Showing papers by "University of Medicine and Dentistry of New Jersey published in 1991"

An analysis of vertebrate mRNA sequences: intimations of translational control.

Abstract: Five structural features in mRNAs have been found to contribute to the fidelity and efficiency of initiation by eukaryotic ribosomes. Scrutiny of vertebrate cDNA sequences in light of these criteria reveals a set of transcripts--encoding oncoproteins, growth factors, transcription factors, and other regulatory proteins--that seem designed to be translated poorly. Thus, throttling at the level of translation may be a critical component of gene regulation in vertebrates. An alternative interpretation is that some (perhaps many) cDNAs with encumbered 5' noncoding sequences represent mRNA precursors, which would imply extensive regulation at a posttranscriptional step that precedes translation.

Lipoarabinomannan, a possible virulence factor involved in persistence of mycobacterium tuberculosis within macrophages

Abstract: Mycobacterium tuberculosis and Mycobacterium leprae, the causative agents of tuberculosis and leprosy, respectively, produce large quantities of lipoarabinomannan (LAM), a highly immunogenic, cell wall-associated glycolipid. This molecule has been previously reported to be a potent inhibitor of gamma interferon-mediated activation of murine macrophages. Studies of the mechanism by which this mycobacterial glycolipid down-regulates macrophage effector functions provide evidence that LAM acts at several levels and that it can (i) scavenge potentially cytotoxic oxygen free radicals, (ii) inhibit protein kinase C activity, and (iii) block the transcriptional activation of gamma interferon-inducible genes in human macrophage-like cell lines. These results suggest that LAM can inhibit macrophage activation and triggering and cytocidal activity and that it may represent a chemically defined virulence factor contributing to the persistence of mycobacteria within mononuclear phagocytes. Images

Binding of general transcription factor TFIIB to an acidic activating region.

Abstract: A CENTRAL issue in eukaryotic transcriptional regulation is the mechanism by which promoter-specific transcription factors (activators) stimulate transcription. Two lines of evidence indicate that the general transcription factor TFIIB is a pivotal component in the mechanism by which an acidic activator functions. First, during assembly of the preinitiation complex TFIIB binding is a rate-limiting step enhanced by an acidic activator1. Second, the TFIIB activity in a HeLa cell nuclear extract is specifically retained on a column containing an acidic activating region1. But because our previous study monitored only TFIIB activity, it remains possible that the interaction between TFIIB and the acidic activating region is mediated through additional proteins, for example, those designated as adaptors2, coactivators3 or mediators4,5. A complementary clone encoding TFIIB has recently been isolated and shown to encode a polypeptide of relative molecular mass 35,000 (ref. 6). Here we report that TFIIB expressed in and purified from Escherichia coli (recombinant TFIIB) binds directly to the potent acidic activating region of the herpes simplex virus-1 VP16 protein.

Tissue Levels of Bone Resorptive Cytokines in Periodontal Disease

Abstract: The levels of 3 bone resorptive cytokines, interleukin 1 alpha (IL-1 alpha), IL-1 beta, and tumor necrosis factor alpha (TNF alpha), were assessed in tissues from sites of periodontal disease. As determined by ELISA of tissue extracts, IL-1 beta and TNF alpha were detected in all diseased sites, whereas IL-1 alpha was present in 8/22 sites, IL-1 beta was present in highest concentration (mean +/- SEM: 11,695 +/- 2,888 pg/ml; 672 pM), followed by TNF alpha (434 +/- 135 pg/ml; 26 pM), and IL-1 alpha (342 +/- 160 pg/ml; 20 pM). The levels of all 3 mediators were significantly lower in clinically healthy tissues. There was a highly significant correlation between levels of IL-1 beta and TNF alpha (rs = 0.61, P less than 0.001), suggesting coordinated expression of these 2 mediators. The numbers of cells containing each mediator was also determined by indirect immunofluorescence on frozen tissue sections. Consistent with findings from tissue extracts, IL-1 beta-containing cells were present in approximately 5-fold higher numbers than TNF alpha-containing cells, and 40-fold higher numbers than IL-1-alpha-containing cells. Taken together with previous findings, these results indicate that IL-1 beta is likely to be an important mediator in the pathogenesis of periodontal disease.

The nonphosphorylated form of RNA polymerase II preferentially associates with the preinitiation complex

Abstract: The two forms of RNA polymerase II that exist in vivo, phosphorylated (IIO) and nonphosphorylated (IIA), were purified to apparent homogeneity from HeLa cells. The nonphosphorylated form preferentially binds to the preinitiation complex. RNA polymerase II in the complex was converted by a cellular protein kinase to the phosphorylated form.

Ethanol consumption inhibits fetal DNA methylation in mice: implications for the fetal alcohol syndrome.

Abstract: Acute ethanol administration (3 g/kg twice a day) to pregnant mice, from the 9th thru the 11th day of gestation, resulted in hypomethylation of fetal deoxyribonucleic acid (DNA) Nuclei isolated from the fetuses of the ethanol-treated mice had lower levels of methylase activity relative to controls even in the presence of excess S-adenosylmethionine, which serves as the methyl donor for the enzyme DNA methyltransferase Acetaldehyde, at concentrations as low as 3 to 10 microM, inhibited DNA methyltransferase activity in vitro Since DNA methylation is thought to play an important role in the regulation of gene expression during embryogenesis, ethanol-associated alterations in fetal DNA methylation may contribute to the developmental abnormalities seen in the fetal alcohol syndrome

Interaction of 1-methyl-4-phenylpyridinium ion (MPP+) and its analogs with the rotenone/piericidin binding site of NADH dehydrogenase.

Abstract: Nigrostriatal cell death in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease results from the inhibition of mitochondrial respiration by 1-methyl-4-phenylpyridinium (MPP+). MPP+ blocks electron flow from NADH dehydrogenase to coenzyme Q at or near the same site as do rotenone and piericidin and protects against binding of and loss of activity due to these inhibitors. The 4'-analogs of MPP+ showed increasing affinity for the site with increasing length of alkyl chain, with the lowest Ki, for 4'-heptyl-MPP+, being 6 microM. The 4'-analogs compete with rotenone for the binding site in a concentration-dependent manner. They protect the activity of the enzyme from inhibition by piericidin in parallel to preventing its binding, indicating that the analogs and piericidin bind at the same inhibitory site(s). The optimum protection, however, was afforded by 4'-propyl-MPP+. The lesser protection by the more lipophilic MPP+ analogs with longer alkyl chains may involve a different orientation in the hydrophobic cleft, allowing rotenone and piericidin to still bind even when the pyridinium cation is in a position to interrupt electron flow from NADH to coenzyme Q.

Cloning of a human gene encoding the general transcription initiation factor IIB

Abstract: Transcription factor IIB (TFIIB) has a central role in transcription of class II genes. The purification of the human TFIIB protein and isolation of a complementary DNA encoding TFIIB activity is reported here. The sequence of TFIIB, which seems to be encoded by a single gene, contains a repeated motif, in addition to a motif with similarity to the prokaryotic sigma-factors. The recombinant protein expressed in bacteria substituted for all the functions attributed to the human TFIIB protein.

The promotion of social competence: longitudinal study of a preventive school-based program.

Abstract: A two-year, intensive, elementary school-based primary prevention program aimed at the promotion of social competence was followed up six years later. Findings suggest beneficial effects for program recipients on indices of social adjustment and psychopathology when compared to controls, although overall strength of effects was not large and notable gender differences emerged.

Reversed polarity of Na(+) -K(+) -ATPase: mislocation to apical plasma membranes in polycystic kidney disease epithelia.

Abstract: Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder in which renal tubules become enormously enlarged due to fluid accumulation. Na(+) -K(+) -ATPase was compared in normal and cystic regions of whole kidneys and in confluent primary cultures of microdissected renal tubule and cyst-lining epithelia. Immunostaining with antibodies directed against the Na(+) -K(+) -ATPase catalytic alpha-subunit was confined to apical, luminal plasma membranes of ADPKD epithelia, which was a complete reversal of the normal renal tubule polarized location in basolateral membranes. Mislocated Na(+) -K(+) -ATPase was shown to be functionally active, because identical intense apical staining was observed by use of a cytochemical assay. In addition, biochemical assays showed a significant increase in these ouabain-inhibitable Na(+) -K(+) -ATPase specific activity levels in ADPKD kidneys compared with age-matched normal kidneys. Specific binding of [3H] ouabain was not only increased but also confined to the apical membrane vesicles prepared from cystic regions of ADPKD kidneys compared with normal age-matched controls, in which binding was confined to basolateral membrane vesicles. Although steady-state levels of Na(+) -K(+) -ATPase alpha- and beta-subunit in mRNAs were increased somewhat in ADPKD kidneys, this alone was not sufficient to account for the observed activation. Confluent ADPKD epithelia grown on dual-chamber, permeable membrane supports also showed reversed polarity of 22NaCl vectorial transport, because this was from basal to apical media compartments. Because this transport could also be blocked by ouabain, this suggested apical Na(+) -K(+) -ATPase was responsible and implicated altered polarity of Na(+) -K(+) -ATPase and resultant Na+ secretion as a mechanism for cyst formation in ADPKD. Because no reversal of polarity of other basolateral or apical membrane proteins was detected, an intracellular sorting defect specific for Na(+) -K(+) -ATPase is proposed.

A short leader sequence impairs the fidelity of initiation by eukaryotic ribosomes

Abstract: The functional consequences of unusually short 5' noncoding sequences on eukaryotic mRNAs are explored here by using an in vitro transcription and translation system As the distance of the first AUG codon from the m7G cap was decreased from 32 to 3 nucleotides, the yield of protein initiated from the first AUG codon progressively decreased, with a corresponding increase in initiation from the second AUG codon The leakiness attributable to a too-short leader sequence was offset, however, by introducing secondary structure downstream from the first AUG codon

Competitive and noncompetitive antagonists at N-methyl-D-aspartate receptors protect against methamphetamine-induced dopaminergic damage in mice.

Abstract: The administration of methamphetamine (METH) to experimental animals results in damage to nigrostriatal dopaminergic neurons. We have demonstrated previously that the excitatory amino acids may be involved in this neurotoxicity. For example, several compounds which bind to the phenyclidine site within the ion channel linked to the N-methyl-D-aspartate (NMDA) receptor protected mice from the METH-induced loss of neostriatal tyrosine hydroxylase activity and dopamine content. The present study was conducted to characterize further the role of the excitatory amino acids in mediating the neurotoxic effects of METH. The administration of three or four injections of METH (10 mg/kg) every 2 hr to mice produced large decrements in neostriatal dopamine content (80-84%) and in tyrosine hydroxylase activity (65-74%). A dose-dependent protection against these METH-induced decreases was seen with two noncompetitive NMDA antagonists, ifenprodil and SL 82.0715 (25-50 mg/kg/injection), both of which are thought to bind to a polyamine or sigma site associated with the NMDA receptor complex, and with two competitive NMDA antagonists, CGS 19755 (25-50 mg/kg/injection) and NPC 12626 (150-300 mg/kg/injection). Moreover, an intrastriatal infusion of NMDA (0.1 mumol) produced a slight but significant loss of neostriatal dopamine which was potentiated in mice that also received a systemic injection of METH. The results of these studies strengthen the hypothesis that the excitatory amino acids play a critical role in the nigrostriatal dopaminergic damage induced by METH.

Young‐onset Parkinson's disease A clinical review

Abstract: Young-onset Parkinson's disease (YOPD) is arbitrarily defined as that which produces initial symptoms between the ages of 21 and 39, inclusive. The special problems and concerns of the patient with YOPD present as much of a challenge and opportunity for the clinician as the disease itself does for the researcher. In contrast to juvenile parkinsonism, which is a heterogeneous group of clinicopathologic entities presenting (also arbitrarily) before age 21, YOPD appears to be the same nosologic entity as older-onset PD. It comprises approximately 5% of referral populations in Western countries and about 10% in Japan. Its annual incidence relative to the population at risk is about 1/10 that of PD at age sixty. YOPD tends to have more gradual progression of parkinsonian signs and symptoms, earlier appearance of levodopa-related dyskinesias and levodopa-dose-related motor fluctuations, and frequent presence of dystonia as an early or presenting sign. Studies conflict with regard to the suspected greater familial frequency and lesser frequency of dementia than in older-onset PD.

RAM2, an essential gene of yeast, and RAM1 encode the two polypeptide components of the farnesyltransferase that prenylates a-factor and Ras proteins.

Abstract: In the yeast Saccharomyces cerevisiae, mutations in either of two unlinked genes, RAM1 or RAM2, abolish the farnesyltransferase activity responsible for prenylation of Ras proteins and the a-factor mating pheromone. Here we report that the function of RAM1 and RAM2 genes is required for the membrane localization of Ras proteins and a-factor. The RAM2 gene was sequenced and can encode a 38-kDa protein. We examined the functional interaction of RAM2 and RAM1 by expressing the genes in Escherichia coli. Extracts derived from an E. coli strain that coexpressed RAM1 and RAM2 efficiently farnesylated a-factor peptide and Ras protein substrates. In contrast, extracts derived from E. coli strains that expressed either RAM gene alone were devoid of activity; however, when the latter extracts were mixed, protein farnesyltransferase activity was reconstituted. These results indicate that the yeast farnesyl-protein transferase is comprised of Ram1 and Ram2 polypeptides. Although Ram1 is a component of the enzyme, disruption of the RAM1 gene in yeast was not lethal, indicating that the Ram1-Ram2 farnesyltransferase is not essential for viability. In contrast, disruption of RAM2 was lethal, suggesting that Ram2 has an essential function in addition to its role with Ram1 in protein farnesylation.

Intermolecular complementation between two defective mutant signal-transducing receptors of Escherichia coli.

Abstract: Taz1 is a hybrid signal-transducing membrane receptor between Tar, an aspartate chemoreceptor, and EnvZ, an osmosensor of Escherichia coli that is able to induce ompC expression by phosphorylating OmpR (a transcriptional activator) in response to aspartate. When the Taz1 His-277, the proposed autophosphorylation site in the cytoplasmic EnvZ domain, was replaced with a valine residue, the mutant Taz1 was unable to induce ompC expression. Similarly, when approximately two-thirds of the EnvZ domain was deleted, Taz1 was nonfunctional. However, when these two defective Taz1 proteins were coexpressed in a cell, ompC was constitutively expressed. Coinciding with this result, two mutant Taz1 molecules were able to intermolecularly complement each other to restore the OmpR kinase activity but not phosphatase activity in vitro. The identical result was also obtained with EnvZ. The present results suggest that the autophosphorylation of Taz1 and EnvZ is an intermolecular phosphorylation reaction, requiring formation of a dimer (or oligomer), and that ligand-dependent ompC expression requires not only kinase but also phosphatase activity.

The small subunit of transcription factor IIF recruits RNA polymerase II into the preinitiation complex.

Abstract: We found that transcription factor IIF mediates the association of RNA polymerase II with promoter sequences containing transcription factors IID, IIB, and IIA (DAB complex). The resulting DNA-protein complex contained RNA polymerase II and the two subunits of transcription factor IIF (RAP 30 and RAP 74). Cloned human RAP 30 was sufficient for the recruitment of RNA polymerase II to the DAB complex. This ability of RAP 30 to recruit RNA polymerase to a promoter is also a characteristic of sigma factors in prokaryotes.

Herpes zoster myelitis.

Abstract: We studied the clinical (10 patients) and pathological (9 patients) findings in 13 patients with herpes zoster myelitis, all of whom had systemic illnesses associated with immunosuppression. The median interval between the onset of the herpes zoster rash and myelopathic symptoms was 12 days, and the subsequent median interval to maximal deficit was 10.5 days. Presenting neurological symptoms were characteristically ipsilateral to the rash, with motor dysfunction predominating, followed by a spinothalamic and, less often, posterior column sensory deficit. Pathological involvement was most severe in the dorsal root entry zone and posterior horn of the spinal cord segment corresponding to the involved dermatome. There was variable spread both horizontally and vertically in the spinal cord. Direct varicella-zoster virus (VZV) infection of neuroectodermal cells, particularly oligodendrocytes, was demonstrated by immunostaining viral antigens (8 cases), and by the presence of Cowdry type A intranuclear inclusions (7 cases) and often was associated with focal demyelination (6 cases). In 4 patients a VZV vasculitis was associated with leptomeningitis and haemorrhagic necrosis (spinal cord in 1; brainstem or cerebellum in 3). The protracted evolution in many cases and the pathologically documented direct viral infection of the spinal cord provide a rational basis for the use of antiviral therapy in preventing or attenuating the evolving myelopathy.

Effect of prenatal exposure to ethanol on the cell cycle kinetics and growth fraction in the proliferative zones of fetal rat cerebral cortex.

Abstract: Prenatal exposure to ethanol produces profound changes in the number of neurons in the mature cortex. These changes in neuronal number may reflect ethanol-induced disturbances in early developmental processes, that is in the proliferation of neuronal precursors. Hence, the present study examined the effect of ethanol on cell proliferation in the two neocortical proliferative zones, the ventricular zone (VZ) and subventricular zone (SZ). From gestational day 5 to 21, pregnant rats were fed an ethanol diet (6.7% v/v), pair-fed an isocaloric control diet, or fed chow and water. Pregnant rats were given a series of one to nine injections of bromodeoxyuridine (BrdU). After immunohistochemical processing, the ratio of cells in each proliferative zone that were labeled with BrdU to the total population was determined. The portion of the population that was cycling (growth fraction), the total length of the cell cycle, and the length of the S-phase of the cell cycle were calculated for VZ and SZ cells. Exposure to moderate levels of ethanol has markedly different effects upon the two neocortical proliferative zones. In the VZ, the length of the total cell cycle was significantly greater in ethanol-treated rats than in controls; however, the growth fraction and the length of the S-phase were unaffected by ethanol. In contrast, in the SZ, the growth fraction was significantly greater in ethanol-treated rats, but ethanol had no effect on the length of the total cell cycle or of the S-phase. These differences may underlie the ethanol-induced abnormalities in neuronal generation.

Regeneration of Achilles tendon with a collagen tendon prosthesis. Results of a one-year implantation study.

Abstract: We previously reported on the short-term biocompatibility of a reconstituted type-I collagen prosthesis that had been tested in the Achilles tendons of rabbits. Preliminary results indicated that, by ten weeks after implantation, carbodiimide-cross-linked implants had been replaced by neotendon in a manner that was similar to that of autogenous tendon grafts that had been used as controls. Also by ten weeks after implantation, glutaraldehyde-cross-linked collagen implants were encapsulated and appeared to have caused an acute inflammatory response. In the present study, carbodiimide and glutaraldehyde-cross-linked collagen implants and autogenous grafts that served as controls were implanted for fifty-two weeks as a replacement for a three-centimeter section of the Achilles tendon of rabbits. The absence of a crimp in a cross-linked implant and the presence of a crimp in normal tendon and in tendon that formed after an implant had been resorbed made it possible to distinguish between a cross-linked implant and new host tendon that had replaced the implant after it was resorbed. New collagen that had replaced the implant and autogenous (control) tendon graft were compared with normal Achilles tendon with respect to the angle and length of the crimp. The autogenous grafts and the carbodiimide-cross-linked collagen implants had been completely resorbed and replaced by neotendon. The neotendon that was present fifty-two weeks after implantation was similar, but not identical, to normal tendon. In contrast, the glutaraldehyde-cross-linked implant was essentially inert, had not been resorbed, and was surrounded by a capsule of collagenous connective tissue. The neotendon in the capsule was also similar, but not identical, to normal tendon. There were more cells in the capsule than in the autogenous grafts or in the carbodiimide-cross-linked implants. The results of the present study indicate that rapid repair is achieved with a carbodiimide-cross-linked collagenous implant that has a structure and mechanical properties that are similar to those of an autogenous tendon graft and that biodegrades at a similar rate. Prolonged biodegradation of a glutaraldehyde-cross-linked collagenous implant results in formation of a capsule and only limited formation of neotendon.

The initiator directs the assembly of a transcription factor IID-dependent transcription complex

Abstract: Highly purified RNA polymerase II was found to be able to weakly recognize the initiator (Inr) present in the adenovirus IVa2 and major late promoters. The association of RNA polymerase II with the Inr was enhanced by the general transcription factors. The Inr was capable of directing the formation of a DNA-protein complex. Transcription competent complexes on the adenovirus major late and IVa2 promoters appear to be formed by alternative pathways mediated through the Inr and/or "TATA" motif. The presence of both motifs, however, is required for efficient transcription utilizing a discrete start site. Complexes formed at either site required transcription factor TFIID, the TATA binding protein. Consistent with this observation, a TFIID requirement was demonstrated for transcription from a mutant adenovirus major late promoter construct lacking a functional TATA motif.

Cerebral Blood Flow and Oxygen Consumption in Cortical Spreading Depression

Abstract: We determined the effects of spreading depression on local cerebral O2 supply, oxygenation, and O2 consumption in the anesthetized rat. Spreading depression was induced by application of 0.5 M KCl to the frontal cortex. Regional cerebral blood flow was determined with [14C]iodoantipyrine and regional O2 extraction was determined microspectrophotometrically. The passage of the spreading depression wave was determined with a multiprobe assembly that recorded NADH redox state (surface fluorometry), extracellular K+ activity, and DC steady potential (surface minielectrodes). As the wave of spreading depression passed, there was an increase in extracellular K+ and a decrease in NADH. Cerebral blood flow was significantly increased (120 +/- 51 ml/min/100 g, mean +/- SD) during the wave as compared with other regions. In the affected cortex, blood flow was not different from that in the contralateral cortex (69 +/- 28 ml/min/100 g) either before or after the wave of spreading depression passed. Arterial and venous O2 saturation were unaffected by the wave and the histogram of O2 saturations of examined veins followed a similar normal distribution in all regions. Oxygen extraction was not altered by the wave of spreading depression. Oxygen consumption was significantly increased during the wave to 7.4 +/- 3.7 ml O2/min/100 g compared with the contralateral cortex (5.1 +/- 2.6 ml/min/100 g) and other regions. It can be concluded that spreading depression caused an increase in cerebral O2 consumption that was adequately matched by an increase in local blood flow. Oxygen delivery was not limited during spreading depression and its effects were quickly over as evidenced by the lack of alteration in oxygenation after the wave of spreading depression passed.

Effects of long 5' leader sequences on initiation by eukaryotic ribosomes in vitro.

Abstract: Lengthening the 5' noncoding sequence on SP6-derived transcripts can increase their translational efficiency by an order of magnitude under some conditions of translation in reticulocyte lysates. This effect was observed upon reiterating three different synthetic oligonucleotides, the sequences of which were designed simply to preclude secondary structure. It seems unlikely that such arbitrarily designed sequences are recognized by sequence-specific translational enhancer proteins. Rather, long 5' leader sequences appear to accumulate extra 40S ribosomal subunits, which may account for their translational advantage. The buildup of 40S subunits on long, unstructured leader sequences is predicted by the scanning model for initiation. Leader sequences such as these may be ideal for in vitro expression vectors.

Conversion of human choriogonadotropin into a follitropin by protein engineering

Abstract: Human reproduction is dependent upon the actions of follicle-stimulating hormone (hFSH), luteinizing hormone (hLH), and chorionic gonadotropin (hCG) While the alpha subunits of these heterodimeric proteins can be interchanged without effect on receptor-binding specificity, their beta subunits differ and direct hormone binding to either LH/CG or FSH receptors Previous studies employing chemical modifications of the hormones, monoclonal antibodies, or synthetic peptides have implicated hCG beta-subunit residues between Cys-38 and Cys-57 and corresponding regions of hLH beta and hFSH beta in receptor recognition and activation Since the beta subunits of hCG or hLH and hFSH exhibit very little sequence similarity in this region, we postulated that these residues might contribute to hormone specificity To test this hypothesis we constructed chimeric hCG/hFSH beta subunits, coexpressed them with the human alpha subunit, and examined their ability to interact with LH and FSH receptors and hormone-specific monoclonal antibodies Surprisingly, substitution of hFSH beta residues 33-52 for hCG beta residues 39-58 had no effect on receptor binding or stimulation However, substitution of hFSH beta residues 88-108 in place of the carboxyl terminus of hCG beta (residues 94-145) resulted in a hormone analog identical to hFSH in its ability to bind and stimulate FSH receptors The altered binding specificity displayed by this analog is not attributable solely to the replacement of hCG beta residues 108-145 or substitution of residues in the "determinant loop" located between hCG beta residues 93 and 100

The five-year cure rate achieved by cryosurgery for skin cancer.

Abstract: Cryosurgery was used to treat 3 540 new basal cell and squamous cell carcinomas of the skin from 1971 to 1989; a cure rate of 98.4% was achieved. To determine the 5-year cure rate in more recent years, the results of treatment of 684 nonmelanotic skin cancers from 1980 to 1984were reviewed. In the group of628 basal cell carcinomas, the 5-year cure rate was 99.0%. In the group of 52 squamous cell carcinomas, the 5-year cure rate was 96,1%. In the series were also four patients with basosquamous cell carcinomas, all of whom were recurrence free for 5 years or more. The overall 5-year cure rate in the 684 cases was 98.8%. On the basis of these data and our cosmetic results, we conclude that cryosurgery is an effective treatment that compares favorably with other established methods of therapy.