Monomeric uni-ligated aluminates.

The tetradentate ligand, common name Salban(But)H4 (N,N'-bis(2-hydroxy-3,5-di-tert-butylbenzyl)-1,4-diaminobutane) combines with appropriate amounts of LiAlH4 to produce the unique monomeric, uni-ligated aluminate [Salban(But)Al]Li(thf)2 (1) and the bimetallic derivative Salban(But)(AlH2Li(thf)2)2 (2).

Fetal and maternal outcomes in Indo-Asian compared to caucasian women with diabetes in pregnancy.

Maternal and fetal complications are increased when pregnancy is complicated by diabetes, and this may be further influenced by racial and cultural differences. We examined fetal and maternal outcomes in Indo-Asian and Caucasian women attending the same antenatal diabetes service to see if there were any differences. Women with diabetes mellitus (type 1, type 2 and gestationally-acquired disease) complicating pregnancy, registered at the combined diabetes/antenatal clinic of this University teaching hospital over the period 1990-1998 were included. Fetal outcomes examined were miscarriage <24 weeks, stillbirths, neonatal deaths up to 28 days of life, perinatal mortality, congenital malformations and size for gestational age. Maternal outcomes examined were rates of caesarean section and vaginal deliveries, and number of pre-term deliveries <37 completed weeks of gestation. Outcomes for Indo-Asian and Caucasian women were similar, with a take-home baby rate of 96% and 92%, respectively. There was no perinatal mortality in Indo-Asian women, who were more likely to have a vaginal delivery and less likely to have a baby large for gestational age. Pregnancies complicated by type 2 diabetes in both groups pose the greatest threat to a successful pregnancy outcome. Indo-Asian and Caucasian women attending the same antenatal diabetes service have comparable outcomes. Attendance for pre-pregnancy care needs to be encouraged to combat the high early pregnancy loss and congenital malformation rate identified, particularly in those with type 2 disease, irrespective of ethnicity.

Pregnancy outcome in women with type 2 diabetes mellitus needs to be addressed.

Maternal diabetes mellitus (types 1 and 2) is the most chronic prevalent medical condition affecting the pregnant population and is associated with a less satisfactory pregnancy outcome for both mother and infant when compared with the non-diabetic population. Most reports have focused on women with type 1 disease, type 2 disease being perceived as a less serious condition. However, type 2 disease is far more common (and is increasing) in some areas of the UK, especially where there is a high proportion of women from the Indian subcontinent. This paper shows that pregnancy complicated by type 2 diabetes mellitus is a high-risk state, with miscarriage and congenital malformations almost twice that seen in type 1 disease. These adverse outcomes are contributed to by poor attendance for pre-pregnancy care, later booking for antenatal clinic and poor glycaemic control at booking. Offspring of pregnancies complicated by type 2 diabetes are more likely to be delivered before 37 weeks gestation and be large in size for gestational age. We must dispel the myth, in women of childbearing age and in their healthcare providers, that diabetes treated with diet and/or tablets (type 2) is a less serious problem than type 1 disease.

Ground-based differential absorption lidar system for day or night measurements of ozone throughout the free troposphere.

The National Oceanic and Atmospheric Administration Aeronomy Laboratory's rapid tunable daylight differential absorption lidar system for monitoring ozone throughout the free troposphere is described. The system components are optimized to provide continuously and rapidly profiles of ozone, day or night, with a vertical resolution of 1 km and an absolute accuracy of +/-10% to the tropopause under clear sky conditions. Routine observations of ozone with frequent error assessments are made by scanning wavelengths between 286 and 292 nm.

Temporal pattern of cysteine endopeptidase (cathepsin B) expression in cartilage and synovium from rabbit knees with experimental osteoarthritis: gene expression in chondrocytes in response to interleukin-1 and matrix depletion.

OBJECTIVE: To determine the temporal pattern of expression of cathepsin-B in chondrocytes and synovium in experimental osteoarthritis, and to determine possible mechanisms for upregulation and secretion of cathepsin-B from chondrocytes. METHODS: Experimental osteoarthritis was induced with partial medial meniscectomy (PM); sham operated (SH) and normal (N) rabbits were used as controls. Cathepsin-B mRNA expression was assessed with northern blotting with a 32P labelled cDNA probe. Cathepsin-B was measured in conditioned media or cell extracts using a fluorogenic substrate Z-Arg-Arg-AMC. Chondrocyte monolayers were used to determine cathepsin-B expression in response to interleukin-1 beta (IL-1 beta). Cartilage explants were used to test the effect of matrix depletion on cathepsin-B release. RESULTS: Chondrocytes obtained from experimental osteoarthritis knees did not show cathepsin-B mRNA upregulation. However, isolated chondrocytes secreted cathepsin-B into the culture medium. Enzyme release was significantly higher at 8 weeks relative to controls, but not at 12 weeks or 4 weeks. Enzyme released from synovium was significantly higher in PM group compared with SH group at 4 and 8 weeks. IL-1 beta was ineffective in upregulating steady state cathepsin-B mRNA in chondrocytes; however, it upregulated the intracellular enzyme, and this was blocked with cycloheximide. Enzymatic depletion of cartilage matrix after exposure of explants to IL-1 resulted in release of significantly higher amounts of cathepsin-B into the medium by matrix depleted chondrocytes compared with intact explants. CONCLUSIONS: In experimental osteoarthritis, cathepsin-B is upregulated in synovial tissue during the early degenerative phase. Progression of experimental osteoarthritis is accompanied by upregulation of cathepsin-B in cartilage. Cartilage and synovial cathepsin-B levels decline as experimental osteoarthritis advances to more degenerative states. IL-1 upregulates intracellular cathepsin-B by increasing cathepsin-B protein synthesis; it is not an effective stimulus for enzyme secretion. Depletion of cartilage matrix during progression of experimental osteoarthritis may contribute to secretion of cathepsin-B and perpetuation of cartilage destruction.

HIV infection among Brazilian transvestites in a prison population.

Eighty-two male transvestites imprisoned in Casa de Detenção (São Paulo, Brazil) were tested for HIV antibodies, and completed a questionnaire investigating their demographics, arrest and imprisonment records, sexual practices, and drug use. Data were then analyzed to evaluate the incidence of HIV infection and its association with various behavioral and other factors. Sixty-four of 82 (78%, 95% confidence interval [CI], 67-87%) transvestites were positive for HIV infection. The factors associated with significant differences in positivity among these individuals were the time spent in prison and the number of sexual partners during the previous year. It appears that the high rate of infection in this group obscured the importance of other risk factors and behavioral patterns potentially associated with infection. Given the social environment and the high rate of HIV infection among imprisoned transvestites, their role as "vectors" for dissemination of HIV in urban areas of Brazil may be significant.

Rapid detection of HSV with an enzyme-linked virus inducible system (ELVIS) employing a genetically modified cell line.

BACKGROUND: Infections with herpes simplex viruses (HSV) are common and may cause severe disease in immunocompromised hosts and in neonates. Isolation of infectious HSV in tissue culture is the most sensitive method of detection, but is not the most rapid. Recently, however, an Enzyme-Linked Virus Inducible System (ELVIS) for rapid detection of HSV in culture has been developed. The system employs genetically engineered baby hamster kidney (BHK) cells (ELVIS cells) whose DNA bears and HSV inducible promoter gene chimerically linked to an E. coli LacZ "reporter" gene. Induction of the promoter by HSV leads to the production of LacZ product, beta-galactosidase, which is readily detected histochemically. OBJECTIVE: To evaluate these ELVIS cells, as a test for HSV, in comparison with HSV detection in MRC-5 cells in shell vial cultures confirmed by staining with fluorescent antibodies. STUDY DESIGN: Over a period of one month, 167 specimens submitted to the laboratory for detection of HSV were evaluated. Specimens were inoculated onto MRC-5 cells growing on glass coverslips in each of two shell vials and into two wells of a 24-well cluster plate containing ELVIS cells. MRC-5 shell vial cultures were observed daily for cpe for up to 7 days. With the appearance of cpe, the coverslips were fixed and the cells were typed for HSV-1 and HSV-2 with monoclonal antibodies. Specimens inoculated onto ELVIS cells were incubated for 16-24 h, then substrate was added to stain for beta-galactosidase. ELVIS cells, induced by HSV infection to express beta-galactosidase, stained blue upon reaction with substrate. RESULTS: Of 167 specimens inoculated onto MRC-5 cells, 13 were excluded because of contamination or toxicity. Among the remaining 154 specimens, 24 were positive for HSV in the MRC-5 shell vials. Of 166 specimens inoculated into the ELVIS cell, all were completed within 24 h. Twenty-three (23) of the 24 shell-vial-positive cultures also were positive on the ELVIS cells. All 23 specimens detected in the ELVIS cells were positive within 24 h, whereas only nine were positive within 24 hours in MRC-5 shell vial cultures. The remaining 15 became positive after 24 h. Specimens positive for viruses other than HSV-1 or HSV-2 were not positive on the ELVIS cells. CONCLUSIONS: The ELVIS assay for HSV is simple to perform, is rapid, sensitive, and specific. The assay detects both HSV-1 and HSV-2. No antibodies are required unless typing, which can be done on the ELVIS cells, is necessary.

Removal of Stratospheric O3 by Radicals: In Situ Measurements of OH, HO2, NO, NO2, ClO, and BrO.

Simultaneous in situ measurements of the concentrations of OH, HO(2), ClO, BrO, NO, and NO(2) demonstrate the predominance of odd-hydrogen and halogen free-radical catalysis in determining the rate of removal of ozone in the lower stratosphere during May 1993. A single catalytic cycle, in which the rate-limiting step is the reaction of HO(2) with ozone, accounted for nearly one-half of the total O(3) removal in this region of the atmosphere. Halogen-radical chemistry was responsible for approximately one-third of the photochemical removal of O(3); reactions involving BrO account for one-half of this loss. Catalytic destruction by NO(2), which for two decades was considered to be the predominant loss process, accounted for less than 20 percent of the O(3) removal. The measurements demonstrate quantitatively the coupling that exists between the radical families. The concentrations of HO(2) and ClO are inversely correlated with those of NO and NO(2). The direct determination of the relative importance of the catalytic loss processes, combined with a demonstration of the reactions linking the hydrogen, halogen, and nitrogen radical concentrations, shows that in the air sampled the rate of O(3) removal was inversely correlated with total NOx, loading.

Chemical loss of ozone in the arctic polar vortex in the winter of 1991-1992.

In situ measurements of chlorine monoxide, bromine monoxide, and ozone are extrapolated globally, with the use of meteorological tracers, to infer the loss rates for ozone in the Arctic lower stratosphere during the Airborne Arctic Stratospheric Expedition II (AASE II) in the winter of 1991-1992. The analysis indicates removal of 15 to 20 percent of ambient ozone because of elevated concentrations of chlorine monoxide and bromine monoxide. Observations during AASE II define rates of removal of chlorine monoxide attributable to reaction with nitrogen dioxide (produced by photolysis of nitric acid) and to production of hydrochloric acid. Ozone loss ceased in March as concentrations of chlorine monoxide declined. Ozone losses could approach 50 percent if regeneration of nitrogen dioxide were inhibited by irreversible removal of nitrogen oxides (denitrification), as presently observed in the Antarctic, or without denitrification if inorganic chlorine concentrations were to double.

Ozone loss inside the northern polar vortex during the 1991-1992 winter.

Measurements made in the outer ring of the northern polar vortex from October 1991 through March 1992 reveal an altitude-dependent change in ozone, with a decrease at the bottom of the vortex and a substantial increase at the highest altitudes accessible to measurement. The increase is the result of ozone-rich air entering the vortex, and the decrease reflects ozone loss accumulated after the descent of the air through high concentrations of reactive chlorine. The depleted air that is released out of the bottom of the vortex is sufficient to significantly reduce column ozone at mid-latitudes.

Laboratory diagnosis of human immunodeficiency virus infection.

HIV infection and AIDS will continue to grow as a major medical and social problem. The incidence of heterosexual transmission is rising, and it will become increasingly difficult for physicians and counselors to assess an individual's risk of infection. In coming years, physicians can expect to see patients who are infected, but whose risk may not be apparent, and who may not present with conditions immediately suggestive of their infection. The majority of these patients may not even suspect they are infected. Many of the tests currently available for diagnosing HIV infection are very good. They are both highly sensitive and highly specific and their predictive values are good when their limits are understood. But, as HIV infection expands to an ever larger number of women and children and as the ability to sharply define risk groups fades, demand for a broader range of tests that can reliably confirm infection and are easy to perform can only increase. We have attempted to describe some of the common serologic tests currently used to diagnose HIV infection and some of the limitations of these tests. We also have pointed out that criteria used by laboratories for interpreting tests such as the Western blot may not always be uniform, and physicians should know the criteria used by their reference laboratory and the quality control measures taken. We also have attempted to describe some of the tests available to detect the virus, its genes, or its gene products. PCR and other rapidly evolving gene amplification techniques hold great promise as highly sensitive and specific tests for the diagnosis/confirmation of HIV infection. As with the serologic tests, it is important for those who may use these tests to understand their value as well as their limitations.

Risk factors for HIV infection in homosexual men: the Cleveland men's study of risks in a low-prevalence area.

Detailed questionnaires concerning alcohol and drug use, sexual practices, and medical history were completed by 301 homosexual men living in the Cleveland metropolitan area. Their sera were subsequently tested for antibodies to the human immunodeficiency virus. Fifty-six (18.6%) were seropositive. In a univariate analysis, age, drug use, and four specific sexual practices were associated with seropositivity. In a multiple logistic regression analysis, intravenous drug use and receptive anal-genital sex remained independent predictors of seropositivity.

Evaluation of the Genetic Systems Corp. Integra HIV-1 Pageblot system.

The Genetic Systems Corp. Integra HIV-1 Pageblot system was evaluated as a supplementary assay to confirm the presence of antibodies to human immunodeficiency virus type 1 in 57 specimens from individuals at high risk of infection with the virus. Forty-one specimens identified as reactive in the Genetic Systems Integra HIV-1 Pageblot system were likewise identified as reactive in a U.S. Food and Drug Administration-licensed (Biotech/Dupont) Western blot (immunoblot). Six specimens identified as indeterminate in either or both immunoblot assays were all identified as nonreactive in a U.S. Food and Drug Administration-licensed enzyme immunoassay with recombinant antigens.

Lymphocytic alveolitis in primary HIV infection.

Primary infection with the human immunodeficiency virus (HIV-1) has been associated with a self-limited illness resembling acute infectious mononucleosis. Pulmonary manifestations have been notably absent in published reports. The authors describe a 28-year-old homosexual male who presented with primary HIV-1 infection associated with CD8+ lymphocytic alveolitis. Diagnosis was delayed because HIV antibody was not detected by the Abbott ELISA, although the same and subsequent specimens were later found to be positive by Genetic Systems' ELISA and Western blot analysis. Lymphocytic alveolitis must be added to the expanding clinical spectrum of acute HIV-1 infection. The time to detection of seroconversion may vary with different immunoassays.

Evaluation of the Recombigen HIV-1 Latex Agglutination Test.

The Recombigen HIV-1 Latex Agglutination (LA) Test was recently licensed by the U.S. Food and Drug Administration for use as a rapid screening assay for human immunodeficiency virus type 1 (HIV-1) antibodies. However, its performance in various settings and in different populations has not been firmly established. Consequently, we evaluated the test in the Cleveland Clinic Retrovirus Laboratory, a regional reference laboratory for HIV diagnostic testing and a testing laboratory for the Ohio Department of Health Anonymous HIV Testing and Counseling Program. Serum samples from 93 individuals presumed to be at high risk for HIV infection were evaluated. The sera were initially tested for HIV antibodies by enzyme-linked immunosorbent assay (ELISA). All repeatedly reactive sera were subjected to confirmatory Western blot (WB; immunoblot) testing. Of 97 serum specimens tested (5 were from one seroconverter), 44 were repeatedly reactive by ELISA and 53 were nonreactive. Of the reactive serum specimens, 31 were confirmed positive and 12 were indeterminate by WB. All of the sera were coded and then retested by the LA test. Of 53 serum specimens nonreactive by ELISA, 51 were also nonreactive in the LA test. Of the 44 serum specimens reactive by ELISA, 16 were nonreactive by LA; however, 3 of the latter were WB positive. No serum specimen with an ELISA ratio (specimen optical density/cutoff optical density) of less than 2.1 scored reactive in the LA test. The LA test was positive for only two of five consecutive serum specimens from a seroconverter despite the fact that all but the earliest of these were ELISA reactive and WB positive. Although the LA test appears to be an adequate first-line screening test when appropriately used according to the directions of the manufacturer, our data suggest that occasional sera with low levels of reactivity by ELISA may not be readily detected as reactive by the LA test.

Systemic vasculitis in association with human immunodeficiency virus infection.

Fourteen cases of vasculitis associated with human immunodeficiency virus infection have thus far been described. Five of these cases may be classified as angiocentric immunoproliferative disorders, including benign lymphocytic angiitis, lymphomatoid granulomatosis, and angiocentric lymphoma. We report a case of benign lymphocytic angiitis of T cell lineage. Extensive studies found no evidence of viral antigens in the inflammatory infiltrates, and immunologic evaluation of the pathologic lesions revealed the infiltrating cells to be predominantly CD3+, CD8+, CD4-. A significant number of these lymphocytes demonstrated a deletion of T cell antigen receptor determinants. We believe that in certain cases of human immunodeficiency virus disease, there occurs a spectrum of lymphoproliferative disorders with angiocentric features that lead to the clinical picture of systemic necrotizing vasculitis. Clinicians should be aware of this association.

Interferon gamma production by human intestinal mucosal mononuclear cells. Decreased levels in inflammatory bowel disease.

Immune (gamma) interferon is a substance produced by immunologically activated mononuclear cells. Besides its antiviral activity, interferon gamma has a crucial role in immunoregulation, by acting directly upon lymphocytes and monocytes, and interacting with other soluble mediators of the immune response. Studies of the interferons system in inflammatory bowel disease have been limited, and little information is available on the generation of interferon during immunological events occurring in the human gut. To investigate the capacity of intestinal mucosal mononuclear cells to produce interferon gamma, lamina proprial mononuclear cells, isolated from Crohn's disease, ulcerative colitis, and control patients, were incubated with interleukin 2 or phytohemagglutinin, and the amounts of interferon gamma present in the culture supernatants were measured by a virus cytopathic effect inhibition assay. Under identical stimulatory conditions, culture supernatants of cells derived from actively involved mucosa of inflammatory bowel disease specimens contained two- to fivefold less interferon gamma than those of cells from control tissue. However, the amount of interferon gamma present in supernatants of cells from uninvolved inflammatory bowel disease mucosa was similar to that found in control supernatants. These results indicate that, in patients with active Crohn's disease and ulcerative colitis, mononuclear cells produce decreased amounts of interferon gamma in the intestinal mucosa. The exact significance of these findings is unclear, but because of the importance of interferon gamma in a variety of cell-mediated immune phenomena, its impaired availability might be relevant to the pathogenesis of inflammatory bowel disease.