Vocal similarity predicts the relative attraction of musical chords.

Musical chords are combinations of two or more tones played together. While many different chords are used in music, some are heard as more attractive (consonant) than others. We have previously suggested that, for reasons of biological advantage, human tonal preferences can be understood in terms of the spectral similarity of tone combinations to harmonic human vocalizations. Using the chromatic scale, we tested this theory further by assessing the perceived consonance of all possible dyads, triads, and tetrads within a single octave. Our results show that the consonance of chords is predicted by their relative similarity to voiced speech sounds. These observations support the hypothesis that the relative attraction of musical tone combinations is due, at least in part, to the biological advantages that accrue from recognizing and responding to conspecific vocal stimuli.

Practical diagnostic approaches to composite plasma cell neoplasm and low grade B-cell lymphoma/clonal infiltrates in the bone marrow.

Composite plasma cell neoplasm (PCN) and low grade B-cell lymphoma (B-NHL) in the bone marrow are uncommon and raise the differential diagnosis of B-NHL with plasmacytic differentiation and PCN with lymphoplasmacytic morphology. This can be a challenging differential diagnosis, and the distinctions are important because of differences in management. We report five cases of composite PCN with B-NHL or clonal B-cell infiltrates involving the bone marrow. By using multiple different diagnostic modalities, including immunophenotyping by flow cytometry and immunohistochemistry, cytogenetic analysis and IGH gene rearrangement studies by polymerase chain reaction, we were able to distinguish two distinct clonally unrelated neoplasms in all cases. We describe the utility and pitfalls of these different diagnostic modalities. Flow cytometric analysis with a panel of antibodies that includes CD19, CD56, CD138, CD45 and other aberrant markers commonly expressed by PCN will allow identification of clonally unrelated PCN and B-NHL in a composite neoplasm, and distinguish them from B-NHL with plasmacytic differentiation and PCN with lymphoplasmacytic morphology. Cytogenetic and molecular analyses can give false-negative or false-positive results. In summary, a multimodal approach utilizing these different tools, including clinical data, should be used to arrive at the correct diagnosis.

MYC protein expression in primary diffuse large B-cell lymphoma of the central nervous system.

Primary diffuse large B-cell lymphoma of the central nervous system (CNS DLBCL) is a rare, aggressive subtype of DLBCL, the biology of which is poorly understood. Recent studies have suggested a prognostic role of MYC protein expression in systemic DLBCL, but little is known about the frequency and significance of MYC protein expression in CNS DLBCL. Hence, we investigated MYC protein expression profiles of CNS DLBCL and assessed the relationship between MYC expression and a variety of histopathologic, immunophenotypic, genetic, and clinical features. Fifty-nine CNS DLBCL diagnosed at our institution over the past 13 years were evaluated. The majority of cases (80%) showed centroblastic morphology, and 12 (20%) displayed a perivascular pattern of infiltration. According to the Hans criteria, 41 (69%) cases had a non-germinal center B-cell and 18 (31%) had a germinal center B-cell cell-of-origin (COO) phenotype. Mean MYC protein expression was 50% (median: 50%, range: 10-80%). Forty-three cases (73%) showed MYC overexpression (≥ 40%), and 35 (60%) showed MYC/BCL2 coexpression. MYC overexpression was seen in the single case harboring MYC translocation and in the cases showing increased copies of MYC (27%); however, no significant difference in mean MYC expression was seen between groups harboring or lacking MYC aberrations. In our series, age was associated with a significantly increased risk of death, and the perivascular pattern of infiltration was associated with a significantly increased risk of disease progression. Neither MYC expression (with or without BCL2 coexpression) nor other variables, including COO subtype were predictive of clinical outcome. Our findings indicate that the proportion of CNS DLBCL overexpressing MYC is higher compared to systemic DLBCL, and MYC overexpression appears to be independent of genetic MYC abnormalities. Thus, MYC expression and other immunophenotypic markers used for prognostication of systemic DLBCL might not apply to CNS DLBCL due to differences in disease biology.

C-myc protein expression in B-cell acute lymphoblastic leukemia, prognostic significance?

C-myc protein expression has been studied in mature B-cell lymphomas and overexpression has been associated with poor prognosis. We sought to determine the prognostic significance of c-myc protein expression in B-ALL. We found ≥ 20% c-myc expression to predict risk of persistent disease in all age groups (odds ratio 7.487, p=0.013). There was no statistically significant association between c-myc expression and risk of relapse or death in our study. Routine c-myc immunostaining may help identify higher risk patients and guide management of B-ALL. Additional studies are needed to further determine the molecular mechanisms and role of c-myc expression in B-ALL.

CD30-positive lymphoproliferative disorders arising after regional therapy for recurrent melanoma: a report of two cases and analysis of CD30 expression.

BACKGROUND AND OBJECTIVES: Primary cutaneous CD30-positive T-cell lymphoproliferative disorders (CD30(+) LPD), including primary cutaneous anaplastic large cell lymphoma (CALCL) and lymphomatoid papulosis (LyP), comprise the second most common group of cutaneous T-cell lymphomas (CTCL). The etiology of these disorders is not known. Isolated limb perfusion (ILP) and isolated limb infusion (ILI) are forms of regional chemotherapy used to treat recurrent tumors of the extremity, most commonly, melanoma. Secondary malignancy following regional therapy is rarely reported. METHODS/RESULTS: We identified two cases of CD30(+) LPD arising in the affected limbs of patients treated with ILP/ILI. We subsequently performed CD30 immunohistochemical stains on 11 pre- and post-treatment skin specimens from melanoma patients treated with ILP/ILI and found that 5 of the 11 cases showed an increase in CD30(+) lymphocytes following ILP/ILI. CONCLUSIONS: We hypothesize that ILP/ILI causes upregulation of CD30 expression in the extremities of treated patients, and suggest that this may be a marker of treatment response. However, a rare but long-term effect may be an increased risk of T-cell cutaneous lymphoproliferative disease in the affected limb.

A tumor suppressor function for the lipid phosphatase INPP4B in melanocytic neoplasms.

The phosphoinositide-3 kinase (PI3K) pathway is deregulated in a significant proportion of melanomas, and PI3K pathway activation in combination with constitutively active mitogen-activated protein kinase signaling shows synergistic effects in the process of melanoma tumorigenesis. Recently, a tumor suppressor function for the lipid phosphatase inositol polyphosphate 4-phosphatase type II (INPP4B) has been described in breast and prostate cancers, with impact on PI3K signaling output. Given the importance of PI3K pathway activity for melanoma formation and growth, we aimed to assess the role of INPP4B in melanocytic tumors. Our studies in native tumors suggest that decreased INPP4B expression is an event correlating with tumor progression in melanocytic neoplasms. We further demonstrate that INPP4B regulates PI3K/Akt signaling and exerts a tumor suppressor effect, impacting the proliferative, invasive, and tumorigenic capacity of melanoma cells. INPP4B expression in melanocytic neoplasms may therefore have potential as a biomarker for disease progression and as a modulator for the prediction of treatment outcome.

Expression of immune inhibitory receptor ILT3 in acute myeloid leukemia with monocytic differentiation.

BACKGROUND: The diagnosis of AML with monocytic differentiation is limited by the lack of highly sensitive and specific monocytic markers. Immunoglobulin-like transcript 3 (ILT3) is an immune inhibitory receptor expressed by myelomonocytic cells and at high levels by tolerogenic dendritic cells. METHODS: Using flow cytometry, we analyzed the expression of ILT3 in 37 patients with AML and 20 patients with no detectable disease. RESULTS: We showed that ILT3 was expressed in all cases of AML displaying monocytic differentiation (FAB M4/M5; N = 18), but not in AML M1/M2 and M3 (N = 19; P < 0.0001). Co-expression of ILT3 and immature cell markers, such as CD34 and CD117, was observed in monoblastic leukemia. ILT3 expression was preserved after treatment in M4/M5 patients with refractory or relapsed disease. ILT3 expression was associated with the presence of cytogenetic abnormalities linked to an intermediate prognosis (P = 0.001). Rare CD45dimCD34+CD117+ILT3+ cells were identified in noninvolved bone marrow, suggesting that ILT3 expression is acquired at an early stage by normal myelomonocytic precursors. CONCLUSIONS: ILT3 is a highly sensitive and specific marker which distinguishes AML with monocytic differentiation from other types of AML. Testing of ILT3 expression should be incorporated into the initial diagnostic work-up and monitoring of patients with AML.

The use of angiogenic-antimicrobial agents in experimental wounds in animals: problems and solutions.

A topical combination (silvathymosin) of natural proangiogeneic protein thymosin ß4 (Tß4) and antimicrobial silver sulfadiazine was hypothesized to promote the healing of large, full-thickness, clean or infected wounds in rats. Silvathymosin showed the fastest wound healing (85%) followed by silver sulfadiazine (84%) and Tß4 (72%). In the infected groups, the healing pattern was different, as Tß4 and silvathymosin groups did not show similar wound healing. Wound histopathology and VEGF and KI67 immunohistochemical assessment of angiogenesis was consistent and correlated well with the tempo of healing of the acute wounds. These preliminary data demonstrate the more rapid acute wound healing properties of the combination formulation of thymosin ß4 and silver sulfadiazine as compared to these agents alone. This novel agent could prove an effective treatment modality for debilitating chronic wounds and decubitus ulcers.

Aberrant T-cell antigen expression in B lymphoblastic leukaemia.

B lymphoblastic leukaemia (B-ALL) cells are characterized by the expression of various B-cell antigens. Expression of T/Natural Killer-cell antigens, however, has rarely been reported in B-ALL (TAg+ B-ALL), and the significance of this aberrant antigen expression is unclear. We thus analysed the frequency of TAg+ B-ALL at our institution and investigated its significance in the context of immunophenotypes, cytogenetic/molecular findings, and prognosis. We reviewed 134 consecutive cases of B-ALL and found 18 cases (13·4%) of TAg+ B-ALL. The most common aberrant T-cell antigens expressed were CD2, CD5, and CD7 at equivalent rates (each in six cases), CD4 (two cases), and CD56 (three cases). Adverse cytogenetic abnormalities were seen in a significantly larger proportion of the TAg+ cases (72·2%) than the TAg- cases (32·2%; P = 0·003). Multivariate Cox-regression analysis showed that the risk of relapse over time was higher in the TAg+ cases, independent of high risk status (based on age and white blood cell count) and the presence of adverse cytogenetic abnormalities (hazard ratio = 2·256, P = 0·065). These findings suggest that T-cell antigen expression in B-ALL may be an independent predictor of poor prognosis, and a useful marker to identify patients at increased risk for relapse and for harbouring adverse cytogenetic abnormalities.

Primary squamous cell carcinoma arising at a gastrostomy tube site.

Gastrostomy tubes are commonly used in children with feeding impairment. Postoperative complications such as the formation of granulation tissue are common and represent a type of chronic nonhealing wound. We present a case of a 24-year-old man with no history of malignancy who developed a primary cutaneous squamous cell carcinoma at a long-term gastrostomy tube site.

Major and minor music compared to excited and subdued speech.

The affective impact of music arises from a variety of factors, including intensity, tempo, rhythm, and tonal relationships. The emotional coloring evoked by intensity, tempo, and rhythm appears to arise from association with the characteristics of human behavior in the corresponding condition; however, how and why particular tonal relationships in music convey distinct emotional effects are not clear. The hypothesis examined here is that major and minor tone collections elicit different affective reactions because their spectra are similar to the spectra of voiced speech uttered in different emotional states. To evaluate this possibility the spectra of the intervals that distinguish major and minor music were compared to the spectra of voiced segments in excited and subdued speech using fundamental frequency and frequency ratios as measures. Consistent with the hypothesis, the spectra of major intervals are more similar to spectra found in excited speech, whereas the spectra of particular minor intervals are more similar to the spectra of subdued speech. These results suggest that the characteristic affective impact of major and minor tone collections arises from associations routinely made between particular musical intervals and voiced speech.

A biological rationale for musical scales.

Scales are collections of tones that divide octaves into specific intervals used to create music. Since humans can distinguish about 240 different pitches over an octave in the mid-range of hearing, in principle a very large number of tone combinations could have been used for this purpose. Nonetheless, compositions in Western classical, folk and popular music as well as in many other musical traditions are based on a relatively small number of scales that typically comprise only five to seven tones. Why humans employ only a few of the enormous number of possible tone combinations to create music is not known. Here we show that the component intervals of the most widely used scales throughout history and across cultures are those with the greatest overall spectral similarity to a harmonic series. These findings suggest that humans prefer tone combinations that reflect the spectral characteristics of conspecific vocalizations. The analysis also highlights the spectral similarity among the scales used by different cultures.