Estimating the sensitivity and specificity of matching name-based with non-name-based case registries.

Because non-name-based case registries have recently been used for reporting human immunodeficiency virus infection, this study attempted to define the sensitivity, specificity and accuracy of case registry matches using non-name-based registries. The AIDS, sexually transmitted disease (STD), and tuberculosis (TB) case registries were matched using all available information to establish the standard. The registries were then matched again using five increasingly less specific criteria to compare sensitivity, specificity and accuracy. The registries were then also transformed into non-name-based codes as if they were the HIV registry and matched again. With name-based registries, sensitivities increased as the matching criteria became less exacting, while the accuracy declined slightly. Specificities remained close to 100% due to the relatively small number of matched cases. Results from matches of non-name-based registry matches were similar to those of the name-based registry matches. Non-name reporting can be used for data matching with acceptable accuracy.

Non-Hodgkin's lymphoma in women with breast cancer.

PURPOSE: The purpose of this study was to describe a series of patients with breast cancer and non-Hodgkin's lymphoma and to determine the usual sequence of the diagnoses. Therapy for both neoplasms and its relationship to the development of the second neoplasm were also evaluated. PATIENTS AND METHODS: Patients were identified primarily from cancer registries at various institutions. The observed proportion of women diagnosed with breast cancer first, after, or simultaneously with non-Hodgkin's lymphoma was compared with the expected proportion by employing New York State and Surveillance, Epidemiology, and End Results program cancer incidence rates. RESULTS: The expected number of lymphoma cases that were diagnosed after or simultaneously with breast cancer was 31.6 (New York state data) to 39.1 (New York State and Surveillance, Epidemiology, and End Results data), and 78 such cases were identified from a total group of 87 (P < or = .001). There was no evidence that in this study, lymphoma as a second neoplasm was therapy induced. DISCUSSION: Anecdotal case reports suggest a relationship between breast cancer and non-Hodgkin's lymphoma. Mouse mammary tumor virus induces breast cancer and, in some circumstances, lymphoma in mice. The mouse mammary tumor virus ENV gene has been identified in approximately one third of human breast cancers. Women with both breast cancer and lymphoma are diagnosed first with breast cancer or simultaneously with both cancers more frequently than expected, and the lymphoma is not therapy induced. In some women with both breast cancer and lymphoma, the two neoplasms may have a common etiology, perhaps viral.

Mouse mammary tumor virus-like ENV gene sequences in human breast tumors and in a lymphoma of a breast cancer patient.

DNA sequences with very high similarity (95-98%) to the mouse mammary tumor virus (MMTV) ENV gene have been amplified by PCR in 38.5% of human breast tumors and in <2% of normal breast tissue (Wang et al., Cancer Res., 55: 5173-5179, 1995). Intrigued by these findings, which suggested an exogenous viral etiology for a certain percentage of human breast tumors, we have screened a panel of human breast tumors and normal breast tissue for the presence of MMTV-like DNA sequences. Using similar PCR procedures and stringent hybridization techniques, we have detected the presence of MMTV-like ENV gene sequences in 37% of the human breast tumors that we have analyzed. DNA sequencing has shown these sequences to be 99% homologous to the BR6 strain of MMTV and 100% homologous to the GR and C3H strains of MMTV. We have not detected these MMTV-like sequences in normal breast tissue. However, we have detected these sequences by PCR and stringent hybridization in a T-cell lymphoma of a breast cancer patient who was simultaneously diagnosed with both diseases. Our results support the possibility of an exogenous retroviral etiology for a certain percentage of human breast tumors. Our results also suggest that a similar exogenous retroviral etiology may exist for certain human T-cell lymphomas. In many inbred strains of mice, both breast cancer and T-cell lymphoma are caused by MMTV, hence, in a certain percentage of humans, one or both of these diseases may be caused by an MMTV-like retroviral entity.

Prognostic significance of platelet immunorelated GPIb expression in breast cancer.

PURPOSE: Prior reports have indicated that adhesive glycoprotein receptors expressed by tumor cells enhance their invasive and metastatic properties. We have recently isolated and characterized a platelet immunorelated GPIb receptor expressed by cultured breast tumor cell lines that participates in initial adhesive events in the metastatic process. Whether expression of this receptor predicts tumor behavior or clinical prognosis remains unknown. PATIENTS AND METHODS: Forty sequential breast tissue specimens were examined for GPIb alpha, GPIb/IX, and alpha IIb beta 3 (GPIIb/IIIa) expression by immunohistochemical staining. Of 35 assessable breast specimens, 20 were invasive ductal carcinomas or lobular invasive carcinomas, six were ductal carcinomas in situ (DCIS), and the remaining nine consisted of nonmalignant pathologies. RESULTS: The expression of an immunorelated GPIb alpha and GPIb/IX complex by invasive mammary carcinoma specimens was highly significant (P < 0.0001). However, there was no correlation between alpha IIb beta 3 expression and invasive breast cancer. A GPIb alpha or GPIb/IX staining score of < or = 2.0 and > 2.0 correlated highly with the diagnosis DCIS and invasive carcinoma, respectively (P < 0.0039). Invasive breast carcinoma specimens demonstrated a 120% (P < 0.001) and 140% (P < 0.027) increase in GPIb alpha and GPIb/IX staining score in comparison with DCIS specimens. Expression of GPIb alpha and GPIb/IX correlated significantly with a tumor stage of > or = III (P < 0.008), a tumor size of > 3 cm (P < 0.012), involved axillary nodes (P < 0.004), and estrogen receptor negativity (P < 0.008). Finally, a significant correlation was observed between this receptor's expression and the presence of nodal and/or visceral metastases (P < 0.0035). DISCUSSION: These results demonstrate a significant correlation between GPIb expression and breast malignancy. The expression of the GPIb receptor appears to represent an unfavorable prognostic factor and a biomarker predictive of aggressive disease.

Type 1 HERV-K genome is spliced into subgenomic transcripts in the human breast tumor cell line T47D.

Two types of HERV-K genomes exist which differ in the absence (type 1) or the presence (type 2) of a sequence of 292 nucleotides between the putative pol and env genes. Previously published results from teratocarcinoma cell studies had firmly concluded that the type 1 HERV-K genome was defective in splicing and that only the nondeleted type 2 HERV-K genome containing the 292-nucleotide sequence was capable of being spliced. We now show that in the T47D human breast tumor cell line it is the type 1 HERV-K genome, and not the type 2, which is spliced to subgenomic transcripts.

Neonatal chlamydial infections in Massachusetts, 1992-1993.

INTRODUCTION: An increase in the numbers of babies reported with Chlamydia trachomatis infections in Massachusetts prompted a review of the medical records of both infants and mothers to evaluate the clinical presentation, the maternal epidemiologic profile, risks of transmission, and the screening practices of health care providers. METHODS: Medical records of 44/47 infants reported with a chlamydial infection in 1992-1993 were analyzed, as were 40 of the maternal records. RESULTS: Almost all of the infants (39, or 89%) had conjunctivitis, despite the fact that ocular prophylaxis with erythromycin was documented at birth for 34 infants. Five other infants presented with respiratory tract infections without conjunctivitis, and they had all received prophylaxis at birth either with erythromycin (3) or silver nitrate instillation (2). More than one fifth (10, or 22.7%) had a respiratory tract infection. Seventy percent of the mothers were younger than 25. More than 85% were receiving prenatal care by the end of the second trimester. Twenty-five (62.5%) were screened for chlamydia. Nine women tested positive, seven of whom were tested beyond the first trimester. Seventy-five percent of the women who tested negative were tested in the first trimester. DISCUSSION: This case series supports previous data documenting that ocular prophylaxis can fail to prevent neonatal chlamydial conjunctivitis, and does not prevent colonization or infection at other sites. This study reinforces the importance of primary prevention of neonatal infections through prenatal screening in the third trimester, treatment of infected mothers and their sexual partner(s), and active follow-up.

Human breast carcinoma cells synthesize a protein immunorelated to platelet glycoprotein-Ib alpha with different functional properties.

Although tumor cell-induced platelet aggregation is thought to mediate an early step in the metastatic process, little is known about tumor adhesive receptors responsible for the initial platelet-tumor attachments. Because our preliminary work demonstrated that a platelet-immunorelated glycoprotein Ib alpha (GPIb alpha) receptor expressed by the human breast carcinoma cell line MCF-7 participates in tumor-induced platelet aggregation, we examined the synthesis and functional characteristics of this MCF-7-immunorelated GPIb alpha. When 35S-cysteine-labeled, digitonin-lysed MCF-7 cells were immunoprecipitated with platelet-specific monoclonal antibodies (mAbs) to GPIb alpha, major radioactive bands were observed. Northern blots showed MCF-7 transcripts for GPIb alpha under both high- and low-stringency hybridization conditions. In the presence of purified human iodine 125-labeled von Willebrand factor (125I-labeled vWf) with or without the addition of ristocetin, unlabeled vWf was observed to competitively bind to fixed MCF-7 cells (50% inhibitory concentration = 10 microg/ml, dissociation constant = approximately 3.8 +/- 1.9 nmol/L, 2.7 x 106 + 445,000 binding sites/cell) in which non-GPIb alpha vWf binding sites were blocked. 125I-vWf binding to blocked MCF-7 cells could be selectively and completely inhibited by mAbs specific for the vWf binding domain of GPIb alpha but not by mAbs against the GPIX subunit, the GPIb alpha subunit, or alternate GPIb alpha epitopes other than the vWf-binding domain. Finally, when whole blood substrate was incubated with a mAb specific for the GPIb binding epitope of vWf, MCF-7-induced platelet aggregation was virtually abolished in comparison with control specimens (N = 8; p < 0.0009). These findings (1) confirm the synthesis and expression of an MCF-7 protein with homology to platelet GPIb alpha, (2) confirm that the functional activity of this MCF-7-immunorelated GPIb alpha differs from that of platelet GPIb alpha, and (3) suggest that MCF-7-immunorelated GPIb alpha in its adhesive interactions with plasma vWf may constitute an initial event in MCF-7-induced platelet aggregation.

A GPIb alpha-related protein is expressed by fresh human breast carcinoma tissue and is regulated by a PKC-sensitive mechanism.

Fresh frozen breast carcinoma tissues were examined for the presence of GPIb alpha by immunohistochemistry. GPIb alpha was detected in six of seven primary invasive intraductal breast carcinoma tissues whereas staining was negative in seven of seven nonmalignant breast specimens. When biotin-labeled, triton-lysed, phorbol-12-myristate 13-acetate (PMA)-incubated breast carcinoma MCF-7 cells were immunoprecipitated with a MoAb directed against the platelet GPIb/IX complex, expression of GPIb was significantly enhanced in comparison to control preparations. Furthermore, incubation of MCF-7 cells for 84 h with 16 nmol/L PMA, but not with its biologically inactive derivative MePMA, induced a three- to fourfold increase in the surface expression of both GPIb alpha and GPIb/IX by flow cytometry. This PMA-enhanced GPIb alpha expression was almost completely abrogated when MCF-7 cells were first preincubated with the specific protein kinase C (PKC) inhibitor, H-7, prior to PMA treatment. Finally, PMA-incubated MCF-7 cells demonstrated a 63% (N = 6; P < 0.001) increase in tumor-induced platelet agglutination when added to platelets in comparison to control tumor cells. This enhancement could be abrogated by H-7. These findings confirm the expression of a protein with homology to platelet GPIb alpha expressed by fresh human breast carcinoma tissues, demonstrate that PMA enhances GPIb membrane expression by MCF-7 cells, and suggest that PKC plays a role in this process.

The impact of the Medicare Influenza Demonstration Project on influenza vaccination in a county in Massachusetts, 1988-1992.

Influenza and related pneumonia continue to cause significant amounts of morbidity and mortality despite the availability of effective vaccines. Two comparable counties in Massachusetts served as project areas of a national trial to see if reimbursement for immunizing Medicare-B eligible recipients against influenza would increase the use of the vaccine and reduce the costs attributed to related morbidity. Providers of health and social services to elders were recruited to participate in one county. A variety of professional and public education campaigns and media were used to promote influenza immunizations. Laboratory-based surveillance was instituted in both counties to assess the extent of circulating virus in each. Vaccine was made available to medical providers in both counties. While the amount of vaccine used in the comparison county increased by 6% from pre-project time (16,000 to 17,000 doses administered), vaccine use increased 219% in the intervention county (21,250 to 46,494 doses administered). In a post-project survey of participating physicians, 88% of 238 respondents reported administering less than 100 doses of influenza vaccine per year prior to the project. By the end of the project, only 32% administered less than 100 in the previous year. This project demonstrated the need for educating both the provider and the public in order to successfully promote immunizations. It was not clear, however, if reimbursement was a more important factor for promoting influenza immunizations than was universal distribution of free vaccine.

The importance of social histories for assessing sexually transmitted disease risk.

BACKGROUND: Although identifying risk groups for sexually transmitted diseases based on age or race may be useful for targeting screening efforts, clinicians should recognize that even members of most "low-risk" groups include some individuals at higher risk of infection. GOAL OF THIS STUDY: This case series of generally older people with sexually transmitted diseases illustrates how assumptions regarding age and risk group can lead to missed opportunities for sexually transmitted disease prevention. STUDY DESIGN: Records were compiled from two clusters of patients with sexually transmitted diseases seen at a Springfield, Mass., health center between March and September 1992. RESULTS: Nine patients with a sexually transmitted disease (one with syphilis/human immunodeficiency virus co-infection, one with herpes/human immunodeficiency virus co-infection, two with human immunodeficiency virus infections, and five with syphilis) are described. Eight of the patients are linked epidemiologically. CONCLUSIONS: A social history is essential during a medical encounter for sexually transmitted disease prevention purposes. Relying on assumptions regarding risk groups, as well as sexual activity, age, or other medical conditions, may lead to a patient's level of risk of infection going unrecognized. Discomfort associated with asking the sensitive questions involved in a social history also is a barrier to recognizing risks or infections. Non-judgmental sexual histories are appropriate when evaluating all patients.

Characterization of acute promyelocytic leukemia cases with PML-RAR alpha break/fusion sites in PML exon 6: identification of a subgroup with decreased in vitro responsiveness to all-trans retinoic acid.

Of 113 acute promyelocytic leukemia cases documented to have diagnostic PML-RAR alpha hybrid mRNA, 10 cases (8.8%) had fusion sites in PML gene exon 6 (V-forms) rather than in the two common hybrid mRNA configurations resulting from breaksites in either PML gene intron 6 (L-forms) or intron 3 (S-forms). In 4 V-form cases, a common break/fusion site was discovered at PML gene nucleotide (nt) 1685, abutting a 3' cryptic splice donor sequence. The fusion site was proximal to the common site in 1 case and more distal in 5 cases. The open reading frame encoding a PML-RAR alpha gene was consistently preserved, either by an in-frame fusion site or by the insertion of 3 to 127 unidentified nts. In 2 V-form cases, hybridization analysis of the reverse transcriptase-polymerase chain reaction products with a PML-RAR alpha juction probe was required for discrimination from L-form cases. Two V-form subgroups were defined by in vitro sensitivity to all-trans retinoic acid (tRA)-induced differentiation: 4 of 4 cases tested with fusion sites at or 5' to nt 1685 (subgroup E6S) had reduced sensitivity (EC50 > or = 10(-7) mol/L), whereas 4 of 4 cases with fusion sites at or 3' to nt 1709 (subgroup E6L) had high sensitivity (EC50 < 10(-8) mol/L) indistinguishable from that of L-form and S-form cases. These results provide the first link between PML-RAR alpha configuration and tRA sensitivity in vitro and support the importance of subclassifying APL cases according to PML-RAR alpha transcript type.

Amplification of the Int-2 gene in head and neck squamous cell carcinoma.

Cellular oncogenes have been implicated in head and neck cancer development since 1986. More recently interest has focused on chromosome 11q13; oncogenes therein undergoing ongoing investigation include Bcl-1/Prad-1, Hst-1 and Int-2. Our laboratory has studied the Int-2 oncogene for several years, primarily in the breast. This paper presents our investigations of Int-2 in the head and neck. Thirty-four paraffin-embedded primary squamous cell carcinomas were studied for Int-2 gene amplification using a carefully controlled method of sequence quantification by DNA dot blots. Amplification, mostly low level, was identified in 62 per cent of samples studied. No clinical correlation to amplification could be found. Further studies are underway looking for evidence of expression of Int-2 in fresh tissues and for amplification and expression of other oncogenes on this amplicon.

Dietary effects on gene expression in mammary tumorigenesis.

Studies were undertaken to determine the effect a high fat diet has on the hormonally controlled transcription of the Mtv-1 locus in C3Hf mice. The expression of this locus in the initiating event in mammary tumor development in the C3Hf mouse. Mice were weaned at 21 days to either a high fat diet containing 23.5 percent corn oil or to a low fat diet containing 5 percent corn oil. Mice were sacrificed at first, second, and third parity, or when they had developed mammary tumors, and their mammary glands and mammary tumors were isolated. RNA was isolated from all mammary glands and breast tumors and analyzed. The high fat diet accelerated the transcription of the Mtv-1 locus. The transcripts of this locus, which are never seen in C3Hf mouse mammary glands until second parity, were present in first parity mammary glands of 6 out of 10 high fat diet C3Hf mice which were studied. The mammary glands of 15 first parity C3Hf mice which were on the low fat diet were analyzed and none contained the Mtv-1 specific transcripts. In addition, mammary tumor development was detected earlier (11 vs 17.8 months) and after fewer litters (2.1 vs. 4.2) on the average in high fat diet C3Hf mice. One C3Hf mouse on the high fat diet developed a breast tumor at six months without going through pregnancy. These results indicate that a high fat diet of 23.5 percent corn oil can accelerate hormonally controlled gene expression specifically linked to mammary tumorigenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Dietary fat: gene expression and mammary tumorigenesis.

Although discovered as an exogenous agent of mammary carcinoma, the mouse mammary tumor virus (MMTV) is also transmitted vertically as endogenous proviral DNA present in the germ line of all inbred mice. In the C3Hf mouse, which receives no exogenous virus, the initial event of mammary tumorigenesis is the transcription of the endogenous MMTV proviral DNA present at the Mtv-1 locus. Transcription occurs as a result of the hormonal effects of pregnancy, and Mtv-1 specific transcripts are seen in second-parity lactating mammary glands of these mice. As a means of studying the effects of diet on mammary carcinoma at the molecular/genetic level, we have studied the transcription of the Mtv-1 locus in C3Hf mice on a high-fat diet containing 46% fat in calories or a low-fat diet containing 10% fat in calories. We have detected an accelerated transcription of the Mtv-1 locus (first- vs. second-parity lactating mammary glands) in > 50% of the C3Hf mice on the high-fat diet. In addition, mice on the high-fat diet developed mammary tumors earlier (11 vs. 17.8 mos) and after fewer litters (2.1 vs. 4.2). Our results indicate that fat in the diet can affect gene expression related to mammary carcinoma.

Pertussis in Massachusetts, 1981-1991: incidence, serologic diagnosis, and vaccine effectiveness.

Massachusetts provides diphtheria-tetanus toxoid-pertussis (DTP) vaccine, and since 1980 has monitored pertussis with a statewide diagnostic service. The incidence of bacteriologically confirmed pertussis was 104.5 per 100,000 person-years in 1-month-old infants and declined progressively thereafter. Infants < 6 months old experienced disproportionate morbidity: 44% of bacteriologically confirmed pertussis, 64% of hospitalizations, and 71% of hospital days. Most children with pertussis had received < 3 DTP doses during childhood, whereas 87% of adolescents with pertussis had received > or = 4 doses. Serodiagnosis by single serum anti-pertussis toxin antibody ELISA increased the incidence of confirmed pertussis in persons 11-19 years old from 3.0 to 12.9 per 100,000 and in persons > or = 20 years old from 0.16 to 0.56 per 100,000. Bacteriologic methods underestimate pertussis incidence, but a single serum anti-pertussis toxin antibody ELISA is a practical method for population-based diagnosis in adolescents and adults.

Homozygous deletion, rearrangement and hypermethylation implicate chromosome region 3p14.3-3p21.3 in sporadic breast-cancer development.

DNAs from 19 malignant human breast tumors and 2 benign fibroadenomas were analyzed for heterozygosity at 5 polymorphic loci on the short arm of chromosome 3. One homozygous deletion and one rearrangement were identified using probe D3S2 which maps to 3p14.3-3p21.1. This probe also detected novel hybridizing fragments of 2.0 kb and/or 3.4 kb in 6/18 (33%) of the malignant tumor samples that hybridized with the D3S2 probe following digestion with the 5'-methylcytosine-insensitive enzyme MspI. Comparisons of HpaII and MspI digestion showed that all but one of the tumor DNAs analyzed were hypermethylated. The two fibroadenoma DNAs were not as highly methylated and had hybridizing fragments of 3.4 kb after HpaII digestion. These malignant breast-tumor DNAs exhibit 3 mechanisms by which a tumor-suppressor gene hypothesized to reside at 3p14-3p21 could be inactivated: homozygous deletion, rearrangement and hypermethylation, and strongly implicate this 3p chromosome region in breast-tumor development.

Concurrent mutations of coding and regulatory sequences of the Ha-ras gene in urinary bladder carcinomas.

This report concerns the study of Ha-ras gene mutations and ras p21 expression in primary tumors of the urinary bladder. Polymerase chain reaction-based techniques and computerized image analysis were used. The data obtained were related to tumor grade, DNA ploidy, and tumor invasion. A point mutation (G-->T) at Ha-ras codon 12 was found in 30 of 67 tumors. The mutation frequency was greater in grade III (65%) than in grade II (44%) tumors; no mutations were observed in grade I tumors. The mutation was observed more often in aneuploid (58%) than in diploid (28%) tumors. No other substitution at codon 12 was seen and no codon 61 mutation was detected. The tumors were also tested for the A-->G mutation at position 2719 of Ha-ras intron D. Concurrent codon 12 and intron D mutations were identified in seven high-grade aneuploid tumors; six were invasive. The levels of the ras gene product p21 were approximately 10 times higher in tumors with intron D mutation than in those without. These findings confirm on human bladder tumors the observations of the effect of synchronous exon-intron mutations reported on the bladder cancer cell line T24. Our results are the first demonstration of Ha-ras intron D alterations in human tumor tissues and suggest that concurrent mutations at codon 12 and intron D of this gene within the same tumor may contribute to the aggressive behavior of human bladder carcinomas.

Pertussis outbreaks in groups claiming religious exemptions to vaccinations.

Four recent outbreaks of pertussis in Massachusetts illustrate some features that contribute to the increased incidence of the disease. The outbreaks involved unimmunized groups of children with philosophical or religious exemptions from school or day-care immunization requirements and children and adults who were reluctant to undergo antibiotic prophylaxis or therapy. Parents and physicians should be aware that failure to immunize and to cooperate in follow-up preventive measures can have public health and potential medicolegal repercussions.