Practical consensus recommendations for gestational breast cancer.

This manuscript provides a practical and easy to use consensus recommendation to community oncologists on how to manage gestational breast cancer.

Transfusion support for a patient with McLeod phenotype without chronic granulomatous disease and with antibodies to Kx and Km.

BACKGROUND AND OBJECTIVES: Kell antigens are encoded by the KEL gene on the long arm of chromosome 7. Kx antigen is encoded by the XK gene on the short arm of the X chromosome. Kell and Kx proteins in the red cell membrane are covalently linked by a disulphide bond. The McLeod phenotype is characterized by weakened expression of antigens in the Kell blood group system, absence of Km and Kx antigens, and acanthocytosis. It has an X-linked mode of inheritance with transmission through carrier females. Some males with the McLeod syndrome also have chronic granulomatous disease (CGD). It is generally believed that patients with non-CGD McLeod may develop anti-Km but not anti-Kx, but that those with CGD McLeod can develop both anti-Km and anti-Kx. MATERIALS AND METHODS: We present serological data, DNA genotyping and gene sequencing, monocyte monolayer assay and neutrophil oxidative burst test from a patient with the McLeod phenotype without clinical evidence of CGD. RESULTS: We report here the second example of a patient with non-CGD McLeod who developed anti-Kx in addition to anti-Km. Sequencing of our patient's XK gene confirmed the presence of a mutation resulting in a premature stop codon and lack of Kx protein in the red cell membrane, which is consistent with the diagnosis of McLeod syndrome. Neutrophil oxidative burst test was normal, indicating that our patient did not have CGD. The challenge of providing 10 compatible blood units for multiple surgeries was met. CONCLUSION: The second case of a rare entity, a patient with non-CGD McLeod who developed anti-Kx and anti-Km, was managed successfully with a combination of autologous donations and procurement of compatible units from national and international sources.

Genetic variation and structure of the people of Uttarakhand, central Himalayas, India.

The Indian Himalayas, being semi-isolated geographically, provide ideal conditions for population genetics investigations. The main aim of this study is to genetically characterize and analyze the genetic structure of the people of Uttarakhand, a newly created North Indian hill state in the Central Himalayas, using original phenotype and allele-frequency data on a battery of seven red cell enzyme polymorphisms. For this analysis, blood samples were collected from 3,222 unrelated subjects belonging to various endogamous caste populations (Brahmin, Rajput, and Shilpkar) and tribal Bhotia inhabiting seven different districts in the Garhwal (northern) and Kumaon (southern) regions of Uttarakhand. Hemolysates were typed for isozymes of ESD, PGM1, ADA, AK1, GLO1, ACP1, and GPI using standard electrophoretic techniques. The genetic structure of these regional caste and tribal population groups was investigated with the help of different statistical measures. The present biochemical marker results show that the overall genetic constitution of the different populations of Uttarakhand is rather heterogeneous but similar to that of various caste and tribal populations of the neighboring hill state of Himachal Pradesh, situated on Uttarakhand's western border. The extent of genic differentiation observed in different contemporary populations of Garhwal was twice as high as that of Kumaon. Interestingly, in genetic distance dendrograms of both the regions and of all of Uttarakhand, all the Shilpkar groups are differentiated from the remaining groups of Brahmin, Rajput, and Bhotia. The genetic constitution of the Shilpkar (a scheduled caste population of Uttarakhand) and to a lesser extent that of the Bhotia (a scheduled tribe population of Uttarakhand) are rather different from both the Brahmin and Rajput high-caste populations, which tend to show genetic similarities between them. These observations are corroborated by the known ethnohistory of different populations of Uttarakhand.

Molecular cloning, purification and characterisation of myosin of human lymphatic filarial parasite Brugia malayi.

Global efforts have been made towards development of vaccine for prevention of lymphatic filariasis. However, lack of thorough knowledge about developmental biology and pathogenesis of filarial parasite restricts us from developing an effective vaccine. A limited number of immunodominant antigens of human lymphatic filariid Brugia malayi have been characterised; however, none of these recombinant antigens so far induced significant degree of protective immunity to challenge infection. In the present study, we identified a approximately 2.0 Kb cDNA clone by immunoscreening of cDNA library of adult female Brugia malayi. The nucleotide sequence of the identified clone showed 94.3% homology with C-terminal part of myosin heavy chain gene of Brugia malayi. This cDNA insert was sub-cloned into pET28b vector and expressed in BL21(DE3). The recombinant protein was purified to near homogeneity by immobilised metal affinity chromatography (IMAC) with yield of approximately 25 mg/l. The purified protein was recognised in western blot with anti-His tag antibody as also with the antibodies present in the sera of human W. bancrofti patients of all categories and infected/immunized rodent serum demonstrating its functional role. Recombinant myosin induced marked cellular immune response as observed by lymphoproliferation assay. The present findings demonstrate the usefulness of B. malayi recombinant myosin as vaccine candidate against human lymphatic filariasis.

Pinpoint papular variant of polymorphous light eruption: clinical and pathological correlation.

BACKGROUND: Polymorphous light eruption (PMLE) is the most common chronic idiopathic photodermatosis usually manifesting as a papular eruption along with several other morphological variants including a pinpoint papular variant. METHODS AND MATERIALS: Between June 1998 and August 2003, 10 PMLE patients presented to the Department of Dermatology at Henry Ford Hospital with complaints of a pruritic pinpoint papular eruption associated with sun exposure. In six patients skin biopsies were performed along with a detailed history and complete skin examination. We correlated the histology with the clinical course of disease corresponding to acute and subacute disease presentation. We also performed immunohistochemistry on three cases to study the immunophenotype in PMLE. RESULTS: The clinical, histologic and immunostain findings are summarized. Acute: Clinically pinpoint papules and vesicles, some with erythematous base, were seen. Histology showed focal vesicle formation, spongiosis, oedema, red blood cells extravasation, and superficial and deep perivascular and interstitial lymphocytic infiltrate with occasional eosinophils. Subacute: Clinically pinpoint papules with or without erythema were seen. Histology of the pinpoint lesion showed a nodular collection of lymphocytes and histiocytes with claw-like extension of epidermal rete ridges at the lateral boundaries of the lesion. Overlying epidermal atrophy with adjacent spongiosis, exocytosis, oedema and a superficial perivascular lymphocytic infiltrate and parakeratosis was also observed. The histologic differential diagnosis included lichen nitidus. Immunohistochemical stains revealed the following results: CD8, CD68 positive, CD4 variable (strongly positive to negative) and S-100 negative. CONCLUSION: (i) Pinpoint papular variant of PMLE is a distinct entity, which shows characteristic histology corresponding to the clinical course of the disease (acute and subacute). (ii) The histologic and immunophenotypic differential diagnosis of this variant during the subacute phase includes lichen nitidus.

Malignancy in AIDS: institutional management or home care?

In India, the first sero-positive person was reported from Chennai in 1986 and the first case of AIDS from Mumbai 1987. Since then the epidemic is growing steadily and WHO/UNAIDS estimate that by the year 2000 AD India has around 3-5 million people suffering from HIV/AIDS and this is the largest burden of HIV in single country. Over 40% of all patients with HIV infection will develop malignant disease at sometime during their course of illness. AIDS and malignancy together constitute a deadly combination. The authors recommend that the care of patients having malignancy with AIDS should be mainly at home rather than in an oncology center. This will ensure the patient's and family's comfort as most of the specialized cancer centers in India are at a considerable distance away from patient's homes. Frequent visit to a cancer center will exhaust the patient and attendants emotionally, physically and financially. This is especially true because irrespective of the pains taken by the family and the specialists, a cure is an unlikely possibility. Only one specialist from oncology and one primary health physician, who are completely aware of the patient's physical, psychological, financial and social background, should be responsible for the care of a patient having malignancy with AIDS in India. The main advantages of the home care of such patients are: patient's and family's comfort; lesser mental, physical, social, emotional and financial agony; and minimum need for institutional care, which may be instituted as and when necessary.

Genetic epidemiology of non-insulin-dependent diabetes mellitus in north India: preliminary analyses of some genetic markers in Punjabis.

Studies on monozygotic (MZ) twins and admixed populations show that the predisposition to non-insulin-dependent diabetes mellitus has a large genetic component. We have examined the distribution of some genetic polymorphisms (ABO, GLO, ESD, AK, ACPA, and GPI) in control and diabetic Punjabis from north India. The distribution of various genetic markers indicate that the differences between the control and diabetic samples are statistically not significant. Moreover, a contingency chi-square analysis over all loci suggests nonsignificant genetic differentiation (p = 0.50) between the Punjabi samples.

Serogenetic variation in four caste populations of Haryana, India.

The phenotypes and gene frequencies of 3 blood groups, 7 red-cell enzymes and a serum protein were studied in 4 caste population groups of Haryana, North India. The results indicate that the distribution of these blood markers is rather homogeneous in the 4 groups and generally resembles that observed in various populations from neighbouring North Indian states.

Electrophoretic variants of red cell phosphoglucose isomerase in some caste populations of Punjab.

Hemolysates from a total of 640 blood samples from seven endogamous caste groups of the Patiala and Faridkot districts of Punjab, North-West India, were subjected to horizontal starch gel electrophoresis to study the phosphoglucose isomerase (PGI) types. In addition to the usual pattern PGI 1, the only rare phenotype encountered in the present material was PGI 3-1, present in four out of the seven groups investigated. Examination of the available data from Punjab suggests that apparently rare PGI types other than PGI 3-1 are lacking in populations studied.

Genetic variation of esterase D (EsD) polymorphism in Indian populations.

Data are presented on the phenotypes and gene frequencies of esterase D (EsD) polymorphism in various endogamous caste groups of Patiala and Faridkot districts of Punjab, north-west India. The frequency of the EsD2 allele in these groups varies from a minimum of 0.157 in Khatris to a maximum of 0.253 in Ramdasia Sikhs, a range quite typical of the north Indian populations. Examination of the available data on esterase D system in indigenous populations demonstrates the existence of a north-south cline in the distribution of the EsD2 allele in India.

Population genetics of glyoxalase I (GLO) polymorphism in India.

Phenotype and gene frequency data are presented on the glyoxalase I (GLO) polymorphism in seven endogamous caste groups: Jat Sikh, Ramdasia Sikh, Ramgarhia Sikh, Khatri, Brahmin and Bania of Patiala district, and Jat Sikh of Faridkot district of Punjab, North-West India. Apparently, there is considerable heterogeneity in the frequency distribution of the GLO1 gene that varies from 0.168 in Bania to 0.287 in Brahmin. However, these differences are not statistically significant, and the overall GLO1 frequency in Punjab is well within the North Indian range.

Serum proteins among Dusads of Bihar.

Horizontal starch gel electrophoresis has been employed for the detection of haptoglobin, transferrin and albumin phenotypes among 88 Dusads of Bihar. No variant of the haptoglobins or transferrins has been found in this sample, whereas one individual showed bisalbuminemia.

Genetic polymorphism of erythrocyte acid phosphatase in Indian populations.

The polymorphism of erythrocyte acid phosphatase has been investigated in seven endogamous caste groups of Patiala and Faridkot districts of Punjab in north-west India. The frequency of the Pa allele in these groups varies from 26.8 to 38.3%, but there is no evidence for any significant heterogeneity in the total sample. The Pc allele is present in some of the groups, though in non-polymorphic proportions. Furthermore, the distribution of this polymorphism in Indian populations has been examined using gene frequency data available in the literature. The present study shows that while no clinal component is discernible in the distribution of this red cell enzyme in India, the populations of north India stand out with comparatively high Pa and Pc frequencies, and in almost all regions the incidence of these two alleles is higher in the non-tribals as compared to the tribals. The possible causes of this heterogeneity are discussed.

Placental alkaline phosphatase polymorphism in some Punjabi populations.

Placental isozyme of alkaline phosphatase (orthophosphoric monoester hydrolase, EC 3.1.3.1.) has been studied in very few Indian populations with respect to its polymorphic form. The present study surveys the alleles encountered in some Punjabi groups of Northern India. The distinguishing physico-chemical properties of this isozyme, viz. heat stability, steady increase in maternal plasma during the course of pregnancy, and unique electrophoretic mobility have been used for its typing. The Punjabi groups surveyed are Jat (Sikh), Baniya and Khatri (all endogamous castes) and Lower Castes and others (two mixed caste groups). These groups were found to be in Hardy-Weinberg-equilibrium, and some of them revealed intergroup heterogeneity, when compared with each other. Further comparison with other Indian populations, for which data were available, also revealed interesting results.

A study of some genetic markers among Ramgarhias, an artisan caste of Punjab.

156 males and 63 females belonging to the Ramgarhia community, an endogamous group of Punjab, were taken for the study of genetical markers like taste ability to PTC, mid digital hair and colourblindness, whereas 75 (50 males and 25 females) were tested for serum proteins. 71.70% males and 73.85% females were found to be tasters. The mid digital hair was absent in 67.34% of females and 64.74% of males. No female was found to be colourblind, however, 4.48% males were found having defective colourvision. The phenotypic frequencies of Hp 2--2, Hp 2--1 and Hp 1--1 were found to be 64.00%, 32.00% and 4.00%, respectively. No variant of transferrins and albumin was found.

Ethnic diversity in Punjab as based on finger dermatoglyphics.

Four ethnic groups of Punjab having same dialect viz. Khatris, Jats, Brahmins and Muslims were taken to see ethnic differences in regards to the distribution of whorls, loops, and arches of finger dermatoglyphics. The results show that there is a great diversity in the four groups for these parameters. These groups were compared with similar ethnic groups of other places having different dialect. The results reveal that there seems to be ethnic affinity between the group known by same name and which is true for all the four groups.