The National Institute of Health and the Italian Poison Centers Network: results of a collaborative study for the surveillance of exposures to chemicals.

Background: The Public Health Surveillance Systems are essential to improve and protect public health, as highlighted by the World Health Organization. According with this consideration, a systematic collaboration between the National Institute of Health and the Poison Centers of Northern, Central and Southern Italy was established. Its aim was to improve the national network for the surveillance of dangerous exposures to chemicals. The developed network provided harmonized data essential for evidence-based interventions and significantly ameliorated the data flow between the Poison Centers and the Central Health Institutions. Methods: The improvement of the system was obtained through several actions, such as the development of the "Online Surveillance Card" for the detection of sentinel events in real time and the harmonization of the data collection flow, including the product categorization according to the European Product Categorization System. Data analysis was carried out by Microsoft's IBM SPSS Statistics version 26, Access and Excel. Results: Important information was obtained, regarding also exposures to chemicals and their management in pediatric populations. The surveillance network was proved effective not only under "normal" conditions but also to promptly monitor changes during exceptional health emergencies, such as the COVID-19 pandemic. During the 2020 lockdown the surveillance system registered a significant increase in the frequency of exposures to disinfectants (p-value=0.002), an evidence that highlighted the need of tailored intervention. Conclusions: This Italian Project model proves to be reliable and suitable to be transferred to other European countries, in order to realize an European Poison Centers' Network, able to overcome unsolved health problems and to globally improve the "evidence-based" prevention of exposures to chemicals.

Transvaginal ultrasound predicts delayed response to chemotherapy and drug resistance in stage I low-risk trophoblastic neoplasia.

OBJECTIVES: Methotrexate (MTX) resistance is defined on the basis of the human chorionic gonadotropin (hCG) curve. The aim of this study was to identify low-risk non-metastatic patients with gestational trophoblastic neoplasia (GTN) who can achieve resolution by continuing MTX treatment despite a transient hCG plateau. METHODS: Before starting chemotherapy, 24 patients with FIGO Stage I GTN underwent transvaginal ultrasonography with power Doppler in order to identify myometrial lesions (areas of increased echogenicity and increased power Doppler signal). Ultrasound response to chemotherapy was defined when myometrial lesions decreased in echogenicity, Doppler signal or size. When ultrasound response occurred, despite chemoresistance defined by hCG values, MTX treatment was continued. RESULTS: MTX was continued in three out of seven chemoresistant patients because ultrasound suggested response to MTX. All three of these patients achieved a complete response, thus nearly halving the MTX-resistance rate. CONCLUSION: Among patients who are candidates for second-line treatment on the basis of hCG, ultrasound may identify those in whom further MTX administration can induce a delayed complete response.

Molecular surveillance of pandemic influenza A(H1N1) viruses circulating in Italy from May 2009 to February 2010: association between haemagglutinin mutations and clinical outcome.

Haemagglutinin sequences of pandemic influenza A(H1N1) viruses circulating in Italy were examined, focusing on amino acid changes at position 222 because of its suggested pathogenic relevance. Among 169 patients, the D222G substitution was detected in three of 52 (5.8%) severe cases and in one of 117 (0.9%) mild cases, whereas the D222E mutation was more frequent and evenly distributed in mild (31.6%) and severe cases (38.4%). A cluster of D222E viruses among school children confirms reported human-to-human transmission of viruses mutated at amino acid position 222.

The CD30 gene promoter microsatellite binds transcription factor Yin Yang 1 (YY1) and shows genetic instability in anaplastic large cell lymphoma.

CD30 is a member of the TNF receptor family. Our interest lies in understanding the control of CD30 expression, particularly as its over-expression provides a diagnostic marker for a subset of non-Hodgkin's lymphomas, particularly anaplastic large cell lymphoma (ALCL), and because anti-CD30 treatment has been shown to be efficacious. We have identified a number of regulatory regions, including an Sp1 element in the minimal promoter, and a downstream promoter element that is required for start site selection. The discovery of both an activating AP1 site and an upstream microsatellite that represses transcriptional activity of CD30 suggests that this region is involved in dysregulation of CD30 expression. We have now identified the major microsatellite binding activity as transcription factor Yin Yang 1 by both one-hybrid cDNA library screening and peptide mass fingerprinting. Due to the strong repressive effect of the microsatellite, we also investigated whether microsatellite instability may induce changes in CD30 expression and hence explain the over-expression of CD30 in ALCL. Laser capture microdissection of ALCL biopsies and CD30 microsatellite typing indicated that the neoplastic cells show a high degree of variation, but this does not correlate with high CD30 expression seen in ALCL.

Tumoral, quasitumoral and pseudotumoral lesions of the superficial and somatic soft tissue: new entities and new variants of old entities recorded during the last 25 years. Part XII: appendix.

In an eleven part series published in Pathologica, we have presented various tumoral, quasitumoral and pseudotumoral lesions of the superficial and somatic soft tissue (ST), which emerged as new entities or as variants of established entities during the last quarter of a century. Detailed clinicomorphological and differential diagnostic features of approximately sixty entities were chosen on the basis of their clinical significance and morphologic distinctiveness. The series included fibrous and myofibroblastic tumors (e.g. solitary fibrous tumor, high grade classic and pigmented dermatofibrosarcoma protuberans, inflammatory myofibroblastic tumor and myofibrosarcomas), fibromyxoid and fibrohistiocytic neoplasms (e.g., Evans' tumor, phosphaturic mesenchymal tumor, inflammatory myxohyaline tumor), special adipocytic/vascular/and smooth muscle lesions (e.g., chondroid lipoma, Dabska's tumor, ST hemangioblastoma, lipoleiomyosarcoma), epithelioid mesenchymal malignancies of diverse lineages (e.g., epithelioid liposarcoma, proximal-type epithelioid sarcoma, neuroendocrine extraskeletal chondromyxoid sarcoma), ST Ewing's tumor and peripheral nerve sheath tumors (perineuriomas and pigmented and rosetting tumors of the schwannoma/neurofibroma group), extranodal dendritic or histiocytic proliferative processes (follicular dendritic cell sarcoma, Rosai-Dorfman disease, Castleman's disease, and plexiform xanthomatous tumor), and tumors with myoepithelial differentiation. The section devoted to selected pseudotumoral entities considered representatives of the hamartoma group (neural fibrolipomatous hamartoma, ectopic hamartomatous thymoma, rudimentary meningocele), metabolic diseases (amyloid tumor, nephrogenic fibrosing dermopathy, tophaceous pseudogout, pseudoinfiltrative parathyromatosis), stromal tissue reactions to trauma (fibroosseous pseudotumors of digits) and infections (bacillary angiomatosis), and normal organs (glomus coccygeum). To conclude the descriptive phase, supplementary material has now been collected and appended in an attempt to provide a quick digest of essential knowledge both for comparison and differential diagnosis. The data have been tailored to synthesize diverse sources, integrating clinical elements and references to articles that previously appeared in Part I ("Introduction"), Part II ("The List and Review of New Entities") and Parts III to XI ("Excerpta"). At the very least we hope this final part ("Appendix") will provide the reader with a useful tabular organization of ST lesions and a reference resource.

Crystalline plasma cell inclusions in helicobacter-associated gastritis.

BACKGROUND: Crystalline cytoplasmic inclusions are well documented in B cell lymphomas but have rarely been described in reactive plasmacytic infiltrates. AIM: Three cases of Lelicobacter-associated gastritis are described in which plasma cells focally contained rhomboid and needle-shaped crystalline inclusions. METHODS: Crystalline inclusions were identified in the gastric biopsy specimens from three patients undergoing routine upper gastrointestinal endoscopy. The cells were characterised immunohistochemically using the following antisera: cytokeratin, leucocyte common antigen, desmin, CD20, CD68, CD79a, CD138, immunoglobulin (Ig)G, IgA and IgM heavy chains, and kappa and lambda Ig light chains. Clinical follow-up data were obtained. RESULTS: All biopsies showed a Lelicobacter-associated active chronic gastritis. Variable numbers of plasma cells with intracytoplasmic crystalline inclusions in the superficial lamina propria were seen. The crystals were not stained with any of the antisera tested, but the cells containing the crystals expressed CD79a and CD138 and, in the two assessable cases, showed IgA and lambda light chain immunoreactivity. The more numerous morphologically normal plasma cells in each patient were polytypic, and there were no histological features to suggest lymphoma. Crystals were not identified in the plasma cells in mucosal biopsy specimens from other sites in any of the patients. CONCLUSIONS: Crystalline inclusions in plasma cells can occur in association with Lelicobacter gastritis. Although light chain restriction was shown in two patients, the overall histological and clinical findings indicated a reactive process. The presence of plasma cell crystals in isolation should not be considered to be diagnostic of lymphoma.

Aldosterone synthase alleles and cardiovascular phenotype in young adults.

The C(-344)T promoter polymorphism of the human aldosterone synthase (CYP11B2) gene has been associated with hypertension and cardiac hypertrophy, but there were contrasting data. We analysed the genotype/phenotype associations between this polymorphism and cardiovascular variables in a young adult population, where interactions among genes, gene-environment, and acquired ageing-related organ damage are reduced. Anthropometric measurements, blood pressure, heart rate, left ventricular variables (by echocardiography), and carotid artery wall intimal-media thickness (by high-resolution sonography and digitalized morphometry) were taken in 420 white Caucasian students (mean age 23.5 years, s.d. 2.5 years). CYP11B2 alleles were detected by genomic polymerase chain reaction followed by digestion. Taking into account the three possible models of inheritance, we found no differences in the considered variables, except for an independent effect of the C(-344) allele on SBP in males (TT 125.6 (1.6), TC 128.4 (1.2) and CC 130.5 (2.2), mmHg, media (ES), P=0.03), and on interventricular septum thickness in diastole in females (CC 6.98 (0.12) vs TT 6.87 (0.09) and TC 6.87 (0.07), mmHg, P<0.01), in the codominant model. In conclusion, the CYP11B2 C(-344)T polymorphism appears to have a slight role in the cardiovascular phenotype of young healthy adults, even if these genotype/phenotype relationships might change with ageing.

Extraskeletal myxoid chondrosarcoma: a light microscopic, immunohistochemical, ultrastructural and immuno-ultrastructural study indicating neuroendocrine differentiation.

AIMS: Extraskeletal myxoid chondrosarcoma is a rare low-grade soft-tissue sarcoma with locally aggressive and metastasizing potential. Extraskeletal myxoid chondrosarcoma has distinctive clinical, light microscopic, immunophenotypic, cytogenetic and ultrastructural features. Evidence that extraskeletal myxoid chondrosarcoma often shows neuroendocrine features was first provided by Chhieng et al. on the basis of an immunohistochemical and ultrastructural study of seven cases. Our study aims to further confirm by immunohistochemistry and ultrastructural studies, including immunoelectron microscopy, that extraskeletal myxoid chondrosarcoma indeed may show neuroendocrine differentiation. METHODS AND RESULTS: Fifteen cases of extraskeletal myxoid chondrosarcoma and seven control cases of skeletal chondrosarcomas were studied. Extensive immunohistochemical analysis was performed in all cases and ultrastructural studies were done in 11 extraskeletal myxoid chondrosarcomas and three skeletal chondrosarcomas. Immunoelectron microscopy was performed on one case each of extraskeletal myxoid chondrosarcoma and skeletal chondrosarcoma. Extraskeletal myxoid chondrosarcomas expressed neuron-specific enolase (100%), synaptophysin (87%), S100 (50%), PGP 9.5 (40%), and epithelial membrane antigen (25%). Co-expression of synaptophysin and PGP 9.5 was observed in six tumours. Skeletal chondrosarcomas showed expression of S100 protein, vimentin and neuron-specific enolase in all cases. Synaptophysin, chromogranin and PGP 9.5 were not expressed in any skeletal chondrosarcoma case. Ultrastructurally, extraskeletal myxoid chondrosarcoma was characterized by distinct cords of cells immersed in a glycosaminoglycan-rich matrix. The cells were rich in mitochondria, had well-developed Golgi apparatus and there were numerous smooth vesicles. In three cases there were easily found 140-180 nm diameter membrane-bound dense-core granules in cell bodies and in processes, unrelated to the Golgi, compatible with neurosecretory granules. Fewer such granules were present in the remaining extraskeletal myxoid chondrosarcoma cases, three of which also contained intracisternal tubules typical of extraskeletal myxoid chondrosarcoma. The skeletal chondrosarcomas had scalloped cell surfaces, prominent rough endoplasmic reticulum focally distended with secretory product, and lacked neurosecretory granules. Intermediate filaments were prominent in both extraskeletal myxoid chondrosarcoma and skeletal chondrosarcomas. Immunoelectron microscopy showed synaptophysin expression in the extraskeletal myxoid chondrosarcoma but not in the skeletal chondrosarcoma case. CONCLUSIONS: This study confirms that a substantial proportion of extraskeletal myxoid chondrosarcomas show immunophenotypic and/or ultrastructural evidence of neuroendocrine differentiation, and are unlikely to be related to conventional skeletal chondrosarcomas.

Cardiovascular phenotype of young adults and angiotensinogen alleles.

OBJECTIVES AND DESIGN: Angiotensinogen (AGT) gene variants influence angiotensinogen plasma levels in children and young adults. The angiotensinogen promoter (-6)A variant facilitates gene transcription in human tissues and it has been associated with high blood pressure in older adults. A young adult population can be used as a model to study genotype/phenotype associations between AGT (-6) variants and cardiovascular variables. METHODS AND RESULTS: Anthropometric measurements, blood pressure and heart rate were taken in 422 white Caucasian students (mean age 23.5 years, SD 2.5 years). Family history for hypertension, physical activity and smoking history were evaluated. Left ventricular variables were measured by echocardiography. Carotid artery wall intimal-media thickness (IMT) was measured by high resolution sonography and digitalized morphometry. The AGT G(-6)A alleles were evaluated by mutagenically separated polymerase chain reaction controlled by direct sequencing. No significant associations were found between angiotensinogen genotype and blood pressure, cardiac variables [except for deceleration time in females which increased with the number of (-6)A alleles] and IMT. Allele frequencies were similar between the first and third tertile of blood pressure and left ventricular mass, and were also similar between negative or positive family history for hypertension (the last group having significantly higher systolic blood pressure in males, P = 0.04 and diastolic blood pressure in females, P < 0.01). Moreover, no relevant interaction on the cardiovascular variables was found between AGT genotype and body mass index. CONCLUSIONS: The angiotensinogen G(-6)A variants do not affect cardiovascular parameters in young adults, but an effect of this polymorphism on cardiovascular phenotype (and hypertension) in older adults cannot be excluded. Additional factors, associated with ageing, should be present to unleash the supposed unfavourable potential of the (-6)A angiotensinogen variant.

The diagnositc significance of Myf-3 hypermethylation in malignant lymphoproliferative disorders.

Deregulated methylation of cytosine in DNA is a frequent finding in malignancy that is reflected by general genomic hypomethylation and regional hypermethylation that includes the myogenic gene Myf-3. In this study of 198 DNA samples from 186 patients with a wide range of lymphoproliferative disorders (LPD), the methylation status of Myf-3 was assessed to evaluate its significance in the diagnosis of malignant LPD. DNA was digested with the restriction endonucleases HpaII and MspI, and using the Southern blot (SB) technique, the size and density of fragments that hybridized with a Myf-3 probe were used to assign the methylation status. None of the samples from 45 patients from a wide age range with benign LPDs had evidence of altered Myf-3 methylation and there was no age-related methylation change. By contrast, 115/123 (93%) of samples from patients with non-Hodgkin lymphoma (NHL) or lymphoid leukemia had increased Myf-3 methylation. There was no methylation alteration in 22/24 (92%) of samples from patients with Hodgkin lymphoma (HL), nor in five of six samples from LPDs that had atypical histopathologic features which were not diagnostic of lymphoma, while the remaining sample of atypical LPD had hypermethylated Myf-3 fragments. There was an association between increasing Myf-3 methylation and higher histopathologic grade of malignancy within specific lymphoma categories. It is concluded that the detection of increased Myf-3 methylation is a sensitive and specific test of malignancy which may complement other molecular methods that are currently used for the assessment of clonality. It may be of particular diagnostic use in natural killer (NK) and null cell malignancies for which other indicators of clonality are lacking. Furthermore, methylation status may prove to be of potential prognostic value.

Pulmonary toxicity of inhaled aerosolized prostacyclin therapy--an observational study.

Large white/landrace piglets (mass 11 to 21 kg) were exposed to aerosolized alkaline glycine diluent (n = 2) or inhaled aerosolized prostacyclin (n = 2) for five to eight hours. Pigs receiving these aerosols developed mild acute sterile tracheitis, involving the superficial layers of the trachea, shown histologically and ultrastructurally. Pigs receiving the diluent aerosol also showed mild inflammatory changes in the bronchioles. These findings suggest caution with the use of high volumes of aerosolized alkaline glycine diluent during inhaled aerosolized prostacyclin therapy.

A novel promoter variant of the natriuretic peptide clearance receptor gene is associated with lower atrial natriuretic peptide and higher blood pressure in obese hypertensives.

OBJECTIVE AND DESIGN: The clearance receptor for natriuretic peptides (NPRC), a candidate gene for essential hypertension, is highly expressed in adipose tissue, where is nutritionally regulated. The objectives of the present study were to sequence the human 5'-flanking regulatory region of NPRC, to identify allelic variants and their frequencies, and to study the genotype/phenotype correlation in hypertensive patients. METHODS AND RESULTS: Using polymerase chain reaction (PCR) and direct automated sequencing, a biallelic (A/C) polymorphism was detected at position -55 in a conserved promoter element named P1. The novel C(-55) variant makes the promoter sequence identical to the mouse gene and introduces a second Hgal site in the amplified DNA, allowing the genotyping of a large number of subjects. In a random sample of 232 white Caucasians the C(-55) allele was more commonly found (81.7% of all alleles) with 155 CC (66.8%), 69 AC (29.7%) and only eight AA (3.5%) genotypes. Atrial natriuretic peptide (ANP) levels were determined in 84 patients with essential hypertension. In the presence of obesity (body mass index (BMI) > or = 30 kg/m2) the homozygous CC hypertensives (n = 21) had significantly lower plasma ANP (33.6 +/- 11.1 pg/ml) compared with the AC patients (n = 11; 46.8 +/- 15.9 pg/ml; P = 0.01), whereas systolic blood pressure (SBP) and mean blood pressure (MBP) had the opposite association (SBP 163.9 +/- 18.7 versus 150.9 +/- 12.9 and MBP 123.3 +/- 12 versus 114.5 +/- 5.9 mmHg; P< 0.05). The difference in ANP levels were also present when overweight patients (BMI > or = 27 kg/m2) were considered. CONCLUSION: A common 'ancestral' C(-55) variant of the NPRC P1 promoter is associated with lower ANP levels and higher SBP and MBP in obese hypertensives. The C(-55) variant, in the presence of increased adiposity, might reduce plasma ANP through increased NPRC-mediated ANP clearance, contributing to higher blood pressure.

Vertebral synovial osteochondromatosis with compressive myelopathy.

STUDY DESIGN: A case report of vertebral synovial osteochondromatosis with compressive myelopathy. OBJECTIVES: To describe the clinical, radiologic, and histopathologic features of vertebral facet synovial osteochondromatosis with compressive myelopathy. SUMMARY OF BACKGROUND DATA: There has been only one previously reported case of synovial osteochondromatosis affecting the vertebral facet joint and no previous report of associated compressive myelopathy. METHODS: The case history, radiology, surgical findings, and histopathology are reviewed. RESULTS: Vertebral facet synovial osteochondromatosis is a potential and readily manageable cause of spinal cord compression. CONCLUSIONS: Synovial osteochondromatosis of the vertebral facet joint should be considered as a cause of compressive myelopathy.

Low calorie diet enhances renal, hemodynamic, and humoral effects of exogenous atrial natriuretic peptide in obese hypertensives.

The expression of the natriuretic peptide clearance receptor is abundant in human and rat adipose tissue, where it is specifically inhibited by fasting. In obese hypertensives, plasma atrial natriuretic peptide (ANP) levels were found to be lower than in obese normotensives. Therefore, the increased adipose mass might influence ANP levels and/or its biological activity. The aim of the present study was to evaluate whether the humoral, hemodynamic, and renal effects of exogenous ANP in obese hypertensives might be enhanced by a very low calorie diet. Eight obese hypertensives received a bolus injection of ANP (0.6 mg/kg) after 2 weeks of a normal calorie/normal sodium diet, and blood pressure (BP), heart rate, ANP, cGMP, plasma renin activity, and aldosterone were evaluated for 2 hours before and after the injection. Diuresis and natriuresis were measured every 30 minutes. The patients then started a low calorie/normal sodium diet (510 kcal/150 mmol/d) for 4 days, and then the ANP injection protocol was repeated. The low calorie diet induced a slight weight loss (from 90.6+/-1.1 to 87. 7+/-1.2 kg; P<0.01), which was accompanied by increase of cGMP excretion (from 146.0+/-10.1 to 154.5+/-9.5 nmol/24 h; P<0.05) together with a reduction of BP (P<0.01 versus basal levels). ANP injection after diet was followed by an increase of ANP levels similar to that observed before diet, but plasma cGMP, diuresis, and natriuresis increased significantly only after diet. Similarly, the decrease of BP after ANP administration was significantly higher after diet (change in mean arterial pressure, -6.4+/-0.7 versus -4. 0+/-0.6 mm Hg; P<0.05) as well as that of aldosterone (P<0.01). These data show that a low calorie diet enhances the humoral, renal, and hemodynamic effects of ANP in obese hypertensives and confirm the importance of caloric intake in modulating the biological activity of ANP, suggesting that the natriuretic peptide system can play a role in the acute changes of natriuresis and diuresis associated with caloric restriction.

Medullary carcinoma of the thyroid: accuracy of diagnosis of fine-needle aspiration cytology.

BACKGROUND: A preoperative diagnosis of medullary carcinoma of the thyroid (MCT) allows for the investigation of associated multiple endocrine neoplasia/ pheochromocytoma, and definitive surgery without the need for frozen section. Criteria for cytodiagnosis are well known but variable patterns of presentation may cause diagnostic difficulty. METHODS: This study examines the accuracy of cytodiagnosis and the value of ancillary tests in 17 patients seen between 1976 and 1997. Nine patients underwent thyroid gland aspirations, five patients underwent fine-needle aspiration (FNA) of the thyroid and cervical lymph nodes, and three patients underwent cervical lymph node aspiration alone. Electron microscopy (EM) of aspirated material was performed in nine cases and immunocytochemistry in two cases. RESULTS: In all cases the diagnosis was suggested by FNA. In four cases, diagnosis and management were based on cytology alone. EM of FNA material was confirmatory in nine cases, two of which also showed positive calcitonin immunocytochemistry. In three cases the diagnosis was not proven until surgical resection, and in one case FNA confirmed lymph node metastasis in known MCT. Frozen section in five patients did not change the level of diagnostic confidence over the FNA diagnosis in any case. In four other thyroid tumors (one Hürthle cell follicular carcinoma, two anaplastic carcinomas, and one hyperplastic nodule) MCT was suspected in the FNA differential diagnosis but later excluded. In the Hürthle cell tumor immunoperoxidase staining was positive for calcitonin and in one anaplastic carcinoma, a neuroendocrine phenotype was suggested. In the latter case, additional EM excluded MCT. CONCLUSIONS: Although correct diagnosis is made by cytology in the majority of instances, other tumors may show cytologic findings similar to MCT. EM of FNA material was found to be the most definitive method of proving or excluding MCT. Immunocytochemistry may be misleading for rarely performed tests.

Granulomatous glomerulonephritis in intravenous drug users: a report of three cases in oxycodone addicts.

Various well-documented renal lesions are associated with intravenous drug use; however, intraglomerular mesangial granulomas have not been previously described. We report three patients who developed an unusual granulomatous glomerulonephritis and interstitial nephritis after intravenous injection of oxycodone, derived from suppositories. Granulomas were seen in an intraglomerular mesangial and also interstitial location. In both sites, the granulomas were associated with filamentous material, presumably derived from a component of the suppositories. This material was periodic acid-Schiff-positive, but negative with Congo red and silver stains. Ultrastructurally, the filamentous material was seen within the mesangial granulomas and also in a subendothelial location, suggesting derivation from the circulation with subsequent transport across the basement membrane and accumulation in the mesangium, where a granulomatous reaction was elicited. All patients developed a degree of renal failure; two of the patients require hemodialysis 20 and 30 months after presentation.

A novel MspI PCR-RFLP in the human cytosine 5-methyltransferase gene: lack of relevance for malignant lymphoproliferative disease and breast cancer.

Two alternate allelic forms of human cytosine 5-methyltransferase, 5-MT I and 5-MT II, which differ by the absence or presence of an intronic MspI recognition sequence, have been recognised. The polymorphic region was localised using a series of subprobes prepared upon MspI digestion of the 2.5-kb cDNA probe (hmt-2.5). A PCR-based method was then developed for rapid 5-MT genotyping. The gene and phenotype frequencies of 5-MT I and 5-MT II were not significantly different in genomic DNA samples from a series of non-Hodgkin's lymphomas and breast cancer cases compared with DNA from normal subjects. Allelism of 5-MT allows new approaches to the assessment of variation in gene copy number of 5-MT in different types of neoplasia.