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Biomedical subjects

A Afifi

Publications and source records attributed to A Afifi.

At least 19 recordsLinked to original sources

Mutation and biochemical analysis in carnitine palmitoyltransferase type II (CPT II) deficiency.

Carnitine palmitoyltransferase type II (CPT II) deficiency has three basic phenotypes, late-onset muscular (mild), infantile/juvenile hepatic (intermediate) and severe neonatal. We have measured fatty acid oxidation and CPT II activity and performed mutation studies in 24 symptomatic patients representing the full clinical spectrum of disease. Severe and intermediate phenotypes show a clear correlation with biochemical indices and genetic analysis revealed causative mutations in most patients. Studies of mild phenotypes suggest a more complex interaction, with higher residual fatty acid oxidation, a wider range of CPT II activity (10-60%) but little evidence of genotype-phenotype correlation. Residual CPT II mutant protein from myopathic patients shows thermal instability at 41 degrees C. The common 'polymorphisms' V3681 and M647V are strikingly overrepresented in the myopathic patients, the implication being that they may significantly influence the manifestation of clinical disease and could therefore potentially be considered as a susceptibility variants. Among myopathic individuals, males comprised 88% of patients, suggesting increased susceptibility to clinical disease. A small number of symptomatic patients appear to have significant residual CPT II activity (42-60%) The synergistic interaction of partial deficiencies of CPT II, muscle adenosine monophosphate deaminase and possibly other enzymes of muscle energy metabolism in the aetiology of episodic myopathy deserves wider consideration.

AMP Deaminase↗

Role of IgE in primary murine Schistosomiasis mansoni.

Schistosoma mansoni infection proceeds in normal mice in the absence of detectable levels of polyclonal or specific immunoglobulin (Ig)E until worms mature and deposit eggs. Hence, the course of a primary S. mansoni infection is not expected to vary appreciably in mice with defects in the IgE production. Experimental increase of IgE production early after infection may, however, influence worm development. In the first approach towards this goal, BALB/c mice were injected with interleukin(IL)4 to raise the level of endogenously synthesized IgE. A significant increase in serum polyclonal IgE and antischistosome IgG1 during the prepatent period was not associated with significant changes in worm and egg burden or liver pathology. During the second approach, mice were injected with IgE which was affinity purified from serum of BALB/c mice infected for 16 weeks with S. mansoni. The purified IgE bound to carbohydrate-independent epitopes of soluble antigens from 3 h larvae, adult worms and eggs and recognized the schistosomular surface membrane. No differences in worm and egg load or granuloma number and size were noted between untreated and exogenous IgE-injected mice. Together, the data demonstrate that by itself IgE does not influence the outcome of infection in primary murine S. mansoni.

Animals↗

Human and murine humoral immune recognition of multiple peptides from Schistosoma mansoni glyceraldehyde 3-P dehydrogenase is associated with resistance to Schistosomiasis.

Schistosoma mansoni glyceraldehyde 3-phosphate dehydrogenase (SG3PDH) is a target of cellular and humoral immune responses of Brazilian and Egyptian subjects putatively resistant to reinfection with S. mansoni. In an aim to develop a safe, stable and effective vaccine based on this promising molecule, six peptides derived from its primary sequence were selected based on the lowest homology to human G3PDH. The synthetic peptides were tested by ELISA against plasma of humans putatively susceptible or resistant to reinfection with S. mansoni or S. haematobium following chemotherapeutic cure of previous infection. Repeat experiments indicated that the six peptides bear human B-cell epitopes that bind immunoglobulin (Ig)M, IgG1 and IgG3 antibodies. Resistance to reinfection appeared to be significantly associated with humoral immune responses to multiple peptides. This contention was supported by studies in the murine model, whereby we examined the B cell immune responses of Swiss and inbred BALB/c and C57BL/6 mice immunized with recombinant SG3PDH (rSG3PDH) to the six SG3PDH-derived peptides. The serum antibodies of rSG3PDH-immunized Swiss mice were directed to only one of the six peptides tested by ELISA. Antibodies from rSG3PDH-immunized C57BL/6 and BALB/c mice bound, respectively, to four and six out of six peptides. In contrast to Swiss mice, immunization of C57BL/6 and BALB/c mice with rSG3PDH induced protection against challenge cercariae which reached the level of significance (P < 0.05) for BALB/c mice. The data together indicate that host recognition of multiple peptides of a candidate vaccine antigen is necessary for the expression of its ability to contribute to protective immunity against Schistosomiasis.

Adult↗

Human T- and B-cell responses to Schistosoma mansoni recombinant glyceraldehyde 3-phosphate dehydrogenase correlate with resistance to reinfection with S. mansoni or Schistosoma haematobium after chemotherapy.

Recently we reported that human T- and B-cell recognition of a 42-kDa protein (p42) in soluble extracts of adult Schistosoma mansoni worms correlates with resistance to reinfection with S. mansoni or S. haematobium. Amino acid microsequencing of p42 revealed that it consists predominantly of schistosome glyceraldehyde 3-phosphate dehydrogenase (SG3PDH). We have expressed SG3PDH in Escherichia coli and purified the recombinant protein in a soluble and enzymatically active form. Recombinant SG3PDH (rSG3PDH) reacted with human monospecific antibodies to p42. Lymphoproliferation and production of interleukin-4 and gamma interferon (IFN-gamma) after in vitro stimulation with rSG3PDH and serum isotype responses to rSG3PDH were examined in individuals with extremes of resistance and susceptibility to reinfection after treatment of previous S. mansoni or S. haematobium infection. Lymphoproliferation and IFN-gamma production in response to rSG3PDH and the presence of serum immunoglobulin G1 (IgG1), IgG3, and IgA antibodies to rSG3PDH generally characterized individuals who are resistant to reinfection after chemotherapy. The data indicate that T- and B-cell immune reactivity to rSG3PDH correlates with resistance to reinfection, confirming previous studies identifying SG3PDH as a target of protective immunity in humans, and suggest that SG3PDH should be investigated as a possible vaccine for human schistosomiasis.

Animals↗

Myxoma involving the atrial valve chordae.

Primary cardiac valve tumors are rare and comprise less than 10% of all cardiac tumors. They are, however, of clinical importance because of their unique locations. We report an unusual case of myxoma involving the tricuspid valve chordae in a young woman presenting with syncope. The myxoma was diagnosed by echocardiography and successfully removed by excision of the involved tricuspid valve chordae with valve preservation. (Curr Surg 57:357-358)

Journal Article↗

Hemiplegic migraine induced by exertion.

BACKGROUND: It is known that exertion can aggravate migraine headache. However, the relationship between exertion and migraine aura is unknown. OBJECTIVE: To study the relationship between exertion and migraine aura. DESIGN: Case report. SETTING: Tertiary care hospital. PATIENT: A 67-year-old man presented with recurrent attacks of exertion-induced hemiplegic migraine. Since the hemiparetic attacks were exertion induced, they were initially ascribed to recurrent transient ischemic attacks. However, the clinical picture, normal findings on cerebral angiography and neuroimaging (during the period of hemiparesis), lack of response to treatment with antiplatelets and anticoagulants, and successful treatment with verapamil suggested that the hemiparesis was not due to ischemia, but was indeed a migraine aura. We suggest that exertion induced the aura of hemiparesis by lowering the threshold for the development of cortical spreading depression. Even though our patient had no family history of hemiplegic migraine, a mutation in an ion channel gene (eg, the CACNA1A gene on chromosome 19) might account for his episodic attacks. CONCLUSION: Migraine aura should be included in the differential diagnosis of exertion-induced focal neurologic deficit.

Aged↗

Knowledge, attitude and behaviour towards AIDS among educated youth in Lahore, Pakistan.

OBJECTIVE: To assess the knowledge, attitude and behaviour regarding AIDS among educated young people in Lahore, Pakistan. METHODS: An anonymous survey of 733 males and 355 females was carried out using structured questionnaire among educated youth, selected randomly from non-medical educational institutions and work places. RESULTS: Knowledge on exsistance of AIDS in Pakistan was expressed by 698 (95.2%) males and 273 (76.9%) females, in, while only 189 (25.7%) males and 76 (21.4%) females knew its cause. Knowledge of the different modes of transmission was good, however 59%, 48%, 68% and 43% males; 28%, 45%, 59% and 35% females believed that it could be transmitted through sharing of utensils, mouth kissing, casual contact and mosquito bite, respectively. Ninety one percent males and 86% females believed that AIDS sufferers should be isolated. Extra marital sex was experienced by 6% subjects and only 5% used condoms. Generally, males had better knowledge than females except in attitudes towards monogamy and having sex with someone known. CONCLUSIONS: The study revealed gaps in the knowledge of females regarding AIDS and its transmission. The results indicates an urgent need to include health education syllabi emphasising AIDS and other Sexually Transmitted Diseases in the Curriculum of schools/colleges to convey the message adequately to the youth.

Acquired Immunodeficiency Syndrome↗

Identification of Schistosoma haematobium soluble egg antigens that elicit human granuloma formation in vitro.

Schistosoma haematobium soluble egg antigens (SH SEAs) induce intense granulomas in human hosts that often culminate in severe disease. In an attempt to identify the SH SEA fractions that are responsible for pathology, we combined T-cell Western blotting and an in vitro model of granuloma formation. Whole SH SEAs were dotted onto nitrocellulose pieces or were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electrotransferred onto nitrocellulose paper. Horizontal strips bearing the separated antigens were solubilized in dimethylsulfoxide and precipitated in carbonate/bicarbonate buffer. Antigen-free and antigen-bearing particles were used to stimulate peripheral blood mononuclear cells (PBMCs) obtained from S. haematobium-infected patients and sex- and age-matched healthy controls to form granulomas in vitro. Whole SH SEA-bearing nitrocellulose particles elicited in vitro formation of granulomas by PBMCs from infected donors. The response was similar in sensitivity, specificity, and reproducibility to that evoked by SH SEA-bound polyacrylamide beads. The results obtained in samples form 30 patients and 10 controls tested with SH SEA-separated fractions revealed that SEA bands of 84,000, 63,000, 57,000, 55,000, 40,000, 30,000, and 28,000 Da elicited in vitro granuloma reactions by PBMCs of almost all infected patients. Conversely, separated soluble adult-worm antigens failed to stimulate PBMCs of infected patients to form granulomas. This study is the first to identify the SH SEA fractions that evoke in vitro granuloma formation and represents an initial step toward the development of an anti-urinary schistosomiasis pathology vaccine.

Adolescent↗

Serum and endometrial copper, zinc, iron and cobalt with inert and copper-containing IUCDs.

Serum and endometrial copper (Cu), zinc (Zn), iron (Fe) and serum cobalt (Co) were measured in the mid-follicular and mid-luteal phases of the menstrual cycles in 30 Lippes loops users, 30 CuT-200 IUCD users and 24 matched controls by atomic absorption spectrophotometry. In the control group, there was no statistically significant difference in mean mid-luteal, compared to mid-follicular, levels of serum Cu, Zn, Fe and Co and endometrial Zn. Mid-luteal endometrium contained significantly higher mean Cu, and lower mean Fe levels. In Lippes loop users, compared to controls, the only statistically significant differences were lower mean mid-follicular serum Zn, lower mean endometrial Zn and Fe, and higher mean mid-luteal endometrial Fe. In CuT-200 users, compared to controls, there was significantly higher mean mid-follicular serum Zn and lower mean mid-luteal serum Co, higher mean mid-follicular endometrial Cu and lower mean mid-follicular endometrial Fe levels. Compared to Lippes loop, CuT-200 users had significantly higher mean mid-follicular serum Co and endometrial Cu and Zn, and lower mean mid-follicular endometrial Fe.

Adult↗

Serum and endometrial sodium and potassium levels with inert and copper-containing IUCDs and relation to serum steroid levels.

Serum and endometrial sodium (Na) and potassium (K) levels and serum estradiol, progesterone, testosterone and cortisol were measured in the mid-follicular and mid-luteal phases of the menstrual cycle in 20 Lippes loop and 20 CuT-200 IUCD users and 20 matched controls. Na and K were measured by atomic absorption spectrophotometry, while serum steroids were measured by RIA. Regarding steroids, the only significant difference between the three groups was a significantly lower mean mid-luteal serum estradiol in CuT-200 IUCD users compared to Lippes loop users (p less than 0.05). Regarding sodium in the control group, there was significantly lower mean mid-luteal serum and endometrial Na (p less than 0.01) that was not found in both groups of IUCD users. In the mid-follicular phase, there was significantly higher mean serum Na in both Lippes loop and CuT-200 groups compared to controls (p less than 0.05). Mean endometrial Na showed no significant difference between the three groups in both phases of the menstrual cycle. Regarding potassium in the control group, there was significantly lower mean levels in the mid-luteal-phase of the cycle (p less than 0.01) that was not seen with both groups of IUCD users. Serum K showed no significant difference in the three groups in both phases of the menstrual cycle. Endometrial K showed a significantly higher mean level in both Lippes loop and CuT-200 IUCD users compared to controls in the mid-luteal (p less than 0.01), but not in the mid-follicular phases of the cycle.

Analysis of Variance↗

Identification of the Schistosoma haematobium soluble egg antigens inducing antibody production and/or T cell proliferation in humans.

Soluble antigens were prepared from Schistosoma haematobium eggs collected from urine of 6-16 year-old children with urinary schistosomiasis. The electrophoretic profile of the soluble egg antigen (SEAH) preparation was almost identical to that (SEAh) obtained from UNDP/World Bank/WHO, Switzerland and prepared from S. haematobium eggs retrieved from intestines of infected hamsters. Reactivity of 50 individual patients with S. haematobium in Western blots led to the identification of the SEA protein bands carrying human B cell epitopes. Some, but not all, of these SEA proteins initiated peripheral blood T lymphocyte proliferation in T cell Western assays. These antigens are probably the ones inducing granulomatous response in vivo, and that are responsible for the immunopathology of the disease.

Adolescent↗

Levels of serum steroid hormones in intrauterine contraceptive device users.

Serum progesterone, estradiol, testosterone and cortisol were assayed in the mid-follicular and mid-luteal phases of the menstrual cycles in 30 Lippe's loop and 30 Cu T-200 IUCD users, compared to 24 controls. Mean serum progesterone and estradiol levels were significantly higher in the mid-luteal, compared to the mid-follicular phase in each group (p less than 0.01). There were no significant differences between the mean levels of progesterone, testosterone and cortisol in IUCD users and controls in both the mid-follicular and mid-luteal phases. IUCD users had significantly higher levels of estradiol (p less than 0.01) in the mid-luteal phase but not in the mid-follicular phase, compared to controls. There was hormonal evidence of corpus luteum insufficiency in 8.3%, 14.3% and 20% in the controls, Lippe's loop and Cu T-200 IUCD users, respectively.

Adolescent↗

Effect of olfactory bulb ablation on spread of a neurotropic coronavirus into the mouse brain.

Previous results suggested that, after intranasal inoculation, mouse hepatitis virus (MHV), a neurotropic coronavirus, entered the central nervous system (CNS) via the olfactory and trigeminal nerves. To prove this hypothesis, the effect of interruption of the olfactory pathway on spread of the virus was studied using in situ hybridization. Unilateral surgical ablation of this pathway prevented spread of the virus via the olfactory tract on the side of the lesion. MHV RNA could be detected, however, at distal sites on the operated side, indicating that the virus spread via well-described circuits involving the anterior commissure from the control (intact) side of the brain. Viral transport via the trigeminal nerve was not affected by removal of the olfactory bulb, showing that the surgical procedure was specific for the olfactory pathway. These results prove conclusively that MHV gains entry to the CNS via a transneuronal route, and spreads to additional sites in the brain via known neuroanatomic pathways.

Animals↗

Identification of the spinal cord as a major site of persistence during chronic infection with a murine coronavirus.

After intranasal inoculation, mouse hepatitis virus (MHV) gains entry into the central nervous system (CNS) via the olfactory and trigeminal nerves. Under the appropriate conditions, some mice develop clinically apparent demyelinating encephalomyelitis several weeks later, with virus always present in the spinal cord. To determine the pathway by which virus reaches the cord, brains and spinal cords of infected, asymptomatic mice were analyzed by in situ hybridization. Viral RNA was always detected in the anterior part of the upper spinal cord. A similar analysis of mice with the recent onset of hindlimb weakness showed that viral RNA was detected in the same location. The results suggest that MHV is transported to the spinal cord via well-defined neuroanatomic pathways and that viral amplification with resultant clinical disease occurs from this site of persistence in the anterior spinal cord. This process of viral amplification may involve the generation of viral variants as has been described for MHV-infected rats. No major changes in viral RNA or protein could be detected when MHV isolated from mice with hindlimb paralysis was analyzed. The data suggest that the generation of viral variants is not important in the pathogenesis of the late onset of neurological disease induced by MHV in mice.

Animals↗

[Primary fibroblastic tumor of the breast. Review of the literature apropos of a case of desmoid tumor of the breast posing nosologic problems with a low-grade fibrosarcoma].

The authors present a case of fibromatosis in the breast in a young nulliparous patient. These are rare tumours comparable to abdominal desmoid tumours. They are characterised by their ability to recur if spread locally, that is why they have to be widely removed. After having studied the anatomical and clinical characteristics as well as the biological ones of breast fibromatoses the authors discuss the problems of nosology which are often very difficult for this kind of a tumour and also of the therapy that has to be adapted.

Adolescent↗

[Icteric complications related to pregnancy vomiting in the 1st trimester (hyperemesis gravidarum). Review of the literature apropos of a case].

The authors report a case of jaundice occurring secondary to severe vomiting in pregnancy in the first trimester. This is a rare clinical entity (occurring in 0.2-3 cases per thousand) although some people say it does not exist. The physiopathology is still badly understood but it occurs most often between the fourth and eighth week of amenorrhoea. It is characterised by jaundice occurring secondarily to vomiting in the first trimester, with a rise in the bilirubin level in the blood and in the alkaline phosphatases. Sometimes there is a slight rise in the transaminases. The diagnosis can only be arrived at after having excluded all the other possible causes of jaundice which are mentioned in the text. Furthermore the way the condition progresses is an important argument for its aetiology because once vomiting ceases the jaundice goes. The treatment has to be symptomatic with correction of the dehydration.

Adult↗