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PubMed2004

Recurrent laryngeal nerve identification and assessment during thyroid surgery: laryngeal palpation.

Electrical identification and monitoring of the recurrent laryngeal nerve (RLN) has been proposed as an adjunct to standard visual identification of the nerve during thyroid and parathyroid surgery. This study was undertaken to assess laryngeal palpation as an intraoperative technique for identifying and assessing the RLN during surgery and to investigate the relation between laryngeal palpation and associated laryngeal electromyographic (EMG) activity. The postcricoid region of the larynx during surgery was palpated through the posterior hypopharyngeal wall to sense posterior cricoarytenoid muscle contraction in response to ipsilateral RLN stimulation (i.e., the "laryngeal twitch response.") Laryngeal palpation was performed in a series of 449 consecutive thyroid and parathyroid surgeries with 586 RLNs at risk. All patients underwent preoperative and postoperative laryngoscopy to assess vocal cord mobility. In a subset of patients, laryngeal palpation and simultaneous laryngeal EMG recordings were compared during intraoperative RLN stimulation. In this series, there was no permanent RLN paralysis. There was one case of temporary RLN paralysis secondary to neural stretch that resolved 6 weeks postoperatively (temporary paralysis rate: 0.2% of patients, 0.2% of nerves at risk). Intraoperative laryngeal palpation of the laryngeal twitch response reliably correlated with normal postoperative vocal cord function. Loss of the laryngeal twitch response occurred in the single case of temporary paralysis in the setting of an anatomically intact nerve. Laryngeal palpation correlated well with simultaneous laryngeal EMG activity. There were no palpation-induced laryngeal injuries or laryngeal edema. There were also no RLN injuries due to repetitive neural stimulation. Intraoperative laryngeal palpation during RLN stimulation is a safe, reliable method for neural monitoring that can assist in RLN identification and assessment during thyroid and parathyroid surgery. Most importantly, it provides important prognostic information regarding ipsilateral vocal cord function at the completion of the initial side of the thyroid or parathyroid surgery. Intraoperative laryngeal palpation allows the surgeon to stage contralateral surgery if RLN damage is diagnosed, thereby avoiding the potential for bilateral vocal cord paralysis. We believe that laryngeal palpation is useful as an adjunct to formal EMG monitoring during thyroid and parathyroid surgery.

Adolescent↗

PubMed2002

Loss of Pin1 function in the mouse causes phenotypes resembling cyclin D1-null phenotypes.

Phosphorylation of proteins on serine/threonine residues preceding proline is a key signaling mechanism. The conformation and function of a subset of these phosphorylated proteins is regulated by the prolyl isomerase Pin1 through isomerization of phosphorylated Ser/Thr-Pro bonds. Although young Pin1(-/-) mice have been previously shown to develop normally, we show here that they displayed a range of cell-proliferative abnormalities, including decreased body weight and testicular and retinal atrophies. Furthermore, in Pin1(-/-) adult females, the breast epithelial compartment failed to undergo the massive proliferative changes associated with pregnancy. Interestingly, many of these Pin1-deficient phenotypes such as retinal hypoplasia and mammary gland impairment are also the characteristic of cyclin D1-deficient mice. Cyclin D1 levels were significantly reduced in many tissues in Pin1-deficient mice, including retina and breast epithelial cells from pregnant mice. Moreover, Pin1 directly bound to cyclin D1 phosphorylated on Thr-286-Pro increased cyclin D1 in the nucleus and stabilized cyclin D1. These results indicate that Pin1 positively regulates cyclin D1 function at the transcriptional level, as demonstrated previously, and also through posttranslational stabilization, which together explain why Pin1 loss-of-function phenotypes in the mouse resemble cyclin D1-null phenotypes. Our results provide genetic evidence for an essential role of Pin1 in maintaining cell proliferation and regulating cyclin D1 function.

Animals↗

PubMed2000

Reciprocal modulation of transcriptional activities between HIV-1 Tat and MHC class II transactivator CIITA.

HIV-1 is the etiologic agent of acquired immune deficiency syndrome (AIDS). Functional loss of antigen-presenting cells (APC) in HIV-1 infection is considered to be involved in AIDS pathogenesis. We found that actions of the viral transactivator Tat and the transactivator of MHC class II genes, CIITA, are mutually inhibitory. While Tat inhibited expression of MHC class II genes in APC, overexpression of CIITA inhibited Tat and subsequently HIV-1 replication. This action of Tat appears to be mediated by sequestering the common cofactor, cyclin T1, but not p300 and CBP. These reciprocal actions between Tat and CIITA not only explains the functional impairment of APC in HIV-1 infection but also rationalizes the suppression of HIV-1 virus load by induction of CIITA such as IFN-gamma.

Cell Line↗

PubMed1994

Complex correlation between excitatory amino acid-induced increase in the intracellular Ca2+ concentration and subsequent loss of neuronal function in individual neocortical neurons in culture.

Primary cultures of cerebral cortical neurons and single-cell imaging of intracellular free Ca2+ concentration ([Ca2+]i) with the ratiometric dye fura-2 were used to assess excitatory amino acid (EAA)-induced neurotoxicity; the loss of neuronal function as defined by the ability of the cells to respond to K(+)-induced depolarization by a transient increase in Ca2+ influx was measured. The responsiveness of individual neurons was measured quantitatively as the [Ca2+]i values of the second KCl (2.KCl) stimulation divided by those of the first KCl (1.KCl) stimulation, giving the value of the ratio (2.KCl/1.KCl). Exposure to EAAs led to an increase in [Ca2+]i, but no simple correlation between the increase in [Ca2+]i and neuronal responsiveness could be demonstrated. Rather, below a threshold level of [Ca2+]i (ca. 1 microM), the neuronal responsiveness was largely independent of the glutamate receptor-agonist-induced increase in [Ca2+]i. However, when [Ca2+]i increased above this threshold level, the neurons almost invariably lost the ability to respond to a K(+)-induced depolarization, particularly after exposure to glutamate. Therefore, the cortical neurons were found to be exceptionally vulnerable to the glutamate-induced loss of function when compared with the effect induced by the glutamate receptor subtype-specific agonists, N-methyl-D-aspartate, quisqualate, and 2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl) propionate. The findings suggest that the loss of neuronal membrane polarization precedes plasma membrane disruption and is a sensitive marker of EAA-induced neurodegeneration observed at the single-cell level.

Animals↗

PubMed1996

Longitudinal study of respiratory findings in rubber workers.

A cross-sectional assessment of respiratory function and symptoms was performed in 1985 on 409 male rubber workers and 172 unexposed control workers. A follow-up study in 311 of the original rubber workers was performed 6 years later. Ventilatory capacity was measured by recording maximum expiratory flow-volume (MEFV) curves. At the time of the initial study, significantly higher prevalences of all chronic respiratory symptoms, except for asthma, were found among the rubber workers compared to controls. Smokers had a significantly higher prevalence of most of the chronic respiratory symptoms compared with nonsmokers. A high prevalence of acute symptoms during the workshift was recorded among the rubber workers at both surveys. Rubber workers demonstrated significantly lower ventilatory capacity measurements compared to predicted. Ventilatory capacity measurements diminished significantly across the workshift, particularly FEF50 and FEF25. Metaproterenol inhaled at the end of the workshift significantly improved lung function in a small group of sensitive rubber workers. Annual lung function loss among both smokers and nonsmokers was in excess of predicted. Our data suggest that exposure to noxious agents in the rubber industry are associated with the development of acute and chronic respiratory impairment.

Adolescent↗

PubMed2003

Homozygous deletion of the CRABPI gene in AB1 embryonic stem cells results in increased CRABPII gene expression and decreased intracellular retinoic acid concentration.

The cellular retinoic acid (RA) binding proteins I and II (CRABPI and CRABPII), intracellular proteins which bind retinoic acid with high affinity, are involved in the actions of RA, though their exact roles are not fully understood. We have generated several genetically engineered AB1 cell lines in which both alleles of the CRABPI gene have been deleted by homologous recombination. We have used these CRABPI knockout cell lines to examine the consequences of functional loss of CRABPI on RA-induced gene expression and RA metabolism in the murine embryonic stem cell line, AB1, which undergoes differentiation in response to RA. Complete lack of CRABPI results in decreased intracellular [3H]RA concentrations under conditions in which external concentrations of [3H]RA are low (1-10nM) and in an altered distribution of [3H] polar metabolites of [3H]RA in the cell and in the medium. Fewer [3H] polar metabolites are retained within the CRABPI(-/-) cells compared to the wild-type cells. These data suggest that CRABPI functions to regulate the intracellular concentrations of retinoic acid and to maintain high levels of oxidized retinoic acid metabolites such as 4-oxoretinoic acid within cells.

Animals↗

PubMed1995

Preservation of fetal ventral mesencephalic cells by cool storage: in-vitro viability and TH-positive neuron survival after microtransplantation to the striatum.

Preservation of fetal ventral mesencephalic (VM) dopaminergic tissue prior to transplantation has been hampered by the fact that the cells are vulnerable to mechanical and osmotic stress after storage. Previous quantitative studies have shown that cool storage in a so-called 'hibernation medium' prior to grafting, can be used safely for up to 2 days without morphological or functional losses [16,32] using standard transplantation techniques. In the present study on rat fetal VM tissue we have investigated (i) the accuracy of different vital stains (trypan blue exclusion and ethidium bromide stain) to predict in vivo viability of VM cell suspensions after grafting; (ii) the influence of different storage media (glucose-saline, HBSS, DMEM, CO2-independent medium and hibernation medium), temperatures (+4 degrees C or +21 degrees C) and preparations (cell suspension or intact pieces) on the viability scores and total number of cells in vitro; and (iii) the survival and functional effects of intrastriatally grafted VM tissue after preservation by cool storage for up to 12 days using a less traumatic microtransplantation technique. The results show that cool storage at +4 degrees C of intact VM pieces in hibernation medium gives the best in vitro viability scores. Microtransplantation of cell suspensions prepared from cool-stored VM tissue produced good survival of tyrosine hydroxylase (TH)-positive graft neurons for up to 8 days of storage, and functional compensation in the amphetamine-rotation test for up to 12 days of storage. The total yield of surviving TH-positive neurons was unchanged, compared to fresh grafts, after 5 and 8 days of storage, and only reduced by 48% in the grafts stored for 12 days prior to implantation. These findings highlight the potential usefulness of a combination of cool storage and microtransplantation techniques to be able to extend the preservation periods of VM tissue. Such procedures may ultimately help to increase the safety and flexibility in experimental and clinical studies on neural transplantation of dopaminergic neurons.

Animals↗

PubMed1995

Differences between anti-myeloperoxidase- and anti-proteinase 3-associated renal disease.

We performed a retrospective study of the clinical features, the pattern of the pre-treatment renal function loss, the renal morphology and the outcome in 92 patients with anti-neutrophil cytoplasmic autoantibodies directed against proteinase 3 (aPR3; N = 46) or myeloperoxidase (aMPO; N = 46). Patients with aMPO had a higher median age than patients with a PR3 (63 and 56 years; P < 0.05). The mean (+/- SD) number of affected organs in the aPR3 group exceeded that of the aMPO group (3.9 +/- 1.4 and 2.2 +/- 1.1; P < 0.01). The prevalence of renal involvement did not differ between patients with aPR3 and aMPO (83% and 67%, respectively; NS). Pre-treatment renal function deteriorated significantly faster in aPR3- than in aMPO-associated renal disease. The kidney biopsies from patients with aPR3 showed a higher activity index (10.2 +/- 3.8 and 7.3 +/- 3.2; P < 0.03) and a lower chronicity index (4.5 +/- 2.6 and 7.0 +/- 3.1; P < 0.02) than biopsies from patients with aMPO. The kidney survival at two years was 73% in patients with aPR3- and 61% in patients with aMPO-associated renal disease (NS). We conclude that renal function generally deteriorates faster in aPR3- than in aMPO-associated renal disease. This goes together with more active renal lesions in patients with aPR3 and more chronic renal lesions in patients with aMPO. Despite these differences, there is no difference in outcomes between both antibody groups.

Adult↗

PubMed2005

Multidisciplinary ALS care improves quality of life in patients with ALS.

OBJECTIVE: To examine the effect of multidisciplinary ALS care on the quality-of-life (QoL) in patients with ALS and their caregivers. METHODS: In a cross-sectional study, 208 patients with ALS and their caregivers were interviewed. QoL was assessed using the 36-item Short Form Health Survey (SF-36) and two visual analogue scales (VAS). Criteria for multidisciplinary ALS care were: an ALS team headed by a consultant in rehabilitation medicine and consisting of at least a physical therapist, occupational therapist, speech pathologist, dietician and a social worker; use of the Dutch ALS consensus guidelines for ALS care; and at least six incident ALS patients per year. RESULTS: Clinical characteristics and functional loss of the 133 patients receiving multidisciplinary ALS care and the 75 patients receiving general ALS care were similar. The percentage of patients with adequate aids and appliances was higher in those with multidisciplinary ALS care (93.1 vs 81.3%, p = 0.008), whereas the number of visits to professional caregivers was similar in both groups. Patients in the multidisciplinary ALS care group had a better mental QoL on the SF-36 Mental Summary Score than those in the general care group (p = 0.01). The difference in QoL was most pronounced in the domains of Social Functioning and Mental Health, and was independent of the presence of aids and appliances. No significant differences were found in the SF-36 Physical Summary Score, VAS, or in QoL of caregivers of patients with ALS. CONCLUSION: High standard of care improves mental quality-of-life in patients with ALS.

Aged↗

PubMed2000

TNF-alpha-induced secretion of C-C chemokines modulates C-C chemokine receptor 5 expression on peripheral blood lymphocytes.

Peripheral blood lymphocytes express CCR5, a chemokine receptor for immune cell migration and calcium signaling that serves as an important coreceptor for the HIV. After in vitro stimulation, CCR5 expression is dramatically increased on mature T lymphocytes, especially on the CD45RO+ memory subset. In this study, we report that TNF-alpha delays the surface expression of CCR5 on PBLs after activation and diminishes CCR5 irrespective of its initial level. Functional loss of CCR5 is reflected in a decreased capability of the treated cells to migrate and signal calcium after MIP-1beta stimulation. The effect is mediated via the p80 type II TNF receptor (TNFR2), which induces NF-kappaB among other factors, leading to an enhanced secretion of the chemokines macrophage-inflammatory protein-1alpha, macrophage-inflammatory protein-1beta, and RANTES. Expression of these chemokines directly down-regulates CCR5. These findings reveal a new regulatory mechanism utilized by activated peripheral T cells to modulate their chemotaxis and potentially other functions mediated by CCR5, including the infection of T lymphocytes by macrophage-tropic HIV strains.

Antibodies↗

PubMed2004

NMDA receptor alterations in neurons from pediatric cortical dysplasia tissue.

The subunit composition of glutamate receptors affects their functional properties, and could contribute to abnormal electrophysiology in pediatric cortical dysplasia (CD). We examined electrophysiological responses and subunit assembly of N-methyl-D-aspartate (NMDA) receptors in acutely dissociated normal-appearing pyramidal and cytomegalic neurons from CD tissue and normal-appearing pyramidal neurons from non-CD tissue. In most cytomegalic and approximately 30% of normal-appearing pyramidal neurons from CD tissue, NMDA currents showed decreased Mg(2+) sensitivity compared with neurons from non-CD tissue. Ifenprodil had less effect in CD compared with non-CD neurons, indicating a functional loss of NR2B subunits. NMDA-evoked current density was decreased in cytomegalic compared with normal-appearing neurons. Single-cell reverse transcriptase polymerase chain reaction showed that all non-CD neurons expressed NR2B subunit mRNA. By comparison, 22% of pyramidal neurons in CD tissue lacked NR2B mRNA. Immunofluorescence showed a decrease in NR2B subunit expression in cytomegalic neurons and a subset of normal-appearing pyramidal neurons from CD tissue. Taken together, these results demonstrate the presence of NMDA receptors with altered subunit composition and Mg(2+) sensitivity that could contribute to functional abnormalities in CD.

Adolescent↗

PubMed1998

Chondroitin sulfate: S/DMOAD (structure/disease modifying anti-osteoarthritis drug) in the treatment of finger joint OA.

A total of 119 patients were included in a randomized, double-blind, placebo-controlled trial in order to assess the S/DMOAD properties in OA of chondroitin sulfate (CS 4&6, 3 x 400 mg/day, Condrosulf IBSA, Lugano, CH). Posteranterior roentgenographies of the interphalangeal (IP) joints were carried out at the start of the study and at yearly intervals. This enabled the investigators to document the radiological progression of the anatomical lesions in the pathological finger joints over a 3-year period. It was shown that the progression of OA in the IP finger joints in an individual can be determined by the evolution of his finger joints through previously described anatomical phases: 'N' (not affected), 'S' (classical OA), 'J' (loss of joint space), 'E' (erosive OA) and 'R' (remodeled joint). Structure/disease-modifying anti-OA drug (S/DMOAD) properties were searched for by assaying the number of patients developing OA in previously normal IP joints ('N' > 'S'), or progressing through the described anatomical phases of the disease ('S' > 'J', 'S' > 'E', 'J' > 'E', 'S' > 'R', 'J' > 'R', 'E' > 'R'). In the CS 4&6 group we observed a significant decrease in the number of patients with new 'erosive' OA finger joints. This result is particularly important since OA of the finger joints becomes a clinical problem (pain, functional loss) when 'S' joints progress to 'J' and especially 'E' phases. During and after these 'E' phases, joints will remodel and show the nodular deformities characteristic of Heberden's and Bouchard's nodes. Treated patients were protected against erosive evolution.

Aged↗

PubMed2001

Thrombin attenuation is neuroprotective in the injured rat optic nerve.

The functional loss that often follows injury of the mammalian CNS has been attributed not only to the immediate neural loss, but also to secondary neuronal degeneration caused by toxic biochemical mediators in the environment of the injured nerve. We report here that a high thrombin content, produced as a result of injury-induced activation of prothrombin, appears to be an important mediator of secondary damage. Measurement of post-traumatic neuronal survival in vivo revealed that post-traumatic local application of the thrombin inhibitor N-alpha-(2-naphthylsulphonylglycyl)-4-(D,L)-amidinophenylalanine piperidide acetate in the rat optic nerve subjected to mild partial crush injury left twice as many retinal ganglion cells with functioning axons as in controls. Thus, by readjusting thrombin activity, thereby possibly obtaining a moderate post-traumatic increase and thus gaining the benefit of thrombin without its toxic effects, it may be possible to create an environment that is more favourable for post-traumatic survival.

Administration, Topical↗

PubMed2004

Mutations in the JARID1C gene, which is involved in transcriptional regulation and chromatin remodeling, cause X-linked mental retardation.

In families with nonsyndromic X-linked mental retardation (NS-XLMR), >30% of mutations seem to cluster on proximal Xp and in the pericentric region. In a systematic screen of brain-expressed genes from this region in 210 families with XLMR, we identified seven different mutations in JARID1C, including one frameshift mutation and two nonsense mutations that introduce premature stop codons, as well as four missense mutations that alter evolutionarily conserved amino acids. In two of these families, expression studies revealed the almost complete absence of the mutated JARID1C transcript, suggesting that the phenotype in these families results from functional loss of the JARID1C protein. JARID1C (Jumonji AT-rich interactive domain 1C), formerly known as "SMCX," is highly similar to the Y-chromosomal gene JARID1D/SMCY, which encodes the H-Y antigen. The JARID1C protein belongs to the highly conserved ARID protein family. It contains several DNA-binding motifs that link it to transcriptional regulation and chromatin remodeling, processes that are defective in various other forms of mental retardation. Our results suggest that JARID1C mutations are a relatively common cause of XLMR and that this gene might play an important role in human brain function.

Adult↗

PubMed2005

Long-term follow-up of renal function after peptide receptor radiation therapy with (90)Y-DOTA(0),Tyr(3)-octreotide and (177)Lu-DOTA(0), Tyr(3)-octreotate.

UNLABELLED: The kidneys are critical organs in peptide receptor radiation therapy (PRRT). Renal function loss may become apparent many years after PRRT. We analyzed the time course of decline in creatinine clearance (CLR) in patients during a follow-up of at least 18 mo after the start of PRRT with (90)Y-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA),Tyr(3)-octreotide ((90)Y-DOTATOC) or (177)Lu-DOTA(0),Tyr(3)-octreotate ((177)Lu-DOTATATE). METHODS: Twenty-eight patients with metastasized neuroendocrine tumors received 1-5 cycles of (90)Y-DOTATOC, leading to renal radiation doses of 5.9-26.9 Gy per cycle and a total of 18.3-38.7 Gy. Median follow-up was 2.9 y (range, 1.5-5.4 y), with a median of 16 measurements (range, 5-53) per patient. Thirty-seven patients with metastasized neuroendocrine tumors received 3-7 cycles of (177)Lu-DOTATATE, leading to renal radiation doses of 1.8-7.8 Gy per cycle and a total of 7.3-26.7 Gy. Median follow-up was 2.4 y (range, 1.7-4.0 y), with a median of 10 (range, 6-27) measurements per patient. All renal dose estimates were calculated with the MIRDOSE3 model. All patients were infused with renoprotective amino acids during the administration of the radioactive peptides. The time trend of CLR was determined by fitting a monoexponential function through the data of individual patients, yielding the decline in CLR in terms of percentage change per year. RESULTS: The median decline in CLR was 7.3% per y in patients treated with (90)Y-DOTATOC and 3.8% per y in patients treated with (177)Lu-DOTATATE (P = 0.06). The time trend of decline in CLR was sustained during the follow-up period. Eleven patients had a >15% per y decline in CLR. Cumulative renal radiation dose, per-cycle renal radiation dose, age, hypertension, and diabetes are probable contributing factors to the rate of decline in CLR after PRRT. CONCLUSION: This study showed that the time course of CLR after PRRT was compatible with the pattern of sustained CLR loss in progressive chronic kidney disease.

Adult↗

PubMed2001

Increased synaptic plasticity in the surround of visual cortex lesions in rats.

Lesion-induced functional loss is reduced when new synaptic connections are established in the surround of a cortical lesion. For this, long-term synaptic plasticity can play a key role. We studied long-term potentiation (LTP) and long-term depression (LTD) in slices of rat visual cortex with small cortical lesions. Surprisingly, the normal balance between LTP and LTD was significantly altered in the first week following cortical injury. Theta-burst induced LTP was increased, whereas LTD evoked by low frequency stimulation was not affected. The increased potentiation of subcortical inputs after cortical lesions opens a window for facilitated early functional reorganization by repetitive visual training.

Animals↗

PubMed1993

Distortion-product emissions in rabbit: II. Prediction of chronic-noise effects by brief pure-tone exposures.

In an attempt to predict the susceptibility of the cochlea to the harmful influences of excessive sound, the effects of initially exposing the same rabbits to brief pure-tones were related to the subsequent effects of octave-band noise (OBN) exposure using measures of distortion-product otoacoustic emissions (DPOAEs). The pure-tone exposure paradigm consisted of determining the rate at which a 100-dB SPL, low-frequency tone reduced the amplitude of a 1.5-kHz DPOAE, elicited by 50-dB SPL primaries. To establish the stability of the rate-reduction index, the tonal-exposure protocol was repeated on three separate occasions for each subject. Subsequently, the same rabbits were exposed chronically to a 95-dB SPL OBN, centered at 1-kHz, until DPOAE amplitudes between 1-5 kHz were diminished to noise-floor levels, i.e., by 10-30 dB, in response to 45-dB SPL primaries. The results revealed a visually apparent relation between the slope of the tonal-induced DPOAE-loss functions and the number of days required to reach the criterion decrement in emission level during chronic exposure to noise. Analysis of the frequency extent of the noise-induced changes revealed significant correlations between the previously measured rate of pure-tone induced reductions of DPOAE amplitude and the subsequent amount of decrement produced by OBN exposure. Thus, rabbits exhibiting slow rates of tonal-induced decrements in low-frequency DPOAEs were resistant to the amplitude-reducing effects of a subsequent chronic OBN exposure in that it typically took more than four days to achieve the targeted amount of DPOAE loss.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Stimulation↗

PubMed1991

Lack of nuclear RB protein staining in G0/middle G1 cells: correlation to changes in total RB protein level.

Functional loss of the retinoblastoma (RB) gene has been implicated in a diverse group of human malignancies. The potential clinical importance of such loss demands a reproducible RB cell staining method to distinguish RB+ from RB- tumors. We report that normal and known RB+ tumor cells either in culture or in vivo display a mosaic RB staining pattern with variable proportions of cells having unstained nuclei which are indistinguishable from truly RB- tumor cells. We also show that the apparent lack of nuclear staining corresponds to RB+ cells which are in the G0 or middle G1 phase, where as much as 10-fold decrease in total cellular RB protein occurs compared to their G2/M phase counterparts. These findings not only provide new clues to RB protein function in cell growth and differentiation, but also need to be considered when evaluating the RB status in primary malignancies for its role in tumor initiation/progression or as a prognostic parameter.

Animals↗