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J L Clark

Publications and source records attributed to J L Clark.

At least 19 recordsLinked to original sources
PubMed2001

Molecular recognition in cyclodextrin complexes of amino acid derivatives. 1. Crystallographic studies of beta-cyclodextrin complexes with N-acetyl-L-phenylalanine methyl ester and N-acetyl-L-phenylalanine amide pseudopeptides.

Cyclodextrins (CDs) are widely utilized in studies of chiral and molecular recognition. By changing the functionality of the guest molecule, the effect of such changes on recognition by the host CD molecule can be examined. We report crystal structure determinations for two nearly isomorphous complexes of phenylalanine derivatives: beta-CD/N-acetyl-L-phenylalanine methyl ester and beta-CD/N-acetyl-L-phenylalanine amide. The complexes crystallize as hydrated head-to-head host dimers with two included guest molecules in space group P1. The crystal packing is such that it presents a nonconstraining hydrophobic pocket adjacent to a hydrophilic region, where potential hydrogen-bonding interactions with hydroxyl groups of neighboring cyclodextrin molecules and waters of hydration can occur. The two host molecules display very similar conformations; only a few of the primary hydroxyl groups are conformationally disordered. There are a number of changes in the location of water of hydration molecules, some of which are the result of different hydrogen-bonding interactions. For the different guest molecules, similar modes of penetration are observed in the CD torus; however, there is a 0.985-A shift in the position of the guest molecules in the host torus, which takes place without changing the hydrophobic interactions displayed by the phenyl side chains. This observation and the thermal motion of the guest molecules in the ester complex are taken as evidence that complex binding forces are weak. The pseudopeptides experience a significant degree of flexibility in the crystalline environment provided by CD dimers. Conformational differences of the pseudopeptide backbones and the presence of disordered water molecules in the host-guest interface provide examples of different hydrogen-bonding schemes of similar potential energy. The crystal system presents an opportunity to establish a database of molecular interactions for small peptides and peptide analogues with waters of hydration and functional groups in nonconstraining binding environments.

Crystallography, X-Ray↗
PubMed2001

Molecular recognition in cyclodextrin complexes of amino acid derivatives. 2. A new perturbation: the room-temperature crystallographic structure determination for the N-acetyl-p-methoxy-L-phenylalanine methyl ester/beta-cyclodextrin complex.

Cyclodextrins (CDs) are cyclic oligosaccharides that encapsulate various small organic molecules, forming inclusion complexes. Because CD complexes are held together purely by noncovalent interactions, they function as excellent models for the study of chiral and molecular recognition mechanisms. Recently, room-temperature crystallographic studies of both the 2:2 N-acetyl-L-phenylalanine methyl ester/beta-CD and 2:2 N-acetyl-L-phenylalanine amide/beta-CD complexes were reported. The effect of changes in carboxyl backbone functional group on molecular recognition by the host CD molecule was examined for the nearly isomorphous supramolecular complexes. A new perturbation of the system is now examined, specifically perturbation of the aromatic side chain. We report a room-temperature crystal structure determination for the 2:2 N-acetyl-p-methoxy-L-phenylalanine methyl ester/beta-CD inclusion complex. The complex crystallizes isomorphously with the two previously reported examples in space group P1; the asymmetric unit consists of a hydrated head-to-head host dimer with two included guest molecules. The crystal packing provides both a nonconstraining extended hydrophobic pocket and an adjacent hydrophilic region, where hydrogen-bonding interactions can potentially occur with primary hydroxyl groups of neighboring CD molecules and waters of hydration. The rigid host molecules show no sign of conformational disorder, and water of hydration molecules exhibit the same type of disorder observed for the other two complexes, with a few significant differences in locations of water molecules in the hydrophilic region near guest molecules. There is evidence for modest disorder in the guest region of an electron density map. In comparing this system with the two previously reported complexes of phenylalanine derivatives, it is found that the packing of the guest molecules inside the torus of the CD changes upon substitution of a methoxy group at the para position of the aromatic phenyl ring. Backbone hydrogen-bonding interactions for the guest molecules with the CD primary hydroxyls and waters also change. This structure determination is a new and revealing addition to a small but growing database of amino acid and peptidomimetic interactions with carbohydrates.

Crystallography, X-Ray↗
PubMed2001

Ventral incisional hernia recurrence.

During the period October 1993 to December 1996, 31 patients were operated on by the author for primary or recurrent ventral incisional hernia (VIH). Three patients were excluded from analysis because their records were unavailable for review. The median age of the 28 remaining patients at their initial procedure was 57.5 years (range, 37-78 years). The repair was performed with interrupted O-Ethibond sutures in all but 3 cases where Prolene suture was used secondary to noniatrogenic contamination or recurrent hernia. There were no unplanned enterotomies in the entire series and prophylactic intravenous antibiotics were used in all cases. The only significant complications were skin hyperemia after five repairs in 3 patients who were treated empirically with intravenous antibiotics, and 1 patient who had an antibiotic-associated rash. There were no 30-day mortalities. Prolene mesh was used exclusively in all repairs performed with mesh. Seven of these repairs (25%) were for recurrent VIH. Three of these seven patients had previous mesh repairs. Six of these seven patients who presented with recurrent VIH had a mesh repair and four developed a recurrence. Five of seven were active smokers, with one having severe obstructive lung disease. Four of seven related significant occupational lifting. Of the 21 patients having initial repair of VIH, mesh was used in 8 (38%). After a median follow-up of 13 months, there were 2 recurrent hernias (25%). The remaining 13 patients had primary closure of their hernias. After median follow-up of 25 months, there were 5 recurrences (38%). A total of 34 VIH repairs were performed on these 28 patients, of which 13 were for recurrent hernias. Five of thirteen (38%) of the mesh repairs for recurrent VIH failed. The median body mass index (BMI) for the 13 patients having primary repair was 26.4, and that for all 21 cases having mesh repair was 28.8. Patients with recurrent VIH frequently recur despite use of mesh, avoidance of contamination, and consistent technique. No difference in BMI was apparent in those who recurred. Continued smoking and occupational lifting may be important risk factors for recurrent VIH.

Adult↗
PubMed2000

Invasive properties of murine squamous carcinoma cells: secretion of matrix-degrading cathepsins is attributable to a deficiency in the mannose 6-phosphate/insulin-like growth factor II receptor.

Penetration of basement membrane layers is a hallmark feature of metastatic tumor cells. The invasive propensity of murine SCC-VII squamous carcinoma cells is in part attributable to the extracellular action of the lysosomal cysteine proteinase cathepsin B. Although most noncancerous cells store this enzyme in the lysosomes, we found that SCC-VII cells release a large fraction (42%) of their newly synthesized procathepsin B into the culture medium. Procathepsins D and L, the precursors of other major lysosomal proteinases, are also secreted in significant amounts (24 and 75%, respectively). In contrast, normal murine 3T3-L1 fibroblasts exocytose only minor amounts of their newly synthesized procathepsins B (10%), D (<1%), and L (16%). Western blotting analysis revealed that SCC-VII cells are deficient in the 300 kDa mannose 6-phosphate/insulin-like growth factor-II receptor (M6P/IGF2R), a tumor suppressor with a central role in the intracellular transport of lysosomal enzymes. Consistent with the absence of M6P/IGF2R, SCC-VII cells lack dense lysosomes, with the bulk of intracellular acid hydrolases residing in late endosomes/ prelysosomes. On the other hand, the synthesis of the M6P recognition marker on lysosomal enzymes is not impaired in SCC-VII cells, because [33P]Pi is incorporated into the carbohydrate moieties of procathepsins B, D, and L. Furthermore, 69% of the phosphorylated N-linked oligosaccharides synthesized by SCC-VII cells carry phosphomonoester groups and as such constitute high-affinity ligands for M6P receptors. SCC-VII cells express the 46 kDa cation-dependent M6P receptor (MPR46), but intracellular retention of procathepsins B, D, and L is not affected by ammonium chloride and chloroquine, agents known to perturb the M6P receptor system. Our results indicate that failure to express the 300 kDa M6P/IGF2R may enhance the metastatic capacity of tumor cells by inducing the secretion of procathepsins B, D, and L.

3T3 Cells↗
PubMed2000

Prognostic variables in male breast cancer.

The prognostic role of ploidy status, S phase fraction, estrogen and progesterone receptor status, and the expression of p53 and erbB-2 protein in male breast carcinoma (MBC) remains controversial. The primary objective of this study was to determine which of the common prognostic factors for female breast cancer predict prognosis in MBC. A secondary objective was to assess the impact of comorbid illnesses on survival. A retrospective review of demographic data, surgical treatment, pathological staging, adjuvant treatment and follow-up was completed for 16 patients with MBC (1 intraductal and 15 invasive). Formalin-fixed, paraffin-embedded tissue was processed for ploidy, S phase fraction, and immunohistochemical detection of estrogen and progesterone receptors plus expression of p53 and erbB-2 protein. Six of 15 patients with infiltrating ductal carcinoma are currently alive without evidence of disease and a median survival of 61 months. Nine patients died after a median survival of 52 months, with 6 patients having no evidence of recurrent breast cancer. Two of 3 deaths secondary to advanced breast cancer occurred in patients who initially presented with T4 lesions and were staged IIIB. Two of 15 tumors were erbB-2 positive, whereas only 1 tested weakly positive for p53 protein. We observed that MBCs express erbB-2 and p53 proteins infrequently. Neither ploidy status, S phase fraction, nor erbB-2/p53 status provided any apparent improvement in establishing prognosis beyond routine pathological staging. Advanced TNM stage was associated with diminished survival. The majority of MBCs express estrogen and progesterone receptors. Survivals in MBC were reduced in association with comorbid medical conditions.

Adult↗
PubMed1999

Modulation of invasive properties of murine squamous carcinoma cells by heterologous expression of cathepsin B and cystatin C.

Murine SCC-VII squamous carcinoma cells have the capacity to penetrate reconstituted basement membranes (Matrigel) in vitro. The invasion of Matrigel layers by SCC-VII cells was significantly reduced by E-64, a specific inhibitor of lysosomal cysteine proteinases. The cathepsin-B-selective E-64 derivative, CA-074, inhibited penetration of Matrigel by SCC-VII cells to the same extent, indicating a major role for this particular lysosomal enzyme in extracellular-matrix degradation during squamous-carcinoma-cell invasion. SCC-VII cells were stably transfected with a cDNA encoding human procathepsin B, in an attempt to modulate the invasive properties of the cell line. The transfected cells expressed the heterologous gene, secreted increased amounts of procathepsin B and displayed enhanced invasive potential. In vivo, the activity of cathepsin B is strictly regulated by endogenous inhibitors. SCC-VII cells were therefore also stably transfected with a cDNA encoding human cystatin C, the most potent cysteine-proteinase inhibitor in mammalian tissues. The expression of this transgene resulted in the production of active recombinant cystatin C and a pronounced reduction in Matrigel invasion. These studies demonstrate that the invasive properties of squamous-cell carcinomas can be changed by modulation of the balance between cathepsin B and its endogenous inhibitors, and provide further evidence for the involvement of this lysosomal cysteine proteinase in tumour invasion and metastasis.

Animals↗
PubMed1999

Population genetics and phylogenetic analysis of Colorado Borrelia burgdorferi.

Borrelia burgdorferi is transmitted in an enzootic cycle in Colorado between the tick Ixodes spinipalpis and the woodrat Neotoma mexicana. The genetic relationship of Colorado isolates to other B. burgdorferi isolates is unknown nor have relationships among various Colorado isolates been determined. Portions of the flagellin (fla), 66-kD protein, and outer surface protein A (ospA) genes were amplified from 71 Colorado isolates, screened for genetic variability using single strand conformation polymorphism analysis, and unique alleles were sequenced. Colorado isolates were most similar to tick isolates from California and New York isolate 25015. Genetic distances among Colorado ospA sequences were the same or higher than distances among other isolates whereas distances among fla sequences tended to be the same or lower. The index of association (I(A)) was calculated among all loci as a measure of clonality. The I(A) among Colorado isolates was similar to I(A) previously estimated among other United States isolates.

Amino Acid Sequence↗
PubMed1998

Drug therapy in haemodialysis patients. Special considerations in the elderly.

End-stage renal disease (ESRD) is the stage of renal failure at which an individual requires dialysis therapy or a renal transplant to survive. The prevalence of ESRD is disproportionately higher among patients aged > 65 years, and the average age of new ESRD patients is continually rising in the US Medicare population. Medication management in this population is challenging because of the combination of multiple comorbid disease states, a plethora of medications and the added dimension of dialysis therapy, as well as pharmacokinetic and pharmacodynamic changes attributable to the aging process. Cardiovascular disorders such as hypertension, coronary artery disease, congestive heart failure and arrhythmias are common in elderly patients with ESRD, and account for most of the deaths in this population. Constipation is common in patients aged > 65 years, and its incidence is even higher among those receiving dialysis. Pain management is of particular concern because elderly dialysis patients are frequently prescribed inappropriate pain relief regimens. Many healthcare practitioners do not realise that patients with uraemia are at a higher risk of bleeding caused by nonsteroidal anti-inflammatory drugs than are patients with normal renal function. In addition, most practitioners do not appreciate that virtually all opioids (narcotics) and their active metabolites accumulate in patients with renal failure, leading to an increased risk of narcosis. Infectious complications are frequent in the ESRD population, with dialysis access infections and pneumonia being the 2 most common infections seen in hospitalized patients receiving dialysis treatment. The establishment of vaccination programmes for the prevention of hepatitis B, influenza and pneumococcal infections is important because of the increased risk of these disease in this population. Unfortunately, these high-risk patients display, in general, a decreased immunogenic response to vaccinations. This article addresses some of the practical issues that surround the medication management or prevention of these particular diseases in elderly patients undergoing haemodialysis. Specifically, we discuss the pharmacokinetic and pharmacodynamic changes that occur with specific medications in such patients. Drug dialysability is also discussed.

Aged↗
PubMed1998

Real-ear characteristics of the ALGO2 acoustic transducer assembly.

Clinical reports regarding the use of the ALGO2 neonatal automated auditory brainstem response (AABR) screening device have been concerned only with issues of sensitivity and specificity. This study was undertaken to evaluate how couplers and their placement affect the ALGO2 click spectral properties. Although not recommended by the manufacturer, substituting less expensive, uncalibrated couplers for the standard earphone may be a tempting alternative in clinical practice. Click spectra of an ALGO2 were analyzed with a real-ear system so that comparisons could be made between probe tips and the standard coupler. In addition, ALGO2 screening data from neonates using the standard earphone and a substitute probe tip were compared. The results are in agreement with the manufacturer's specifications when the ALGO2 is used as prescribed. However, with probe tip couplers, SPL values were markedly increased, particularly as insertion depth of the probes varied. The neonatal AABR results show that coupler type and placement can also produce inaccurate screening evaluations and erroneous conclusions.

Acoustics↗
PubMed1997

Preclinical antitumor activity of water-soluble paclitaxel derivatives.

PURPOSE: Five water-soluble paclitaxel derivatives were extensively evaluated for their antitumor activities relative to the parent drug. METHODS: Both subcutaneous (s.c.) murine (M109 lung) and human (A2780 ovarian, L2987 lung) tumor models were used for this purpose. RESULTS: Consecutive daily intravenous (i.v.) paclitaxel therapy of mice bearing s.c. M109, beginning on day 4 or 5 posttumor implant and continuing for 5 days, resulted in a range of maximum gross log cell kill (LCK) values (reflective of delays in tumor growth) and maximum relative median survival time (% T/C) values (reflective of increases in lifespan) of 1.0-2.1 and 132-162% (and one outlying result of 235%), respectively. Against the same tumor model, using the same treatment schedule, each of the water-soluble derivatives was active, with maximum LCK of 1.3-2.5 and T/C of 124-254%. These LCK and %T/C values were always within 0.5 LCK and 15%, respectively, of the concomitantly obtained maximum effects of paclitaxel. When tested in several experiments against staged (50-100 mg) s.c. A2780 tumors, using various i.v. treatment schedules, the water-soluble derivatives achieved a maximum LCK of 1.4-3.8. Evaluated in parallel, paclitaxel achieved a maximum LCK of 2.1-4.5 following every other day x 5 i.v. therapy. When paclitaxel was assayed in several experiments using the staged (50-100 mg) s.c. L2987 tumor model, maximum LCK of 0.9->4.1 were produced following every other day x 5 i.v. therapy. Concomitant testing of the water-soluble derivatives, using the same i.v. treatment schedule, resulted in maximum LCK of 0.2->4.1. In each of the tumor models used, the consistently active, and usually the most active, water-soluble derivative was BMS-185660. The levels of activity observed were comparable (within 1 LCK) to those achieved concomitantly using paclitaxel, and its potency was only slightly inferior to the parent drug. CONCLUSIONS: Based on the evaluations performed in three distal site tumor models, we conclude that BMS-185660 is a water-soluble paclitaxel derivative with preclinical antitumor activity comparable to that of the parent drug.

Animals↗
PubMed1997

Culturing selects for specific genotypes of Borrelia burgdorferi in an enzootic cycle in Colorado.

In Colorado, Borrelia burgdorferi sensu stricto, the etiologic agent of Lyme disease, is maintained in an enzootic cycle between Ixodes spinipalpis ticks and Neotoma mexicana rats (27). The frequencies of flagellin (fla), 66-kDa protein (p66), and outer surface protein A (ospA) alleles were examined in 71 B. burgdorferi isolates from samples from Colorado. Approximately two-thirds of these samples were isolates from I. spinipalpis ticks that had been cultured in BSK-H medium prior to DNA extraction. The remaining samples were from total DNA extracted directly from infected I. spinipalpis ticks. A portion of each gene was amplified by PCR and screened for genetic variability by single-strand conformation polymorphism (SSCP) analysis. We identified three alleles in the fla gene, seven in the p66 gene, and seven in the ospA gene. Sequencing verified that the amplified products originated from B. burgdorferi template DNA and indicated 100% sensitivity and specificity of the SSCP analysis. The frequencies of the p66 and ospA alleles were significantly different between cultured and uncultured spirochetes. The number of three-locus genotypes and the genetic diversity of alleles at all loci were consistently lower in cultured spirochetes, suggesting that culturing of B. burgdorferi in BSK-H medium may select for specific genotypes.

Alleles↗
PubMed1997

Interaural time effects on the frequency-following response.

Frequency-following responses (FFRs) were recorded to evaluate differences between monaural and binaural waveforms and waveforms evoked by stimuli with interaural time disparities. Eight normal-hearing adult females served as subjects. The stimuli were monaural and binaural 450-Hz tonebursts at 65 and 60 dB SL and interaural time differences of 0 and 660 microseconds, respectively. Normalized amplitudes and periodicities of FFR waveforms within and between subjects were compared. The results showed asymmetric FFR to the various stimuli used in this study. Binaural FFR waveforms were greater than monaural but smaller than summed monaural FFRs. Binaural FFR amplitudes evoked by a zero time difference were greater than amplitudes evoked by a 660-microseconds difference. Additionally, tight phase-locked periodicities were evoked in the FFR monaurally and binaurally. The averaged FFR periodicity to all stimulus conditions from all subjects was 2.29 msec, differing only 6.8 microseconds from the period of the 450-Hz stimulus. In contrast, monaural and binaural neurons in the lower brain stem typically exhibit much less synchroneities to low-frequency tones than the FFR. These data provide evidence that the FFR is not simply a sum of neuronal action potentials. The findings suggest instead the presence of brainstem neuronal networks. Such putative neuronal ensembles apparently maintain a closer correspondence to the period of a low-frequency sound, whether monaural or binaural, than the discharge patterns of single neurons.

Adult↗
PubMed1995

Near-drowning.

Near-drowning and drowning are major causes of neurologic injury and death in young persons. Most victims aspirate water, and pulmonary edema develops in many of these cases. Prolonged submersion causes cerebral asphyxia and adversely affects the brain within five minutes. Immediate ventilation and oxygenation are essential in the reversal of cerebral anoxia. During field resuscitation, precautions should be taken to protect the cervical spine because of the possibility of injury. The Heimlich maneuver is used only after unsuccessful attempts at ventilation suggest foreign-body obstruction. Prehospital advanced cardiac life support with tracheal intubation is indicated in patients with severe injuries. On arrival at the hospital, ventilation with continuous positive airway pressure or positive end-expiratory pressure enhances pulmonary function. Many water submersion accidents are avoidable; close supervision of infants and toddlers, installation of a fence around home swimming pools, and abstinence from alcohol during participation in water sports are some practical precautions.

Cardiopulmonary Resuscitation↗
PubMed1995

Effective treatment of severe cancer pain of the head using low-dose ketamine in an opioid-tolerant patient.

We report the case of a 39-year-old man with severe pain due to unresectable squamous-cell carcinoma of the maxillary sinus that had invaded cranial bone and had metastasized to the cervical spine. Tolerance to opioids had developed, and high doses of transdermal, continuous intravenous, and epidural opioids did not control his pain. An acute episode of extremely severe head pain was immediately controlled with a subanesthetic dose of ketamine after failure of a stress dose of corticosteroid and intravenous lidocaine. Because the patient was terminally ill and invasive procedures were not options, we controlled his pain using a low-dose ketamine infusion until his death 13 days later. Ketamine may be a good co-analgesic for breakthrough pain and for severe pain caused by terminal cancer when invasive techniques are inappropriate. Its mechanism of action may include reversal of opioid tolerance in addition to an inherent analgesic effect.

Adult↗
PubMed1995

Phase II trial of etoposide, doxorubicin, and cisplatin combination in advanced measurable gastric cancer. An Eastern Cooperative Oncology Group study.

A phase II study was performed to determine the efficacy and toxicity of the etoposide, doxorubicin, cisplatin (EAP) regimen in the treatment of patients with advanced measurable gastric cancer in a multi-institutional cooperative group setting. Thirty-one evaluable patients with advanced measurable gastric adenocarcinoma were treated with etoposide 120 mg/m2 on days 3, 4, and 5, doxorubicin 20 mg/m2 on days 1 and 8, and cisplatin 40 mg/m2 on days 2 and 9. The treatment was repeated every 28 days. Objective responses were seen in 7 (23%) patients, all achieving partial remissions. Median survival was 9 months for the entire group. Toxicity was mostly hematologic, with grade 3 leukopenia in 26% and grade 4 leukopenia in 55% of the patients. There were 4 treatment-related deaths that were attributable to severe leukopenia and sepsis. Because of the high toxicity and moderate response rate, this regimen is not superior to other less toxic regimens and cannot be recommended for the treatment of advanced gastric cancer outside of an investigational protocol.

Adenocarcinoma↗
PubMed1995

Management of genital herpes.

Genital herpes affects over 30 million persons in the United States. Genital herpes has three distinct presenting syndromes, depending on the patient's immune status with regard to the herpes simplex virus. Current diagnostic strategy relies on clinical findings and the selective use of viral culture. Acyclovir is the drug of choice for the treatment of genital herpes. Drug resistance is an increasing problem, requiring the use of newer agents. Treatment of the immunocompromised patient is a special area of concern. In addition to the medical aspects in the treatment of genital herpes, psychosocial requirements should also be addressed.

Acyclovir↗
PubMed1995

Apoptosis in 7-hydroxystaurosporine-treated T lymphoblasts correlates with activation of cyclin-dependent kinases 1 and 2.

7-Hydroxystaurosporine (UCN-01) is a potent inhibitor of protein kinase C (PKC) isozymes alpha, beta, and gamma [Seynaeve et al., Mol. Pharmacol, 45: 1207-1214, 1994] that also has antitumor effects in vivo. To determine whether inhibition of PKC can be related to inhibition of cell growth with induction of apoptosis, we compared the effects of UCN-01 to those of the highly selective bisindolylmaleimide PKC antagonist GF 109203X in leukemic T-cell lines. Both compounds potently inhibited PKC activity when added to T-cell membrane preparations and reversed phorbol ester-induced c-fos gene expression in intact cells. However, whereas UCN-01 potently inhibited growth of Jurkat, Molt-3, Molt-4, and Hut-78 cells (IC50 = 20-65 nM, irreversible after 24 h of exposure), GF 109203X had IC50s for cell growth of 3.6-5.0 muM. Less than 3 h after addition, UCN-01 but not GF 109203X-treated cells displayed loss of cells with G2-M DNA content, appearance of a hypodiploid DNA fraction, and evidence of internucleosomal DNA fragmentation. Six h after treatment, cells appeared to accumulate with S-phase DNA content. These effects correlated with selective UCN-01 but not GF 109203X-induced decrease in total and tyrosine phosphorylation of cyclin-dependent kinases (cdks) 1 and 2, and with increases in the histone H1 kinase activities of cdk1 and cdk2. UCN-01 was relatively less potent in inhibition of properly activated cdk1 and cdk2 when added in vitro to H1 kinase assays (IC50 = 1000 and 600 nM, respectively). We conclude that inhibition of PKC alone is not sufficient to account for the actions of UCN-01 and are led to the hypothesis that inappropriate cdk activation either correlates with or actually mediates cell growth inhibition with apoptosis in T lymphoblasts exposed to UCN-01.

Alkaloids↗