Biomedical subjects
Publications and source records attributed to S Blum.
This case report documents the first patient from mainland China with an HTLV-1-associated myelopathy. The available epidemiological data suggest a low rate of HTLV1 infection in China, although the surveys are comparatively small. Possible transmission routes and the risk of encountering the disease outside endemic areas are discussed.
To investigate the role of protein kinase C (PKC), one of the key factors in cellular signalling, in the integrity of cell contacts, we studied the effects of PKC activation and inhibition on cell-cell and cell-substratum contacts. We localized PKC, actin and two major elements of zonula adherens (vinculin, E-cadherin) and focal contacts (vinculin) in primary cultures of normal human keratinocytes (nHEK) by fluorescent analogue cytochemistry. The activity of PKC was influenced by administration of TPA (12-O-tetradecanoylphorbol-13-acetate, a specific PKC activator) and H-7 [1-(5-isoquinolinesulphonyl)-2-methylpiperazine, a PKC inhibitor] for various periods of time. Our results show varying effects of TPA and H-7 on zonula adherens and focal contacts, suggesting differences in modulation of both types of adherens junctions by mechanisms partially involving PKC. In addition, TPA treatment of nHEK leads to changes in actin cytoskeletal organization.
133 patients attending the colposcopy-laser outpatient consultations were examined simultaneously by cytology, colposcopy and punch biopsy. A cone biopsy was taken 25 patients and one patient was hysterectomised later. A comparison between cytology and histology revealed 17.1% false negative smear results. Cytology and histology showed the same result in 84.6%. The highest percentage of high-grade dysplasia was found in colposcopy with signs of punctation and/or mosaicism. A similar diagnosis was achieved in 92.3% of cases comparing punch with cone biopsy. Simultaneous use of cytology, colposcopy and punch biopsy enables reliable diagnosis and follow-up of dysplastic lesions of the cervix. Besides, one can use punch biopsy as basic histology for local destructive manoeuvres such as laser vaporisation.
Among 20- to 59-year-old residents of New York City who have septicemia, gastroenteritis, urinary tract infection, and multiple site infections due to Salmonella, those listed in the New York City AIDS Registry were highly overrepresented. Among the patients listed in the registry, males outnumbered females by 4:1 (septicemia), 9:1 (multiple site infections), 5.6:1 (gastroenteritis), and 2.5:1 (urinary tract infection); among patients not listed, males outnumbered females by 2.7:1 (septicemia), 3:1 (multiple site infections), 1.2:1 (gastroenteritis), and 1.6:1 (urinary tract infection). These results strongly suggest that most nonlisted males with septicemia and multiple site infections, and a minority with gastroenteritis and urinary tract infection, were human immunodeficiency virus (HIV)-positive. Among individuals who were HIV-positive, or likely to be so, Salmonella enteritidis was more competent in causing septicemia and less competent in causing gastroenteritis than was Salmonella typhimurium; among HIV-negative individuals, the reverse was true. The different capacities for infection with and invasiveness of S. enteritidis, S. typhimurium, and other Salmonella serotypes in HIV-positive and HIV-negative individuals and the use of HIV testing for Salmonella-infected individuals are discussed.
We present the case of a 47-year-old woman with bilateral iridocorneal endothelial syndrome. The iridocorneal endothelial syndrome has heretofore been considered a unilateral disorder. However, a review of the literature and examination of the patient presented in this report indicate that bilateral occurrence of the iridocorneal endothelial syndrome is not uncommon. Consequently, it may be inappropriate to include unilaterality as a feature distinguishing the iridocorneal endothelial syndrome from similar conditions, most notably posterior polymorphous endothelial dystrophy.
One approach to adoptive cancer immunotherapy is based on the use of bispecific monoclonal antibodies (mAb) capable to redirect ex vivo generated cytolytic T lymphocytes (CTL) onto tumour cells. The efficiency of the CD28 T-cell activation pathway to induce CD3-dependent cytolytic activity was investigated while avoiding modulation of the TCR/CD3 complex needed for targeting by bispecific mAb. When used e.g. in conjunction with anti-CD2 antibodies or diacylglycerol derivatives, the in vitro stimulation of T cells with anti-CD28 mAb resulted within 36 h in high levels of CD3-dependent cytolysis (tested on a FcR+ target in the presence of anti-CD3 mAb) and sustained lymphokine production, such as TNF alpha, IFN gamma and IL-2, which may affect tumour growth when delivered locally by the transferred T cells. Rapid activation may reduce costly in vitro procedures, preserve homing capacities of retransfused T cells, and thus facilitate implementation of clinical trials based on the use of bispecific antibodies.
The etiology of lacunar CCT lesions is controversial. We report a patient with recurrent ischemia in the territory of the right internal carotid artery. CCT initially showed a fresh non-lacunar lesion in the area of the basal ganglia and internal capsule. Subsequently, repeat CCT revealed a singular lacunar defect in the internal capsule. The Doppler sonographic investigations showed an internal carotid artery occlusion. This case supports the hypothesis that an embolic or hemodynamic etiology of the lacunae is possible.
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Two cold pressor tests were administered to 18 healthy normotensive males on two occasions, after 2 weeks of dietary sodium loading and after 2 weeks of maintaining their normal diet. While the addition of an extra 10 g/day of sodium to the diet had no overall effect on resting cardiovascular activity, it produced significantly greater diastolic blood pressure and smaller heart rate responses to the pain stimuli. As well, consistent with the large animal literature indicating a relationship between high blood pressure and diminished pain sensitivity, pain ratings were found to be significantly lower during the sodium loaded testing session. The ratings were corroborated by evidence of lower skin conductance reactivity to the second cold pressor test in the sodium loaded condition. Information concerning an elevation of risk for hypertension, perhaps provided by baroreceptors, may lead to compensatory reactions with hypoalgesia as one effect.
The amplitude and latency of the N100 wave (auditory evoked potentials) were studied in 28 normals, 85 parkinsonians, 24 extrapyramidal syndromes induced by neuroleptics and 12 neurological control patients. The latency decreases as an inverse function of the intensity of stimulation in normals, controls, treated parkinsonians and in extrapyramidal syndrome induced by neuroleptics. Untreated parkinsonians do not show an evident relation between the latency and the stimulation level. The amplitude of the N100 decreases when neuroleptic induced parkinsonism improves.
This study contrasts the acquired immunodeficiency syndrome mortality experience of residents of Puerto Rico with that of New York City residents identified as either Puerto Rico-born and non-Puerto Rico-born Hispanics. Portions of the mortality data examined in this investigation update and extend the data previously published describing selected groups in New York City through the end of 1987 but which did not consider residents of Puerto Rico. The nine-year cumulative, age-adjusted acquired immunodeficiency syndrome mortality rate for males was found to be 5 x higher among Puerto Rico-born New York City residents compared with residents of Puerto Rico (702/100,000 v 141/100,000) and 1 1/2 x greater than that of other male Hispanic New York City residents (447/100,000). In New York City, Puerto Rico-born females had higher age-adjusted mortality rates (121/100,000) than female residents of Puerto Rico (25/100,000) and other female Hispanic residents of New York City (70/100,000). Within five of the six age categories considered, acquired immunodeficiency syndrome mortality rates for adult males and females are higher for Puerto-Rico-born, New York City residents. Limitations of acquired immunodeficiency syndrome incidence data, as they pertain to persons of Puerto Rican ancestry, are discussed.
Saccharomyces cerevisiae translation initiation factor eIF-4A, an RNA helicase of the Asp-Glu-Ala-Asp (DEAD) box protein family, was mutated in the putative ATP binding site and expressed in Escherichia coli. Mutant proteins with alanine at position 66 replaced by glycine [eIF-4A(A66G)] or valine [eIF-4A(A66V)] were purified from Escherichia coli extracts and analyzed in vitro for activity in ATP crosslinking, ATP hydrolysis, RNA helicase, and translation assays. The results show that in vitro ATP hydrolysis activity, RNA helicase activity, and translation activity of eIF-4A correlate with in vivo activity of the factor. Whereas eIF-4A(A66G) showed wild-type activity in all assays, eIF-4A(A66V) was active in ATP crosslinking but inactive in ATP hydrolysis and RNA helicase assays. In vitro translation was supported by wild-type eIF-4A and eIF-4A(A66G) but not by eIF-4A(A66V). The results show that, for their translation, the majority of mRNAs from Saccharomyces cerevisiae including an mRNA with the initiator AUG positioned 8 nucleotides downstream of the cap structure require eIF-4A that is able to hydrolyze ATP.
Long-term survival of patients with high-grade gliomas remains extremely poor. The main reason for such an outcome is local failure, or recurrence, after surgery and/or radiotherapy. Higher doses of radiation may result in decreased local failure rates provided that the location (and extent) of gross tumor and microscopic disease can be defined accurately. The abnormalities appearing in images from diagnostic modalities, such as CT and MRI, are being used as a starting point and as a guide for the clinical definition of tumor and its extensions. However, some recent studies on two-dimensional specimens, correlating histopathological findings to CT and MRI images, showed that the resulting definition of tumor cell extensions was unsatisfactory, different, and in need of ample margins. We carried out a retrospective analysis to compare the target volumes that would have been defined by CT, T2-weighted MRI, and T1-weighted postgadolinium MRI images of the same individual and to explore the implications of the resulting volume definitions for radiotherapy. The results of our limited study, based on the margins used, indicate that the CT-defined target volume is consistently larger than that from either of the two MRI modalities and suggest that noncoplanar approaches for its treatment and other local approaches for tumor boost should be considered. We conclude that until more definitive histopathological guidelines correlated to image features have been formulated and agreed upon, one should try to make full use of all available diagnostic information in order to minimize the possibility of geographical miss of target extensions.
To better understand the natural history of severe pediatric human immunodeficiency virus infection, reported cases of perinatally acquired pediatric acquired immunodeficiency syndrome (AIDS) in New York City were examined for differences in survival and age at diagnosis before and after implementation of an expanded case definition in 1987. One hundred ninety-six children reported through August, 1987, and 333 children reported between September, 1987, and February, 1990, and diagnosed through 1989 were compared. Significant differences were not found in survival by either gender or race/ethnicity although Hispanics were slightly more likely to be diagnosed with Pneumocystis carinii pneumonia (PCP) and blacks with lymphocytic interstitial pneumonitis (LIP). The most striking differences were noted regardless of race between children whose earliest AIDS-specific diagnosis was PCP and those whose earliest diagnosis was LIP. In the group reported through August, 1987, median survival from birth was 10 months with PCP vs. 54 months with LIP, median age at diagnosis 5 months vs. 20 months, and median survival after diagnosis 2 months vs. 22 months, respectively. Twelve-month survival for PCP improved in the two time periods examined, but survival with LIP did not. After implementation of the 1987 case definition, bacterial infections replaced LIP as the second most common diagnosis. This study provides data on children diagnosed and reported with AIDS. Ongoing prospective studies of children who have a full spectrum of human immunodeficiency virus infection with and without reportable AIDS wil further elucidate survival in children infected with human immunodeficiency virus.
In this study of 162 third graders in New York City public schools, we found that slightly over half of the children in special education were males who had Medicaid coverage at birth and mothers with medical conditions or adverse health habits noted on the birth certificate; two thirds of the children with this combination of characteristics actually were placed in special education. These findings suggest that newborns at risk for later learning disabilities can be targeted to receive preventive interventions.
The microcompartmentation of aldolase and glyceraldehyde-3-phosphate-dehydrogenase (GAPDH) was investigated in four different cell types (3T3 cells, SV 40 transformed 3T3 cells, mouse fibroblasts, chick embryo cardiomyocytes) combining cell permeabilization and indirect immunofluorescence technique. Permeabilization of the cells prior to fixation released the soluble fractions, whilst the total amount of enzymes was preserved in nonpermeabilized cells. Both enzymes exist in a soluble as well as in a structure-bound form. The soluble fraction of aldolase and GAPDH is distributed homogeneously throughout the cytoplasm, excluding the nucleus and vesicles. The permeabilization-resistant form is associated with the actin cytoskeleton. A considerable amount of both enzymes is located in the perinuclear region and cannot be attributed to a definite structure. Comparing the staining patterns of aldolase and GAPDH in four different cell types we found that the distribution of the enzymes corresponds with diverse forms of actin cytoskeletal organization of these cells. The codistribution is maintained in cells treated with cytochalasin D.
BACKGROUND: The occurrence of pulmonary tuberculosis in human immunodeficiency virus (HIV)-infected persons is believed to represent a less severe stage of HIV-related disease with a more favorable prognosis than other acquired immunodeficiency syndrome (AIDS)-defining conditions; therefore, it has been excluded from the AIDS definition established by the Centers for Disease Control (Atlanta, Ga) criteria. METHODS: To determine the prognosis of patients with HIV-related tuberculosis, we assessed the clinical, immunologic, and HIV infection status of a cohort of male subjects aged 20 to 44 years who were hospitalized with tuberculosis but without AIDS in New York City hospitals from 1985 through 1986, and we determined their mortality through May 1991. RESULTS: The 58 patients who agreed to participate were largely (90%) nonwhite and had a high prevalence of pulmonary tuberculosis (90%) and HIV infection (53%). Patients who were HIV seropositive had significantly lower CD4 cell counts (median, 0.136 x 10(9)/L; range, 0.013 x 10(9) to 2.314 x 10(9)/L vs median, 0.765 x 10(9)/L; range, 0.284 x 10(9) to 2.333 x 10(9)/L), and, during the follow-up period, an 83% mortality rate that was 7.5 times higher than the 11% rate in seronegative subjects. Survival analyses revealed that for all HIV-seropositive subjects the probability of death at 30 months was 72% and the median survival was 21 months (95% confidence interval, 15.5 to 26.5 months), while for HIV-seropositive subjects with CD4 cell counts of 0.2 x 10(9)/L or less, the probability of death at 30 months was 92% and the median survival was 15.75 months (95% confidence interval, 14.0 to 17.6 months). CONCLUSION: The prognosis for patients with HIV-related pulmonary tuberculosis is poor, and those with CD4 cell counts of 0.2 x 10(9)/L or less have survival patterns similar to that of patients with AIDS. We believe that these data support the expansion of the AIDS case definition to include persons with both pulmonary tuberculosis and severe HIV-related immunosuppression.
There are few data available on the dynamics of heterosexual human immunodeficiency virus (HIV) transmission among women whose only risk factor is sexual contact with intravenous drug-using males. Unlike models which rely on unconfirmed estimates regarding sexual partner selectivity and contact rates between infected and uninfected populations, data from a survey conducted between November 1988 and February 1989 of 1,842 women in New York City provide empirical values for these variables which the authors use in a straightforward estimation model. The authors estimate that the number of new infections among women aged 15-44 years in New York City during 1988 was between 876 and 1,668 and that the number of women already infected through heterosexual contact with male intravenous drug users is between 5,390 and 10,230 among the 1,844,285 women in this age group. These conclusions indicate that male-to-female transmission in New York City is of substantial magnitude and that prevention efforts among male intravenous drug users and their female sexual partners must be appropriately directed.