Biomedical subjects
Publications and source records attributed to J Jaffe.
Genetic theories still flounder on the fact that similarity of hand preference is the same in monozygotic (MZ) and dizygotic (DZ) twins. Lateral preference on a well-designed set of 5 activities was obtained from 2,131 male pairs. On item analysis, only "throw" discriminated zygosity, attributable to "excess" nondextral MZ pairs. This item is remarkably free of the intense cultural bias against sinistrality.
Although theories of early social development emphasize the advantage of mother-infant rhythmic coupling and bidirectional coordination, empirical demonstrations remain sparse. We therefore test the hypothesis that vocal rhythm coordination at age 4 months predicts attachment and cognition at age 12 months. Partner and site novelty were studied by recording mother-infant, stranger-infant, and mother-stranger face-to-face interactions in both home and laboratory sites for 88 4-month-old infants, for a total of 410 recordings. An automated dialogic coding scheme, appropriate to the nonperiodic rhythms of our data, implemented a systems concept of every action as jointly produced by both partners. Adult-infant coordination at age 4 months indeed predicted both outcomes at age 12 months, but midrange degree of mother-infant and stranger-infant coordination was optimal for attachment (Strange Situation), whereas high ("tight") stranger-infant coordination in the lab was optimal for cognition (Bayley Scales). Thus, high coordination can index more or less optimal outcomes, as a function of outcome measure, partner, and site. Bidirectional coordination patterns were salient in both attachment and cognition predictions. Comparison of mother-infant and stranger-infant interactions was particularly informative, suggesting the dynamics of infants' early differentiation from mothers. Stranger and infant showed different patterns of vocal rhythm activity level, were more bidirectional, accounted for 8 times more variance in Bayley scores, predicted attachment just as well as mother and infant, and revealed more varied contingency structures and a wider range of attachment outcomes. To explain why vocal timing measures at age 4 months predict outcomes at age 12 months, our dialogue model was construed as containing procedures for regulating the pragmatics of proto-conversation. The timing patterns of the 4-month-olds were seen as procedural or performance knowledge, and as precursors of various kinesic patterns in the outcomes of 12-month-olds. Thus, our work further defines a fundamental dyadic timing matrix--a system that guides the trajectory of relatedness, informing all relational theories of development.
This study examined the sensitivity, specificity, and receiver operating characteristics (ROC) curves of a modified version of the CAGE, a screening measure used in the detection of older alcohol- and drug-abusing individuals. In a retrospective review of clinical records of 976 patients screened by a geriatric substance abuse program, the authors examined patients' responses on a modified version of the CAGE that included queries regarding drug use. The CAGE was administered to individuals age 50 or over draw from three diagnostic groups: alcohol abuse/dependence, drug abuse/dependence, and normal controls. Analysis of variance and discriminant function analyses revealed that the modified CAGE was able to discriminate both alcohol and drug abusers from controls. Analyses examining test sensitivity, specificity, and ROC curves revealed the CAGE to demonstrate excellent sensitivity but poor specificity. Omitting the "cut down'' item from the CAGE significantly improved specificity with only a modest drop in sensitivity. Given the ease of administration and sensitivity to both alcohol and drug abuse, these data suggest that the modified CAGE is well suited as a screening instrument for geriatric drug and alcohol abuse.
JRS4(HE), a highly encapsulated, mouse-passaged variant of group A streptococcal strain JRS4, was characterized. The mucoid phenotype of JRS4(HE) was preserved after extensive passage in vitro. The level and size of csrRS transcript in JRS4(HE) was similar to that of JRS4, yet JRS4(HE) expressed high levels of has and sagA and exhibited an increased activity of streptolysin S. These findings indicate that the CsrRS repressor system was inactive in JRS4(HE). JRS4(HE) adhered to HEp-2 cells at the stationary phase but did not internalize these cells. At midlogarithmic phase, JRS4(HE) neither adhered to nor internalized cells, because of an increased amount of hyaluronic acid. Mice injected subcutaneously with JRS4(HE) developed large, deep necrotic lesions. In contrast, mice challenged with JRS4 developed small, superficial lesions. Despite the use of a high inoculum, mice challenged with JRS4(HE) did not develop a lethal bacteremic infection. It is concluded that inactivation of CsrRS in vivo is insufficient to cause a spreading necrotic disease.
BACKGROUND: Clinically, cyclosporine (CSA, Neoral) is titrated to concentrations, and not to pharmacological effect. METHODS: Intracellular interleukin- (IL) 2 was measured in phorbol myristic acid-ionomycin-stimulated peripheral lymphocytes by flow cytometry, after isolation from 14 renal transplant recipients receiving CSA+prednisone, and double-blind rapamycin (rapamycin:placebo=4:1). RESULTS: The proportion (%) of CD4+IL-2+ lymphocytes corresponding to CSA levels (mean+/-SD ng/ml) measured preoperatively (TO=O), and on postoperative day 8, before (356+/-63), and 2 hr after the morning dose (Cmax=1567+/-669), decreased from 39+/-16 to 15+/-8 and 3+/-1.6, respectively. Reciprocally, unresponsive lymphocytes (%CD4+IL-2-) increased with increasing CSA levels and predicted an EC50 of 249 ng/ml (CSA concentration at which CD4+IL-2- cells increased by 50% over baseline) in an Emax pharmacodynamic model. CONCLUSIONS: Clinically, the pharmacological effect of CSA is quantifiable, and lies in the upper end of the predicted range. In our Neoral-treated sample population, Cmax was associated with the least variable "cyclosporine effect." Such information could potentially individualize immunosuppression, and lead to rational dosing strategies.
BACKGROUND: Venous thromboembolism (VTE) is an important complication in blunt trauma patients. At our Level I trauma center, we had a deep venous thrombosis (DVT) rate of 3.2% from 1993 to 1997 despite an aggressive VTE prophylaxis program. During this time period, we placed vena caval filters (VCF) for both traditional and prophylactic indications. This project was developed to establish a VCF registry for trauma patients to determine the long-term complications of VCF placement. METHODS: A letter was sent to all trauma patients who had a VCF placed from 1993 through 1997. Patients were asked to return for a history and physical examination to detect signs and symptoms related to VTE, a duplex ultrasound of the inferior vena cava, and a plain abdominal radiograph to determine filter migration. RESULTS: There were 191 VCFs inserted in our trauma population from 1993 to 1997. There were 105 patients (75 male and 30 female) available for evaluation, with a mean follow-up of 28.9 months. Forty-one VCFs were placed in patients with DVT or pulmonary embolism, and 64 were placed in patients for prophylactic indications as per the guidelines developed by the Eastern Association for the Surgery of Trauma. There were no clinically identifiable complications related to insertion of the VCF. There were no pulmonary embolisms detected after VCF insertion. In follow-up, only one filter (0.95%) migrated, and this was minimal (1 cm cephalad). One (0.95%) vena cava was occluded, based on duplex ultrasonography, and 11 patients (10.4%) had signs or symptoms of leg swelling after hospital discharge. Twenty eight (44%) of the 64 patients with prophylactic VCFs developed a DVT after filter placement. CONCLUSION: VCFs placed in trauma patients have acceptable short- and long-term complication rates. Consideration should be given to prophylactic VCF placement in patients at high risk for VTE. Randomized controlled trials are needed to evaluate whether VCF insertion increases the risk for subsequent DVT.
This project evaluated whether clinical case managers (CCMs) could increase access and utilization of social services in the community; and thereby improve outcomes of addiction treatment. No case management (NoCM)--patients received standard, group-based, abstinence-oriented, outpatient drug abuse counseling, approximately twice weekly. Clinical case management (CCM)--patients were treated in the same programs but also were assigned a CCM who provided access to pre-contracted, support services such as drug free housing, medical care, legal referral, and parenting classes from community agencies. CCM patients received more alcohol, medical, employment, and legal services than NoCM patients during treatment. At 6 month follow-up CCM patients showed significantly more improvement in alcohol use, medical status, employment, family relations, and legal status than NoCM patients. We conclude that CCM was an effective method of improving outcomes for substance abuse patients in community treatment programs. Essential elements for successful implementation included extensive training to foster collaboration; and pre-contracting of services to assure availability.
In 1985, a hand preference survey was completed by 973 dizygotic and 1158 monozygotic male twin pairs, all veterans of World War II. This is the largest single twin study of handedness on record. As in state-of-the-art animal research, the laterality criterion was sensitive to both direction and consistency (degree, strong or weak) of handedness. Significant pairwise concordance was shown for the total group, and for consistency and directional factors separately. However, no zygosity differences were demonstrated.
OBJECTIVE: To review the success rate of embolization in stopping hemorrhage for unstable patients with severe pelvic fractures, to calculate the time to achieve embolization, and to determine the yield from angiography. DESIGN: Retrospective review of patients admitted to a Level I trauma center with pelvic fractures during a 5-year period. MATERIALS AND METHODS: Charts were reviewed for Injury Severity Score, age, blood pressure, prothrombin time/partial thromboplastin time, pelvic fracture type, mortality, time to reach the angiography suite, time to achieve embolization, and mechanism of injury. MEASUREMENTS AND MAIN RESULTS: Of 806 patients admitted with pelvic fractures, 35 underwent pelvic angiography, and 15 (1.9%) required embolization. Embolization was successful for all patients. No deaths resulted from ongoing hemorrhage. Angiography yield in initially unstable patients was 64%. The mean age and initial hemodynamic instability were significantly greater in nonsurvivors. The time from arrival in the trauma bay to arrival in the angiography suite ranged from 50 to 1,140 minutes, and the time spent in the angiography suite performing embolization ranged from 50 to 140 minutes, with an average time of 90 minutes. Patients who were embolized within 3 hours of arrival had a significantly greater survival rate. CONCLUSION: Only a small percentage of patients with pelvic fractures require embolization, but when it is used, embolization can be 100% effective. Age, time to achieve embolization, and initial hemodynamic instability appear to be important factors in survival.
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Two mathematical models of social contingency are examined in terms of their development over the first year of life. The interactions of 53 mothers and their infants were recorded at 6 weeks, 4 months, and 12 months. The infants' gazes at 6 weeks, the mothers' vocal behavior at 6 weeks, and the vocal behavior of the mother and infant at 4 and 12 months were automatically coded in terms of four states. The conditional dependence model and the response effects model were computed for each interaction at each age, and the coefficients of the models were examined as a function of age. The relative success of the models as estimates of moment-to-moment contingency as well as their variations with age are discussed.
Binding of the group A streptococcus (GAS) to respiratory epithelium is mediated by the fibronectin (Fn)-binding adhesin, protein F1. Previous studies have suggested that certain GAS strains express Fn-binding proteins that are different from protein F1. In this study, we have cloned, sequenced, and characterized a gene (prtF2) from GAS strain 100076 encoding a novel Fn-binding protein, termed protein F2. Insertional inactivation of prtF2 in strain 100076 abolishes its high-affinity Fn binding. prtF2-related genes exist in most GAS strains that lack prtF1 (encoding protein F1) but bind Fn with high affinity. These observations suggest that protein F2 is a major Fn-binding protein in GAS. Protein F2 is highly homologous to Fn-binding proteins from Streptococcus dysgalactiae and Streptococcus equisimilis, particularly in its carboxy-terminal portion. Two domains are responsible for Fn binding by protein F2. One domains (FBRD) consists of three consecutive repeats, whereas the other domain (UFBD) resides on a non-repeated stretch of approximately 100 amino acids and is located 100 amino acids aminoterminal of FBRD. Each of these domains is capable of binding Fn when expressed as a separate protein. In strain 100076, protein F2 activity is regulated in response to alterations in the concentration of atmospheric oxygen.
In this study, we report that differences between T-cell receptor (TCR) V beta gene family usage in CD4+ and CD8+ T cells are significantly greater in a subgroup of patients with common variable immunodeficiency (CVI) and high levels of activated CD8+ T cells (CD8hi CVI) than in controls (P < 0.001). In CD8hi CVI patients, such differences were also significantly greater for V beta 12 than for other V beta families. As the causes of the differential usage of V beta gene families by CD4+ and CD8+ T cells are under investigation, it was interesting that the combined differences between V beta gene family usage in the CD4+ and CD8+ T-cell subpopulations as a whole were significantly lower than the combined differences between individual V beta gene family usage in either CD4+ or CD8+ T-cell subpopulations (P < 0.001 in both control and CD8hi CVI patients). Further, the pattern of V beta gene family usage in CD4+ T cells was remarkably similar to that in CD8+ T cells in both groups. These data strongly suggest that differences in V beta gene family usage arising from coselection by major histocompatibility complex (MHC) class I versus MHC class II restriction elements do not fundamentally distort 'basic' V beta gene family usage patterns. They also support the concept that differences in CD4+ and CD8+ T-cell V beta gene family usage, which were increased in CD8hi CVI, can arise from high-affinity interactions between disease-associated antigens or superantigens and T cells in the post-thymic T-cell compartment.
Oct-1 is a ubiquitously expressed regulatory gene of the POU domain family. The Oct-1 protein binds to the octamer motif present in the control regions of a variety of genes such as the immunoglobulins, histone H2B and snRNAs. To learn about Oct-1 and its possible role in B-cell maturation, we have used oct-2 cDNA to screen a murine pre-B cell, cDNA library. Two cDNA clones were identical in their POU-homeo box DNA binding domain, but differed in their 3'-region. Whereas one clone (oct-1a) was very similar to its human oct-1 homologue, the other (oct-1b), contained an additional 72 bp sequence (designated E1) at the serine threonine rich coding region (position 1485 of the human oct-1), and a deletion of another 72 bp sequence (designated E2) downstream (position 1920). These changes preserve the protein reading frame. DNA blot analysis indicates that murine oct-1 is a single copy gene and that the two oct-1 isoforms oct-1 is expressed as a large approximately 10 kb transcript in all the cell are generated by alternative RNA splicing. RNA blots showed that oct-1 is expressed as a large approximately 10 kb transcript in all the cell lines tested. PCR analysis of the E1 and E2 72 bp regions, indicated the presence of a third isoform containing both E1 and E2 (Oct-1c). Oct-1a and Oct-1b were present in all cell types examined, but the level of expression was lower in liver and spleen as compared to testis, thymus and kidney. The ratio of Oct-1b to Oct-1a ranged between 0.2 to 0.5, for all tissues examined except for testis which expressed higher amounts of oct-1b and/or oct-1c. Our findings thus show that the pattern of expression of the oct-1 gene is more complex than hitherto thought.
The Sézary syndrome (SzS) and adult T-cell leukemia (ATL) are malignant proliferations of mature T-lymphocytes that possess distinct functions. Sézary cells function as helper cells, whereas ATL cells are usually suppressor effectors. Although phenotypically similar (CD4+/CD7-/CD8-), these functional differences between the T-cell lymphoproliferative disorders suggest different patterns of cytokine expression. We wished to delineate the cytokine mechanisms potentially underlying the diverse functional characteristics of SzS and ATL. Therefore, we analyzed the expression of interleukins (IL) 2, 4, and 5, gamma-interferon, and transforming growth factor beta 1 in the highly purified leukemic T-cells from 5 SzS and 5 ATL patients. Decreased mRNA and protein levels of IL-2, gamma-interferon, and IL-5 were detected in mitogen-stimulated ATL and SzS cells when compared to similarly cultured normal CD4+ cells. In contrast, IL-4 production was markedly up-regulated in the leukemic cells of 4/5 SzS patients as compared to ATL and normal controls. Finally, fresh ATL cells secreted higher levels of transforming growth factor beta 1 into the culture medium than the malignant T-cells from SzS patients. Collectively these results suggest that, similar to the murine CD4-expressing T-cell subsets Th1 and Th2, different cytokine profiles exist in a human population of CD4+ T-cells. Moreover, the distinct patterns of IL-4 and transforming growth factor beta 1 expression by SzS and ATL cells, respectively, are most consistent with the functional differences (i.e., helper versus suppressor activity) between these T-cell malignancies and thus may play important roles in the pathogenesis of the paraneoplastic features associated with these two leukemias.
The study reported here compared the gaze behavior of infants with Down syndrome (DS) and nondelayed infants during interactions with their mothers. The subjects were 10 DS infants and 11 nondelayed infants. Five of the DS infants and 6 of the nondelayed infants were 4 months old; the rest were 9 months old. The results support the expectation that infants with DS gazed at their mothers longer than did nondelayed infants during face-to-face play, and also indicate that all the infants visually attended to their mothers less at 9 months than at 4 months of age. It is conjectured that the increased gaze of the infants with DS may well facilitate attachment in the 1st year of life.
This report describes a patient with both Eagle syndrome and temporomandibular joint (TMJ) internal derangement. The patient's pain was relieved by styloidectomy and arthroscopy.
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