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Biomedical subjects

G Manfredi

Publications and source records attributed to G Manfredi.

At least 55 records · Page 3Linked to original sources
PubMed1994

Ophthalmoplegia, demyelinating neuropathy, leukoencephalopathy, myopathy, and gastrointestinal dysfunction with multiple deletions of mitochondrial DNA: a mitochondrial multisystem disorder in search of a name.

This article describes a 37-year-old woman with progressive external ophthalmoplegia, peripheral neuropathy, and chronic intractable diarrhea. Laboratory studies disclosed lactic acidosis, ragged red fibers lacking cytochrome c oxidase, high-normal muscular mitochondrial enzymes, demyelinating neuropathy, leukoencephalopathy and multiple mitochondrial DNA deletions. This is the fourth patient described with this clinical syndrome, which represents a separate entity among multisystemic mitochondrial disorders. The patient described here is the first with this syndrome to have multiple mitochondrial DNA deletions.

Adult↗
PubMed1994

Autosomal recessive hypermyelinating neuropathy.

We studied three patients from two kinships, affected by early onset hereditary motor and sensory neuropathy with probable autosomal recessive inheritance (HMSN type III). Morphological studies of sural nerve biopsies revealed an abnormal myelin proliferation. Two adult patients with long-term follow up, lost ability to walk at 28 and 22 years and showed severe involvement of the cranial nerves. Our observations suggest that "hypermyelination neuropathy" with early onset is a progressive disease with poor long-term prognosis. In one kinship the occurrence of the disease in two sibs of both sexes but not in parents, is consistent with an autosomal recessive inheritance. Familial cases of hypermyelination neuropathy have not been described in previous reports. Morphological aspects of this condition are compared with other forms of hypermyelination neuropathy.

Adult↗
PubMed1993

Mechanism of the oxidation reaction of deoxyhemoglobin as studied by isolation of the intermediates suggests tertiary structure dependent cooperativity.

The intermediates in the oxidation of deoxyhemoglobin by ferricyanide in 0.1 M KCl, at 20 degrees C and three pH values, were studied by cryogenic techniques. Data analysis was carried out according to a simple four rate constant model, ignoring the functional heterogeneity of the subunits, to simulate the time courses of the oxidation reaction, as studied by the stopped-flow technique [Antonini et al., (1965) Biochemistry 4, 345], which show anticooperativity at neutral pH and cooperativity at alkaline pH. Data analysis according to a 12 rate constant model indicated that the rate of oxidation of the beta subunit in the first oxidation reaction was 4 times faster than the rate of oxidation of the alpha subunit at pH 6.2 and 12 times faster at pH 8.5. The reactions involving the alpha subunit were noncooperative except for the last oxidation step at acid and neutral pH, but were cooperative at alkaline pH. The reactions involving the beta subunit were partly noncooperative and partly anticooperative. These complex mechanistic patterns suggest that a simple two-state model requiring the concerted transition of the tertiary structures of the subunits from the T to the R conformation is not adequate to interpret the oxidation reaction and that tertiary structures contribute, positively and negatively, to cooperativity. A structural hypothesis is suggested to explain the difference in the reactivities of the alpha and beta subunits.

Ferricyanides↗
PubMed1993

Pseudopseudohypoparathyroidism associated with idiopathic growth hormone deficiency. Role of treatment with biosynthetic growth hormone.

A case is presented of a prepubertal girl with the characteristic somatic features of Albright's hereditary osteodystrophy, including severe short stature, cataracts and shortening of all metacarpals and metatarsals and of the second middle hand phalanges, whose diagnosis of pseudopseudohypoparathyroidism (PPHP) was confirmed by laboratory evaluation (normocalcemia, normophosphatemia, normal levels of circulating PTH and normal response to exogenous PTH). Since an isolated idiopathic GH deficiency has been diagnosed at the age of 9.7 yr, by an abnormal GH response to standard provocation tests, a poor spontaneous nocturnal GH secretion and a blunted response to GHRH test, our patient was treated with biosynthetic GH during a 3.5-year period. Although a good improvement of growth velocity was obtained when comparing pretreatment height velocity (4 cm/yr) with growth velocity evaluated during GH treatment (6.6, 6.2 and 5.9 cm/yr in the first, the second and the third year of therapy, respectively), bone age advanced more rapidly than chronological age, so that it is uncertain whether the growth acceleration promoted by GH administration really improved final height, which remained below the third centile. Our patient is the first described case of PPHP associated with idiopathic GH deficiency, and the second report of long-term GH treatment in a subject with PPHP. Further observations are necessary to define the frequency and significance of GH deficiency and the role of GH replacement therapy in pseudohypoparathyroidism- and PPHP-associated short stature.

Child↗
PubMed1993

Manifesting heterozygotes in McArdle's disease: clinical, morphological and biochemical studies in a family.

We report a family with McArdle's disease with several affected individuals in two generations. This unusual pedigree for an autosomal recessive disease is explained by the existence of manifesting heterozygotes in the maternal line. The presence of symptoms in heterozygotes seems to be due to a decrease in myophosphorylase activity below a critical threshold, ranging between 30% and 45% of normal mean value. The occurrence of several manifesting heterozygotes in the maternal line only can be explained by compound heterozygosity of a defective allele and a pseudodeficient allele for myophosphorylase, or by a genetic factor which regulates the phenotypic expression of the gene.

Adolescent↗
PubMed1993

Cardiomyopathy may be the only clinical manifestation in female carriers of Duchenne muscular dystrophy.

Cardiomyopathy was reported in a few Duchenne muscular dystrophy (DMD) carriers with clinical evidence of myopathy. We report two carriers with dilated cardiomyopathy, increased serum CK, and no symptoms of muscle weakness. In heart biopsies of both patients, dystrophin-the protein product of DMD locus--was absent in many fibers. Dilated cardiomyopathy may be the only manifestation of dystrophin gene mutation in carriers.

Adult↗
PubMed1993

Acid maltase deficiency in childhood. Early diagnosis and clinical follow-up of late-onset glycogen storage disease type II.

A case is described of late-onset glycogenosis type II presenting with an isolated rise in serum transaminase levels. Histological, histochemical, ultrastructural and biochemical examinations performed on muscle biopsy showed the typical laboratory features of late-onset glycogenosis type II, which was diagnosed more than four years before the first appearance of disease-related signs and symptoms. A heterozygote status for the same defect was also demonstrated by enzyme assays in both parents, thus confirming the autosomal recessive mode of inheritance of the disorder. Even though an elevation in transaminases and other serum enzymes of possible muscle origin has been previously described as a diagnostic clue in some unsuspected muscular diseases in childhood, as far as we know no other patient with a sporadic form of glycogenosis type II has been identified when still completely asymptomatic. The possibility of silent primary metabolic diseases and myopathies should be carefully considered when evaluating children with persistently elevated serum transaminases, even in the absence of suggestive anamnestic, familial and physical findings, in order to obtain an early diagnosis and to provide an appropriate genetic counselling.

Age of Onset↗
PubMed1992

Fatal infantile liver failure associated with mitochondrial DNA depletion.

A 3-month-old girl was admitted to the hospital because of hypotonia and frequent vomiting. She had severe metabolic acidosis and her liver function was abnormal. Hepatomegaly and rapidly progressive liver failure developed, and she died at 4 months of age. Two half-siblings from a different mother had died in infancy of an undiagnosed myopathy. The liver was fatty and hepatocytes were filled with large and small lipid droplets. Other tissues were morphologically normal. The respiratory chain enzymes containing subunits encoded by mitochondrial DNA were markedly decreased in liver, partially decreased in muscle, but normal in other tissues. Southern blot analysis showed 90% depletion of mitochondrial DNA in liver, 53% depletion in muscle, and normal amounts in other tissues. This is the second case of fatal infantile liver failure associated with mitochondrial DNA depletion. This pathogenetic mechanism should be considered in infants with multiple respiratory chain defects and variable tissue expression.

Acidosis, Lactic↗
PubMed1991

Dominantly inherited mitochondrial myopathy with multiple deletions of mitochondrial DNA: clinical, morphologic, and biochemical studies.

We studied a large family with a dominantly inherited mitochondrial myopathy characterized by progressive external ophthalmoplegia, dysphagia, cataract, lactic acidosis, exercise intolerance, and early death. Morphologic studies of muscle biopsies suggested mitochondrial heteroplasmy and revealed ragged-red fibers and decreased histochemical reactions for cytochrome c oxidase and succinate dehydrogenase. Biochemistry showed a partial defect of cytochrome c oxidase and a mild generalized reduction of other mitochondrial enzymes requiring mitochondrial DNA-encoded subunits. Southern blot analysis and PCR amplification showed mitochondrial DNA deletions in muscle of all affected members, but not in lymphocytes or fibroblasts, suggesting a tissue-specific distribution. Deletions were multiple and seemed to increase with time and to correlate with the severity of the disease.

Adult↗
PubMed1989

[Study of pollen of allergologic significance in the urban atmosphere of Parma in the years 1983-1984].

From 1983 to 1984 pollen air samples from Parma's urban atmosphere were collected weekly by means of a Burkard recording volumetric spore trap. Data regarding a few of the meteorologic variables were also collected at the same time: temperature, insulation, water precipitation, humidity and wind speed. Some of the more allergenic pollens and their concentration/m3 air were determined from the collected samples: Graminea, Urticaceae, Fagaceae, Salicaceae and Betulaceae. Looking at the results from the period of study, it can be seen that Graminea and Urticaceae were the most represented in comparison with the other families. Graminea was most represented in May 1983, in June 1984 and during the first week of September 1984; Urticaceae in September 1983, May 1984 and September 1984. These pollen concentrations were also compared to the meteorologic data.

Italy↗
PubMed1987

A horizontal apparatus for isoelectric protein purification in a segmented immobilized pH gradient.

A modification of the previously described apparatus (Faupel et al. (1987) J. Biochem. Biophys. Methods 15, 147-162), for recycling isoelectric focusing in a segmented immobilized pH gradient, is here reported. The most important improvements are: (1) a horizontal, vs. the previously vertical assembly; (2) a reduction of the thickness of the central flow chamber to 6 mm, vs. the previous 3 cm length and (3) the introduction, at both gel extremities of each Immobiline segment, of polypropylene filters, thus efficiently blocking the gel in situ. The advantages are: (i) the spontaneous removal of air bubbles, which in the vertical apparatus tend to accumulate in the ceiling of the flow chamber and to obstruct the flow of electric current; (ii) a more efficient hydraulic flow with a reduced chance of heating the liquid stream in the flow chamber, due to its reduced length along the separation path and (iii) a reduced risk of gel detachment from the tube walls, due to osmotic swelling caused by focused protein zones in the gel phase and by the fixed Immobiline charges in the polyacrylamide matrix.

Adult↗
PubMed1983

Imbalance in phenotypic expression of T cell subpopulations during different evolutional stages of lichen planus lesions.

Immunoenzymatic (in light and in electron microscopy) and immunofluorescence techniques were performed, using monoclonal antibodies, on tissue sections of early lichen planus (LP) lesions versus late LP lesions from 20 patients. Control procedures were carried out in peripheral blood T cells from the same patients and from healthy donors. The OKT4-Leu3A/OKT8-Leu2A ratio in peripheral blood from LP patients and from donors was lower than in dermal infiltrate of early LP lesions, but higher than in dermal infiltrate of late LP lesions. It is conceivable that in early LP lesions OKT4-Leu3A-positive cells may be antigen-specifically 'educated' by immunostimulatory cells. In late LP lesions, OKT8-Leu2A-positive cells could be cytotoxic to keratinocytes; it is likely, however, that this latter population may moreover have immunoregulatory, resolutional functions.

Antibodies, Monoclonal↗
PubMed1983

Inhibition of gastric emptying by angiotensin in the rat and its antagonism by saralasin.

Angiotensin, administered by intraperitoneal route (0.1 - 100 micrograms/kg) significantly delayed gastric emptying in the conscious rat. This action, most probably connected with the spasmogenic effect on the gastroduodenal junction, was antagonized by saralasin (125 and 250 micrograms/kg intraperitoneally). Our data seem to suggest an action of the peptide on the stomach mediated through an interaction with specific receptors.

Angiotensins↗