In vitro bacterial fermentation of tropical fruit fibres.

Tropical fruits such as mango, papaya, pineapple and banana are rich sources of dietary fibre. However, few studies have examined the potential physiological effects of fibre from these tropical fruits. The aim of this study was to characterise the fermentability of dietary fibre found in banana, papaya, pineapple and mango as an estimate of the physiological effects of consuming these fruits. Freeze-dried fruit was subjected to in vitro digestion to remove digestible carbohydrates. Digestion residues were freeze-dried prior to fermentation. In vitro fermentation was carried for 24 h under anaerobic conditions to simulate conditions in the large intestine. Gas volume, pH and short chain fatty acids (SCFAs) concentration were measured at 0, 4, 8, 12, and 24 h. SCFAs were analysed by gas chromatography. There was no gas production from 0 to 8 h time points for all samples. Mango fibre resulted in more gas at 12 and 24 h than pineapple, papaya and banana fibres. The slurry pH was significantly lower for mango fibre at 12 and 24 h compared to other samples. Mango fibre resulted in significantly more propionate at 8 h compared to papaya and pineapple fibres. Butyrate concentrations were only significantly different at 4 h. At 24 h total and individual SCFA production did not differ among samples. All fruit fibres were fermentable, with mango fibre being the most rapidly fermented. Additional work is necessary to confirm a benefit on digestive health.

Microarray analysis of homocysteine-responsive genes in cardiac neural crest cells in vitro.

The amino acid homocysteine increases in the serum when there is insufficient folic acid or vitamin B(12), or with certain mutations in enzymes important in methionine metabolism. Elevated homocysteine is related to increased risk for cardiovascular and other diseases in adults and elevated maternal homocysteine increases the risk for certain congenital defects, especially those that result from abnormal development of the neural crest and neural tube. Experiments with the avian embryo model have shown that elevated homocysteine perturbs neural crest/neural tube migration in vitro and in vivo. Whereas there have been numerous studies of homocysteine-induced changes in gene expression in adult cells, there is no previous report of a homocysteine-responsive transcriptome in the embryonic neural crest. We treated neural crest cells in vitro with exogenous homocysteine in a protocol that induces significant changes in neural crest cell migration. We used microarray analysis and expression profiling to identify 65 transcripts of genes of known function that were altered by homocysteine. The largest set of effected genes (19) included those with a role in cell migration and adhesion. Other major groups were genes involved in metabolism (13); DNA/RNA interaction (11); cell proliferation/apoptosis (10); and transporter/receptor (6). Although the genes identified in this experiment were consistent with prior observations of the effect of homocysteine upon neural crest cell function, none had been identified previously as response to homocysteine in adult cells.

Cemental tear: a case report.

AIM: To report a case of a cemental tear. SUMMARY: A case is reported of a patient with a history of trauma, root canal treatment and retreatment procedures to eliminate recurring sinus tracts. An exploratory surgery, extraction, and biopsy resulted in a diagnosis of cemental tear. KEY LEARNING POINTS: * The detachment of a fragment of cementum is described as a cemental tear. * Cemental tears have been reported in the periodontal literature associated with localized, rapid periodontal breakdown. Common causative factors are aging and traumatic occlusion but the exact aetiology is unknown. * Trauma may be considered as a potential aetiologic factor for cemental tears in addition to occlusal traumatism and aging.

Sleeping sickness and the brain.

Recent progress in understanding the neuropathological mechanisms of sleeping sickness reveals a complex relationship between the trypanosome parasite that causes this disease and the host nervous system. The pathology of late-stage sleeping sickness, in which the central nervous system is involved, is complicated and is associated with disturbances in the circadian rhythm of sleep. The blood-brain barrier, which separates circulating blood from the central nervous system, regulates the flow of materials to and from the brain. During the course of disease, the integrity of the blood-brain barrier is compromised. Dysfunction of the nervous system may be exacerbated by factors of trypanosomal origin or by host responses to parasites. Microscopic examination of cerebrospinal fluid remains the best way to confirm late-stage sleeping sickness, but this necessitates a risky lumbar puncture. Most drugs, including many trypanocides, do not cross the blood-brain barrier efficiently. Improved diagnostic and therapeutic approaches are thus urgently required. The latter might benefit from approaches which manipulate the blood-brain barrier to enhance permeability or to limit drug efflux. This review summarizes our current understanding of the neurological aspects of sleeping sickness, and envisages new research into blood-brain barrier models that are necessary to understand the interactions between trypanosomes and drugs active against them within the host nervous system.

Induction of matrix metalloproteinase activation cascades based on membrane-type 1 matrix metalloproteinase: associated activation of gelatinase A, gelatinase B and collagenase 3.

SW1353 chondrosarcoma cells cultured in the presence of interleukin-1, concanavalin A or PMA secreted procollagenase 3 (matrix metalloproteinase-13). The enzyme was detected in the culture medium by Western blotting using a specific polyclonal antibody raised against recombinant human procollagenase 3. Oncostatin M enhanced the interleukin-1-induced production of procollagenase 3, whereas interleukin-4 decreased procollagenase 3 synthesis. The enzyme was latent except when the cells had been treated with concanavalin A, when a processed form of 48 kDa, which corresponds to the active form, was found in the culture medium and collagenolytic activity was detected by degradation of 14C-labelled type I collagen. The concanavalin A-induced activation of procollagenase 3 coincided with the processing of progelatinase A (matrix metalloproteinase-2) by the cells, as measured by gelatin zymography. In addition, progelatinase B (matrix metalloproteinase-9) was activated when gelatinase A and collagenase 3 were in their active forms. Concanavalin A treatment of SW1353 cells increased the amount of membrane-type-1 matrix metalloproteinase protein in the cell membranes, suggesting that this membrane-bound enzyme participates in an activation cascade involving collagenase 3 and the gelatinases. This cascade was effectively inhibited by tissue inhibitors of metalloproteinases-2 and -3. Tissue inhibitor of metalloproteinases-1, which is a much weaker inhibitor of membrane-type 1 matrix metalloproteinase than tissue inhibitors of metalloproteinases-2 and -3 [Will, Atkinson, Butler, Smith and Murphy (1996) J. Biol. Chem. 271, 17119-17123], was a weaker inhibitor of the activation cascade.

Peer group training of pragmatic skills in adolescents with acquired brain injury.

OBJECTIVE: To empirically evaluate a method of treating adolescents with cognitive communication disorders, including pragmatic deficits, secondary to acquired brain injury (ABI) in a group setting by objectively measuring outcomes before treatment and immediately after treatment and at 6 months posttreatment. DESIGN: A before-after trial with follow-up in a consecutive sample, with no control group. SETTING: Inpatient and outpatient pediatric rehabilitation center. SUBJECTS: Adolescents who demonstrated pragmatic deficits and scored a rating of 3 or less on each subdomain of the Rehabilitation Institute of Chicago Rating Scale of Pragmatic Communication Skills (RICE-RSPCS) were eligible for the study. Eight subjects were recruited into the study, and two subjects were lost to follow-up. Thus, six of the eight completed the study. MAIN OUTCOME MEASURES: RICE-RSPCS, Communication Performance Scale (CPS). RESULTS: Clinically relevant and statistically significant (P <.01) changes occurred during the treatment and were maintained at follow-up for the four RICE-RSPCS subscales and the CPS. CONCLUSION: These results suggest that the potential and often typical long-term pragmatic and subsequent social difficulties associated with ABI can possibly be lessened through effective intervention.

Regional cerebral blood flow after hemorrhagic hypotension in the preterm, near-term, and newborn lamb.

Developmental changes in regional cerebral blood flow (CBF) responses to hemorrhagic hypotension during normoxia and normocapnia were determined using radioactively labeled microspheres to measure flow to the cortex, brainstem, cerebellum, white matter, caudate nucleus, and choroid plexus in three groups of chronically catheterized lambs: 90- to 100-d preterm fetal lambs (n = 9); 125- to 136-d near-term fetal lambs (n = 9); and newborn lambs 5- to 35-d-old (n = 8). Heart rate, central venous pressure, and arterial blood pressure were monitored continuously and arterial blood gas tensions, pH, Hb, and oxygen saturation together with regional CBF were measured periodically. Hemorrhagic hypotension produced a mean decrease in arterial blood pressure of 27 +/- 4, 23 +/- 2, and 41 +/- 4% in the three groups, respectively, whereas reinfusion of the lamb's blood resulted in a return to control blood pressure within 3% in all three groups. In the pre-term fetal lamb, CBF decreased significantly in all regions during hypotension. In the near-term fetal lamb, only blood flow to the cortex decreased significantly during hypotension. In the newborn lamb, only the choroid plexus demonstrated a significant decrease in blood flow during hypotension. The lower limit of regional CBF autoregulation was identical to the resting mean arterial pressure in fetal life but significantly lower in newborn lambs. These experiments demonstrate for the first time that vulnerability to hypotension decreases with increasing maturity and that the brainstem, the phylogenetically oldest region of the brain, is the least vulnerable to the effects of hypotension at any age in the lamb model.

Milk intakes of genetically obese (ob/ob) and lean mouse pups differ with enhanced milk supply.

Although obese (C57Bl/6J, ob/ob) pups have greater avidity for nonnutritive suckling than leans as early as 15 days postpartum, previous research has not found differences in milk intake between ob/ob and lean mice during the preweaning period. Because ob/ob pups suckle longer than leans, their perseveration should enhance their opportunity to ingest milk if (a) maternal milk supply is not limited and (b) longer sucking durations reflect increased pup willingness to ingest milk. Accordingly, the present study was designed to evaluate the milk intake of ob/ob and lean pups when they had access to an enhanced supply of maternal milk. Intact litters of pups, from heterozygous lean (ob/+) parents, were randomly assigned to be tested at either 6, 12, or 18 days. Pups were neither dam- nor milk-deprived before being cross-fostered successively to milk-replete surrogate dams for 60 min each. Obese pups showed a greater percentage body weight gain (the index of milk intake) than leans did, with younger pups showing larger increments than 18-day-olds. Although early adiposity in ob/ob pups may not rely on increased intake in the single-dam, nest situation, these data emphasize an early predisposition to overeating in this mutant.

Metabolism of the Z and E isomers of N-nitroso-N-methyl-(2-oxopropyl)amine by rat hepatocytes.

The metabolism of N-nitroso-N-methyl-N-(2-oxopropyl)amine was examined using freshly isolated hepatocytes from Fischer 344 rats. As determined by high performance liquid chromatography, it was found that the E isomer was preferentially metabolized when the parent mixture was used. When the two isomers were studied separately, the E isomer was efficiently metabolized in the hepatocytic system, whereas the Z isomer was not. The kinetics of disappearance of the Z isomer during metabolism was identical to that for the reequilibration of the Z isomer to the mixture of isomers in the absence of a metabolizing system.

The metabolism of N-nitrosobis(2-oxopropyl)amine by microsomes and hepatocytes from Fischer 344 rats.

The metabolism of N-nitrosobis(2-oxopropyl)amine (BOP) was examined in microsomes from uninduced F-344 rats. Even when the conditions were varied, no metabolism of this compound was detected. On the other hand, freshly isolated hepatocytes from F-344 rats metabolized BOP efficiently to CO2. The kinetics of conversion showed there were at least two components. The high affinity component had a Km of 0.13 mM while the lower had a Km of 1.3 mM. As products of the metabolism, N-nitroso(2-hydroxypropyl)(2-oxopropyl)-amine (HPOP) and N-nitrosobis(2-hydroxypropyl)amine (BHP) were found whereas little acetol and no N-nitrosomethyl-2-oxopropylamine (MOP) were detected.

Squamous cell carcinoma of the skin in black patients with discoid lupus erythematosus.

Skin cancer is relatively uncommon among black individuals. Squamous cell carcinoma occurred in a scar of chronic discoid lupus erythematosus in a black patient. A review of 7 previously reported cases of squamous cell carcinoma in blacks with chronic discoid lupus erythematosus indicates a tendency of the cancer to metastasize. Sun exposure of the hypopigmented lesions of chronic discoid lupus and possibly other factors predispose to cancer of the skin. Poorly healing skin lesions in chronic discoid lupus should arouse suspicion of malignant change.

Transplantation of normal bone marrow into a pig with severe von Willebrand's disease.

Bone marrow from a normal male pig was transplanted into a related female pig with severe homozygous von Willebrand's disease (vWd). After engraftment the circulating leukocytes were of the male karyotype, and the platelets were strongly positive for von Willebrand factor (vWF) by indirect immunofluorescence. The average level of vWF was 1.96 U/dl and of ristocetin cofactor was 2.8 U/dl. The ear immersion bleeding time before transplantation was consistently more than 15 min and afterwards varied between 5 min and more than 15 min. Transfused vWF corrected the bleeding time at a level of 10 U/dl, which is lower than that required for a von Willebrand pig. We concluded that: the plasmatic compartment is only minimally replenished by the vWF from platelets and megakaryocytes; and the platelet vWF alone only partially corrects the abnormal tests of the hemostatic mechanism in severe vWd.

Serum beta-2 microglobulin levels in homosexual men with AIDS and with persistent, generalized lymphadenopathy.

In order to investigate the nature of the immune disorders associated with the acquired immune deficiency syndrome (AIDS) and the AIDS-related condition of persistent, generalized lymphadenopathy (PGL), serum beta-2 microglobulin (beta 2-M) levels were determined in patients with AIDS and PGL and in asymptomatic homosexual and heterosexual controls. Sixteen of 20 (80%) patients with AIDS exhibited elevated beta 2-M levels. In contrast, 20 of 44 (45%) patients with PGL, 4 of 20 (20%) asymptomatic homosexuals, and only 3 of 46 (7%) heterosexuals had increased serum beta 2-M levels (P less than 0.001). When considering mean levels of beta 2-M, only the asymptomatic control individuals had normal values. AIDS patients had significantly higher mean beta 2-M levels when compared to all other groups (P less than 0.05). The mean level for PGL patients was greater than that in the homosexual and heterosexual controls (P less than 0.05). No relationship was found between presence of antibody to human T-lymphotropic retrovirus (HTLV-III) and beta 2-M levels in the patients with AIDS or PGL. The authors conclude that beta 2-M is elevated in patients with AIDS and PGL, suggesting an increased turnover of a certain subpopulation of lymphocytes in these patients. Beta 2-M levels also appear to parallel disease activity, as well as immune dysfunction, with the greatest elevation occurring in patients with AIDS, followed by those with PGL, and asymptomatic homosexuals. Beta 2-M levels may be a useful confirmatory marker in AIDS and its related disorders.

Leg volume changes with EPIC and posturing in dependent pregnancy edema.

This study explored the differential effects of external pneumatic intermittent compression (EPIC) and posturing on leg volume changes in healthy pregnant women with dependent leg edema. Thirty-five healthy pregnant women with severe pedal edema were randomly assigned to one of two treatment groups. The experimental group (n = 17) received EPIC for 30 minutes at 40 torr while in the left lateral recumbent position. Control women (n = 18) were similarly positioned, but received no EPIC. Both groups walked for 10 minutes following left lateral posturing. Circumference measures required for leg volume estimates were made: prior to posturing (Time 1), immediately after posturing (Time 2), and following the ambulation period (Time 3). Volume losses for the experimental group were greater than for the control group at Time 2. Although volume losses for the experimental group had reversed somewhat at Time 3, they remained greater than control group losses, which did not change from Time 2 to Time 3. Analysis of covariance revealed significant mean volume losses for both experimental and control groups, with ponderal index the only significant covariate.

Large noncleaved follicular center cell lymphoma. Clinical features in 53 patients.

To clarify the clinical characteristics of large noncleaved lymphoma (LNC-FCC; intermediate grade, large cell, noncleaved, Working formulation), 53 patients were studied. Thirty-one were male and 22 female. Median age was 54 years. Initial symptoms included lymphadenopathy (40%), pain (34%), and B symptoms (21%). Stage I disease was present in 6, Stage II in 9, Stage III in 14, and Stage IV in 24 (72% Stage III or IV). Gastrointestinal (GI) tract involvement was present in 13. Central nervous system (CNS) disease was present at diagnosis in two patients, occurred during therapy in two, and was the sole site of relapse in two. Bone marrow involvement was found in 7 of 50 patients (14%). Complete remission was attained in 60% of all patients. Twenty-nine Stage III and IV patients received intensive multiagent chemotherapy; complete remission (CR) was attained in 69%. In contrast, zero of nine patients with Stage III or IV disease who did not receive an anthracycline-containing regimen, attained CR. Median survival for the entire group was 25 months. It was concluded that, in our patients with LNC-FCC, GI involvement was prominent (25%) and CNS disease was not uncommon (11%). Long-term disease-free survival may be achieved in patients with more advanced disease after the administration of anthracycline-containing combination chemotherapy.

Vitamin/mineral supplement use: a telephone survey of adults in the United States.

Vitamin/mineral supplement use in the United States was assessed through a national telephone interview survey of an age-stratified random sample of 2,991 adults 16 years old and older. A vitamin/mineral supplement was defined as any product containing one or more of 33 specific vitamins, minerals, or "miscellaneous dietary components." Excluding pregnant/lactating women, 39.9% of the population consumed one or more supplements. Of those users, 52.4% consumed one supplement only; 10.9% consumed five or more (up to a maximum of 14 separate products). Confirming other research, above-average consumption of supplements occurred in the western United States. The most widely consumed product type was the single vitamin/miscellaneous dietary component (45.2% of supplement users). Vitamin C, either alone or in combination with other nutrients, was the most widely consumed nutrient (90.6% of supplement users). Use of supplements was more prevalent among women than among men in each of the three age groups examined: 16 to 24 years, 25 to 64 years, and 65 years and older. Although consumption of the B vitamins was more widespread among women than among men, more men than women consumed zinc, iodine, copper, magnesium, and manganese. There was a wide range of intake of both vitamins and minerals, which extended to 10 to 50 times the RDAs for individual nutrients.

Metabolic studies of 15N-labeled N-nitrosoproline in isolated rat hepatocytes and subcellular fractions.

The metabolism of the non-carcinogenic N-nitrosoproline (NPRO) was investigated in vitro using both S9 preparations and isolated hepatocytes from F344 rats. The studies were performed using 15N-labeled nitrosamine and the reaction mixtures were examined mass spectrometrically for the presence of 15N2 or other 15N-labeled gaseous products. In addition, the metabolism of NPRO was monitored by capillary gas chromatography. The results indicated no 15N2 production from either the hepatocyte or S9 preparations, as well as no detectable loss of substrate from the reaction mixtures. Mass spectrometric analysis failed to reveal any metabolites of NPRO. The results suggest that NPRO may be refractory to the normal nitrosamine activating enzymes, confirming its suitability for use in human epidemiological studies of endogenous nitrosation.

Simultaneous occurrence of Pneumocystis carinii pneumonia, cytomegalovirus infection, Kaposi's sarcoma, and B-immunoblastic sarcoma in a homosexual man.

The most common manifestations of the acquired immunodeficiency syndrome include Pneumocystis carinii pneumonia and/or Kaposi's sarcoma. High-grade B-cell lymphomas have also been reported in homosexual men at risk for the acquired immunodeficiency syndrome. We herein present the case of a homosexual man, who presented simultaneously with Pneumocystis carinii pneumonia, acute cytomegalovirus infection, Kaposi's sarcoma, and B-cell immunoblastic sarcoma. Severe compromise of both the B- and T-cell arms of the immune system was documented. The patient had evidence of exposure to the human T-lymphotropic retrovirus III, evidence of reactivation of Epstein-Barr virus infection, and cytomegalovirus inclusions within Kaposi's sarcoma tissue. We conclude that exposure to these viral agents in the setting of severe immunocompromise may have led to the observed "opportunistic" neoplasms.

The metabolism of nitrosodi-n-propylamine, nitrosodiallylamine and nitrosodiethanolamine.

Nitrosodiallylamine has been reported to be non-carcinogenic in rats while nitrosodipropylamine and nitrosodiethanolamine are liver carcinogens. That nitrosodipropylamine is metabolized at the alpha-position by liver microsomes from Fischer-344 rats supports the widely held contention that such metabolism is responsible for the carcinogenicity of nitrosamines. Nitrosodiallylamine is also metabolized at the alpha-position by the same microsomal preparations. Thus, although alpha-oxidation may be responsible for the carcinogenicity of some nitrosamines, this mechanism alone cannot account for tumorigenicity. Nitrosodiethanolamine is not metabolized by rat liver microsomes, but is metabolized by hepatocytes for Fischer-344 rats. In this case, a mechanism other than the oxidation at the alpha-position may be responsible for the carcinogenic action.

Metabolism of 15N-labelled N-nitrosodimethylamine and N-nitroso-N-methylaniline by isolated rat hepatocytes.

The N-demethylation of 15N-labeled N-nitrosodimethylamine (DMN) and N-nitroso-N-methylaniline (NMA) by isolated rat hepatic cells has been investigated. The values obtained in this system for molecular nitrogen formed during metabolism, compared with substrate consumed, were DMN 47%, NMA 23%, and N-nitroso-N-methylurea (NMU) 105%. The results for DMN are roughly halfway between those previously determined with rat liver S-9 fraction in vitro (33%) and in vivo (67%). For NMA, the hepatocyte data are closer to those obtained from S-9 in vitro (19%), rather than the in vivo (52%). No mixed nitrogen ( 15N14N ) or labeled nitrogen oxides were found.