Subacute T1-low intensity area reflects neurological prognosis for patients with cervical spinal cord injury without major bone injury.

STUDY DESIGN: A retrospective imaging and clinical study. OBJECTIVES: To evaluate the relationship between magnetic resonance imaging (MRI) features and neurological prognosis in patients with traumatic cervical spinal cord injury (CSCI) without major bone injury. METHODS: A total of 72 patients with CSCI without major bone injury were treated conservatively in our hospital. MRI was performed for all patients at admission and 1 month following injury. We measured the antero-posterior and cranio-caudal diameter of intramedullary intensity changed area with T1-weighted images at the injured segment. Neurological evaluations were performed using the American Spinal Injury Association (ASIA) motor score and the modified Frankel grade at the time of admission and discharge. RESULTS: There was a significant relationship between the antero-posterior diameter ratio of the T1-weighted low-intensity area on MRI at the subacute stage and the ASIA motor score. The optimal threshold of the T1-weighted low-intensity diameter ratio for predicting the patient's ability to walk with or without assistance at discharge was determined to be 46%. Moreover, 96.8% of the patients with <50% T1-weighted low-intensity area recovered to walk with or without a cane at discharge. CONCLUSION: The T1-low intensity area may be an important predictive factor for the neurological recovery of CSCI without major bone injury.

Rapid progressive clinical deterioration of cervical spondylotic myelopathy.

STUDY DESIGN: Retrospective clinical study. OBJECTIVE: To elucidate the pathophysiology of rapid progressive clinical deterioration following the onset of cervical myelopathy. SETTING: Spinal Injuries Center, Fukuoka, Japan. METHODS: A total of 43 cervical spondylotic myelopathy (CSM) patients were treated surgically by a senior surgeon. All patients showed intramedullary intensity changes on magnetic resonance (MR) imaging. Overall, eight patients suffered rapid progressive clinical deterioration; four of them had obvious anamnesis of minor trauma. We assessed the responsible injured segment by MR T2-weighted images. Clinical instabilities at the focal segment were evaluated using functional sagittal plain radiographs. Neurological evaluations were performed preoperatively and at 12 months postoperatively using American Spinal Injury Association (ASIA) motor scores and Japanese Orthopaedic Association (JOA) scores for cervical myelopathy. Intraoperatively, we evaluated the presence of adhesive scar tissue on the dura mater at the focal segment. RESULTS: The responsible injured segment was C3-4 in 75% of the rapid progressive (rp)-CSM and in 28.57% of the conventional CSM subjects. One with rp-CSM showed sagittal translational segmental instability. Preoperative ASIA motor scores and JOA scores in the rp-CSM were significantly lower than those in the conventional CSM subjects. Postoperative ASIA motor scores between the subjects showed no significant differences; however, postoperative JOA scores in the rp-CSM subjects were significantly lower. Moreover, an epidural membrane was observed in 62.5% of rp-CSM and 11.4% of conventional CSM subjects. CONCLUSIONS: We hypothesized that the pathophysiology of rp-CSM might be additional cervical cord disorder following the onset of cervical myelopathy. Early decompression surgery is recommended in such patients.

Close relationship between T helper (Th)17 and Th2 response in murine allergic contact dermatitis.

BACKGROUND: Repeated exposure to allergens induces chronic allergic lesions in the skin and a shift in the cutaneous cytokine milieu to T helper (Th)2. AIM: To assess the relationships between Th17 and Th2 response during allergic contact dermatitis (ACD) in mice. METHODS: ACD was induced in C57BL/6 mice by single or repeated epicutaneous challenge of 2,4,6-trinitro-1-chlorobenzene. Relationships between Th17 and Th2 response were analyzed by immunohistochemical observations and activity of cytokines on days 8 (first challenge), 18 (11th challenge), 28 (21st challenge) and 38 (31st challenge). RESULTS: On day 8, tissue levels of interleukin (IL)-17 and IL-22 were high, whereas tissue levels of IL-4 and serum IgE concentration were low. Following acute contact dermatitis, mice developed chronic eczematous lesions on day 18, and gradually improved on days 28 and 38. Tissue IL-4 and serum IgE levels corresponded to the development and improvement of chronic eczematous lesions. Numbers of Th17 cells and tissue levels of IL-17 and IL-22 rapidly decreased as IL-4 and IgE levels increased on day 18. As levels of IL-4 and IgE decreased, the number of Th17 cells and tissue levels of IL-17 and IL-22 increased again on days 28 and 38. On day 18, tissue levels of Th17 response-inducing cytokines (IL-6, IL-23 and transforming growth factor-ß) were high, and IL-23-expressing cells appeared in abundance, when Th2 response was extremely high. IL-17 injection decreased tissue IL-4 and serum IgE levels. CONCLUSIONS: Th17 correlates closely with Th2 in murine chronic ACD induced by repeated epicutaneous challenge.

Histamine H(4) receptor antagonist ameliorates chronic allergic contact dermatitis induced by repeated challenge.

BACKGROUND: The present study observed effects of the histamine H(4) receptor on chronic allergic contact dermatitis induced by repeated challenge in mice. METHODS: Acute contact dermatitis was induced by single epicutaneous challenge of 2,4,6-trinitro-1-chlorobenzene (TNCB) to the ear. Chronic allergic contact dermatitis was developed by repeated epicutaneous challenge using TNCB on the dorsal back skin. H(4) receptor antagonist JNJ7777120 was administered to wild-type mice, while H(4) receptor agonist 4-methylhistamine was administered to histidine decarboxylase (HDC) (-/-) mice that synthesized no histamine. RESULTS: HDC (-/-) mice did not differ phenotypically from HDC (+/+) mice, and H(4) receptor antagonist/agonist did not have clinical effects in terms of acute contact dermatitis reactions. H(4) receptor antagonist ameliorated skin eczematous lesions induced by repeated TNCB challenge in HDC (+/+) mice. On the contrary, H(4) receptor agonist exacerbated skin lesions exclusively in HDC (-/-) mice. Application of H(4) receptor agonist induced migration of mast cells and eosinophils in skin lesions, and H(4) receptor antagonist suppressed these changes. H(4) receptor was immunohistochemically detected on mast cells in eczematous lesions. Levels of interleukin (IL)-4, -5, and -6 in lesions were decreased, whereas levels of interferon-gamma and IL-12 were increased by H(4) receptor antagonistic activity. Serum Immunoglobulin E levels rapidly increased with repeated challenge, but decreased with H(4) receptor antagonist. CONCLUSION: Because chronic allergic contact dermatitis is developed by H(4) receptor stimulation, H(4) receptor antagonists might represent new candidate drugs for treating chronic allergic contact dermatitis.

Emergent thyroidectomy with sternotomy due to acute respiratory failure with severe thyroid storm.

Huge cervical and mediastinal masses may lead to acute respiratory failure caused by laryngotracheal compression and airway obstruction. Thyroid storm is also a life-threatening endocrine emergency originating almost exclusively from uncontrolled Graves' disease. We report a case of a 42-year-old man with acute upper airway obstruction and tachycardia from progressive swelling of a giant thyroid, in conjunction with thyroid storm resulting from uncontrolled Graves' disease. Fibreoptic-assisted nasal intubation was performed while the patient was awake, immediately followed by emergency total thyroidectomy via a cervical and sternal approach. The patient had an uneventful postoperative course and recovered well. Respiratory failure due to swelling of a giant thyroid is a life-threatening condition and should be treated immediately with endotracheal intubation while the patient is awake following emergent total thyroidectomy, even with a sternotomy.

Alterations in the stimulatory G protein of the rat liver after partial hepatectomy.

In adult male rat livers, cAMP generation in response to beta-adrenergic agonists was dramatically stimulated after partial hepatectomy. Quantitation of the alpha subunits of the stimulatory G protein (Gs alpha) using ADP-ribosylation catalyzed by cholera toxin revealed the increment in the amounts of two forms of Gs alpha, Gs alpha-S and Gs alpha-L, during liver regeneration. These increases in the amounts of both Gs alpha proteins were associated with the stimulation in their mRNA levels. In addition, partial hepatectomy gave rise to a shift in the proportion of beta-adrenergic receptor (beta-AR) in the high affinity state produced by beta-AR-Gs complex. The susceptibility of Gs alpha to trypsin was used as a probe for beta-AR-Gs coupling. The GTP-bound forms of both Gs alpha-S and Gs alpha-L were more trypsin-sensitive than their GDP-bound forms. Preincubation of liver plasma membranes prepared from partially hepatectomized rats with the agonist isoproterenol resulted in an enhancement of trypsin-sensitivity of Gs alpha-L, but not Gs alpha-S. This effect was retarded by the addition of the antagonist propranolol. We conclude that the increase in the amount of Gs alpha can be contributed to the rise in beta-response after partial hepatectomy, and suggest that beta-AR is preferentially coupled with Gs alpha-L rather than Gs alpha-S.

Benzodiazepine inverse agonists augment long-term potentiation in CA1 and CA3 of guinea pig hippocampal slices.

The effects of benzodiazepine inverse agonists on the long-term potentiation of synaptic transmission in hippocampal slices of the guinea pig were examined using an extracellular recording technique. Benzodiazepine inverse agonists, beta-carboline-3-carboxylate (beta-CCE), 2-phenylpyrazolo [4,3-c]quinolin-3(5H)-one (CGS-8216) and 2-[5-methylthien-3-yl]-2,5-dihydro-3H-pyrazolo [4,3-c]quinolin-3-one (S-135), augmented the magnitude of long-term potentiation induced by tetanic stimulation of input fibers in both the CA1 and the CA3 regions. beta-Carboline-3-carboxylate was more effective in augmenting long-term potentiation in CA1 than in CA3. Augmentation of long-term potentiation produced by beta-CCE was antagonized by concomitant application of flumazenil, a benzodiazepine receptor antagonist. Therefore, the enhancing action of benzodiazepine inverse agonists on long-term potentiation, which is suggested to be a specific action, mediated by the GABA/benzodiazepine receptor complex, might help to explain the mechanism of the memory-enhancing effects of benzodiazepine inverse agonists, observed in some in vivo behavioral paradigms.

Thienylpyrazoloquinolines with high affinity to benzodiazepine receptors: continuous shift from inverse agonist to agonist properties depending on the size of the alkyl substituent.

2-(5-Alkylthien-3-yl)-(1),2-(4-alkylthien-2-yl)-(2), and 2-(5-alkylthien-2-yl)-2,5-dihydro-3H-pyrazolo[4,3-c]quinolines (3) were prepared in four steps starting from ethyl 4-chloroquinoline-3-carboxylate (4) and hydrazinothiophene-carboxylates 5, 8, and 9. All the assayed compounds possessed high affinities for benzodiazepine receptors (Ki = 0.3-2.6 nM). The activities of agonists and inverse agonists were assessed on the basis of inhibition or facilitation of pentylenetetrazole-induced convulsions, respectively. Introduction of alkyl groups of different sizes into the unsubstituted inverse agonistic compounds results in a corresponding shift in the activity from an inverse agonist to an antagonist to an agonist. The susceptibility of such a shift increases in the order of 1 less than 2 less than 3. This tendency may be explained by slight differences in the geometry of the alkyl substituents among the three series.

Thienylpyrazoloquinolines: potent agonists and inverse agonists to benzodiazepine receptors.

Synthesis and structure-activity relationships of a series of 2-(thien-3-yl)- and 2-(thien-2-yl)-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-ones are reported. A number of the compounds possessed 1 order of magnitude higher affinity for the receptors than diazepam. Planarity was one of the structural requirements for binding to benzodiazepine receptors. The activities of agonists and inverse agonists were assessed on the basis of inhibition or facilitation of the pentylenetetrazole-induced convulsions, respectively. Thien-3-yl compounds exhibited inverse agonist activity whereas thien-2-yl analogues with a 5'-alkyl group showed agonist activity. Substitution on the quinoline moiety did not enhance in vivo activity. The most potent compounds were the 5-methylthien-3-yl derivative 6a as an inverse agonist and the 5-methylthien-2-yl compound 13a as an agonist.

1-Azacycloalkyl-1,4-benzodiazepin-2-ones with antianxiety-antidepressant actions.

A series of 1-azacycloalkyl-1,4-benzodiazepin-2-ones were synthesized from 1-azacycloalkyl-2-benzoylanilines and corresponding imines and then evaluated for their central nervous system activities. Pharmacological data showed that some of these compounds have potent antidepressant properties, as assessed by their antagonism of tetrabenzine (TBZ) induced ptosis and their inhibition of [3H]norepinephrine uptake into rat brain synaptosomes, as well as their moderate antianxiety properties of preventing of pentylenetetrazol (PTZ) convulsion, suppressing conflict behavior, and displacing potential for [3H]diazepam binding. Introduction of a halogen substituent at position 7 of the 1,4-benzodiazepine ring lengthened the anti-PTZ effects, although the peak effect was slightly reduced and clearly enhanced the anti-PTZ and anticonflict properties. Introduction of Cl to the ortho position of the phenyl ring at position 5 greatly reduced the antidepressant properties. The secondary amine function of the azacyclic ring at position 1 was essential for the production of the antidepressant properties. Of these new series, 7-fluoro-5-(2-fluorophenyl)-1,3-dihydro-1-(4-piperidinyl)-2H-1,4-benzodi azepin-2 -one has the potential to become a useful antidepressant drug with a moderate antianxiety property.

Synthesis and structure--activity relationships of fused imidazopyridines: a new series of benzodiazepine receptor ligands.

2-Arylimidazo[4,5-c]quinolines and analogous fused imidazopyridines were synthesized and evaluated as benzodiazepine receptor ligands. Affinity to the receptors was greatly affected by the bulkiness of the aryl group at the 2-position, compared to the pyrazoloquinolines such as CGS-9896. Derivatives with an isoxazole moiety at the 2-position showed high binding affinity and in vivo activity. In the imidazo[4,5-c]quinoline series, substitution at the 6-position decreased or abolished activity. Most derivatives with an unsubstituted isoxazolyl group showed antagonist or inverse agonist activity except for the 7-halo analogues, which exhibited agonist activity. On the other hand, 5-methylisoxazol-3-yl or 3-methylisoxazol-5-yl derivatives generally exhibited agonist activity. A similar substitution effect on the isoxazole moiety was observed in the imidazopyridines fused with a nonaromatic ring. From the detailed pharmacological evaluation, S-8510, 2-(3-isoxazolyl)-3,6,7,9-tetrahydroimidazo[4,5-d]pyrano++ +[4,3-b]pyridine monophosphate, possessing weak inverse agonist activity was selected as a therapeutic candidate for the treatment of some symptoms of senile dementia.

Very strong correlation between dominant negative activities of mutant thyroid hormone receptors and their binding avidity for corepressor SMRT.

The syndrome of resistance to thyroid hormone (RTH) is an inherited disorder involving a mutation of the thyroid hormone receptor (TR) gene. Mutant (m) TR inhibits wild-type (wt) TR functions in a dominant negative manner, and this dominant negative effect (DNE) is a crucial factor in RTH pathogenesis. The molecular mechanism of the DNE is still unclear, although several possibilities (including competition between wt- and mTRs at the T(3) response element (TRE), sequestration of TR-associated protein(s) and titration out of functional TR) have been considered. Here we report that the DNE of mTRs is strongly correlated with their binding avidity for the retinoid X receptor (RXR), and especially for corepressor SMRT (silencing mediator for retinoid and thyroid hormone receptor), but not for the nuclear receptor corepressor, NCoR. The DNE of six natural TRs and four artificially constructed mTRs was assayed using a TR reporter gene containing TRE-DR4 (DR=direct repeat), TRE-pal (pal=palindrome) or TRE-lap (lap=inverted palindrome) in CV1 cells treated with 10 nM T(3). Of the mTRs examined, F451X (with a carboxy-terminal 11-amino-acid truncation) identified in a patient with RTH exhibited the strongest DNE on all TREs. The binding affinities between mTRs and corepressors SMRT or NCoR were quantified using a two-hybrid interference assay system consisting of VP16-TR(LBD) (LBD=ligand binding domain) and Gal4(DBD)-SMRT (DBD=DNA binding domain), or Gal4(DBD)-NCoR respectively, together with the Gal4 reporter gene. In this assay, VP16-TR(LBD) and Gal4(DBD)-SMRT (or Gal4 (DBD)-NCoR) interact with each other and trans-activate the Gal4 reporter gene. When an equal amount of mTR is coexpressed, it reduces the transcriptional activity of the reporter gene, depending on its binding avidity for a corepressor. A very strong correlation was observed between the SMRT-binding activity and the potency of the DNE among six natural mTRs and also among all mTRs, including four artificially constructed ones. The relationship between NCoR and DNE, however, was not significant. When we assayed the binding avidity of mTRs for RXR by using a two-hybrid assay system consisting of Gal4(DBD)-RXR(LBD) and VP16-TR(LBD), a significant correlation between DNE and binding avidity for the RXR was also observed. These results suggest that a corepressor plays an important role in DNE pathogenesis.

Differences between the silencing-related properties of the extreme carboxyl-terminal regions of thyroid hormone receptors alpha 1 and beta 1.

Human thyroid hormone receptor (TR) is encoded by two distinct genes, TR alpha and TR beta. TR heterodimerizes with retinoid X receptor (RXR) and binds efficiently to the thyroid hormone (T(3)) response element (TRE) of target genes. In the absence of T(3), unliganded TR suppresses the basal promoter activity of positively regulated genes (silencing). Silencing mediator for retinoid and thyroid hormone receptors (SMRT) and nuclear receptor co-repressor (N-CoR) interact with unliganded TR and function as corepressor proteins. Previously, we found beta F451X with carboxyl (C)-terminal 11-amino acid deletion had stronger silencing potency than wild-type TR beta 1 and beta E449X with C-terminal 13-amino acid deletion on a subset of TREs. In the present study, to assess the isoform-specific effects of the C-terminal truncations on TR silencing, we constructed two mutant TR alpha 1s (alpha F397X and alpha E395X) with the same respective C-terminal truncations as beta F451X and beta E449X and analysed their silencing activities. Unlike beta F451X and beta E449X, alpha F397X and alpha E395X showed similarly stronger silencing potency than wild-type TR alpha 1. We further studied the abilities of wild-type and the mutant TR beta 1s and alpha 1s on RXR and co-repressor binding by a two-hybrid interference assay. beta F451X had significantly stronger abilities to bind to RXR and SMRT than did wild-type TR beta 1 and beta E449X. In contrast, wild-type TR alpha 1, alpha F397X and alpha E395X showed similar abilities to bind to RXR and SMRT. beta E449X and alpha E395X, which have identical C-terminal truncation, showed less ability to bind to N-CoR than did wild-type TR beta 1 and beta F451X and wild-type TR alpha 1 and alpha F397X respectively. These results indicate that an identical C-terminal truncation gives rise to different effects on TR beta 1 and alpha1 with respect to silencing potency, RXR binding and SMRT binding. The difference in the silencing potency among wild-type TR beta 1, beta F451X and beta E449X correlated well with the difference in the ability to bind co-repressor SMRT.

Compressibility and polygonization of single-walled carbon nanotubes under hydrostatic pressure

Single-walled carbon nanotubes show linear elasticity under hydrostatic pressure up to 1.5 GPa at room temperature. The volume compressibility, measured by in situ synchrotron x-ray diffraction, has been determined to be 0.024 GPa (-1). Theoretical calculations suggest that single-walled carbon nanotubes are polygonized when they form bundles of hexagonal close-packed structure and the intertubular gap is smaller than the equilibrium spacing of graphite (002) (d = 3.35 A). It has also been determined that the deformation of the trigonal nanotube lattice under hydrostatic pressure is reversible up to 4 GPa, beyond which the nanotube lattice is destroyed.

Changes in ambulatory activities and muscle relaxation in rats after repeated doses of diazepam.

Changes in rat ambulatory activity and muscle tone after diazepam treatments (2.5, 5, 10, and 20 mg/kg orally) were compared under single and repeated (for 2, 4, 7, and 14 days) administration schedules. Ambulatory activity in the open field test was enhanced by a single dose of 2.5 mg/kg and reduced by 20 mg/kg. However, after all repeated treatment schedules, diazepam resulted in dose-dependent elevations of activity. Even with a treatment period of only 2 days, 20 mg/kg diazepam produced a marked increase in ambulation, which became more conspicuous with increases in the treatment periods. Acutely administered diazepam produced a dose-dependent reduction in muscle tone, but tolerance was noted to this effect during repeated administrations. Thus, time- and dose-dependent increases in ambulation during repeated treatments with diazepam can be partially explained by time-dependent tolerance development to its muscle relaxant effects. The enhancement in ambulation after short-term repetitive dosings of benzodiazepines can be used as a simple indicator for detecting their disinhibitory potentials.

Activation of CCK-A receptors induces elevation of plasma corticosterone in rats.

Cholecystokinin octapeptide (CCK-8) and ceruletide (1 microgram/kg) produced a pronounced increment of plasma corticosterone levels at 30 min after intraperitoneal administration. The response to these peptides was suppressed by pretreatment with a selective antagonist for CCK-A receptors, (-)L-364,718, in a dose-related manner, but not with an antagonist for CCK-B receptors, (+)L-365,260. However, (-)L-364,718 itself had no effect on basal levels of plasma corticosterone. These results indicate that peripheral administration of CCK-8 and ceruletide stimulates the hypothalamo-pituitary adrenal axis through the activation of CCK-A receptors, but not CCK-B receptors.

Inhibitory effect of ceruletide on haloperidol-induced catalepsy in rats.

Ceruletide (CLT: 160 micrograms/kg, SC) produced a relatively long-lasting inhibition of haloperidol (HPD: 2 mg/kg, PO) catalepsy in rats. Neither bilateral vagotomies nor hypophysectomy abolished the anticataleptic effect of CLT. However, (-)-L-364,718 and proglumide blocked the effect of CLT. CLT (160 micrograms/kg) significantly inhibited HPD (2 mg/kg)-induced increase in dopamine (DA) release from the rat striatum. This effect of CLT was also antagonized by proglumide. These results suggest that CLT (160 micrograms/kg) primarily acts on cholecystokinin-A receptor in the brain, exerts some modulatory influence on HPD binding to striatal DA receptors via unknown neural pathways and, consequently, inhibits HPD catalepsy.

Simultaneous monitoring of 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA) levels in the brains of freely moving rats by differential pulse voltammetry technique.

Differential pulse voltammetry with a newly devised carbon fiber electrode was used to study the nature of striatal electrochemical signals. Voltammograms recorded from the striatum of unanesthetized rats usually yielded the combined oxidation peak (1 + 2) and peak 3. Peaks 1 and 2 could be separated by eliminating peak 1 for ascorbate by electrochemical oxidation in the brain to allow clear monitoring of peak 2 at + 120 mV for catechols and peak 3 at + 270 mV for indoles. The changes in the oxidation potentials and the amplitudes of peaks 2 and 3 corresponded to those of 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA) in vivo because: the oxidation potentials of peak 2 (+ 120 mV) and peak 3 (+ 270 mV) coincided with those of DOPAC and 5-HIAA in vitro; increases in the heights of peaks 2 and 3 were observed after micro-infusion of DOPAC and 5-HIAA, respectively, into the striatum; and peak 2 height increased after injection of haloperidol and gamma-butyrolactone and decreased after amphetamine and pargyline, while peak 3 amplitude increased following injection of gamma-butyrolactone, probenecid and 5-hydroxytryptophan and decreased after pargyline. Thus, the in vivo voltammetry method enabled simultaneous and stable monitoring of the dynamic changes in DOPAC and 5-HIAA levels in the brains of freely moving rats.

Reflectance of rat brain structures mapped by an optical fiber technique.

A method to detect differences in reflectance as a pair of glass fibers is advanced through various brain structures at a constant speed is described. The system has been used to develop a technique for accurate and easy placement of electrodes or cannulae into a limited brain region. The probe consisted of two thin (50 micrometer in diameter) glass optic fibers. A 5 W lamp was used to transmit light down one of these fibers. The relative intensity of light reflected from brain tissue into the other optic fiber was monitored with a photomultiplier and ink-writing recorder. Different brain structures were shown to vary in the amount of reflectance, with white matter having much higher reflectance than gray matter. It was demonstrated in a total of 239 penetrations that the patterns of successive changes in the reflected light response, as the probe was lowered into the brain, was characteristic for each frontal plane. The probe may additionally be itself used as an electrode if plated with silver.

B-cell prolymphocytic leukemia expressing CD13 antigen.

Although the expression of myeloid-associated antigen CD13 has been reported in aggressive B-cell chronic lymphocytic leukemia, its expression in other mature B-cell neoplasms appears to be rare. We report a 74-year-old female with B-cell prolymphocytic leukemia (B-PLL) expressing CD13 antigen. On admission, splenomegaly was noted. Hematological examination revealed a platelet count of 90 x 10(9)/l and a white cell count of 68 x 10(9)/l with 73% PLL cells. The hemoglobin concentration was 10.6 g/dl. A bone marrow aspirate showed a normocellular marrow with 64% PLL cells. Surface marker analysis of the PLL cells was positive for CD11b, CD13, CD19, CD20, CD24, HLA-DR, FMC7, mu and lambda. Simultaneous expression of CD13 and CD19 antigen was confirmed by dual color flow cytometry. Southern blot analysis of DNA from circulating mononuclear cells gave a rearranged band for the immunoglobulin gene (JH) but not for TCR-beta. Cytogenetic analysis of marrow cells showed an abnormal karyotype involving numbers 1, 7, 10, 12, 14, 15 chromosomes.