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Biomedical subjects

H Horowitz

Publications and source records attributed to H Horowitz.

At least 19 recordsLinked to original sources
PubMed2005

Prevalence and severity of dental caries in Costa Rican schoolchildren: results of the 1999 national survey.

UNLABELLED: In 1987, Costa Rica implemented a comprehensive national salt fluoridation programme using sodium fluoride (225-275mg F/kg salt). AIM: To describe dental caries prevalence and severity in Costa Rican children in 1999. METHODS: Eight calibrated examiners (inter-examiner Kappa = 0.70 or higher) recorded information on dental caries, treatment needs, enamel fluorosis, and dentofacial anomalies for schoolchildren aged 6-8,12, and 15-years (N=3758). The survey utilised a multistrata probability sample with fixed allocation to represent seven regions of the country. RESULTS: The overall mean dmft for age 6-8 years was 3.32. The DMFT for age 12 was 2.46 and for age 15 was 4.37. Regional differences were observed; for example, the DMFT at age 12 years ranged from 1.93 to 3.86. Compared with pre-fluoridation data collected in 1984, schoolchildren aged 12 years, experienced a 28 per cent decrease in caries prevalence (100 per cent to 72 per cent) and a 73 per cent decrease in severity (DMFT from 9.13 to 2.46, representing an 8.3 per cent compound annual per cent reduction). CONCLUSIONS: Between 1984 and 1999, Costa Rican schoolchildren experienced substantial reductions in caries prevalence and severity. Many factors may be involved in this decline, but the most important appears to be exposure to fluoridated salt.

Adolescent↗
PubMed2001

Salt fluoridation and dental caries in Jamaica.

PURPOSE: In 1987, Jamaica initiated a comprehensive island-wide salt fluoridation program. A survey was conducted in 1995 to monitor the impact of salt fluoridation among children in Jamaica. METHODS: Dental examinations of 1,120 children aged 6-8, 12, and 15 years were conducted according to World Health Organization criteria to assess dental caries, fluorosis, the presence of and need for dental sealants, and Community Periodontal Treatment Needs (CPI). RESULTS: Age specific DMFT means observed in 1995 were 0.2 at age 7, 0.4 at age 8, 1.1 at age 12 and 3.0 at age 15. The mean DMFT scores in children 6, 12 and 15 years of age were dramatically lower than the corresponding scores of 1.7, 6.7 and 9.6 obtained at the baseline examination in 1984 for children of the same age groups, respectively (baseline data for 7- and 8-year-olds were not collected). The mean percentage of sound permanent teeth for all age groups was 90% in 1995. The percentage of children caries-free at baseline was 27.6% for 6 years, 2.8% for 12 years and 0.3% for 15 years of age. In 1995, the percentage of caries-free children (permanent teeth) was 61%. In 1984, 23 children were scored as having very mild or mild fluorosis. In 1995, five children were scored in the same categories of fluorosis, using Dean's criteria; thus, fluorosis remained at negligible levels in 1995. CONCLUSIONS: The oral health survey conducted in Jamaica in 1995 indicated a significant decline in dental caries compared with findings in 1984. The major change in Jamaica during the interval was the introduction of salt fluoridation in 1987. Dental fluorosis was low in the 1995 survey.

Adolescent↗
PubMed2001

Drosophila rhino encodes a female-specific chromo-domain protein that affects chromosome structure and egg polarity.

Here we describe our analyses of Rhino, a novel member of the Heterochromatin Protein 1(HP1) subfamily of chromo box proteins. rhino (rhi) is expressed only in females and chiefly in the germline, thus providing a new tool to dissect the role of chromo-domain proteins in development. Mutations in rhi disrupt eggshell and embryonic patterning and arrest nurse cell nuclei during a stage-specific reorganization of their polyploid chromosomes, a mitotic-like state called the "five-blob" stage. These visible alterations in chromosome structure do not affect polarity by altering transcription of key patterning genes. Expression levels of gurken (grk), oskar (osk), bicoid (bcd), and decapentaplegic (dpp) transcripts are normal, with a slight delay in the appearance of bcd and dpp mRNAs. Mislocalization of grk and osk transcripts, however, suggests a defect in the microtubule reorganization that occurs during the middle stages of oogenesis and determines axial polarity. This defect likely results from aberrant Grk/Egfr signaling at earlier stages, since rhi mutations delay synthesis of Grk protein in germaria and early egg chambers. In addition, Grk protein accumulates in large, actin-caged vesicles near the endoplasmic reticulum of stages 6-10 egg chambers. We propose two hypotheses to explain these results. First, Rhi may play dual roles in oogenesis, independently regulating chromosome compaction in nurse cells at the end of the unique endoreplication cycle 5 and repressing transcription of genes that inhibit Grk synthesis. Thus, loss-of-function mutations arrest nurse cell chromosome reorganization at the five-blob stage and delay production or processing of Grk protein, leading to axial patterning defects. Second, Rhi may regulate chromosome compaction in both nurse cells and oocyte. Loss-of-function mutations block nurse cell nuclear transitions at the five-blob stage and activate checkpoint controls in the oocyte that arrest Grk synthesis and/or inhibit cytoskeletal functions. These functions may involve direct binding of Rhi to chromosomes or may involve indirect effects on pathways controlling these processes.

Amino Acid Sequence↗
PubMed2001

Intraocular pressure and tear production in captive eland and fallow deer.

Applanation tonometry was used to estimate intraocular pressure (IOP) and Schirmer tear test (STT) I was used to estimate tear production in both eyes of 12 juvenile elands (Taurotragus oryx) and one eye each of 15 Asian fallow deer (Dama mesopotamica). Mean (+/- standard deviation) IOP was 14.6 +/- 4.0 mm Hg in the eland and 11.9 +/- 3.3 mm Hg in the deer. Mean tear production was 18.7 +/- 5.9 mm/min in the eland and 10.5 +/- 6.5 mm/min in the deer. The large variation in IOP between two members of the family Bovidae, the elands reported here and the Thomson gazelle (Gazella thomsoni) for which we previously reported a mean pressure of 7.6 mm Hg, illustrates the need to establish reference values for each species. Tear production may be influenced by the species' natural habitat.

Animals↗
PubMed1999

Activation or destruction of T cells via macrophages.

Macrophages (MPhi) affect the T cell response in two mutually exclusive ways: activation or deletion. A MPhi type with T cell activating functions (M1) is able to express and upregulate receptors of the B7 family. IFN-gamma favours this MPhi differentiation pathway via upregulation of CD80 (B7-1) and CD86 (B7-2). The treatment of MPhi with IFN-gamma enhances the alphaCD3-mediated T cell blast transformation and reduces the fraction of deleted T cells. This MPhi type may prevent antibody-mediated T cell destruction by the expression of costimulatory receptors. An IL-10-induced MPhi type (M2) fails to express costimulatory molecules of the B7 family but is an effective cell for T cell destruction. Forming cellular conjugates with T cells through antibodies or immune complexes, M2-MPhi preferentially delete targeted cells in vitro and in vivo.

Antibodies, Monoclonal↗
PubMed1997

Cytotoxic monocytes in the blood of HIV type 1-infected subjects destroy targeted T cells in a CD95-dependent fashion.

HIV-1 infection changes the functional balance of macrophages in the body; it inhibits the development of macrophages capable of costimulating T cell responses and it favors the development of macrophages that kill T cells with which they form cellular conjugates. Cytotoxic macrophages destroy CD4 T cells, which they target through CD4-reactive immune-complexed HIV-1 envelope molecules on a large scale. They also destroy T cells that they target through presented antigen or mitogen. We show here that cytotoxic macrophages destroy their cellular targets at least partially in a CD95-dependent process in which T cells first modulate expression of most of their membrane receptors and subsequently die.

Adult↗
PubMed1997

Two distinct pathways of human macrophage differentiation are mediated by interferon-gamma and interleukin-10.

Forming cellular conjugates with T cells, macrophages can help their targets to mount an immune response or they can destroy the targeted T cell. The two functions are performed by two distinct macrophage subsets that can be distinguished by cell surface marker phenotypes, B7+ CD16- and B7- CD16+. Interferon-gamma (IFN-gamma) induces the former, interleukin-10 (IL-10) induces the latter phenotype. The two macrophage differentiation pathways are mutually exclusive; each cytokine inhibits the effect of the other cytokine. The second messenger cAMP enhances the macrophage B7 expression and suppresses the macrophage CD16 expression. However, together with IL-10, cAMP blocks the generation of both macrophage phenotypes. In the chimpanzee we noted deviations from this differentiation pattern that are suggestive of an enhanced IL-10 presence in the primate environment.

Animals↗
PubMed1996

AIDS patient monocytes target CD4 T cells for cellular conjugate formation and deletion through the membrane expression of HIV-1 envelope molecules.

The human immunodeficiency virus (HIV) causes in humans the acquired immunodeficiency syndrome (AIDS). It replicates at a high rate in lymphoid organs even before it causes clinical symptoms. It binds to CD4 cell surface markers and destroys T lymphocytes that express the receptor. The immune system replenishes CD4 T cells at a formidable rate but, unable to keep up with the losses, allows the CD4 T cell compartment to disintegrate gradually. The net loss of CD4 T cells is an indicator for disease progression. How the virus destroys CD4 T cells and whether their loss accounts for the ensuing immunodeficiency have not been fully explained. We have reported evidence, and confirm here, that HIV-infected subjects deposit on monocytes immune complexes containing the virus or its envelope molecule gp120. Armed with these immune complexes monocytes form specific cellular conjugates with CD4 T cells and kill them. The destruction of normal CD4 T cells by monocytes from AIDS patients can be blocked by soluble CD4 and by free gp120. Normal monocytes and macrophages can be armed with CD4-binding gp120, and so induced to destroy CD4 T cells, by incubating them with gp120 and gp120-specific antibody. CD4-reactive HIV-1 components have a short half-life on the phagocyte surface. Removed from the HIV-infected environment, monocytes clear their surfaces of antibody-complexed viral components within hours, which abrogates their ability to destroy CD4 T cells. Rearming the monocytes with gp120-anti-gp120 complexes restores their capacity to destroy CD4 T cells. The data imply that for uninterrupted deletion of CD4 T cells, monocytes require a continued productive HIV-1 infection of their host.

Acquired Immunodeficiency Syndrome↗
PubMed1996

The cell surface marker phenotype of macrophages from HIV-1-infected subjects reflects an IL-10-Enriched and IFN-gamma-deprived donor environment.

T cells depend on costimulation by accessory cells for an immune response. Costimulatory macrophage activity involves the expression of B7 molecules whose expression is upregulated by interferon-gamma (IFN-gamma) and downregulated by interleukin-10 (IL-10). The expression of low-affinity Fc gamma IIIR (CD16), in contrast, is upregulated in the presence of IL-10 and downregulated in the presence of IFN-gamma. In human immunodeficiency virus-1 (HIV-1) infection, the balance between IFN-gamma and IL-10 expression shifts toward IL-10 predominance. Herein, we compare B7 and CD16 macrophage phenotypes from healthy and from HIV-1-infected patients. Patient macrophages express B7 molecules in lower density than macrophages from healthy donors and are resistant to the upregulation of costimulatory molecule expression. B7 expression can be normalized in patient macrophages by treating them with anti IL-10 monoclonal antibodies (mAb) and IFN-gamma together but not by treatment with either anti-IL-10 mAb or IFN-gamma alone. This finding suggests an excess of IL-10 in HIV-1 infection and an IFN-gamma deficiency, consistent with previous cytokine assessments in HIV-1-infected subjects. The upregulation of CD16 expression was readily induced in patient macrophages by treatment with IL-10 and was inhibited by treatment with IFN-gamma. CD16 expression identifies the subset of cytotoxic macrophages that has been shown to destroy CD4T cells, which they target through CD4-reactive immune-complexed HIV-1 envelope molecules.

Acquired Immunodeficiency Syndrome↗
PubMed1996

The Drosophila pipsqueak gene encodes a nuclear BTB-domain-containing protein required early in oogenesis.

Mutations at the pipsqueak locus affect early patterning in the Drosophila egg and embryo. We have cloned pipsqueak and found that it is a large and complex gene, encoding multiple transcripts and protein isoforms. One protein, PsqA, is absent in all of the mutants that we have examined. We show that PsqA is a nuclear protein present in the germ cells and somatically derived follicle cells throughout oogenesis and that it is required prior to stage one of oogenesis. PsqA contains a BTB (POZ) domain at its amino terminus; additionally, we have identified an evolutionarily conserved motif of unknown function present four times in tandem at the C terminus of the protein. PZ pipsqueak mutants produce a putative fusion protein containing the pipsqueak BTB domain fused to sequences resident on the PZ element (H. Horowitz and C. Berg, 1995 Genetics 139, 327-335). We demonstrate here that expression of this fusion protein in wild-type flies has a dominant effect, resulting in infertility and eggshell defects. These dominant phenotypes are discussed in light of current theories on the role of the BTB domain in protein-protein interactions.

Alternative Splicing↗
PubMed1995

Aberrant splicing and transcription termination caused by P element insertion into the intron of a Drosophila gene.

Insertional mutagenesis screens using the P[lacZ, rosy+] (PZ) transposable element have provided thousands of mutant lines for analyzing genes of varied function in the fruitfly, Drosophila melanogaster. As have been observed with other P elements, many of the PZ-induced mutations result from insertion of the P element into the promoter or 5' untranslated regions of the affected gene. We document here a novel mechanism for mutagenesis by this element. We show that sequences present within the element direct aberrant splicing and termination events that produce a mRNA composed of 5' sequences from the mutated gene (in this case, pipsqueak) and 3' sequences from within the P[lacZ, rosy+] element. These truncated RNAs could yield proteins with dominant mutant effects.

Alleles↗
PubMed1994

Adverse reactions associated with simultaneous administration of multiple vaccines to travelers.

OBJECTIVE: To determine the frequency of local and systemic adverse reactions following the simultaneous administration of multiple vaccines. DESIGN: Prospective descriptive study using a self-administered questionnaire. All patients seen in a one-year period were given the questionnaire and a stamped, return-addressed envelope to be returned three days after their clinic visits. SETTING: Westchester County (New York) Department of Health Travelers' Clinic. PATIENTS: 984 patients made 1,205 visits. 64% returned the questionnaires. INTERVENTION: The patients reported the occurrence and duration of local and systemic reactions three days after the clinic visit. Demographic data, names of the vaccines, and a description of the injection site of each vaccine were collected separately by clinic staff for each patient at each visit. RESULTS: 58% of the patients reported local reactions and 39.5% at least one systemic complaint. The rate of local reactions increased from 45% with 1 injection in an arm to 78% with > or = 3 (OR = 99). The rate of systemic reactions increased from 25% following the administration of 1 vaccine to 70% with > or = 5 (OR = 7). Number of vaccines did not influence duration or severity of reaction. Age and gender were not associated with frequency of reactions. CONCLUSION: Side effects for vaccination of travelers are common. Increasing the number of vaccines is associated with increasing the rates of local and systemic reactions. These reactions are generally minor and should not be a reason to withhold multiple vaccinations to patients when needed.

Adult↗
PubMed1994

Outbreak of vancomycin-, ampicillin-, and aminoglycoside-resistant Enterococcus faecium bacteremia in an adult oncology unit.

An outbreak of bacteremia caused by Enterococcus faecium with high-level resistance to vancomycin (MIC of > or = 256 micrograms/ml), ampicillin (MIC of > or = 64 micrograms/ml), and gentamicin or streptomycin (MIC of > or = 2,000 micrograms/ml) occurred in an adult oncology unit from June 1991 to May 1992. Active surveillance for the presence of this organism in stool or perianal cultures was begun in September 1991. Between June 1991 and May 1992, seven patients with bacteremia and 22 noninfected carriers of the organism in stool were identified. The vanA gene, tested for by PCR and gene probe, was present in all isolates evaluated. All bacteremic patients also had resistant E. faecium present in a stool or perianal culture; the stool isolates tested were closely related to the respective blood isolates as determined by pulsed-field gel electrophoresis. Antibiotic regimens using high-dose ampicillin and an aminoglycoside were ineffective with four patients. Five patients (71%) had multiple positive blood cultures; four of these patients died. Following a multiple logistic regression analysis, it was found that bacteremic patients received a significantly greater number of total antibiotic days compared with noninfected stool carriers (P = 0.019). The emergence of E. faecium with high-level resistance to vancomycin, ampicillin, and aminoglycosides underscores the importance of performing susceptibility testing on all clinically significant isolates. In the neutropenic adult oncology patient, bacteremia with this organism is of probable gastrointestinal origin, is often persistent, and is refractory to treatment with ampicillin in combination with an aminoglycoside. Prolonged use of antibiotics may predispose patients with gastrointestinal colonization to develop bacteremia.

Adult↗
PubMed1994

Low-dose dexamethasone as adjunctive therapy for disseminated Mycobacterium avium complex infections in AIDS patients.

Five human immunodeficiency virus-infected patients with disseminated Mycobacterium avium complex infection had progressive weight loss and persistent fever despite multidrug antimycobacterial therapy. These patients were given daily low-dose oral dexamethasone (typically 2 mg/day) as adjunctive therapy. All had substantial and sustained weight gain (12 to 50% of pre-steroid treatment body weight [P < 0.03]), reduction in fever, and an improved sense of well-being. The serum albumin level increased during dexamethasone therapy (from 3.06 +/- 0.59 g/dl [mean +/- standard deviation] to 3.9 +/- 0.22 g/dl [P < 0.01]), while the serum alkaline phosphatase level fell (from 368 +/- 247 U/liter to 128 +/- 43.6 U/liter [P < 0.04]). Further studies of the potential role for corticosteroids in the management of disseminated M. avium complex infections in human immunodeficiency virus-infected patients are warranted.

AIDS-Related Opportunistic Infections↗
PubMed1993

Fluconazole prophylaxis of fungal infections in patients with acute leukemia. Results of a randomized placebo-controlled, double-blind, multicenter trial.

OBJECTIVE: To evaluate the efficacy and safety of fluconazole for prevention of fungal infections. DESIGN: A randomized, placebo-controlled, double-blind, multicenter trial. PATIENTS: Adults (257) undergoing chemotherapy for acute leukemia. INTERVENTION: Patients were randomly assigned to receive either fluconazole (400 mg orally once daily or 200 mg intravenously every 12 hours) or placebo. The study drug was started at initiation of chemotherapy and continued until recovery of neutrophil count, development of proven or suspected invasive fungal infection, or the occurrence of a drug-related toxicity. MEASUREMENTS: Fungal colonization, proven superficial or invasive fungal infection, empiric antifungal therapy with amphotericin B, drug-related side effects, and mortality. MAIN RESULTS: Fluconazole decreased fungal colonization (83 of 122 [68%] placebo patients compared with 34 of 119 [29%] fluconazole patients colonized at end of prophylaxis, P < 0.001) and proven fungal infections (27 of 132 [21%] placebo patients compared with 11 of 123 [9%] fluconazole patients infected, P = 0.02). Superficial fungal infections occurred in 20 of 132 (15%) placebo patients but in only 7 of 123 (6%) fluconazole patients (P = 0.01), whereas invasive fungal infections developed in 10 of 132 (8%) placebo patients and in 5 of 123 (4%) fluconazole patients (P = 0.3). Fluconazole was especially effective in eliminating colonization and infection by Candida species other than Candida krusei (66 of 122 [64%] placebo patients colonized at end of prophylaxis compared with 11 of 119 [9%] fluconazole patients, P < 0.001; 22 of 132 [17%] placebo patients infected compared with 7 of 123 [6%] fluconazole patients, P = 0.005). Aspergillus infections were infrequent in both fluconazole (3 cases) and placebo groups (3 cases). The use of amphotericin B, the incidence of drug-related side effects, and overall mortality were similar in both study groups. CONCLUSION: Prophylactic fluconazole prevents colonization and superficial infections by Candida species other than Candida krusei in patients undergoing chemotherapy for acute leukemia and is well tolerated. Fluconazole could not be clearly shown to be effective for preventing invasive fungal infections, reducing the use of amphotericin B, or decreasing the number of deaths.

Acute Disease↗