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Biomedical subjects

G Morpurgo

Publications and source records attributed to G Morpurgo.

At least 37 records · Page 2Linked to original sources

Decreased malaria morbidity in the Tharu people compared to sympatric populations in Nepal.

The Terai region of Nepal has been known to be heavily malarious since remote times, and it has, therefore, been regarded as uninhabitable by most Nepalese people. The Tharu people, who have been living in the Terai for centuries, were reputed to have an innate resistance to malaria. Following successful control of malaria by the Nepal Malaria Eradication Organization (NMEO), a large and heterogeneous non-Tharu population now inhabits the Terai along with Tharus. By analysing NMEO records, we have found that the prevalence of cases of residual malaria is nearly seven times lower among Tharus compared to sympatric non-Tharus. This difference applies to Plasmodium vivax, which is now much more common, and to Plasmodium falciparum. We suggest that the basis for resistance to malaria in the Tharu people is a genetic factor yet to be identified.

Adolescent↗

A comparative study on selected chemical carcinogens for chromosome malsegregation, mitotic crossing-over and forward mutation induction in Aspergillus nidulans.

10 "false negative" chemical carcinogens, i.e. ineffective in bacterial mutagenicity assays, were thoroughly investigated for their genotoxic activity in the mould Aspergillus nidulans. Forward mutations (methionine suppressors), mitotic crossing-over and chromosome malsegregation were the end-points scored. Positive results were obtained in tests for the induction of mitotic segregation with benzene, ethylenethiourea and urethane, which increased the frequency of abnormal presumptive aneuploid colonies with euploid sectors showing whole chromosome segregation (i.e. non-disjunctional diploids and haploids). The same compounds were ineffective in increasing the frequency of mitotic crossing-over or forward mutations. The other chemical carcinogens investigated, namely acetamide, amitrole, dieldrin, heptachlor epoxide, nitrilotriacetic acid, p,p'-DDT and thiourea were ineffective both as inducers of forward mutations and mitotic segregation.

Aspergillus nidulans↗

Genetic studies on the Tharu population of Nepal: restriction endonuclease polymorphisms of mitochondrial DNA.

The mitochondrial DNAs (mtDNAs) of 91 Tharus from Nepal were screened for restriction fragment length polymorphisms (RFLPs) using six highly informative restriction endonucleases. One pattern (morph) was found for BamHI, two for HpaI and HincII, three for HaeII, four for AvaII, and six for MspI. Two of the AvaII and four of the MspI morphs were "new" (not previously described). Virtually all of the "old" morphs found in the Tharus were previously observed in Orientals. The Oriental HaeII morph (HaeII-5) previously observed at a frequency of 5% was present in 25% of the Tharus. Of the 13 Tharu mtDNA types (defined by the six restriction endonuclease morphs) observed, five had previously been described ("old" types), all in Orientals. Three of these were unique for Orientals. All of the remaining eight "new" Tharu mtDNAs were all closely related to Oriental mtDNAs. Two of the "old" Tharu mtDNA types included the HpaI/HincII morph 1, a morph possibly indicative of the earliest human mtDNA types. From these data we have concluded that the Tharu mtDNAs are closely related to those of other Oriental populations. Further, our data support the hypothesis that human mtDNAs radiated from Asia.

Asian People↗

Deregulation of immunoglobulin expression: is this the main cause of Burkitt's lymphoma?

We here examine the role of c-myc in the aetiology of Burkitt's lymphomas. We suggest that c-myc causes cellular clones to become immortal while the deregulation of cell multiplication is the consequence of an altered production and/or structure of immunoglobulin chains caused by the 8-14, 8-2 or 8-22 translocations. Data relative to other immunoproliferative disorders are consistent with the hypothesis that the immunoglobulins play a key role in the regulation of the multiplication of lymphocytic cells.

Burkitt Lymphoma↗

Malignant melanoma in Rome, Italy, 1970-9.

An epidemiological study was conducted in the city of Rome and the incidence of malignant melanoma was determined retrospectively for the years 1970-9. All patients had legal residence in Rome and a histological diagnosis of melanoma during that period; only cases of malignant melanoma of the skin (ICD 172, 8th revision) were considered. A total of 17 public and 82 private hospitals were involved in the study with 11 081 and 6127 hospital beds respectively. All the hospitals in the study had one of the following therapeutic and diagnostic facilities: internal medicine, dermatology, oncology, radiology, surgery, plastic surgery, histopathology. Analyses of incidence are based on 500 cases, 237 males and 263 females, collected in the period 1970-9. The data indicate a positive time trend in incidence; the average annual increase is 0.27 cases/year per 100 000. The data show that in a Mediterranean and Latin country such as Italy the incidence of melanoma presents the same ascending trend as that of other Caucasian countries, whether European or not, the slope of the curves is similar for both sexes. The distribution of the primary site for both sexes is closely parallel to that described for all Caucasian populations, the lower limbs being more affected in females and the trunk in males.

Adult↗

Effect of azelaic acid on human malignant melanoma.

In 23 patients with malignant melanoma, including some with metastases and terminal patients, topical and oral (10--15 g daily) azelaic acid given for 1--12 weeks before surgical excision of the lesions was followed by arrest and subsequent regression of the advancing edge of lesions, reduction in size and flattening of nodular areas, and progressive lightening of pigmentation. Histological and ultrastructural effects included: degeneration and disappearance of malignant epidermal and dermal melanocytes with reduction of junctional activity; epidermal proliferation and return towards normal organisation; reappearance of papillary dermis, pilosebaceous units, and sweat glands; separation of dermal melanoma tumour masses into smaller collections of cells by regenerating connective tissue; and increase in number of dermal mast cells, macrophages, and round cells. These preliminary results indicate a direct cytotoxic effect of azelaic acid on melanocytes of human melanoma.

Administration, Oral↗

A new in vitro method for testing plant metabolism in mutagenicity studies.

A rapid method was proposed to detect whether a harmless agricultural chemical can be converted into a mutagenic one by plant metabolism. The method is based on the use of Nicotiana alata cell cultures. Results obtained with five pesticides (atrazine, dichlorvos, tetrachlorvinphos, Kelevan, and maleic hydrazide) suggest that the proposed method simulates the metabolism of the whole plant. This procedure was also successfully applied to the genetic system of Aspergillus nidulans. One pesticide, atrazine, induced mutations and somatic segregation only after metabolism during cocultivation with N. alata cells.

Atrazine↗

Effect of dicarboxylic acids on lentigo maligna.

Dicarboxylic acids from C8 to C14 are competitive inhibitors of tyrosinase in vitro, and here, the effect of a cream containing 15% azelaic acid (C9) on 3 cases of lentigo maligna is described. The lesions were treated for 90 days, with remarkable clinical and histological effect, maintained for up to 2 yr after cessation of treatment. Progress during treatment of one case was additionally monitored by electron microscopy, which revealed progressive elimination of abnormal melanocytes both basally and suprabasally, and their replacement by essentially normal cells engaged in normal melanogenesis. There was also progressive diminution in the general disorganization of the epidermis, and disappearance of lymphocyte response. It is concluded that dicarboxylic acids have a direct inhibitory and cytotoxic effect on abnormally active or structurally disordered melanocytes in lentigo maligna, but further investigations are required to establish their precise mode of action. Similar application of dicarboxylic acids to normal skin affects only a small proportion of melanocytes, suggesting that some phasic factor, or individual states of activity, may be concerned in their susceptibility.

Aged↗

Effect of dicarboxylic acids on normal human melanocytes in dispersed tissue culture.

Since dicarboxylic acids are competitive inhibitors of tyrosinase, and effective in treatment of hyperpigmentary disorders, such as chloasma and lentigo maligna, probably due to a cytotoxic effect on abnormal melanocytes, it is of interest to examine their effect on normal melanocytes in tissue culture. Azelaic or dodecandioic acids were added (150-200 micrograms/ml) to dispersed cultures of epidermal cells, and melanocytes were examined by electron microscopy after 7, 10, 15, 20 and 30 days. Apart from a stimulation of melanogenesis, the presence of dicarboxylic acids in the culture medium caused no detectable damage to melanocytes, nor did they prevent growth of a second generation of cells.

Culture Techniques↗

Analysis of mitotic nondisjunction with Aspergillus nidulans.

Two methods to detect the induction of nondisjunction with a diploid stable strain of A. nidulans are described. The first method gives only qualitative results, while the second method is quantitative and dose-effect curves can be done. Some physiological parameters affecting the induction of nondisjunction can also be studied, because either quiescent or germinating conidia can be treated with the drug under test. Some agents inducing nondisjunction were also tested for the induction of point mutation and somatic crossing-over with these comparative analysis. Two classes of agents inducing nondisjunction may be detected: the first causes all possible types of genetic damage either on quiescent or germinating conidia (a representative of this class is MMS) and acts presumably on the DNA level; the second acts only on germinating conidia and does not produce point mutation or crossing over. A representative of this class is Benomyl which interferes with spindle microtubules. A list of compounds tests is included.

Aspergillus nidulans↗

Mutagenicity of dichlorvos and other structurally related pesticides in Salmonella and Streptomyces.

The following pesticides: azinphosmethyl, diallate, dichlorvos, EPTC, fenchlorphos, mevinphos, monocrotophos, noruron, parathionmethyl, triallate, trichlorphon and vegadex were tested for the ability to induce his+ revertants in four histidines requiring strains of Salmonella typhimurium--TAI 535(missense), TAI 536, TAI 537 and TAI 538 (frame-shift)- and resistance to low levels of streptomycin in Streptomyces coelicolor. Dichlorvos, which is a phosphoric ester with a dichlorovinyl group as side chain, and trichlorphon, which is known for its spontaneous conversion in dichlorvos, are both mutagenic in Salmonella (strain TAI535) and Streptomyces. Five organophosphorus pesticides similar to dichlorvos but devoid of the vinyl group are not mutagenic. Three carbamates, diallate, triallate and vegadex, which contain a chloroallyl group similar to the vinyl group of dichlorvos are mutagenic in Streptomyes; triallate and vegadex are powerful mutagens also in Salmonella (strain TAI535); two other carbamates devoid of the chlorinated group are not mutagenic. The results suggest that the presence of a vinyl chloride or allyl chloride group in the molecule of these pesticides is responsible for the ability to induce point mutations in Salmonella and Streptomyces.

Animals↗

A quick method for testing recessive lethal damage with a diploid strain of Aspergillus nidulans.

A simple method capable of detecting recessive lethal damage in a diploid strain of Aspergillus nidulans is described. The method scores the recessive lethals on the 1st, the 3rd and the 5th chromosomes, which represent about 40% of the total map of A. nidulans. Two examples of induced lethals, with ultraviolet irradiation and methyl methanesulfonate are shown. The frequency of lethals may reach 36% of the total population with UV irradiation.

Aspergillus nidulans↗

Microbiological titration of proteins and of single amino acid content in biological materials without purification and hydrolysis.

A method is described for the microbiological determination of the protein content of biological materials. This method can also be adopted to titrate the concentration of a single amino acid in the protein and has the following advantages: (1) titration can be done without purification and hydrolysis of proteins; (2) the titration graph is a straight line between 25 and 800 microgram/ml; (3) protein values agree with those obtained using the Kjeldhal method; and (4) each mutant requiring one amino acid may be used to titrate the concentration of a single amino acid of the protein. The leucine content of various kinds of flour was measured with this system.

Amino Acids↗