Urinary prostate specific antigen: is the clinical use likely?

UNLABELLED: Prostate specific antigen (PSA) blood test represents the standard procedure in prostate cancer (CaP) diagnosis and follow-up. However, determination of PSA in the urine, where PSA is present in much higher concentrations than in the blood, still remains in the field of research. OBJECTIVES: To determine urinary concentrations of PSA (uPSA) in different groups of patients (pts.), and to estimate is it possible to differentiate benign and malignant prostate diseases and to follow-up the results of treatment. METHODS: Between January 2001. and November 2003., urinary concentrations of PSA were determined at 142 pts. divided in seven groups: 1. young and healthy volunteers, 2. "BPH-24": pts. with benign prostatic hyperplasia (BPH) who collected the sample of 24-hour voided urine, 3. "BPH-I": pts. with BPH who collected the first portion of first urinary voiding, 4. "TRUS-CaP": pts. with CaP which gave the first portion of urine just prior to transrectal ultrasound-guided prostate biopsy (TRUS- biopsy), 5. "TRUS-non-CaP": pts. who gave first portion of urine prior to TRUS-biopsy, but biopsy did not prove the presence of CaP, 6. "RRP": pts. who underwent radical retropubic prostatectomy (RRP), 7. "AAT": pts. who underwent androgen deprivation therapy. RESULTS: Average uPSA value in the group of young and healthy volunteers, was 13.8 +/- 19.6 ng/ml, in "BPH-24": 38.0 +/- 44.4 ng/ml, in "BPH-I": 140.8 +/- 140.9 ng/ml, in "TRUS-CaP": 234.8 +/- 277.7 ng/ml, in TRUS-non-CaP: 113.1 +/- 148.5 ng/ml, and in the group "RRP": 4.4 +/- 4.7 ng/ml. There was no statistically significant difference of average uPSA values between "BPH-I" and "TRUS-CaP" groups. The significant difference was found between the group of young volunteers and "BPH-I". In "TRUS-CaP" group, there was strong correlation between tumour size and aggressivenes and uPSA concentration. Finally, PSA and uPSA decline during androgen deprivation therapy, strongly correlated (up to r = 0.95). CONCLUSIONS: Determination of uPSA cannot differentiate BPH and CaP. However, in the group of pts. with proven localized CaP, uPSA can provide additional information concerning T-staging. Moreover, simultaneous monitoring of PSA and uPSA response on hormonal therapy, can provide an early recognition of androgen-indiferent CaP (AIPCA) and hormone-resistent CaP (HRPCA).