Notes on Ipomoea L. (Convolvulaceae) in Cuba and neighbouring islands with a checklist of species found in Cuba.

An updated checklist of species of Ipomoea L. found in Cuba is presented with analysis of the different elements represented. I. alterniflora Griseb. is defined broadly to include I. obtusata Griseb. and I. excisa Urb. and its differences from the little-known I. cubensis (House) Urb. are discussed. I. calophylla C. Wright ex Griseb. is reinstated as the correct name for the species generally known as I. lacteola House. I. praecox C. Wright is recognised as a distinct species from I. argentifolia A. Rich. and images are provided to help distinguish the two species. I. flavopurpurea Urb. and I. dajabonensis Alain are shown to be conspecific with I. longeramosa Choisy, whose disjunct distribution is mapped and discussed. The little-known I. montecristina Hadac is described and illustrated and the cited collections show it to be locally common in the Guantánamo region. I. microdonta J. R. I. Wood & Scotland is described as new from Camagüey in central Cuba. Eight species endemic to Cuba collected by Ekman and described by Urban in 1924 - 25 are evaluated but only two, I. balioclada Urb. and I. erosa Urb., are deemed to warrant recognition as distinct endemic species. The origin and typification of I. horsfalliae Hook. are discussed and an epitype designated. Cultivated plants named I. horsfalliae occur in many tropical countries including Cuba but their extreme variation suggests hybrid origin. Four species from Jamaica, I. rubella House, I. lineolata Urb., I. carmesina Proctor and the Jamaican plant called I. horsfalliae are treated as synonyms of a variable I. lineolata, which is endemic to the island. I. saxicola Proctor is treated as var. saxicola J. R. I. Wood & Scotland of I. ternata Jacq. I. cyanantha Griseb. is treated as a synonym of I. lindenii M. Martens & Galeotti. Lectotypes are designated for I. cyanantha, I. lindenii, I. praecox, I. punctata C. Wright, I. geranioides Meisn. and I. grisebachii Urb.

Association and linkage analysis of RGS4 polymorphisms with schizophrenia and bipolar disorder in Brazil.

Linkage and association studies in five independently ascertained samples have suggested that polymorphisms of the regulator of G-protein signaling 4 (RGS4) may confer risk for schizophrenia (SCZ). Suggestive evidence for association with bipolar disorder (BD) has also been presented. However, the associated alleles and haplotypes have differed among the samples. Data from other independent samples may clarify the putative associations. Hence, we investigated an independent, ethnically diverse Brazilian population comprising patients with SCZ (n=271) or BD1 (n=306), who were contrasted with 576 community-based controls. Parents of 49 SCZ cases and 44 BD cases were available for transmission disequilibrium tests (TDTs). Four RGS4 single-nucleotide polymorphisms (SNPs) 1, 4, 7 and 18 putatively associated with SCZ were investigated. In the SCZ samples, significant case-control differences were not observed for individual SNPs or haplotypes, though the TDT suggested transmission distortion similar to that observed in the initial report. For the BD sample, case-control comparisons revealed no significant differences for individual SNPs, but an omnibus test suggested differences in the overall distribution of haplotypes bearing all four SNPs (SNP-EM Omnibus likelihood ratio test; P=0.003). The TDT revealed over-transmission of allele A at SNP7 (P=0.016), as well as haplotypes incorporating this allele. However, global tests incorporating all haplotypes yielded only suggestive trends for association (P=0.19). In conclusion, association with SCZ was not detected in the present analyses. The failure to detect an association may be related to inadequate power or to confounds related to ethnic admixture. Suggestive associations with BD detected here require further investigation in a larger sample.

Do coping styles differ across sociocultural groups? The role of measurement equivalence in making this judgment.

Cross-sociocultural group measurement equivalency is an important issue that generally has not been studied in the coping literature. Measurement equivalency of the COPE (Carver, Scheier, & Weintraub, 1989) was assessed across two sociocultural groups, a sample of 100 Anglo middle-class divorced mothers and a sample of 122 low-income Mexican American/Mexican immigrant mothers. A series of restrictive confirmatory factor analyses revealed that seven of the COPE's subscales may be measuring the same underlying construct across populations. However, scores derived from the subscales may not represent the same magnitude of the construct in these two groups. This study makes an important first step in furthering the understanding of coping strategies in low-income Mexican American/Mexican immigrant mothers. This study also illustrates the importance of testing for measurement equivalency before conducting comparative research in disparate populations.

Inhibition of vascular endothelial growth factor (VEGF) as a novel approach for cancer therapy.

Of the numerous growth factors and cytokines that have been shown to have angiogenic effects, vascular endothelial growth factor (VEGF), also known as vascular permeability factor (VPF), appears to be a key factor in pathological situations which involve neovascularization as well as enhanced vascular permeability. Our aim was to design a low molecular weight synthetic molecule that potently and selectively blocks the VEGF/VEGF receptor system after oral administration, suitable for the chronic therapy of VEGF-dependent pathological neovascularization. PTK787/ZK 222584 is a potent inhibitor of VEGF receptor tyrosine kinases, active in the submicromolar range. It also inhibits other class III kinases, like the PDGFR-beta tyrosine kinase, c-Kit and c-Fms, but at higher concentrations. It is not active against kinases from other receptor families such as EGFR, FGFR-1, c-Met and Tie-2 or intracellular kinases like c-Src, c-Abl, PKC-alpha. PTK787/ZK 222584 inhibits VEGF-induced autophosphorylation of KDR, and endothelial cell proliferation, migration and survival in the nanomolar range in cell based assays. In concentrations up to 1 microM, PTK787/ZK 222584 does not have any cytotoxic or anti-proliferative effect on cells that do not express VEGF receptors. After oral dosing (50 mg/kg) to mice, plasma concentrations of PTK787/ZK 222584 remain above 1 microM for more than 8 h. PTK787/ZK 222584 induces dose-dependent inhibition of VEGF- and PDGF-induced angiogenesis in a growth factor implant model, as well as a tumor cell-driven angiogenesis model after once daily oral dosing (25-100 mg/kg). In the same dose range, it also inhibits the growth of several human carcinomas, grown subcutaneously in nude mice, as well as a murine renal carcinoma and its metastases in syngeneic, orthotopic models. Histological examination of tumors reveals inhibition of microvessel formation in the interior of the tumor. PTK787/ZK 222584 also significantly inhibits ascites formation induced by a human ovarian carcinoma grown in the peritoneum of nude mice as well as pleural effusion induced by a human lung adenocarcinoma in nude mice. PTK787/ZK 222584 is very well tolerated and does not impair wound healing. It also does not have any significant effects on circulating blood cells or bone marrow leukocytes as a single agent, or impair hematopoetic recovery following concomitant cytotoxic anti-cancer agent challenge. These studies indicate that compounds that inhibit the effects of VEGF, such as PTK787/ZK 222584, have the potential to provide a novel, effective and well-tolerated therapy for the treatment of solid tumors. These agents may also provide a new therapeutic approach for the treatment of other diseases where angiogenesis plays an important role.

Inhibition of vascular endothelial growth factor (VEGF) as a novel approach for cancer therapy.

Of the numerous growth factors and cytokines that have been shown to have angiogenic effects, vascular endothelial growth factor (VEGF), also known as vascular permeability factor (VPF), appears to be a key factor in pathological situations which involve neovascularization as well as enhanced vascular permeability. Our aim was to design a low molecular weight synthetic molecule that potently and selectively blocks the VEGF/VEGF receptor system after oral administration, suitable for the chronic therapy of VEGF-dependent pathological neovascularization. PTK787/ZK 222584 is a potent inhibitor of VEGF receptor tyrosine kinases, active in the submicromolar range. It also inhibits other class III kinases, like the PDGFR-beta tyrosine kinase, c-Kit and c-Fms, but at higher concentrations. It is not active against kinases from other receptor families such as EGFR, FGFR-1, c-Met and Tie-2 or intracellular kinases like c-Src, c-Abl, PKC-alpha. PTK787/ZK 222584 inhibits VEGF-induced autophosphorylation of KDR, and endothelial cell proliferation, migration and survival in the nanomolar range in cell based assays. In concentrations up to 1 microM, PTK787/ZK 222584 does not have any cytotoxic or anti-proliferative effect on cells that do not express VEGF receptors. After oral dosing (50 mg/kg) to mice, plasma concentrations of PTK787/ZK 222584 remain above 1 microM for more than 8 h. PTK787/ZK 222584 induces dose-dependent inhibition of VEGF- and PDGF-induced angiogenesis in a growth factor implant model, as well as a tumor cell-driven angiogenesis model after once daily oral dosing (25-100 mg/kg). In the same dose range, it also inhibits the growth of several human carcinomas, grown subcutaneously in nude mice, as well as a murine renal carcinoma and its metastases in syngeneic, orthotopic models. Histological examination of tumors reveals inhibition of microvessel formation in the interior of the tumor. PTK787/ZK 222584 also significantly inhibits ascites formation induced by a human ovarian carcinoma grown in the peritoneum of nude mice as well as pleural effusion induced by a human lung adenocarcinoma in nude mice. PTK787/ZK 222584 is very well tolerated and does not impair wound healing. It also does not have any significant effects on circulating blood cells or bone marrow leukocytes as a single agent, or impair hematopoetic recovery following concomitant cytotoxic anti-cancer agent challenge. These studies indicate that compounds that inhibit the effects of VEGF, such as PTK787/ZK 222584, have the potential to provide a novel, effective and well-tolerated therapy for the treatment of solid tumors. These agents may also provide a new therapeutic approach for the treatment of other diseases where angiogenesis plays an important role.

Inhibition of vascular endothelial growth factor (VEGF) as a novel approach for cancer therapy

Of the numerous growth factors and cytokines that have been shown to have angiogenic effects, vascular endothelial growth factor (VEGF), also known as vascular permeability factor (VPF), appears to be a key factor in pathological situations which involve neovascularization as well as enhanced vascular permeability. Our aim was to design a low molecular weight synthetic molecule that potently and selectively blocks the VEGF/VEGF receptor system after oral administration, suitable for the chronic therapy of VEGF-dependent pathological neovascularization. PTK787/ZK 222584 is a potent inhibitor of VEGF receptor tyrosine kinases, active in the submicromolar range. It also inhibits other class III kinases, like the PDGFR-beta tyrosine kinase, c-Kit and c-Fms, but at higher concentrations. It is not active against kinases from other receptor families such as EGFR, FGFR-1, c-Met and Tie-2 or intracellular kinases like c-Src, c-Abl, PKC-alpha. PTK787/ZK 222584 inhibits VEGF-induced autophosphorylation of KDR, and endothelial cell proliferation, migration and survival in the nanomolar range in cell based assays. In concentrations up to 1 microM, PTK787/ZK 222584 does not have any cytotoxic or anti-proliferative effect on cells that do not express VEGF receptors. After oral dosing (50 mg/kg) to mice, plasma concentrations of PTK787/ZK 222584 remain above 1 microM for more than 8 h. PTK787/ZK 222584 induces dose-dependent inhibition of VEGF- and PDGF-induced angiogenesis in a growth factor implant model, as well as a tumor cell-driven angiogenesis model after once daily oral dosing (25-100 mg/kg). In the same dose range, it also inhibits the growth of several human carcinomas, grown subcutaneously in nude mice, as well as a murine renal carcinoma and its metastases in syngeneic, orthotopic models. Histological examination of tumors reveals inhibition of microvessel formation in the interior of the tumor. PTK787/ZK 222584 also significantly inhibits ascites formation induced by a human ovarian carcinoma grown in the peritoneum of nude mice as well as pleural effusion induced by a human lung adenocarcinoma in nude mice. PTK787/ZK 222584 is very well tolerated and does not impair wound healing. It also does not have any significant effects on circulating blood cells or bone marrow leukocytes as a single agent, or impair hematopoetic recovery following concomitant cytotoxic anti-cancer agent challenge. These studies indicate that compounds that inhibit the effects of VEGF, such as PTK787/ZK 222584, have the potential to provide a novel, effective and well-tolerated therapy for the treatment of solid tumors. These agents may also provide a new therapeutic approach for the treatment of other diseases where angiogenesis plays an important role.

Colitis and colon cancer in cotton-top tamarins (Saguinus oedipus oedipus) living wild in their natural habitat.

The cotton-top tamarin is a nonhuman primate noted for susceptibility to juvenile onset colitis and subsequent colon cancer. About 80% develop colitis in captive environments outside the tropics. The aim was to determine the prevalence of colitis and colorectal cancer in tamarins living wild in their tropical habitat. Endoscopic biopsy was used to compare severity of colitis, inflammatory/immune cell densities, mucosal dysplasia, and occurrence of cancer in wild tamarins in a tropical habitat with tamarins living captive in a temperate climate. Six colon biopsies from each of 69 captives showed severe colitis in 64.5% of biopsies and moderate colitis in 19.5%. Severe colitis was not found in 88 wild tamarins; 13% had moderate colitis. Densities of polymorphonuclear leukocytes, plasma cells, and mononuclear cells in the lamina propria were related directly to the severity of four grades of colitis (normal, mild, moderate, and severe). Histologic or gross signs of carcinoma were detected in 12 captives and low- or high-grade dysplasia in 15. Neither cancer nor dysplasia was found in any of the wild tamarins. The observations suggest that colitis and cancer in the tamarin model are linked to environmental factors.

Passive transfer of growth-inhibitory antibodies raised against yeast-expressed recombinant Plasmodium falciparum merozoite surface protein-1(19).

Purified rabbit immunoglobulin raised against yeast-expressed recombinant FVO or 3D7 Plasmodium falciparum merozoite surface protein-1 (MSP-1) 19k-D C terminal fragment (MSP-1(19)) was transfused into malaria-naive Aotus nancymai monkeys that were immediately challenged with FVO asexual stage malaria parasites. Control monkeys received rabbit immunoglobulin raised against the sexual stage antigen Pfs25 or Aotus hyperimmune serum obtained from monkeys immunized by P. falciparum infection and drug cure. Passive transfer of rabbit anti-MSP-1(19) failed to protect against homologous or heterologous challenge and, when compared with negative controls, there were no differences in prepatent periods or time to treatment. Interestingly, rabbit anti-MSP-1(19), but not anti-Pfs25, immunoglobulin, and immune monkey serum prevented the development of antibodies directed against MSP-1(19) fragment by infected monkeys, indicating that the antibodies were reactive with native MSP-1(19) antigen in vivo. The prepatent period and time to treatment was greatly delayed in the two monkeys that received Aotus immune serum, both of which developed a chronic intermittent low level infection. In vitro parasite growth inhibition assays (GIAs) confirmed the presence of inhibitory activity (40% maximum inhibition) in concentrated anti-MSP-1(19) immunoglobulin (4.8 mg/ml), but the peak concentrations we achieved in vivo (1 mg/ml) were not inhibitory in vitro. Subinhibitory levels of anti-MSP-1(19) antibodies achieved by passive transfer were not protective against P. falciparum challenge.

Proportional hazards analysis of diarrhea due to enterotoxigenic Escherichia coli and breast feeding in a cohort of urban Mexican children.

Ninety-eight women-infant pairs were followed for up to 50 weeks in the northern part of Guadalajara, Mexico, from August 1986 to July 1987 as part of a community-based, prospective study of the relation between infant feeding patterns and enterotoxigenic Escherichia coli producing heat-labile toxin (LT-ETEC) diarrheal disease. Strictly formula-fed children had an incidence of diarrhea over three times that of strictly breast-fed infants and twice that of breast-fed and supplementally fed children. Strictly formula-fed infants colonized by LT-ETEC were symptomatic for diarrhea nearly three times as often as strictly breast-fed infants and twice as often as infants receiving a mixed diet. The fitting of parametric hazard models to durations until LT-ETEC colonization revealed that the hazard for the first colonization was time invariant. The hazard of diarrhea increased by 400-500% during the rainy season or among children 3 months of age or older who received avena, a barley drink. The best-fitting hazard models to durations until symptomatic expression of LT-ETEC infection all increased through time. This hazard was inversely impacted by the overall amount of LT-ETEC-specific, immunoglobulin A antibodies the infant received via the mother's breast milk and by the provision of traditional medicinal teas.

Hermansky-Pudlak syndrome in a Swiss population.

Tyrosinase-positive albinism, previously diagnosed as Hermansky-Pudlak Syndrome (HPS), has been examined in four generations from a village of the canton Valais, Switzerland. Homozygotes, obligate heterozygotes and putative heterozygotes in this geneology yielded lower than normal membrane-associated thioredoxin reductase (TR) activities compared with normal family members and controls. All of the homozygotes and 50% of each the obligate and putative heterozygotes showed an increase in bleeding time associated with storage-pool-deficient platelets lacking dense bodies. The TR activity profile and the platelet-dense body deficiency in the Swiss albinos was the same as that in the HPS population from Puerto Rico. However, in albinos from Puerto Rico, there is an accumulation of ceroid/lipofuscin-like pigment in lysosomal structures causing tissue damage, and, upon kidney involvement, this leads to increased urinary dolichol excretion. Approximately half of the Puerto Rican HPS cases had clinical evidence of storage disease with restrictive lung disease, granulomatous colitis, kidney failure and cardiomyopathy. By comparison, the Swiss HPS geneology had a normal life expectancy with no significant evidence for ceroid accumulation or urinary dolichol excretion. An examination of antioxidant enzymes, catalase, TR and glutathione reductase in epidermal suction blisters from Swiss HPS homozygotes showed a similar result for catalase and TR levels to the depigmented epidermis of patients with vitiligo, except that intracellular TR was found to be calcium free in HPS compared with vitiligo. Intracellular glutathione reductase levels were highest in HPS. Both the Swiss and Puerto Rican HPS homozygotes and heterozygotes have giant melanosomes in skin melanocytes.

Three-day therapy of lower urinary tract infections with nitrofurantoin macrocrystals: a randomized clinical trial.

Forty-nine girls between the ages of 2 and 18 years with a symptomatic urinary tract infection documented by two clean-catch urine cultures completed a double-blind study comparing the effectiveness of three days versus ten days of nitrofurantoin macrocrystal therapy. Localization of the infection to the lower urinary tract was presumed on the basis of clinical presentation. All patients had sterile urine on day two or three of therapy. In the ten-day group, two of 23 patients (8.7%) experienced a single relapse, and seven patients (30%) had 12 episodes of reinfection during a six-month follow-up. In the three-day group, two of 26 patients (7.7%) had a single relapse, and six patients (23%) had 12 episodes of reinfection. The rates of relapse and reinfection in the compared groups were not statistically significantly different (P greater than 0.05). Three days of treatment with nitrofurantoin macrocrystals is an effective regimen for symptomatic girls presumed to have uncomplicated lower urinary tract infections.

Etiology of acute conjunctivitis in children.

To determine the etiology of acute conjunctivitis in children seen in pediatric practice, 99 patients with conjunctivitis and 102 age-and season-matched controls were cultured for aerobic bacteria including Haemophilus influenzae, and for viruses, Chlamydia trachomatis, and mycoplasmas. Agents statistically associated with conjunctivitis included H. influenzae (42% vs 0%), Streptococcus pneumoniae (12% vs 3%), and adenoviruses (20% vs 0%). One of these three etiologic agents was isolated from 71 (72%) of the patients. Simultaneous infection with two pathogens was uncommon. Staphylococcus aureus was equally prevalent in diseased and control eyes; one strain of C. trachomatis was isolated from a control eye. Although there were variations in the clinical features of viral and bacterial conjunctivitis, differentiation in an individual patient was difficult. An adenovirus was isolated from 11 (65%) of 17 patients who had pharyngitis in addition to conjunctivitis. H. influenzae was isolated from 14 (74%) of 19 children who had both otitis and conjunctivitis. Adenovirus conjunctivitis was common in the fall and H. influenzae in winter.

Associated coarctation of the aorta and mitral valve disease: nine cases with surgical correction of both lesions in three.

Nine cases of the combination of coarctation of the aorta and mitral stenosis were evaluated over a seven-year period. Symptoms did not usually cause distress in infancy, but began subtly with pneumonia or cardiac failure at about 2 years of age. Important clues were differences in blood pressure between the arms and legs, paroxysmal dyspnea, congestive heart failure, right ventricular hypertrophy, and left atrial enlargement. Cardiac catheterization studies showed elevated right ventricular and main pulmonary artery wedge pressures. These features in patients with coarctation of the aorta should suggest associated mitral valve disease. The importance of demonstrating associated valvular lesions, particularly mitral stenosis, is emphasized. Two of our children had successful repair of the coarctation of the aorta and mitral stenosis simultaneously. In a third child, resection of the coarctation was followed in six years by mitral valve replacement.