Biomedical subjects

J C Martinez

Publications and source records attributed to J C Martinez.

At least 19 recordsLinked to original sources

PubMed2001

Hyperfractionated chemoradiation with carbogen breathing, with or without erythropoietin: a stepwise developed treatment schedule for advanced head-and-neck cancer.

PURPOSE: To investigate the influence of carbogen breathing on chemoradiation and the effects of erythropoietin on transfusions. METHODS AND MATERIALS: From March 1996 to April 2000, 42 (4 Stage III and 38 Stage IV) patients with head and neck cancer were treated with a twice-a-day hyperfractionated schedule. Each fraction consisted of 5 mg/m(2) of carboplatin plus 115 cGy with carbogen breathing. Treatment was given 5 days per week up to total doses of 350 mg/m(2) of carboplatin plus 8050 cGy in 7 weeks. Anemia was treated either by transfusion or by erythropoietin. RESULTS: Forty-one patients tolerated the treatment as scheduled. All patients tolerated the planned radiation dose. Five transfusions were given in the first group, but no transfusion was needed in the erythropoietin group. Local toxicities remained at the level expected with irradiation alone. Chemotherapy toxicity was moderate. Forty-two complete responses were achieved. At two years actuarial local control, cause-specific survival and overall survival are respectively 85%, 69%, and 68%. At four years estimated probabilities of local control, cause-specific survival and overall survival are also 85%, 69%, and 68%. CONCLUSIONS: These results compare favorably with those of most reported studies. The addition of carbogen breathing appears to improve the results of chemoradiation alone. Erythropoietin therapy avoided transfusions.

Administration, Inhalation↗

PubMed2001

The management of melanoma and nonmelanoma skin cancer: a review for the primary care physician.

In the United States, the incidence of skin cancer is greater than that of all other cancers combined, and early diagnosis can be lifesaving. A substantial public health concern, skin cancer is increasingly being diagnosed and managed by primary care physicians. Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) (known collectively as nonmelanoma skin cancer) and malignant melanoma are the most common cutaneous malignancies. Shave biopsy is usually performed if BCC is suspected; punch biopsy is preferred if SCC is thought to be present. The choice of biopsy techniques depends on the presumed depth of the lesion. Treatment has 3 goals: complete eradication of the cancer and preservation or restoration of normal function and cosmesis. Risk of recurrence or metastasis determines whether the tumor is high risk or low risk. Based on the level of risk, treatment options are considered, including whether the patient can be treated by a primary care physician or should be referred to a dermatologist. Choice of treatment approach depends on the tumor's location, size, borders, and growth rate. The standard treatment approaches are superficial ablative techniques (electro-desiccation and curettage and cryotherapy) used primarily for low-risk tumors and full-thickness techniques (Mohs micrographic surgery, excisional surgery, and radiotherapy) used to treat high-risk tumors. Removal of the entire tumor is essential to limit and prevent tumor recurrence.

Aftercare↗

PubMed1999

New black blood pulse sequence for studies of the heart.

The black blood concept is based on the signal void principle of the sequences in Spin Echo, SE or FSE, which are very useful for studying the mediastinum and heart. In this setting, new sequences are continuously introduced to eliminate the artifacts caused by breathing and heart movements. One such sequence is the Double-IR preparation Black Blood FSE. We report our experience in 97 patients, using this new pulse sequence to evaluate cardiac pathology, and establish comparisons with the conventional Spin Echo sequences. The study comprises mediastinal disease and aorta and heart explorations. We consider this new Double-IR preparation FSE sequence to be an excellent choice for evaluating chest, mediastinal and cardiac images. The sequence offers improved spatial resolution of both the vessels and other chest structures with respect to conventional Spin Echo imaging. With the exception of patients presenting severe heart problems, or in the presence of intense bradycardia, the required 16 cycles in apnea are well tolerated. The purpose of the present study is to present our initial results with this new pulse sequence as applied to cardiac pathology, in comparison with conventional Spin Echo imaging.

Aortic Diseases↗

PubMed1999

Control of severe hyperbilirubinemia in full-term newborns with the inhibitor of bilirubin production Sn-mesoporphyrin.

OBJECTIVE: To assess the efficacy of Sn-mesoporphyrin (SnMP), a potent inhibitor of bilirubin production, in: a) moderating the need for phototherapy (PT) in full-term breastfed infants with plasma bilirubin concentrations (PBC) of >/=256.5 micromol/L and </=307.8 micromol/L (>/=15 mg/dL and </=18 mg/dL, respectively) that were reached between >/=48 and </=96 hours of age; b) diminishing the time required for the PBC to decline to </=222.3 micromol/L (</=13 mg/dL) (closure of the case); c) decreasing the number of bilirubin determinations required for monitoring hyperbilirubinemia. STUDY PARTICIPANTS: Healthy full-term breastfed infants with a PBC between >/=256.5 micromol/L and </=307.8 micromol/L (>/=15 mg/dL and </=18 mg/dL, respectively) reached between 48 to 96 hours of age. DESIGN/METHODS: After obtaining informed consent from the parents, infants were randomized to either the SnMP (6.0 micromol/kg birth weight, single dose, intramuscular) group or the control group. The infants' PBCs were followed by daily measurements either in the hospital or at discharge as outpatients until the hyperbilirubinemia had subsided (PBC </=222.3 micromol/L [13mg/dL]). The total number of newborns enrolled in the study was 84; the SnMP group comprised 40 infants; the control group comprised 44 infants. The groups were similar in sex ratio, birth weight, gestational age, PBC, and age at enrollment. All infants were breastfed. Phototherapy was initiated at a PBC of 333.5 micromol/dL (19.5 mg/dL). RESULTS: SnMP entirely eliminated the need for supplemental PT to control hyperbilirubinemia; in contrast, of the 44 control infants, 12 required treatment with PT (27%) when their PBC reached or exceeded the level (333.5 micromol/dL; 19.5 mg/dL) at which time the use of PT was dictated by hospital guidelines. None of the 40 SnMP-treated infants reached a PBC of 19.5 mg/dL. SnMP also markedly diminished the median hours to case closure (SnMP: median, 86.5 hours; minimum/maximum, 24/216 hours; controls: median, 120 hours; minimum/maximum, 72/336 hours); and significantly reduced the number of bilirubin determinations required for clinical monitoring of the infants (SnMP: median, 3; minimum/maximum, 1/9; controls: median, 5; minimum/maximum, 3/11). No adverse effects of SnMP use were observed. CONCLUSION: A single dose of SnMP proved effective in controlling severe hyperbilirubinemia in full-term breastfed newborns with high bilirubin levels between 48 and 96 hours. In addition, SnMP eliminated the need for PT and reduced the use of medical resources in the clinical treatment of this problem as well as the related, important and painful, emotional costs for both mothers and infants.

Bilirubin↗

PubMed1998

Chemotherapy as a part of each treatment fraction in a twice-a-day hyperfractionated schedule: a new chemoradiotherapy approach for advanced head and neck cancer.

BACKGROUND: Using chemotherapy as a part of each treatment fraction remains unexplored. This study integrates the concomitant administration of carboplatin with hyperfractionated irradiation by optimizing chemopotentiation through carboplatin administration with each irradiation fraction. METHODS: From February 1993 to August 1996, 52 patients with advanced head and neck cancer were treated on a twice-a-day chemoradiotherapy schedule. Each fraction consisted of 115 cGy preceded by 5 mg/m2 of carboplatin. Treatment was given 5 days a week up to total doses of 350 mg/m2 of carboplatin + 8050 cGy in 7 weeks. RESULTS: All (100%) of patients tolerated the treatment (83% as scheduled). Acute and late toxicities were moderate. Rates of 96% complete response (CR) and 4% partial response (PR) were achieved. At 52 months, local control and cause-specific survival rates are 72% and 59%, respectively. Nodal control rate is 95%. CONCLUSION: These results show potential for improvement upon hyperfractionated radiotherapy alone and compare favorably with those of most reported trials.

Adult↗

PubMed1998

Aortico-right ventricular tunnel.

A successful operation on an infant with a tunnel through which the aorta communicated with the right ventricle is reported. The diagnosis was suspected preoperatively on the basis of two-dimensional Doppler color echocardiography and confirmed by cardiac catheterization. The aortico-right ventricular tunnel originated independently from the left coronary ostium and above the sinus of Valsalva. Patch closure from inside the tunnel under deep hypothermia was successfully performed. Follow-up is satisfactory 5 years later.

Aorta↗

PubMed1998

Obligatory steps in protein folding and the conformational diversity of the transition state.

We have analyzed the existence of obligatory steps in the folding reaction of the alpha-spectrin SH3 domain by mutating Asp 48 (D48G), which is at position i+3 of an isolated two-residue type II' beta-turn. Calorimetry and X-ray analysis show an entropic stabilizing effect resulting from local changes at the dihedral angles of the beta-turn. Kinetic analysis of D48G shows that this beta-turn is fully formed in the transition state, while there is no evidence of its formation in an isolated fragment. Introduction of several mutations in the D48G protein reveals that the local stabilization has not significantly altered the transition state ensemble. All these results, together with previous analysis of other alpha-spectrin and src SH3 mutants, indicate that: (i) in the folding reaction there could be obligatory steps which are not necessarily part of the folding nucleus; (ii) transition state ensembles in beta-sheet proteins could be quite defined and conformationally restricted ('mechanic folding nucleus'); and (iii) transition state ensembles in some proteins could be evolutionarily conserved.

Amino Acid Sequence↗

PubMed1998

Immunohistochemical expression of mdm2 and p21WAF1 in invasive cervical cancer: correlation with p53 protein and high risk HPV infection.

AIM: To investigate the immunocytochemical staining pattern of mdm2 and p21WAF1 proteins in invasive cervical cancer and to determine its relation with the expression of p53 and with the high risk HPV infection. METHODS: Immunocytochemistry for p53, mdm2, and p21WAF1 was performed in 31 paraffin embedded sections of invasive cervical cancer. The results were assessed by image analysis, evaluating for each protein the optical density of the immunostained area, scored as percentage of the total nuclear area. The presence of high risk human papillomavirus (HPV) infection was detected by using the polymerase chain reaction. RESULTS: Immunostaining for both mdm2 and p21WAF1 was correlated with p53 expression; however, the correlation between p53 and mdm2 (R = 0.49; p < 0.01) was more significant than between p53 and p21WAF1 (R = 0.31; p < 0.05); the less stringent correlation between p53 and p21WAF1 might reflect the p53 independent mechanisms of p21WAF1 induction. Similar average levels of p53, mdm2, and p21WAF1 immunostaining were found in the presence or absence of high risk HPV-DNA, without significant differences between the two groups. CONCLUSIONS: These data suggest that mdm2 and p21WAF1 proteins are expressed in invasive cervical cancer and that their immunocytochemical staining pattern is not abrogated by the presence of high risk HPV genomic sequences.

Carcinoma, Squamous Cell↗

PubMed1997

Expression of p21WAF1/CIP1 in fetal and adult tissues: simultaneous analysis with Ki67 and p53.

AIMS: To determine the expression of p21WAF1/CIP1 in relation to the expression of Ki67 and p53 in various normal adult and fetal tissues, and to investigate its distribution throughout the cell cycle. METHODS: The expression of p21WAF1/CIP1 in relation to Ki67 and p53 was analysed in adult and fetal tissues using immunohistochemical techniques. Heat induced epitope retrieval techniques were used to characterise the presence of p21WAF1/CIP1 in different tissues, as well as to detect its distribution throughout the cell cycle. In addition, flow cytometry and western blotting were used to test whether the level of p21WAF1/CIP1 expression varied at different phases of the cell cycle in phytohaemagglutinin (PHA) stimulated lymphocytes. RESULTS: p21WAF1/CIP1 expression varied from one tissue to another, and it was restricted mainly to the squamous and glandular epithelium, where it appeared in association with p53. Human tissues in which p21WAF1/CIP1 was found showed a mutually exclusive topographical sequential expression between p21WAF1/CIP1 and Ki67. This was confirmed by double labelling studies, which showed that p21WAF1/CIP1 positive cells were in the G0 phase. Unlike these findings of a decline in p21WAF1/CIP1 expression after the G0 phase, PHA stimulated lymphocytes showed a level of p21WAF1/CIP1 expression that rose as the cell progressed through the cell cycle. CONCLUSIONS: The analysis of p21WAF1/CIP1 expression in relation to the status of p53 should take into account the existence of variable p21WAF1/CIP1 expression in different tissues. This could provide an explanation for the varying frequency of p53 mutations in tumours of different cellular origin. In tissues characterised by regular p21WAF1/CIP1 expression, it appears in a pattern that is consistent with the proposed role of this inhibitor of cyclin dependent kinases in cell cycle arrest-that of inducing cell differentiation. The conflicting results of in vivo and in vitro studies could support the hypothesis that microenvironmental conditions may influence the location of p21WAF1/CIP1 in different phases of the cell cycle.

Adult↗

PubMed1997

Microvessel density, p53 overexpression, and apoptosis in invasive breast carcinoma.

AIM: To investigate the possibility of a correlation among microvessel density, p53 overexpression, and apoptosis in invasive breast carcinoma. METHODS: Microvessel density was analysed in 105 cases of invasive breast carcinoma by immunohistology using antifactor VIII related antibody. The results were correlated with the immunohistochemical expression of p53 and the apoptotic index, detected using the in situ end labelling of fragmented DNA method (TUNEL). Assessment was made with a CAS 200 image analyser. All these studies were performed on formalin fixed, paraffin wax embedded tissue sections of tumour samples. RESULTS: The mean (SD) microvessel count was 47.2 (51.1), with a range from 7 to 250. Thirty five (33%) carcinomas showed overexpression of p53 protein. The apoptotic index of tumours ranged from 0.0 to 28.0, with a mean (SD) of 1.7 (3.2). The results showed that there was a significant inverse correlation between microvessel density and p53 expression (p = 0.04; odds ratio, 0.37). In contrast, no correlation was identified between the microvessel density and apoptotic index. CONCLUSIONS: These results suggest that in invasive breast carcinoma the p53 overexpression phenotype downregulates tumour neoangiogenesis, as does the wild-type of p53 protein. In addition, they suggest that apoptosis and neoangiogenesis in these tumours are independent processes.

Analysis of Variance↗

PubMed1995

MDM2 expression in lymphoid cells and reactive and neoplastic lymphoid tissue. Comparative study with p53 expression.

MDM2 and p53 immunohistochemical protein expression was analysed in lymphocytes and in reactive and neoplastic lymphoid tissue. Phytohaemagglutinin (PHA)-stimulated lymphocytes displayed MDM2 and p53 co-expression. In 8 of 8 tonsils, 24 of 24 Hodgkin's disease (HD), and 10 of 24 high-grade non-Hodgkin's lymphoma (HG-NHL) specimens, MDM2 paralleled p53 nuclear expression in non-tumour and tumour cells. The number of positive cells was greater and the staining intensity was stronger for p53 than for MDM2. In another nine of the 24 HG-NHL cases studied, dissociated expression was observed, with high p53 expression and very low or absent MDM2 expression. In five cases, both MDM2 and p53 were negative. The eight low-grade NHL (LG-NHL) cases were also MDM2- and p53-negative. MDM2 and p53 expression in PHA-activated lymphocytes and reactive lymphoid tissue is probably an expression of opposing biological signals regulating cell proliferation. Parallel MDM2 and p53 expression in all HD and in 10 out of 24 HG/NHL cases may indicate that this growth suppressive pathway is maintained in those cases. However, dissociated MDM2/p53 expression (nine cases) and the absence of expression of both proteins (five cases) may represent examples of deregulation of this growth control pathway. These findings are in agreement with previous in vitro studies in cell lines regarding the role of MDM2/p53 lymphoid tissue, suggesting a possible role for MDM2 deregulation in lymphomagenesis.

Blotting, Western↗

PubMed1995

p53, Rb and bcl-2 expression during the cell cycle: a study in phytohaemagglutinin stimulated lymphocytes and microwave irradiated lymphoid tissue sections.

AIMS: To determine the expression of p53, Rb, and bcl-2 during the cell cycle in stimulated peripheral blood lymphocytes (PBLs) and microwave heated reactive lymphoid tissue sections. METHODS: The expression of p53, Rb and bcl-2 proteins in paraffin wax embedded tonsil tissue sections was detected by immunohistochemistry using an (APAAP) technique following microwave irradiation. Flow cytometric analysis as performed on phytohaemagglutinin (PHA) stimulated PBLs, with simultaneous S fraction determination. RESULTS: Expression of p53 protein was detected in reactive tonsil germinal centre cells, in some suprabasal cells in the surface and cryptic epithelium, and in some endothelial cells. Analysis of p53 in PHA stimulated PBLs revealed expression of p53 by non-tumoral activated lymphocytes. Rb protein expression was increased in PHA stimulated PBLs and was usually detected in most germinal centre B cells, in isolated paracortical cells, in a fraction of endothelial cells, and in most epithelial suprabasal cells. Expression of bcl-2 in stimulated lymphocytes was inversely correlated with proliferation. This confirms findings in reactive tonsil tissue samples, where proliferating cells located in the germinal centres and paracortical area are mostly bcl-2 negative. CONCLUSIONS: Expression of these three oncogenic and tumour suppressor proteins varies during the cell cycle in non-tumoral cells. Consequently, tumoral growth fraction must be taken into account when analysing dysregulation of these three genes in lymphomas and other tumours. The p53 protein may be detected in benign conditions, as its expression is not synonymous with malignancy or mutation of the p53 gene.

Cell Cycle↗

PubMed1995

Roles of hypomania and intelligence in antisocial practices when self-esteem and family problems are considered.

A sample of 71 nonpsychiatric adults, including 57 men and 14 women, completed the MMPI-2 and the Otis-Lennon Mental Ability Test. Preliminary support was found for the hypothesis that those who score high both on intelligence and hypomania would express the greatest tendency for antisocial behavior, However, this association occurred only when self-esteem and family problems were not controlled. Moreover, preliminary findings suggest that the interaction between intelligence and hypomania influences self-esteem which then determines antisocial behavior.

Adult↗

PubMed1995

p53 expression in non-Hodgkin's lymphomas: a marker of p53 inactivation?

The p53 gene located in the short arm of chromosome 17 at position 17p13, is involved in the negative regulation of cellular growth. p53 mutation seems to be the most frequent genetic alteration found in human cancer. Mutant conformation of the p53 gene is associated with cell proliferation and tumour progression, and in most cases implies p53 stabilization, which renders the p53 protein detectable through the use of immunohistochemical techniques. p53 expression is a frequent finding in high grade lymphomas of either B or T cell lineage, having been detected in 30% of cases in our series. The focal presence of p53+ cells was seen in a wide range of low and high grade lymphomas, including lymphadenitis and reactive tonsils. In 37.5% of cases this increased expression of p53 was secondary to mutation in highly conserved regions (exons 5-8). Unlike findings reported in other tumours, in lymphomas, p53 expression seems to be secondary to genetic alterations other than p53 mutation. Initial data suggest that the MDM2 protein could be involved in inactivating p53 protein in most of these cases. Finally, p53 expression has been found to be a poor prognostic marker in high grade B-cell lymphomas in a large series of cases. High p53 expression was associated with a short survival, this relation being stronger in cases with simultaneous bcl2 expression.

Gene Expression↗

PubMed1993

Thermodynamic analysis of the chemotactic protein from Escherichia coli, CheY.

CheY, the 129 amino acid chemotactic protein from Escherichia coli, is a good model for studies of folding of parallel alpha/beta proteins. We report here the thermodynamic characterization of the wild-type CheY at different pH values and in different buffers and denaturation conditions. The denaturation of CheY by urea monitored by circular dichroism and fluorescence fits the two-state unfolding model. The stability of the protein is ionic strength dependent, probably due to the presence of three Asp residues in very close proximity in its active site. The presence of a Mg2+ ion, which seems to interact with Asp 13 in the active site, stabilizes the native structure by up to 6.9 kJ mol-1. The CheY maximum stability (31.7 +/- 2.1 kJ mol-1), without magnesium, is reached at pH 5.1. Analysis of scanning calorimetry data has shown that temperature-induced unfolding of CheY is not a two-state process and proceeds through a highly populated intermediate state, corresponding to protein dimers, as was subsequently confirmed by direct cross-linking experiments. According to circular dichroism, fluorescence, nuclear magnetic resonance, and ANS binding experiments, this "intermediate dimer" at pH 2.5 exhibits all known characteristics of the "molten globule" state. The reversible dimerization of "molten globules" might explain such peculiarities as the increased stability or the cooperative unfolding found for the molten globule state of some proteins.

Anilino Naphthalenesulfonates↗

PubMed1993

The expression of p53 protein in non-Hodgkin's lymphomas is not always dependent on p53 gene mutations.

p53 overexpression has been found to be a fairly common feature in high grade lymphomas in the majority of tumoral cells. The results vary from series to series, from 25% to 33% of cases. To assess whether immunohistochemical positivity for p53 correlated with the presence of structural gene abnormalities, DNA from 16 non-Hodgkin's lymphomas with high and low p53 values was amplified and sequenced to determine the existence of point mutations in the highly conserved regions of the p53 gene. In the group of 8 cases containing high levels of protein, 3 cases showed missense point mutations at the codons mapping between exons 5 through 8. Of the 8 cases of tumors containing undetectable or low levels of p53 protein, 1 case presented a nonsense point mutation giving a stop codon. No missense mutations were detected in this group. The finding of p53 mutations in 4 of 16 cases confirms the presence of p53 gene mutations in high grade lymphomas distributed over different histologic groups. These include Burkitt's lymphoma, together with centroblastic, immunoblastic, and large cell lymphoma of mucosa origin. Nevertheless, the absence of mutations in 5 of the 8 cases that overexpressed p53 suggests that the nuclear or cytoplasmic stabilization of p53 protein could also depend on other factors. The absence of detectable levels of p53 protein cannot discount the existence of p53 mutations, as is shown by a case of Burkitt's lymphoma in which a nonsense mutation was detected. The impact of this range of p53 alterations on clinical course and treatment response of the patients deserves to be explored, in an attempt to differentiate the specific consequences of each one.

Base Sequence↗

PubMed1993

Hyperbilirubinemia in the breast-fed newborn: a controlled trial of four interventions.

A controlled clinical trial was conducted to compare the effect of four different interventions on hyperbilirubinemia in 125 full-term breast-fed infants. Of 1685 term infants who met the inclusion criteria, 126 (7.4%) had a serum bilirubin concentration > or = 291 mumol/L (17 mg/dL). When the bilirubin reached this level, babies were assigned at random to one of four interventions: (1) continue breast-feeding and observe; (2) discontinue breast-feeding, substitute formula; (3) discontinue breast-feeding, substitute formula and administer phototherapy; (4) continue breast-feeding, administer phototherapy. The serum bilirubin concentration reached 342 mumol/L (20 mg/dL) in 24% of infants in group 1, 19% in group 2, 3% in group 3, and 14% in group 4. When phototherapy was used, the decline in serum bilirubin was significantly larger and more rapid (compared with no phototherapy). In the majority of breast-fed infants whose serum bilirubin levels reach 291 mumol/L (17 mg/dL) the bilirubin will decline spontaneously and will not reach 342 mumol/L (20 mg/dL). If the infant is significantly jaundiced and a decision is made to intervene, parents can be given a number of options and can make an informed decision regarding which, if any, intervention they prefer.

Analysis of Variance↗

PubMed1992

P53 protein expression in lymphomas and reactive lymphoid tissue.

P53 is a tumour suppressor gene, located in the short arm of chromosome 17, which encodes for a nuclear protein involved in the control of cellular growth, regulating the entry of the cell into the S-phase. P53 mutations have been identified in a progressively increasing number of human malignancies. Nuclear p53 protein is usually present in non-tumour cells in minute concentrations, due to its short half-life. In contrast, tumours with p53 mRNA mutations show a higher nuclear protein concentration, detectable by immunohistological techniques, due to stabilization by complexing with other proteins such as heat-shock protein or wild-type p53 protein. Levels of nuclear p53 protein detected by immunohistochemistry with the monoclonal antibody PAb 1801 were measured with the aid of an image analysis system in 83 non-Hodgkin's lymphomas (NHLs) and 13 cases of Hodgkin's disease, as well as in 14 cases of normal thymus, reactive tonsils, and lymphadenitis. High levels of p53 protein (greater than 5 per cent of the cells) were present only in high-grade lymphomas (in the proportion 13/55), with a peak incidence in Burkitt's lymphoma (5/8 cases). Lower levels (less than 5 per cent) of p53 protein were detected in low-grade B- and T-cell lymphomas, as well as in most of the cases of Hodgkin's disease, where p53 protein was selectively present in Hodgkin and Reed-Sternberg cells. In 5/14 reactive tonsils or lymph nodes, occasional p53-positive cells were identified. These results suggest a relationship between levels of p53 protein and the aggressiveness of NHL.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗