Study on Status of Serum Biochemical and Hematological Parameters in COVID-19 Positive Patients Attending a Tertiary Care Hospital.

Background Coronavirus disease 2019 (COVID-19) presents clinically a variety of pathological and clinical organ dysfunctions, ranging in severity from asymptomatic to fatal. The care and monitoring of COVID-19 patients may benefit from the use of biochemical and hematological markers. Objective To observe the alteration of serum biochemical and hematological parameters in COVID-19 positive patients, attending a Tertiary Care Hospital. Method A descriptive cross-sectional study was conducted on all COVID-19 positive patients attending Nobel Medical College Teaching Hospital, Biratnagar, Nepal from 15th December 2021 to 15th February 2022. The test results of different serum biochemical and hematological parameters done for these patients were recorded in clinical laboratory services and obtained retrospectively for the analysis. The data were entered in MS excel and analyzed by SPSS version 20. Result Out of 1537 COVID-11699 declared positive patients, 712 (46.32%) were male and 825 (53.68%) female. Mean age of COVID positive patients was 40.03±20.08 years. The level of serum SGOT, SGPT, ALP and GGT was significantly elevated in 39.9%, 42.8%, 32.3% and 47.2% of COVID positive patients respectively. Blood Urea, creatinine, uric acid and sugar level were significantly elevated in 63%, 56.1%, 33.1% and 47.6% patients respectively. The serum level of LDH, D-dimer, CRP and procalcitonin (PCT) were significantly increased in 52.1%, 75.9%, 71.6% and 61.2% of patients respectively. The serum value of total cholesterol, triglyceride, HDL and LDL were significantly lowered in 52.2%, 43.8%, 70.1% and 60.3% of patients respectively. RBC concentration and level of hemoglobin was reduced in 56.6% and 53.6% of COVID positive patients respectively whereas total leukocyte count was elevated in 80.7% with increase in neutrophil in 87.9% and decrease in lymphocyte in 79.4%. Conclusion A portion of COVID-19 positive patients showed drastically altered test results for various serum biochemical and hematological markers, although many of them had normal findings.

Primary osteogenic sarcoma of the skull: Report of two cases with review of literature.

Primary calvarial (excluding jaw) osteosarcoma is rare. We report two cases highlighting their unusual presentation and histopathologic variability - a 30-year-old female who presented with progressively increasing headache and a rapidly growing frontal swelling and a 16-year-old girl who had a rapidly growing mass in the left frontoparietal region which had recurred thrice but was otherwise asymptomatic. The lesions were osteolytic on neuroimaging and histopathological examination confirmed osteosarcoma. These two unusual cases are discussed along with a brief review of literature.

Misdiagnosis of Wilson's Disease in a Patient with Psychiatric Symptoms.

Therapeutic outcome of Wilson's disease significantly depends upon its early recognition. As Wilson's disease is a rare disorder with protean manifestations, its diagnosis and subsequent treatment are often delayed. We elaborate here the case of a young boy who had initially presented with psychiatrc symptoms suggestive of dissociative fugue followed by withdrawn behaviour and was treated by a psychiatrist with minimal response. This was associated with symptoms of tremors, hypersalivation, and slowness of movements. This case highlights the delay in diagnosing Wilson's disease when faced with the case of a young adult with psychiatric manifestations. It is extremely important for physicians, psychiatrists and health professionals at primary care level to recognize and diagnose this treatable disease at an early stage.

Hepatoprotective potential of ethanolic extract of Pandanus odoratissimus root against paracetamol-induced hepatotoxicity in rats.

BACKGROUND: Pandanus odoratissimus (Pandanaceae) is popular in the indigenous system of medicines like Ayurveda, Siddha, Unani and Homoeopathy. In the traditional system of medicine various plant parts such as leaves, root, flowers, and oils are used as anthelmintic, tonic, stomachic, digestive and in the treatment of jaundice and various liver disorders. OBJECTIVE: The aim was to investigate the hepatoprotective activity of ethanolic extract of the root of P. odoratissimus against paracetamol (PCM) induced hepatotoxicity in rats. MATERIALS AND METHODS: Hepatotoxicity was induced in male Wistar rat by PCM (2 g/kg b.w. p.o. for 7 days). The ethanolic extract of P. odoratissimus root was administered at the dose level of 200 mg/kg and 400 mg/kg b.w. orally for 7 days and silymarin (100 mg/kg b.w. p.o.) as standard drug was administered once daily for a week. The hepatoprotective effect of ethanolic extract was evaluated by assessment of biochemical parameters such as serum glutamic oxaloacetic transaminase, serum glutamic-pyruvic transaminase, serum alkaline phosphatase, total and direct bilirubin and triglycerides. Histopathological study of rat liver was also done. RESULTS: Experimental findings revealed that the extract at dose level of 200 mg/kg and 400 mg/kg of b.w. showed dose dependant hepatoprotective effect against PCM induced hepatotoxicity by significantly restoring the levels of serum enzymes to normal that was comparable to that of silymarin, but the extract at dose level of 400 mg/kg was found to be more potent when compared to that of 200 mg/kg. Besides, the results obtained from histopathological study also support the study. CONCLUSION: From the results, it can be concluded that ethanolic extract of the root of P. odoratissimus afforded significant protection against PCM induced hepatotoxicity in rats.

Antiinflammatory, Analgesic and Antipyretic Activities of Aerial Parts of Costus speciosus Koen.

In the present study, methanol extracts of Costus speciosus Koen. aerial parts were assessed for antiinflammatory, analgesic and antipyretic activities in experimental animals. The antiinflammatory activity of methanol extract of Costus speciosus (400 and 800 mg/kg, p.o.) was evaluated using carrageenan-induced paw oedema test. Analgesic effect was evaluated using acetic acid-induced writhing and Eddy's hot-plate models and antipyretic activity was assessed by Brewer's yeast-induced pyrexia in rats. The methanol extract of aerial parts of Costus speciosus in a dose of 400 and 800 mg/kg showed significant antiinflammatory activity (19.36 and 40.05% reduction) at 5 h postmedication. In analgesic models extract treated animals at (400 and 800 mg/kg) inhibited writhing's caused by acetic acid by 14.24 and 31.90%, respectively, and it also increased the latency period at both high and low doses which showed the mean reaction time at 16.60±0.355 s and 14.12±0.355 s, respectively, when compared to control in hot-plate test. It also reduces the rectal temperature of the animals at low and high doses significantly 37.03±0.108° and 36.63±0.098°, respectively, in Brewer's yeast induced pyrexia. The obtained results of the present investigation revealed that methanol extract of Costus speciosus has significant antiinflammatory, analgesic and antipyretic activities.

Germ cell-specific disruption of the Meig1 gene causes impaired spermiogenesis in mice.

Meiosis expressed gene 1 (Meig1) was originally identified in a search for mammalian genes potentially involved in meiosis. Seven mouse Meig1 transcripts with the same coding region, but different 5'-UTRs, have been identified. These transcripts have different tissue distributions, two are only present in the testis. In the testis, Meig1 is present in germ cells and Sertoli cells. A Meig1 conditional knockout model has been generated. When Meig1 was inactivated globally by crossing with Cmv-Cre transgenic mice, the Meig1-deficient males were sterile due to severe spermiogenic defects, and had no obvious defects in meiosis. To further study its role in individual cell types in the testis, the Meig1(flox) mice were crossed with Hsp2a-Cre, Prm-Cre, and Amh-Cre mice, in which the Cre recombinase is driven by the heat shock protein 2 (Hsp2a) gene promoter (expressed in spermatocytes), the protamine 1 gene promoter (expressed in post-meiotic spermatids) and the anti-Mullerian hormone (Amh) gene promoter (expressed in Sertoli cells) respectively. Both Meig1 mRNA and protein were undetectable in testis of the Hsp2a-Cre; Meig1(flox/flox) mice and all the mutant adult males tested were sterile. This phenotype mirrors that of the Cmv-Cre; Meig1(flox/flox) mice. Even though the total testicular Meig1 mRNA and protein expression levels were dramatically reduced in testis of the Prm-Cre; Meig1(flox/flox) males, all the mice tested were fertile, and there was no significant difference in sperm count and sperm motility compared with age-matched Meig1(flox/flox) male mice. Disruption of Meig1 in the Sertoli cells did not affect the MEIG1 protein expression. Amh-Cre; Meig1(flox/flox) males were fertile, and produced the same amount of spermatozoa as age-matched Meig1(flox/flox) mice. The testicular histology was also normal. Our results indicate that MEIG1 regulates spermiogenesis through effects in germ cells alone, and that the Meig1 gene must be active during a discrete period in spermatogenesis after which it is dispensable.

Retinal changes in various altitude illnesses.

INTRODUCTION: This study aimed to evaluate the retinal changes associated with altitude illness in young soldiers. METHODS: A total of 50 young soldiers with altitude illness, who were referred to a tertiary care hospital between October 2003 and January 2006, were included in the study. RESULTS: All the soldiers were male. The mean age of the subjects was 30.3 (range 20-44) years. Nine (18 percent) soldiers had acute mountain sickness (AMS), nine (18 percent) had high-altitude pulmonary oedema (HAPE) and 20 (40 percent) had high-altitude cerebral oedema (HACE). Retinal haemorrhages were observed in 29 soldiers (58 percent). Among these 29 cases, two also had symptoms of AMS, five had symptoms of HAPE and twelve had symptoms of HACE. High-altitude retinal haemorrhage alone as a sign of altitude illness was seen in ten cases. Severe grades of high-altitude retinopathy were found mostly in soldiers who suffered from HAPE and HACE. Visual recovery was complete in 22 (76 percent) soldiers. High-altitude retinal haemorrhage was associated with partial visual impairment in five (17 percent) soldiers and permanent visual loss in two (seven percent) soldiers. CONCLUSION: Retinal haemorrhages were noticed in 58 percent of soldiers with altitude illness. The association of severe grades of high-altitude retinopathy with HAPE and HACE was statistically significant. Branch retinal vein occlusion with macular oedema is an additional finding in our study, which has not been previously reported.

Changing tuberculosis trends in Nepal in the period 2001-2008.

To assess the trends on indicators of TB control in Nepal over a period from 2001-2008. Retrospective analysis of information from Annual Reports of NTP, Nepal from 2001-2008. The incidence of New Smear Positive (NSP) TB declined from 58.9 in 2001 to 53.4 in 2006 per 100000 populations then reversed in the period 2006-2008. This TB incidence decreased in males and the age group <45 years (except 0-14 years). The notification rate of all cases of TB declined by 3 % overall over the entire period from 2001 to 2008. Mortality among smear negative and extra pulmonary declined significantly. The failure rate and defaulter rate were declined significantly and the case detection rate (CDR) was increased significantly within the study period. Increasing trend in CDR, Treatment success rate and decreasing trend in failure rate, defaulter rate are the evidence of progress of NTP, in Nepal. Since there is reversal of incidence of NSP from 2006, a detailed analysis of existing TB control measures is required. If the success is continued and quality care is provided as per International Standard of TB Care, the Millennium Development Goals will be an achievable target.

Tear Break-up Time in High Altitude Areas.

BACKGROUND: In high altitude areas, patients report with irritation, redness and foreign body sensation in their eyes suggesting tear film abnormality due to low humidity and windy environmental conditions. METHODS: Tear Break- up Time (TBUT) was studied in 100 subjects consisting of local population and those originally from plains residing in high altitude areas in Ladakh. RESULT: There were 24% individuals with TBUT of < 5 seconds, 30% between 6-10 seconds and 46% with TBUT of > 10 seconds. In symptomatic patients with TBUT of <5 seconds, eight cases had irritation of eyes, six foreign body sensation and two cases had pain, watering, irritation and redness of eyes. Pterygium was seen in 12 individuals and inter palpebral congestion in 4 cases. CONCLUSION: A total of 24% cases showed abnormal (<5 seconds) TBUT. Abnormality of tear film in the presence of low humidity and windy condition with high ultraviolet radiation may lead to ocular discomfort and pterygium in these areas.

External Versus Endoscopic Dacryocystorhinostomy: A Retrospective Study.

BACKGROUND: External dacryocystorhinostomy (DCR) has been the standard surgery for nasolacrimal duct obstruction before the development of endoscopic DCR. METHODS: This retrospective study included 103 patients with 109 cases (6 cases with bilateral disease) of nasolacrimal duct obstruction, of which 55 were treated with external DCR and 54 with endoscopic DCR. They were followed up for a minimum period of six months for surgical outcome. RESULT: The mean age of the patients in both the groups was 30 years. The success rate defined as absence of epiphora in the external DCR group was 90.9% and 95 % in the endoscopic DCR group. Majority of the recurrence, 5 out of the 6 (83.3%) in the external DCR group occurred in the first two months of surgery, while one reported four months after the surgery. The problem of intraoperative hemorrhage encountered in the external DCR group was not faced in the endoscopic DCR group. Revision of DCR was indicated in 9.1 % of cases in external DCR group as compared to 5.5 % in the endoscopic group. Serious complications like keloid formation and cosmetically unacceptable scar were not noticed in the external DCR group. Cerebrospinal fluid (CSF) rhinorrhoea was not encountered in the endoscopic group. CONCLUSION: Both the external DCR and the endoscopic DCR are effective surgical approaches for nasolacrimal duct obstruction with comparable success rate.

First national tuberculin survey in Nepal.

SETTING: The size of the tuberculosis (TB) problem in Nepal is unknown, as no national tuberculin or TB prevalence survey has yet been performed. OBJECTIVE: To assess the prevalence of TB infection and the annual risk of TB infection (ARTI) in primary schoolchildren in the three ecological zones (mountains, hills and terai) and Kathmandu valley. DESIGN: A representative sample of primary schoolchildren were tuberculin skin tested using the Mantoux method. The data were analysed using cut-off levels to define infection and by the mirror method. RESULTS: Of 19577 children registered, 17260 (88.2%) were available for analysis. Seventy-eight per cent had a visible bacille Calmette-Guérin scar. The best estimate of the prevalence of TB infection was 7.0% (95%CI 4.2-9.7), with an ARTI of 0.86% (95%CI 0.49-1.23) using the mirror method, with a mode at 16 mm. Although the ARTI was higher in Kathmandu and the mountains compared to the hills and terai, the difference between the areas was not significant. CONCLUSION: The ARTI in Nepal is lower than previous estimates, indicating a decrease in transmission or overestimation of previous estimates. To obtain information about the trend of the ARTI in Nepal, the survey needs to be repeated in 5 to 7 years.

Conjunctival-Limbal Autograft for Primary and Recurrent Pterygium.

BACKGROUND: It has been postulated that pterygium results from hypo function of limbal stem cells. Therefore conjunctival-limbal autograft has been advocated for the treatment of this condition. This study was undertaken to evaluate the results of conjunctival-limbal autograft procedure in primary and recurrent pterygia. METHODS: 32 eyes of 28 individuals with primary and recurrent pterygium (24 primary, 8 recurrent) were undertaken for conjunctival-limbal autograft procedure under peribulbar anaesthesia followed by topical antibiotic- steroid drops for two weeks. The cases were reviewed as per protocol for 6 to 18 months. RESULT: There was no recurrence of pterygium in these cases and they were free from any major postoperative complications. CONCLUSION: Conjunctival-limbal autograft is the procedure of choice for primary and recurrent pterygia.

Validation of a testis specific serine/threonine kinase [TSSK] family and the substrate of TSSK1 & 2, TSKS, as contraceptive targets.

A family of testis specific serine/threonine kinases, TSSK1-4 and SSTK, in addition to the substrate of TSSK1 & 2, TSKS, have been studied during the past several years in our laboratory. This paper will provide a general background on these kinases through review of pertinent literature and then will summarize data from our laboratory germane to evaluating these kinases as candidate targets for future development of small molecule kinase inhibitors that may serve to regulate male fertility. Bio-informatic and structural analyses of human TSSK1-4 and SSTK indicate that these kinases constitute a unique subfamily belonging to the AMPK branch on the human kinome tree. Expression studies showed that all five kinases and the TSKS substrate are testis abundant, if not strictly testis specific, indicating that tissue specific contraceptive targeting is possible. In situ hybridization further confirmed that mouse TSSK2, SSTK and TSKS are post-meiotic in their expression patterns, a finding that makes them possible targets of reversible contraceptive intervention by preserving spermatogonia and spermatocytes. Our laboratory detected TSSK2, TSKS and SSTK proteins in mature spermatozoa for the first time. TSKS was localized to the centrioles of human spermatozoa, while TSSK2 was observed in the sperm neck, equatorial segment and mid-piece of the sperm tail, and SSTK was localized in the equatorial segment. The interaction and binding between human TSSK2 and TSKS was confirmed by several methods: this substrate and enzyme interaction offers a particularly interesting opportunity for drug design. In vitro kinase assay showed phosphorylation of TSKS by TSSK2. The TSKS phosphopeptide, HGLSPATPIQGCSGPPGS*PEEPPR, was identified by IMAC-LC-FTMS, with serine 285 being phosphorylated (representend by asterisk). These results provide a rationale for high-throughput screening of inhibitors for TSKS phosphorylation and further studies of members of this kinase family as targets for both male contraception and intra-vaginal spermicides.

Evidence for the involvement of proline-directed serine/threonine phosphorylation in sperm capacitation.

To become fertilization competent, mammalian sperm undergo changes in the female reproductive tract termed capacitation. Capacitation correlates with an increase in tyrosine phosphorylation; however, less is known about the role of serine/threonine phosphorylation in this process. Proline-directed phosphorylation is one of the major regulatory phosphorylation events in many cellular processes such as cell proliferation and differentiation. Using mitotic phosphoprotein monoclonal-2 (MPM-2) antibody in this study, we observed that several mouse sperm proteins in the range of 70-250 kDa underwent increased serine/threonine-proline phosphorylation during capacitation. In contrast to the time course of tyrosine phosphorylation, proline-directed phosphorylation could be observed at shorter time points of sperm incubation, and it was found to be independent of NaHCO(3) and adenosine 3'5'-cyclic monophosphate (cAMP). Similar to the regulation of the increase in tyrosine phosphorylation, cholesterol acceptors such as bovine serum albumin (BSA) or 2-hydroxypropyl-beta-cyclodextrin (2-OH-propyl-beta-CD) were essential for the regulation of proline-directed phosphorylation in mouse sperm. Furthermore, it was also found to be BSA dependent in human sperm. Among proline-directed kinases, extracellular signal-regulated kinase 1/2 (ERK1/2) is present in mammalian sperm; nevertheless, U0126 and PD098059, two inhibitors of the ERK pathway, did not block this phosphorylation in mouse sperm. In conclusion, capacitation is associated with an increase in proline-directed phosphorylation linked to cholesterol efflux in the sperm.

Manual Small Incision Cataract Surgery: Experience at a Military Hospital.

BACKGROUND: Small incision cataract surgery came into practice with the advent of phacoemulsification. However, manual small incision cataract surgery (SICS) is a useful alternative for those who do not have access to phacoemulsification machine. METHOD: A total of 69 cases of cataract were undertaken for manual incision cataract surgery and intra ocular lens (IOL) implantation using 6mm straight incision. The surgical technique and postoperative results are compared with the results of phacoemulsification and IOL implantation. RESULT: Average postoperative astigmatism was ± 0.75 dioptres. Postoperative uncorrected visual acuity (UCVA) of 6/18 or better was observed in 51(71.9%) cases after first week of the surgery. CONCLUSION: The study concludes that both phacoemulsification and small incision cataract surgery with intraocular lens (IOL) implantation are effective methods. However SICS with IOL implantation is a useful alternative in the absence of phacoemulsification machine.

Protein tyrosine phosphorylation, hyperactivation and progesterone-induced acrosome reaction are enhanced in IVF media: an effect that is not associated with an increase in protein kinase A activation.

Sperm capacitation is a prerequisite for successful in vitro fertilization (IVF) and therefore a focus of sperm preparation in IVF laboratories. The technology of IVF is, therefore, potentially valuable in advancing our understanding of the molecular processes that occur during sperm capacitation. We have investigated sperm capacitation induced by a commercial IVF medium compared to that occurring in standard capacitating medium (CM) typically used in a nonclinical setting. Percoll-washed spermatozoa were resuspended in Cook Sydney IVF medium, Cook Sydney IVF sperm buffer, Earle's balanced salt medium (capacitating medium) or a modified Earle's balanced salt medium [non-capacitating medium (NCM)] for up to 120 min at 37 degrees C and, if applicable, in the presence of 5% CO2 in air. Sperm protein kinase A (PKA) activity, PKA-dependent serine/threonine phosphorylation, tyrosine phosphorylation, hyperactivation and progesterone-induced acrosome reaction were evaluated. IVF medium was shown to accelerate sperm capacitation (compared with capacitating medium) as determined by tyrosine phosphorylation, sperm hyperactivation and progesterone-induced acrosome reaction. This effect was not associated with enhanced activation of PKA or increased levels of serine/threonine phosphorylation. In contrast, IVF sperm buffer (used for sperm preparation) did not stimulate sperm capacitation when incubated for up to 90 min. We have shown that different capacitating media vary strikingly in their efficacy and that this difference reflects activation of a pathway other than the well-characterized activation of soluble adenylyl cyclase/cAMP/PKA.

Role of signaling pathways in regulating the capacitation of mammalian spermatozoa.

Mammalian testicular spermatozoa are immotile and incompetent for fertilization. They acquire motility during epididymal maturation and fertilizing ability during a second phase of maturation in the female reproductive tract, termed as capacitation. Capacitation was discovered independently by Austin and Cang in early 1950s and was defined as the obligate period of residency of spermatozoa in the female reproductive tract, which confers on the spermatozoa the ability to fertilize an oocyte. Over the years, the definition of capacitation has changed and it has been recognized as a complex phenomenon, which is correlated with changes associated with the spermatozoa in the female tract. These alterations in metabolism, intracellular ion concentration, membrane fluidity, intracellular pH, cAMP concentration and concentration of reactive oxygen species, ultimately make the spermatozoa fertilization-competent. The molecular basis of capacitation is poorly understood despite the fact that it is an important event preceding fertilization. This review presents our current understanding of the signaling events involved in the process of capacitation.

Inhibition of motility of hamster spermatozoa by protein tyrosine kinase inhibitors.

Genistein, tyrphostin and piceatannol, which are specific inhibitors of protein tyrosine kinase, were screened for their effects on the motility of intact and demembranated hamster spermatozoa. Of the three inhibitors only piceatannol inhibited the motility of intact spermatozoa. None of the inhibitors had any inhibitory effect on the reactivation of motility of demembranated hamster spermatozoa. Taken together these results indicated that a protein tyrosine kinase associated with the membrane of hamster spermatozoa was probably involved in sustenance of hamster sperm motility. Therefore in the present study a membrane-associated protein tyrosine kinase was purified from a detergent-soluble extract of plasma membranes of mature hamster spermatozoa. The purification involved cation exchange chromatography on fast protein liquid chromatography (FPLC) followed by affinity chromatography either on an antiphosphotyrosine antibody agarose or poly glu-tyr agarose column. The pure protein tyrosine kinase had an apparent molecular mass of 45 kDa. The enzyme was not inhibited by genistein or herbimycin but was inhibited by piceatannol. This is the first report on the purification of a sperm plasma membrane-associated protein tyrosine kinase, an enzyme which has also been implicated in hamster sperm motility.

Plasma membrane-associated protein tyrosine phosphatase activity in hamster spermatozoa.

Plasma membranes of caput and cauda epididymal spermatozoa of hamster exhibited protein phosphatase activity. This membrane-associated protein phosphatase was identified as a protein tyrosine phosphatase based on its ability to hydrolyse a substrate specific for PTPase, by inhibition of its activity with a specific inhibitor of PTPase (sodium orthovanadate) and by the inability to inhibit its activity with calyculin, okadaic acid, trifluoperazine, calcium, EGTA, and EDTA, which are specific inhibitors of other protein phosphatases, namely PP-1, PP-2A, PP-2B, and PP-2C respectively. The specific activity of the protein tyrosine phosphatase both in the caput and cauda epididymal sperm plasma membranes was similar, implying that the enzyme may not be solely responsible for the differential phosphorylation of membrane proteins observed during maturation (Uma Devi et al. 1997. Mol Reprod Dev 47:341-350). Thus the significance of the PTPase activity in epididymal maturation still remains to be determined. The membrane-associated PTPase may not be essential for acquisition of motility. However, it appears that the activity is essential for the sustenance of motility since sodium orthovanadate, which specifically inhibits PTPase activity, also inhibits motility of spermatozoa and decreases the overall velocity of the spermatozoa by decreasing the average path velocity, straight line velocity, curvilinear velocity, and amplitude of lateral head displacement of the treated spermatozoa.

SV40-Mediated immortalization.

Human diploid cells have a limited life span, ending in replicative senescence, in contrast to cell lines derived from tumors, which show an indefinite life span and are immortal, suggesting that replicative senescence is a tumor suppression mechanism. We have utilized introduction of SV40 sequences to develop matched sets of nonimmortal and immortal cell lines to help dissect the mechanism of immortalization and have found that it has multiple facets, involving both SV40-dependent and -independent aspects. These studies have led to the identification of a novel growth suppressor gene (SEN6) as well as providing a model system for the study of cellular aging, apoptosis, and telomere stabilization among other things. It is anticipated that SV40-transformed cells will continue to provide a very useful experimental system leading to insights into the behavior of cells with altered expression of oncogenes and growth suppressor gene products.