The first case of leukocyte integrin deficiency syndrome in the Czech Republic and successful prenatal diagnosis in the affected family

The syndrome of leukocyte adhesion deficiency (LAD) is a rare congenital immunodeficiency which is usually manifested from birth by serious infections of the skin and mucosal membranes. The molecular basis of the disease is heterogeneous: quantitative or qualitative disorders of the beta 2 integrin sub-unit are involved which lead to the absence or substantially reduced expression of adhesive molecules of the CD11/CD18 complex on leukocytes. The authors describe the case of a boy who suffered from this syndrome. The diagnosis was established at the age of four years, based on the typical clinical picture and confirmed by examination of integrins on lymphocytes and granulocytes which were zero. During the mother's subsequent pregnancy prenatal diagnosis was made by puncture of the umbilical cord during the 22nd week of gestation. Affection of the foetus by this syndrome was ruled out by examination of integrin expression on foetal leukocytes, a normal finding was confirmed also after delivery. During delivery umbilical blood was collected which was frozen and later used for therapeutic transplantation to the sibling suffering from LAD. This is the first case of this syndrome in the Czech Republic and first prenatal diagnosis which led to aimed collection of umbilical blood used for treatment of this rare immunodeficiency.     

Progressive central and peripheral demyelinating disease of adult onset in a Norwegian family

OBJECTIVE: To describe the clinical features of a Norwegian family with a combined central and peripheral demyelinating disease. DESIGN: Multiple case report. SUBJECTS AND MATERIALS: Three generations of a Norwegian family. Medical records were available for all 9 members of the second generation and 5 affected members in the third generation. RESULTS: At least 5 members had clinical features, neuroimaging findings, and electrophysiologic signs indicating a chronic progressive disorder affecting both the central and peripheral nervous systems. The clinical symptoms developed between the ages of 30 and 70 years in affected family members, who gradually developed sensory loss, muscle deterioration, and distal weakness in all extremities, unsteady gait, and dysarthria. Five of 9 persons in the second generation had strokes and experienced mental deterioration. The initial stroke episodes were recognized between the ages of 54 and 68 years, and death occurred between the ages of 62 and 75 years. In 7 subjects, cerebrospinal fluid protein levels were increased, and in 5 agar gel electrophoresis indicated blood-brain barrier dysfunction. Seven family members had neuroimaging signs of a widespread white matter disorder. In 4 subjects, neurophysiological investigations indicated a polyneuropathy, and in 3 subjects, results from a sural nerve biopsy showed a demyelinating neuropathy. There was no evidence of co-inheritance with genetic markers of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (19p), PMP22 (17q), APP (21q), CMTX1 (Xq), or PLP (Xq). CONCLUSIONS: Progressive central and peripheral demyelinating disease seems to be a distinct type of hereditary adult-onset demyelinating disorder affecting both the peripheral and central nervous systems. Its exact nature remains unknown.     

Osteitis pubis: a diagnosis for the family physician

BACKGROUND: This paper describes the inhibitory effect produced by propranolol pre-treatment on lipid synthesis in flank organs from intact, gonadectomized, and isoproterenol-treated male hamsters. Furthermore, the effect induced by the same treatments on gland sebum composition is reported. METHODS: Different groups of male hamsters were injected daily with propranolol, isoproterenol or propranolol plus isoproterenol. Treatment-effect was evaluated determining the in vitro incorporation of radioactive acetate into lipids in hamster flank organs from intact and castrated animals. Additionally, radiolabeled lipids were isolated and identified using TLC and autoradiography as methods. RESULTS: Results demonstrate that castration significantly decreases lipid synthesis in male hamster flank organs. In addition, propranolol treatment inhibits such synthesis in glands from intact, gonadectomized, and isoproterenol-treated animals. However, isoproterenol treatment was ineffective when compared to intact or gonadectomized control vehicle-treated animals. Lipid classes isolated and identified lipids either in castrated or in drug-treated animals were phospholipids, cholesterol, monoglycerides, fatty acids, waxes and cholesterol esters. CONCLUSIONS: Results indicate an inhibitory effect induced on lipid synthesis by beta-adrenergic receptor antagonists; however, beta-adrenergic agonists drugs do not stimulate it. Data suggest a permissive role of adrenergic hormones on lipid synthesis in intact and in gonadectomized animals. Furthermore, castration decreased the synthesis, suggesting that a tight coupling between beta-adrenergic receptors and androgen receptors may be a prerequisite for lipogenesis in this tissue. Pre-treatment does not modify sebum composition in gonadectomized animal glands. These data support the evidence that activation of beta-adrenergic receptors could be an independent factor in the lipid composition regulation process.     

Interferon-delta: the first member of a novel type I interferon family

We have recently described a novel type I interferon (IFN) co-expressed with IFN-gamma by the trophectoderm of the pig conceptus between day 12 and day 18 of gestation, a development stage that corresponds to implantation in the uterus. This IFN, now officially named IFN-delta, is recognized as the first member of a novel type I IFN family. This paper reviews the main published data on IFN-delta, together with some new data, showing that IFN-delta, while being a true type I IFN, has some very specific structural and biological properties. Sequences related to IFN-delta coding sequence were found in the genome of man and other ungulates but the only other potentially functional gene was found, so far, in the horse. The pig IFN-delta mature protein, with 149 amino acids, is the smallest of all known type I IFNs. It is unusually rich in cysteines (seven residues), and has a very basic isoelectric point. Recombinant IFN-delta expressed in insect cells is glycosylated and has a high antiviral activity on porcine cells, but not on human cells. It has high antiproliferative activity, which is significantly enhanced in the presence of IFN-gamma. This new IFN was shown to bind on pig cells to the same type I receptor as IFN-alpha. IFN-delta and IFN-gamma genes are co-regulated in the pig trophectoderm, whose cells on day 14-16 of development simultaneously secrete both IFN proteins. The biological role of porcine IFN-delta in early pregnancy has been found unrelated to the known antiluteolytic effect of trophoblastic IFN-tau in ruminants.     

Lipoprotein glomerulopathy: first case in a white European

Since 1988, 11 cases of a new entity, 'Lipoprotein glomerulopathy' (LG), were described in Japan. Some of these reports suggested that this glomerular lipid storage is due to excess apo E associated with heterozygous E2/3 apo E isoform. We report the first case of LG in a white European with no such lipid abnormalities. Proteinuria was discovered in 1967 when he was 42. Blood pressure and renal function were normal. Family history was negative. Renal biopsy disclosed lesions which were only understood at the time of the Japanese publications. They were composed of endocapillary glomerular deposits. Staining for lipids disclosed capillary loop obstruction with lipid droplets. Electron microscopy showed confluent droplets of various sizes obstructing capillary loops. Proteinuria progressively increased. In 1974 repeat renal biopsy showed the same lipid deposits, now associated with focal-segmental glomerulosclerosis (FSGS). Several serum lipoprotein and apolipoprotein studies ruled out any specific lipid derangement. This suggested a local glomerular disorder, presumably affecting the glomerular endocapillary disposal of lipids. A third biopsy showed progressive glomerular destruction by FSGS with persistence of the lipid droplets. Renal insufficiency progressed and haemodialysis was started in 1992. This observation suggests that LG is a local glomerular, not a general lipid disorder and indicates that this disease is not restricted to Asian patients.     

Behavioral science training in family practice residency education: a first evaluation

Although behavioral science training is an essential component of family practice residency education, there have been few evaluations of its effects. In this study, selected behaviors of senior residents and their patients in two different family practice residency programs were compared. One program emphasized behavioral science, the other did not. Residents in the more behaviorally oriented program had more positive attitudes toward both social factors in illness and the importance of a warm physician-patient relationship. In addition, these residents claimed to know more about non-pharmacologic treatments for depression and anxiety and felt more confident in their ability to handle them than their less behaviorally trained counterparts. In regard to patient care, patients of residents in the program which emphasized behavioral science were more likely to receive a psychosocial diagnosis and resident counseling or mental health referral than patients of residents in the program which did not. On a patient satisfaction questionnaire, patients of the two programs differed on only one subscale which concerned convenience of care. Although these early results are encouraging, behavioral science training needs continuing clarification and evaluation of its goals and accomplishments.     

Human syngamosis: the first case in Korea

Parasites of the genus Mammomonogamus affect the respiratory tract of domestic mammals but have only rarely been reported in humans. In this case report the diagnosis of human syngamosis is described following bronchoscopic examination of a patient whose initial symptoms were simply of community acquired pneumonia. The patient had a persistent and productive cough with intermittent fever during 10 days of observation. After bronchoscopic extraction of the parasites and treatment with albendazole he recovered fully. This is one of the first recognised cases of human syngamosis in Korea.     

Isolation and characterization of a satellite DNA family in the Saccharum complex

EaCIR1, a 371-bp Erianthus-specific satellite DNA sequence, was cloned from TaqI restricted genomic DNA after agarose-gel electrophoresis. This sequence has 77% homology with a 365-bp satellite of Helictotrichon convolutum and 72% homology with a 353-bp tandem repeat sequence from Oryza sativa. PCR primers defined in the conserved regions of these repetitive sequences were used to isolate other satellite DNAs in different representatives of the Saccharum complex: SoCIR1 in Saccharum officinarum, SrCIR1 in Saccharum robustum, SsCIR1 and SsCIR2 in Saccharum spontaneum, and MsCIR1 in Miscanthus sinensis. EaCIR1 and SoCIR1 were localized to subtelomeric regions of the chromosomes by fluorescence in situ hybridization. Southern hybridization experiments, using two representatives of this repeat sequence family as probes, illustrated contrasting species-specificity and demonstrated the existence of similar repetitive elements in sorghum and maize.     

Mucolipidosis II (I cell disease). First case report in the Czech Republic and prenatal diagnosis in a family

The authors describe the first case of mucolipidosis II in the Czech Republic. The cause of this autosomal recessive hereditary disease is deficient synthesis of mannoso-6-phosphate ligand on precursors of lysosomal enzymes which normally make their transport into the lysosomal system possible. The diagnosis was proved by the presence of typical lysosomal cumulation in bioptic specimens and extremely elevated activity of lysosomal enzymes in the patient's serum caused by their non-regulated secretion and subsequent intracellular depletion. During the second pregnancy in the family prenatal diagnosis was made. A normal range of lysosomal enzyme activities in the supernatant of the amniotic fluid and in cultivated chorionic villi along with normal results of ultrastructural examination of the chorionic villus indicated the development of an intact foetus.     

Male involvement in family planning: a case study spanning five generations of a south Indian family

Neospora caninum is a coccidial protozoan parasite that infects a large range of mammals including dogs, cats, mice, and cattle. Morphologically, N. caninum appears indistinguishable from Toxoplasma gondii, although they are genetically distinct. To date there have been no reported cases of this infection in humans, although nonhuman primates may be susceptible to infection. Inbred A/J mice develop no clinical and little histologic evidence of infection in spite of a high-dose inoculum of N. caninum. Splenocytes obtained from infected mice proliferate in vitro in response to both N. caninum and T. gondii-soluble antigen. A transient state of T cell hyporesponsiveness to parasite antigen and mitogen was observed at Day 7 p.i. This downregulatory response could be partially reversed by the addition of the nitric oxide antagonist LNMMA, but not antibody to IL-10. Mice infected with N. caninum produce significant quantities of IL-12 and IFN gamma, most evident shortly after infection. In vivo, antibody to IL-12 is able to neutralize immune resistance to the parasite. Moreover, in vivo depletion of IFN gamma with antibody renders the mice susceptible to infection. These observations suggest that N. caninum induces a T cell immune response in the infected host that is at least partially mediated by IL-12 and IFN gamma.     

Nevoid basal-cell syndrome: literature review and case report in a family

The Nevoid Basal-Cell Carcinoma Syndrome (NBCC), or as it is also referred to, basal-cell nevus syndrome or Gorlin-Goltz syndrome, is characterized by multiple early-appearing basal cell carcinomas, keratocytosis of the mandible, and anomalies of the ocular, skeletal reproductive system. We describe four patients in the same family, all of them possessing a large number of skin tumors associated with other typical clinical and X-Ray anomalies of NBCC. The definitive treatment of NBCC has yet to be established, however, early diagnosis is very important as well as the periodical follow-up examination of ten patients, mainly due to the transformations in the skin lesions that may occur.     

Hereditary exostoses--presentation of a family case

In this article we present a Norwegian family with hereditary multiple exostoses and a review of relevant literature. 21 family members were examined; ten males and six females had multiple exostoses, the youngest from six months of age. The exostoses had led to compression of nerves, disturbance of bone growth with shortening and bowing of the forearm bones, and valgus deformity of the knee and ankle. Physical function and quality of life was generally well preserved. Contrary to most reports, nearly half of the patients had allegedly noticed growth or debut of exostoses in adulthood. Almost half of the patients had had the exostoses removed surgically twice, (median value). Malignant transformation of exostoses has not been observed in the family.     

Struma cordis: first case in Mexico

The Intracardiac ectopic thyroid is an extremely rare condition and there is no previous report on this subject in Mexico. This is the case of a 33 years old woman, with normal thyroid function. She was found to have an intracardiac tumor in the interventricular septum. The intraoperative biopsy showed typical thyroid follicules; tumor removal left a septal defect that was closed with a dacron patch suture. Two years follow-up showed normal echocardiographic images, good clinical status an normal thyroid functioning. A brief review of the literature is included.