Effect of kraft pulp inclusion in calf starter on performance, health, and plasma concentration of glucagon-like peptide 2 in calves.

Kraft pulp (KP), an intermediate product obtained when wood chips are converted to paper, contains highly digestible fiber. This study evaluated the effect of KP inclusion in calf starters on growth performance, health, and plasma glucagon-like peptide 2 (GLP-2) concentration in calves. Twenty-five Holstein heifer calves were raised on a high plane of nutrition program using milk replacer containing 29% crude protein and 18% fat until 49 d after birth, and were fed calf starters containing KP at 0 (CON; n = 14) or 12% (KPS; n = 11) on a dry matter basis. All calves were fed the treatment calf starters and timothy hay ad libitum. Blood was collected at 4, 14, 21, 35, 49, 70, and 91 d after birth. Dry matter intake (DMI) of milk replacer and hay was not affected by treatment, whereas calf starter DMI was lower for KPS (0.93 kg/d) than for CON (1.03 kg/d). Higher neutral detergent fiber (NDF) content in KPS (31.7%) than in the CON starter (22.1%) resulted in higher NDF intake for KPS (0.55 kg/d) than for CON (0.47 kg/d). However, the consumption of starch was lower for KPS (0.29 kg/d) than for CON (0.33 kg/d). Despite the lower starter intake for KPS, body weight and average daily gain did not differ between treatments. No significant difference was observed in the plasma concentrations of metabolites, except for ß-hydroxybutyrate (BHB); BHB concentration was lower for KPS (216 µmol/L) than for CON (257 µmol/L). The area under the curve for plasma GLP-2 concentration was higher for KPS (54.1 ng/mL × d) than for CON (36.0 ng/mL × d). Additionally, the fecal score postweaning (1.19 and 1.48 for KPS and CON, respectively) and the number of days that calves developed diarrhea throughout the experimental period (2.50 d and 8.10 d for KPS and CON, respectively) were lower for KPS than for CON. These results indicate that feeding KP reduces the severity and frequency of diarrhea without adversely affecting growth performance. This could be attributed to the increased plasma GLP-2 concentration induced by higher NDF intake.

Feasibility of cytological diagnosis of sarcoidosis with endobronchial US-guided transbronchial aspiration.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has a high diagnostic value in sarcoidosis if the obtained histological specimen is indicative of a non-caseating epithelioid-cell granuloma. However, EBUS-TBNA in sacoidosis sometimes affords solely cytological specimens. OBJECTIVE: To investigate the relevance of EBUS-TBNA cytology specimens in diagnosing sarcoidosis. DESIGN: The study population comprised 72 patients with sarcoidosis and 116 patients who had thoracic malignancies and intrathoracic lymphadenopathy but were eventually proven to be metastasis-free (controls). The EBUS-TBNA samples obtained for these subjects were blindly evaluated for the presence of epithelioid cell clusters by 2 independent cytoscreeners and a pathologist. RESULTS: Interobserver variability in the specimen grading was minimal. The sensitivity and specificity were 65.3% and 94.0%, respectively. The sensitivity was high, at 87.5%, for the combined cytological and histological examinations. Of 7 controls whose cytological specimens showed epithelioid cell clusters, 3 were also deemed positive for sarcoidosis on histological examination, which indicated that they had sarcoid reaction to cancer. CONCLUSIONS: Cytological evaluation of the EBUS-TBNA specimens had higher sensitivity than histological evaluation alone for intrathoracic lymphadenopathy due to sarcoidosis. It should be recognized, however, that up to 6% of patients with thoracic malignancy may have sarcoid reaction in non-metastatic lymph nodes.

Feasibility of combination chemotherapy with cisplatin and etoposide for haemodialysis patients with lung cancer.

Cancer chemotherapy for haemodialysis patients has never been established. To elucidate the feasibility of cisplatin-based combination chemotherapy for haemodialysis patients with lung cancer, a dose escalation study was conducted. Five haemodialysis patients with lung cancer were treated with cisplatin and etoposide. A starting dose of 40 mg m(-2) of cisplatin on day 1 and 50 mg m(-2) of etoposide on days 1, 3 and 5 were administered as the first course for the first patient. Membrane haemodialysis was regularly performed three times a week and soon after the completion of therapy. By monitoring toxicity and pharmacokinetics data, the dose was escalated course by course and patient by patient. Dose escalation was completed for the first two patients resulting in full-dose chemotherapy consisting of 80 mg m(-2) of cisplatin on day 1 and 100 mg m(-2) of etoposide on days 1, 3 and 5. Multiple courses of the full-dose chemotherapy were administered to the other three patients. Toxicity was manageable and tolerable for all. Pharmacokinetics data were comparable to those from patients with normal renal function, except for potential long-lasting higher levels of free platinum in the renal insufficiency group. In conclusion, this standard-dose combination chemotherapy was feasible even for haemodialysis patients.

Direct-antiglobulin-test-negative immune haemolytic anaemia and thrombocytopenia in a patient with Hodgkin's disease.

A case of direct-antiglobulin-test (DAT)-negative auto-immune haemolytic anaemia (AIHA) and immune thrombocytopenia (ITP) associated with Hodgkin's disease (HD) is reported. A 52-year-old male was admitted with anaemia, thrombocytopenia, and lymphadenopathy. The patient was DAT negative, although he exhibited the clinical features of warm-type AIHA and elevated levels of red-blood-cell-associated IgG (RBC-IgG). The serum level of platelet-associated IgG (PA-IgG) was markedly increased. A biopsy specimen of the inguinal lymph nodes showed HD of mixed cellularity. Marked improvement of subjective symptoms, normalization of haematological values and a decrease in the level of both RBC- and PA-IgG were observed after the start of combination chemotherapy for HD. Although the association of HD, ITP, and/or AIHA has been infrequently reported, the measurement of RBC-IgG is recommended in cases of HD with anaemia even though DAT is negative, since HD is known to be associated with various protean immunological abnormalities.

Hepatic histopathologic range compared with virological studies of hepatitis viruses among autopsy cases in Tokyo.

Few reports exist comparing virological studies on hepatitis viruses with histopathological studies of autopsy cases other than those of liver clinics. Relations between hepatitis virus-related markers and hepatic histopathology were studied in 1044 autopsy cases (779 men and 265 women) at the Medical Examiner's Office, Tokyo. Heart blood was obtained at the autopsy, and the sera were submitted for virus-marker detection of HBV, HCV, and HGV/GBV-C. Hematoxylin and eosin-stained paraffin sections were used for histological assessment. Histopathologically, 463 cases were determined as so-called normal liver; among them 440 cases (95.0%) were negative for all hepatitis virus-related markers, but HBV-DNA was positive in 13 cases, three cases were positive for HCV-RNA (indicating a healthy carrier rate of HCV-RNA of 4.1%), and seven cases were positive for HGV/GBV-C RNA. The incidence of these three virus-related markers was low in cases with fatty liver and micronodular cirrhosis, but in cases with chronic hepatitis, macronodular cirrhosis and hepatocellular carcinoma, the incidence of HBV-DNA and HCV-RNA increased with advancing disease. A positive rate of anti-HBs or anti-HBc (HBV-Ab) or both was found between 30 and 50% in all histopathological groups, and no noticeable relations between the positive rate and microscopical changes were detected. The presence of HGV/GBV-C RNA seemed to be unrelated to hepatic inflammation or generalized inflammatory changes or both occurring together. The decadal age incidence of the virus-related markers and their incidence in various hepatic diseases are also reported.

Liver weight of adult Japanese, especially recent weight values.

Cases of 445 adult Japanese autopsies of the Tokyo Metropolitan Medical Examiner's Office were used in this study. They were either negative for all hepatitis virus-related markers examined or had little or no histopathological hepatic changes. The maximum liver weight was observed in the fifth decade in both sexes, and after the fifth decade the liver weight decreased markedly with increasing age. The sexual difference in the liver weight was most predominant in the third to fifth decades, but the sexual difference was not marked in the older age groups. The highest liver weight to body weight ratio was observed in the fifth decade of both sexes, and a total decadal pattern of the ratio was similar to a parabola. An interesting finding was that the male liver weights in the third to fifth decades considerably increased in recent years, but the female liver weights in the third decade were almost the same despite the difference in investigation period. We suggest the data of this study may be a standard for Japanese people.

Aberrant expression of immunoglobulin heavy chain genes in Epstein-Barr virus-negative, human immunodeficiency virus-related lymphoid interstitial pneumonia.

The two-step polymerase chain reaction (PCR) and sequencing analysis was used to analyze the immunoglobulin heavy chain variable (Ig V(H)) genes of open-chest biopsy or autopsy samples from five patients with Epstein-Barr virus-negative human immunodeficiency virus (HIV)-related lymphoid interstitial pneumonia (LIP), and the results were compared with those for Ig V(H) genes from five HIV-negative LIP patients. The findings of this study are consistent with the different immunological situations of HIV-related and HIV-negative LIP. (a) The Ig V(H)3 subgroup was underexpressed in three of five cases of HIV-related LIP. In contrast, none of the HIV-negative cases showed this abnormality. Because the Ig V(H)3 subgroup encodes the largest portion of Ig V(H) genes, a depletion of B cells expressing Ig V(H)3 genes reflects a major alteration in the B-cell compartment. (b) All HIV-related LIP cases demonstrated two or three oligoclonal populations. HIV-negative cases showed minor monoclonal or polyclonal populations, but not oligoclonal ones. These oligoclonal populations suggest the coexistence of several occult clonal B-cell populations in HIV-related LIP. (c) Some oligoclonal clones in HIV-related LIP showed mutated framework regions not demonstrated in HIV-negative clones. This degree of variation exceeds the usual mutation rate for frameworks, suggesting a role for framework residues in antigen binding. (d) The frequency of D-D fusions of minor oligoclonal clones (HIV-related LIP) is higher than that of minor monoclonal clones (HIV-negative LIP). Such D-D fusions may enhance the probability of expression of antibodies capable of binding HIV glycoproteins.

CDR3 sequences of MALT lymphoma show homology with those of autoreactive B-cell lines.

We have examined the CDR3 sequence and adjacent regions of immunoglobulin genes from B-cell lymphoma of mucosa-associated lymphoid tissue (MALT). Twenty-nine sequences (15 sequences from 13 low-grade MALT lymphomas, marginal zone B-cell lymphomas; 7 sequences from 6 high-grade MALT lymphomas; 7 sequences from 7 diffuse large cell lymphomas) were obtained after cloning of the polymerase chain reaction-amplified segments. In the low-grade MALT, high-grade MALT and diffuse large cell lymphomas, the mean length of the CDR3 region was 47.6+/-10.31 (range 21 to 60), 38.71+/-10.37 (range 27 to 57) and 40.86+/-3.34 (range 39 to 48) nucleotides, respectively. The length of the CDR3 region was significantly greater in the low-grade MALT lymphoma group than in the other two groups. CDR3 sequences in lymphoma cell clones of 14 cases showed 60 to 81% homology with autoantibody-associated lymphocyte clones including rheumatoid factor. The incidences of these autoantibody-associated lymphocyte clones were higher in the high-grade MALT (4/6) and diffuse large lymphomas (5/7) than in the low-grade MALT lymphoma (5/13). Cases with more than 70% homology at the nucleotide level were found to have 71 to 82% homology with autoantibodies at the protein level in the low-grade MALT lymphomas (2/13), and 67% homology in the high-grade MALT lymphomas (2/7). These results indicate that MALT lymphomas may be derived from the malignant transformation of autoreactive B-cells.

Low-grade pulmonary mucosa-associated lymphoid tissue lymphoma with or without intraclonal variation.

We examined the immunoglobulin heavy chain variable (Ig VH) region genes of 11 low-grade pulmonary mucosa-associated lymphoid tissue (MALT) lymphomas by a two-step polymerase chain reaction (PCR) and sequencing analysis. We observed frequent somatic mutations with the positive selective pressure of the rearranged Ig VH genes in all cases, indicative of postgerminal center cell origin. Eight cases demonstrated intraclonal variations (hypermutation with intraclonal variation type), but the other cases showed only one major clone without intraclonal heterogeneity (hypermutation without intraclonal variation type). The former might reflect the reentry of marginal zone B cells into a germinal center environment leading to further mutations. The latter might be no longer susceptible to hypermutation mechanisms and seemed to be stable. Four cases used Ig VH genes (hv3019b9, VH26, and VH4.21), which are frequently found in a variety of autoantibodies, such as cold agglutinins, rheumatoid factors, and anti-DNA antibodies.

Type I interferon induces inhibitory 16-kD CCAAT/ enhancer binding protein (C/EBP)beta, repressing the HIV-1 long terminal repeat in macrophages: pulmonary tuberculosis alters C/EBP expression, enhancing HIV-1 replication.

We have previously observed that HIV-1 replication is suppressed in uninflamed lung and increased during tuberculosis. In vitro THP-1 cell-derived macrophages inhibited HIV-1 replication after infection with Mycobacterium tuberculosis. Suppression of HIV-1 replication was associated with inhibition of the HIV-1 long terminal repeat (LTR) and induction of ISGF-3, a type I interferon (IFN)-specific transcription factor. Repression of the HIV-1 LTR required intact CCAAT/enhancer binding protein (C/EBP) sites. THP-1 cell-derived macrophages infected with M. tuberculosis, lipopolysaccharide, or IFN-beta induced the 16-kD inhibitory C/EBPbeta isoform and coincidentally repressed HIV-1 LTR transcription. C/EBPbeta was the predominant C/EBP family member produced in THP-1 macrophages during HIV-1 LTR repression. In vivo, alveolar macrophages from uninflamed lung strongly expressed inhibitory 16-kD C/EBPbeta, but pulmonary tuberculosis abolished inhibitory C/EBPbeta expression and induced a novel C/EBP DNA binding protein. Therefore, in vitro, proinflammatory stimulation produces an IFN response inhibiting viral replication by induction of a C/EBPbeta transcriptional repressor. THP-1 cell-derived macrophages stimulated with type I IFN are similar to alveolar macrophages in the uninflamed lung in vivo. In contrast, the cellular immune response in active pulmonary tuberculosis disrupts this innate immunity, switching C/EBP expression and allowing high level viral replication.

[A case of marginal zone B-cell lymphoma].

A 60-year-old woman had an abnormal shadow in the right lower lung field on chest roentgenogram. Transbronchial lung biopsy revealed findings consistent with malignant lymphoma, and a right middle lobectomy was performed. Pathological findings showed that tumor cells had infiltrated the epithelium, forming so-called lymphoepithelial lesions. Flow cytometric analysis of the resected specimen revealed that B-cell associated antigens (CD 19, 20) were expressed, and that the tumor cells were CD 5-, CD 10-. A marked increase in the number of lymphocytes with an IgM kappa component suggested monoclonal origin for the tumor cells in the resected specimen. Southern blot analysis showed clonal rearrangement of the heavy chain of the immunoglobulin gene. A diagnosis of malignant lymphoma of bronchus-associated lymphoid tissue was made. This tumor was defined according to the revised European. American classification of lymphoid neoplasms as a marginal zone B-cell lymphoma.

Alleviation of monocrotaline-induced pulmonary hypertension by antibodies to monocyte chemotactic and activating factor/monocyte chemoattractant protein-1.

Administration of monocrotaline (MCT) causes pulmonary vascular lesions consisting of monocyte/macrophage infiltration in the early phase and medial thickening in pulmonary arteries and arterioles associated with pulmonary hypertension (PH) in the later phase. However, the molecular mechanism of monocyte/macrophage infiltration and its roles remain elusive. Herein, we have evaluated the role of a potent monocyte chemotactic and activating chemokine/monocyte chemoattractant protein-1 (MCAF/MCP-1) in MCT-induced PH in rats. A single injection of MCT induced PH at Day 21, as evidenced by increases in the ratio of right ventricular to left ventricular and septum weights (RV/LV+S) and right ventricular systolic pressure (RVSP). A significant increase in macrophage number in lungs started at Day 14, reaching a maximum at Day 21. MCAF/MCP-1 levels in bronchoalveolar lavage fluids were elevated significantly at Day 14 and remained high until Day 28, whereas plasma MCAF/MCP-1 levels increased at Day 7, returning to normal levels by Day 21. Immunoreactive MCAF/MCP-1 proteins were mainly detected in macrophages in alveoli and in perivascular regions of pulmonary arterioles and venules. Intravenous administration of anti-MCAF/MCP-1 antibodies with MCT significantly decreased macrophage infiltration and eventually reduced the increases in RV/LV+S and RVSP, as well as medial thickening of pulmonary arterioles. Thus, MCAF/MCP-1 is essentially involved in MCT-induced PH by recruiting and activating macrophages.

A particular characteristic of IgH complementarity-determining region 3 suggests autoreactive B-cell origin of primary gastric B-cell lymphomas.

To clarify the origin of tumor cells and the possible role of antigen in the pathogenesis of mucosa-associated lymphoid tissue (MALT) lymphoma, we analyzed the third complementarity determining region of IgH gene in nine primary gastric B-cell lymphomas by PCR. The presence of vacA gene of Helicobacter pylori was also determined. These cases were diagnosed histopathologically as three low (extranodal marginal zone B-cell lymphoma)- and three high-grade MALT lymphomas and three diffuse large-cell lymphomas without evidence of MALT lymphoma. All cases showed a monoclonally rearranged JH band. A single dominant clone was detected by sequencing the IgH CDR3 regions in eight cases. In the remaining cases. In the remaining case, two major sequences were identified. Complementarity-determining region 3 (CDR3) sequences in lymphoma cell clones of seven cases showed 61% to 81% homology with autoantibody-associated lymphocyte clones including rheumatoid factor. The N-D-N region in the low-grade MALT lymphoma group was significantly longer than in the high-grade lymphoma groups. Although vacA gene of H. pylori was detected in five of nine cases, all lymphoma cell clones showed no association with foreign antigen. These results indicate that autoantigen may be responsible for the clonal selection of lymphoma cells, and thus autoimmunity may play a role in the pathogenesis of primary gastric B-cell lymphomas.

Third complementarity-determining-region sequence analysis of lymphocytic interstitial pneumonia: most cases demonstrate a minor monoclonal population hidden among normal lymphocyte clones.

We analyzed the third complementarity-determining region (CDR3) of the immunoglobulin heavy chain (IgH) gene in five patients with lymphoid interstitial pneumonia (LIP) through a two-step polymerase chain reaction (PCR) and sequencing analysis. By sequencing analysis of the PCR products, morphologic LIP could be divided into two groups: a polyclonal type and a minor monoclonal type. Because of their high frequencies, minor monoclonal clones seemed to be neoplastic clones hidden in normally reactive lymphocyte clones. Consequently, only the polyclonal type might have represented true LIP. Sequencing of the PCR products from open-chest biopsy and transbronchial lung biopsy (TBLB) specimens obtained 8 yr later in one patient with minor monoclonal type LIP confirmed this possibility. In true LIP, six of 20 lymphocyte clones showed 67 to 86% homology with lymphocyte clones derived from fetal tissue. In three of these six clones, the D-region (N-D-N) lengths were very short, whereas four clones showed a high homology with autoreactive lymphocytes (rheumatoid factor, anti-DNA antibody, and G6-positive lymphocytes). Since rheumatoid factors, anti-DNA antibodies, and G6 are autoreactive antibodies, immature B cells stimulated by autoantigens might play some role in the pathogenesis of true LIP.

Intranasal administration of midazolam: pharmacokinetic and pharmacodynamic properties and sedative potential.

This study investigated the pharmacodynamic effects and sedative potential of midazolam administered by the intranasal route to adult volunteers. A double-blind, randomized, controlled study was carried out on seventeen healthy, male volunteers to study plasma level changes, sedative effects and variations in vital signs following intranasal administration of 0.2 mg/kg and 0.3 mg/kg doses of midazolam. Eight subjects received 0.2 mg/kg midazolam, seven received 0.3 mg/kg. Each subject rested for 15-20 minutes after placement of vital sign monitors and venipuncture needles before administration of midazolam. Behavior during the rest period was designated as the control so that each subject acted as his own control. Each subject's behavior was assessed on a scale of 1 (asleep) to 8 (excited). Plasma concentrations of midazolam were analyzed using venous blood samples from each of three randomly selected subjects for each of the two doses. Vital signs, monitored continuously, included electrocardiogram, heart rate, blood pressure, respiratory rate and oxygen saturation (SPO2). Plasma concentration of midazolam in both groups maintained adequate sedation levels with each group sustaining favorable sedation conditions from 15-20 minutes to 55-60 minutes. Individual variations of midazolam plasma concentration within the 0.3 mg/kg group were greater than those of the 0.2 mg/kg group. Normal vital sign variations due to the nasal instillation of midazolam were observed in both groups. Some minor respiratory depression was observed in the 0.2 mg/kg group. One instance of severe respiratory depression was observed in the higher dose group. Although both doses of midazolam were effective, no benefit was observed using a dose of 0.3 mg/kg. Indeed, a 0.3 mg/kg intranasal dose of midazolam may actually produce severe respiratory depression.

Reappraisal of the relationship between immunoglobulin heavy chain gene rearrangement and Epstein-Barr virus infection in Reed-Sternberg cells of Hodgkin's disease.

We investigated 44 cases of Hodgkin's disease for Epstein-Barr virus genome with EBER-1 in situ hybridization. Twenty of 44 (45.5%) were positive for EBV. Simultaneously, immunoglobulin gene rearrangements were assessed in 32 of these 44 cases with PCR on DNA extracted from Reed-Sternberg cell (RS-cell) -rich areas microdissected from paraffin sections. Clonally rearranged immunoglobulin (IgH) gene was observed in 15 cases (46.9%). EBV-negative cases showed more frequent IgH rearrangement than EBV-positive cases (10 and 5 cases, respectively). In 9 cases, the RS cells were CD20-positive immunohistochemically and these were all EBV negative and the IgH gene was rearranged in all except one. These findings may suggest that EBV infection has occurred before the immunoglobulin gene rearrangement or that EBV infection has influenced the rearrangement of the immunoglobulin gene. The results may also hint towards the obscure B-cell nature of the RS cells.

Damage to the primary dentition resulting from thumb and finger (digit) sucking.

It is estimated that approximately 50 percent of infants at one year of age suck a thumb or finger. The number decreases rapidly by ages four to five years. The average age for spontaneous cessation of the habit is 3.8 years of age. Anterior open bite is the most frequent malocclusion reported with digit sucking. In this study the authors investigated the influence of thumb and finger-sucking in the anterior and posterior sections of the primary dentition in three age-groups: three, four, and five years. The study population included 930 subjects. Data for the non-oral-habit group were compared with the data for the thumb and/ or finger-sucking group. At all ages the frequencies of open-bite and maxillary protrusion for the thumb and finger-sucking group were higher than the non-oral-habit group. The frequencies did not appear age-related. There appeared to be an increased tendency to a permanent malocclusion in children who continued after four years of age.

Monoclonality of B-cell lineage in primary pulmonary lymphoma demonstrated by immunoglobulin heavy chain gene sequence analysis of histologically non-definitive transbronchial biopsy specimens.

Immunoglobulin heavy chain (IgH) gene rearrangements were amplified in transbronchial lung biopsy (TBLB) specimens taken from five patients with primary lymphoma of the lung in whom the diagnosis was established by surgical specimens. By histopathological analysis of TBLB specimens, only two of the five cases were diagnosed as lymphoma, the other three cases being classified as equivocal due mainly to low levels of cellular atypia and to artefactual distortion. All five TBLB specimens, as well as the subsequent surgical specimens, showed a sharp monoclonal band of IgH gene rearrangement on electrophoresis of polymerase chain reaction (PCR) products. By contrast, three surgical biopsy specimens from cases of lymphoid interstitial pneumonia (LIP) showed smear polyclonal bands. No clonal rearrangements were detected in six non-neoplastic controls, including five cases of chronic bronchitis and one of sarcoidosis. The PCR products of three of the lymphoma cases were sequenced from both TBLB and surgical specimens. In all three cases, there was dominant expression of a particular rearrangement, assumed to be tumour-derived. In each case, the major clones derived from the TBLB and the surgical specimen were identical. In both lymphoma and LIP cases, more frequent usages of JH4 and JH6 were evident. The diagnosis of lymphoma can be confirmed on TBLB specimens by use of this technique.

Third complementarity determining region sequence analysis of low-grade bronchus-associated lymphoid tissue lymphoma: genotypic analysis reveals heterogeneity in maturation.

It has recently been suggested that autoimmunity may play a role in the pathogenesis of low-grade mucosa-associated lymphoid tissue lymphomas, but precise genotypic analysis of antigen binding sites of low-grade bronchus-associated lymphoid tissue (BALT) lymphomas has not been reported. We analyzed the third complementarity determining region (CDR3) in eight cases of low-grade BALT lymphoma by 2-step PCR and sequencing analysis. All cases showed a distinct monoclonal band (about 100 base pairs) on electrophoresis. In seven cases, a single major CDR3 sequence was identified with five to nine clones among 10 vector clones being identical; and in the remaining case, two major sequences were obtained, with four clones among nine vector clones being identical. Findings suggestive of the autoimmunity of low-grade BALT lymphoma were obtained: (1) VHDJH rearrangements in seven of the eight lymphoma cell clones were potentially functional; (2) genotypically, two lymphoma cell clones showed 60 to 74% homology with G6 positive lymphocyte clones; and (3) five lymphoma cell clones showed 61 to 71 % homology with lymphocyte clones derived from fetal liver or cord blood. In one case, the N-D-N length of the neoplastic clone was very short and lacked N nucleotides at the D-JH junction. Therefore, our study demonstrates genotypic heterogeneity in maturation in low-grade BALT lymphoma.