Patterns of effective connectivity during memory encoding and retrieval differ between patients with mild cognitive impairment and healthy older adults.

Previous research has shown that there is considerable overlap in the neural networks mediating successful memory encoding and retrieval. However, little is known about how the relevant human brain regions interact during these distinct phases of memory or how such interactions are affected by memory deficits that characterize mild cognitive impairment (MCI), a condition that often precedes dementia due to Alzheimer's disease. Here we employed multivariate Granger causality analysis using autoregressive modeling of inferred neuronal time series obtained by deconvolving the hemodynamic response function from measured blood oxygenation level-dependent (BOLD) time series data, in order to examine the effective connectivity between brain regions during successful encoding and/or retrieval of object location associations in MCI patients and comparable healthy older adults. During encoding, healthy older adults demonstrated a left hemisphere dominant pattern where the inferior frontal junction, anterior intraparietal sulcus (likely involving the parietal eye fields), and posterior cingulate cortex drove activation in most left hemisphere regions and virtually every right hemisphere region tested. These regions are part of a frontoparietal network that mediates top-down cognitive control and is implicated in successful memory formation. In contrast, in the MCI patients, the right frontal eye field drove activation in every left hemisphere region examined, suggesting reliance on more basic visual search processes. Retrieval in the healthy older adults was primarily driven by the right hippocampus with lesser contributions of the right anterior thalamic nuclei and right inferior frontal sulcus, consistent with theoretical models holding the hippocampus as critical for the successful retrieval of memories. The pattern differed in MCI patients, in whom the right inferior frontal junction and right anterior thalamus drove successful memory retrieval, reflecting the characteristic hippocampal dysfunction of these patients. These findings demonstrate that neural network interactions differ markedly between MCI patients and healthy older adults. Future efforts will investigate the impact of cognitive rehabilitation of memory on these connectivity patterns.

Benign esophagorespiratory fistula: a case series and a novel technique of definitive management.

Benign esophagorespiratory fistula is a relatively rare condition in adults that poses a technical challenge to manage. This case series describes our experience in the treatment of benign esophagorespiratory fistula in 12 adults. A retrospective review of case records of 12 patients with benign esophagorespiratory fistula was done. There were eight tracheoesophageal fistulae and four bronchoesophageal fistulae. Among them, four fistulae were congenital, one was secondary to corrosive injury, three were due to foreign body (dentures), one was secondary to erosion because of prolonged endotracheal intubation, one was secondary to penetrating trauma, and two were infective in etiology. Of the 12 patients, there were nine males and three females. The mean age of presentation was 30.16 years (range 15-53 years). Nine patients had a definitive surgical intervention. The esophageal end of the fistula was managed by primary closure of the esophageal defect and reinforcement with pleural or intercostal muscle flap or a subtotal esophagectomy. The respiratory end of the fistula was dealt with by primary closure of the defect or by a novel technique of neomembranous airway formation, whereby the tracheal defect was closed with the help of a vascularized patch of the esophageal wall. The technique of this neomembranous airway formation is described in detail, and to our knowledge, this is the first time that this technique is being reported in the English literature. This technique is a novel method for definitive repair and can be considered as an option for repair of esophagorespiratory fistula with large defects.

Mutations of FAM111B gene are not associated with Systemic Sclerosis.

Systemic sclerosis (SSc) is a prototypic systemic fibrotic disease with unclearly characterized genetic basis. We have discovered that mutations in family with sequence similarity 111, member B (FAM111B) gene cause hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis, a multisystem fibrotic condition with clinical similarities to SSc. This observation has established FAM111B as a candidate gene for SSc. PATIENTS AND METHODS: Demographic and clinical characteristics of consenting adults with definite SSc were recorded. Blood DNA analysis was performed using the High-Resolution Melt technique, and samples with abnormal electropherograms were selected for Sanger sequencing to identify mutations. Ethnically-matched controls from the general South African population were used to verify the frequency of variants in FAM111B. Public databases such as 1000 Genomes and ExAC were also used to verify the frequency of variants in FAM111B. RESULTS: Of 131 patients, 118 (90.1%) were female, and 78 (59.5%) were black Africans. Genetic analysis revealed two FAM111B genetic variants. The c.917 A > G variant (rs200497516) was found in one SSc patients, and one control, and was classified as a missense variant of unknown significance. The c.988 C > T variant (rs35732637) occurred in three SSc patients and 42/243 (17.3%) of healthy controls, and is a known polymorphism. CONCLUSION: One rare variant was found in a patient with SSc but has no functional or structural impact on the FAM111B gene. In this cohort, FAM111B gene mutations are not associated with SSc.

scute (sis-b) function in Drosophila sex determination.

The primary sex determination signal, the X chromosome-to-autosome (X/A) ratio, controls the choice of sexual identity in the Drosophila melanogaster embryo by regulating the activity of the early promoter of the Sex-lethal gene, Sxl-Pe. This promoter is activated in females (2X/2A), while it remains off in males (1X/2A). Promoter activation in females is dependent upon X-linked numerator genes. One of these genes, sisterless-b (sis-b), corresponds to the scute (sc) locus of the achaete-scute complex, and it encodes a helix-loop-helix transcription factor. In the studies reported here we have used monoclonal antibodies to study the expression and functioning of the sc(sis-b) protein. Sc is first detected at nuclear cycle 6 to 7, well before Sxl-Pe is first active. At this stage, the protein is in the cytoplasm, not the nucleus. Only after the formation of the syncytial blastoderm, at nuclear cycle 10 to 11, does a substantial fraction of the protein enter the nucleus, and this nuclear import closely coincides with the initial activation of Sxl-Pe. Consistent with the idea that the dose of sc(sis-b) is critical for its function as an X-chromosome counting element, wild-type syncytial blastoderm embryos could be grouped into two classes based on the level of protein. Western blot (immunoblot) analysis demonstrates that this difference in protein level correlates directly with the activity state of the Sxl gene. Finally, we provide the first direct evidence that Sc forms heteromeric complexes in vivo in early embryos with the maternally derived helix-loop-helix protein Daughterless. This in vivo complex is likely to be critical for Sc function in Sxl-Pe activation.

Sex-lethal interacts with splicing factors in vitro and in vivo.

The Drosophila sex determination gene Sex-lethal controls its own expression and the expression of downstream target genes such as transformer by regulating RNA splicing. Genetic and molecular studies have established that Sxl requires the product of another gene, snf, to autoregulate the splicing of its own transcripts. snf has recently been shown to encode a Drosophila U1 and U2 small nuclear ribonucleoprotein particle protein. In the work reported here, we demonstrate that the Sxl and Snf proteins can interact directly in vitro and that these two proteins are part of an RNase-sensitive complex in vivo which can be immunoprecipitated with the Sxl antibody. Unlike bulk Snf protein, which sediments slowly in sucrose gradients, the Snf protein associated with Sxl is in a large, rapidly sedimenting complex. Detailed characterization of the Sxl-Snf complexes from cross-linked extracts indicates that these complexes contain additional small nuclear ribonucleoprotein particle proteins and the U1 and U2 small nuclear RNAs. Finally, consistent with the RNase sensitivity of the Sxl-Snf complexes, Sxl transcripts can also be immunoprecipitated by Sxl antibodies. On the basis of the physical interactions between Sxl and Snf, we present a model for Sxl splicing regulation. This model helps explain how the Sxl protein is able to promote the sex-specific splicing of Sxl transcripts, utilizing target sequences that are distant from the regulated splice sites.

An N-terminal truncation uncouples the sex-transforming and dosage compensation functions of sex-lethal.

In Drosophila melanogaster, Sex-lethal (Sxl) controls autoregulation and sexual differentiation by alternative splicing but regulates dosage compensation by translational repression. To elucidate how Sxl functions in splicing and translational regulation, we have ectopically expressed a full-length Sxl protein (Sx.FL) and a protein lacking the N-terminal 40 amino acids (Sx-N). The Sx.FL protein recapitulates the activity of Sxl gain-of-function mutations, as it is both sex transforming and lethal in males. In contrast, the Sx-N protein unlinks the sex-transforming and male-lethal effects of Sxl. The Sx-N proteins are compromised in splicing functions required for sexual differentiation, displaying only partial autoregulatory activity and almost no sex-transforming activity. On the other hand, the Sx-N protein does retain substantial dosage compensation function and kills males almost as effectively as the Sx.FL protein. In the course of our analysis of the Sx.FL and Sx-N transgenes, we have also uncovered a novel, negative autoregulatory activity, in which Sxl proteins bind to the 3' untranslated region of Sxl mRNAs and decrease Sxl protein expression. This negative autoregulatory activity may be a homeostasis mechanism.

Tumor Thickness: A predictor of nodal disease in early squamous cell carcinomas of buccal mucosa.

Squamous cell carcinomas of buccal mucosa is one the highest number of malignancies seen in the Southeast Asian region. It is related to chewing a combination of tobacco mixed with betel leaves, areca nut, and lime shell called quid. As it is most commonly due to substance abuse and affects younger population, it has tremendous economical and social consequences. Surgery is the most successful modality of management in these patients. The surgery involves wide excision of the diseased mucosa and neck dissection. Neck dissection is associated with certain morbidities, but is routinely practiced in some centers like ours. We have attempted to evaluate the occurrence of the nodal disease in relation to the thickness of the tumor in cases of early cancers of buccal mucosa (stage I and II). We have used ultrasound of the lesion as our modality to assess the tumor thickness preoperatively. AJCC 7th edition was used to assess the clinical and pathological stage of the disease. We have studied 52 patients of early buccal mucosal squamous cell carcinoma, and we observed that tumors thicker than 7mm (p-0.05) have highest co-relation with nodal metastases. This study also recommends that neck dissection should be prophylactically performed for tumors thicker than 4mm. Tumor characteristics such as grade, perineural invasion, and lymphatic invasion should be considered as predictors for early nodal involvement.

Rearrangement and overexpression of the gene coding for tumor antigen p53 in a rat histiocytoma AK-5.

The gene coding for the cellular tumor antigen p53 is rearranged and overexpressed in a rat histiocytoma, AK-5. The protein coded by the gene was detected by immunofluorescence and its full size was confirmed by immunoprecipitation using monoclonal antibodies against p53. Southern hybridizations with a full length cDNA probe specific for p53 indicated rearrangement of the gene. Alterations in the upstream region, which probably disrupt the normal regulatory control are suggested by the pattern obtained using a 5'-specific p53 probe in Southern hybridization.

Uraemia suppresses central dopaminergic metabolism and impairs motor activity in rats.

OBJECTIVE: Uraemia often provokes various neurological disorders, such as mental changes, malperception, confusion, seizures and coma. Since changes in neurotransmissions induce neurological symptoms, we investigated changes in the monoamine metabolism and motor activity in uraemic rats. DESIGN: Prospective, randomised, controlled animal study. SUBJECTS: Male Wistar rats. INTERVENTIONS: Acute renal failure was induced by occlusion of bilateral renal arteries for 60 min, and the motor activity and brain monoamine turnover were examined 48 h later. The brain monoamine turnover was evaluated by the depletion of norepinephrine (NE) and dopamine (DA) induced by alpha-methyl-p-tyrosine (alpha-MT), or the accumulation of 5-hydroxyindoleacetic acid (5-HIAA) induced by probenecid. MEASUREMENTS AND RESULTS: Marked damage in renal function was found in animals subjected to renal ischaemia 48 h after the operation. The motor activity of the uraemic rats was impaired. The turnover of DA in the striatum, mesencephalon and hypothalamus was decreased in these rats. The turnover of NE and 5-hydroxytryptamine (5-HT) was unchanged in all regions examined. CONCLUSIONS: Suppression of the central DA turnover appears to be involved in the impairment of motor activity in uraemic rats.

In vitro and ex vivo hydrolysis rates of ethacrynate esters and their relationship to intraocular pressure in the rabbit eye.

Esters of ethacrynic acid and partial structural analogs were synthesized and evaluated for topical antiglaucoma activity in rabbits. Maximum activity was shown by analogs 2 and 6 (34% and 30% reduction in intraocular pressure recovery rate, respectively). Among the esters, only the ethyl ester (2) was found to be active; the methyl and n-propyl esters (1 and 3) were inactive. Analogs 1-3 were subjected to an estimation of physicochemical properties and chemical stability. However, no correlation was found to exist between the biological activity/inactivity and the physicochemical properties of the analogs. The analogs were evaluated for ex vivo hydrolysis using rabbit aqueous humor (AH), corneal (C) homogenate and iris-ciliary body (ICB) homogenate. For all tissues, the rate of enzymatic hydrolysis increased significantly with an increasing ester chain length. The ICB-mediated hydrolysis was the fastest among the three tissues for all of the analogs. The relationship between the rate constants for the tissue-mediated hydrolyses were: analog 1, ICB>C>AH; analog 2, ICB>C=AH and analog 3, ICB>AH>C. Apparent Michaelis-Menten kinetic parameters were determined for the three analogs using corneal homogenate. Analog 2 showed the highest v0 for all substrate concentrations studied. The conventional Michaelis-Menten equation did not fit the data as well as a sigmoidal model. Both fits of the data showed the fastest enzyme-mediated hydrolysis for analog 2. The parameters of the sigmoidal fit of the data correlated with the activity/inactivity of the analogs. The data indicate that the major factors responsible for the observed activity/inactivity are the differences in the corneal enzymatic hydrolysis of the esters in conjunction with the rapid dynamics of ocular prodrug absorption.

Penetration into the anterior chamber via the conjunctival/scleral pathway.

The importance of the conjunctival/scleral pathway as a route of entry into the ciliary body, and in particular uptake and deposition by vessels, was investigated. A constant concentration of methazolamide analogs as well as 6-carboxyfluorescein (6-CB) and rhodamine B (RB) was maintained on either the cornea or the conjunctiva/sclera tissue, the latter excluding the cornea. The solutions were applied with the use of a cylindrical well affixed to the cornea of an anesthetized white rabbit. After two hours, concentrations of drug or dye were measured in cornea, aqueous humor or iris/ciliary body for both routes of entry. Confocal microscopy methods were used to determine reflected fluorescence images for 6-CB and RB. Carbonic anhydrase inhibition, partitioning, solubility and intraocular pressure (IOP) measurements were also determined. Permeability calculations were estimated for drug diffusing against aqueous flow within the posterior chamber. The conjunctival/scleral route of entry produced higher iris/ciliary body concentrations for all compounds except for the lipophilic RB. Confocal microscopy results suggested that drug is gaining entry into the ciliary body through vessel uptake in the sclera. Following entry of drug into the conjunctival/scleral tissue, a significant portion enters scleral vessels and deposits within the ciliary body. Calculations are given that indicate that once drug penetrates the cornea it is highly unlikely drug diffuses through the pupil against aqueous flow to enter the posterior chamber and reach the ciliary body.

Cerebellopontine angle metastasis from clear-cell renal carcinoma presenting as bleeding from the ear.

Metastatic lesions in the cerebellopontine angle are rare. We encountered one such metastatic lesion from clear-cell renal carcinoma that had a striking clinical appearance, bleeding from the ear and multiple lower cranial nerves' involvement. While the overall prognosis in CNS metastasis from systemic malignancy is gloomy, useful palliation can be achieved in patients with solitary lesions.

Spectrum of renal lesions in HIV patients.

BACKGROUND: A variety of renal lesions have been reported in HIV positive patients from western world however there is paucity of Indian data. METHODS: Over a four year period, all hospitalised HIV positive patients were screened for renal involvement. Screening was done with urinalysis. Those with abnormality in urine examination underwent further assessment with clinical, biochemical, immunological profile and renal biopsy. Renal histology was studied by light and electron microscopy. RESULTS: Twenty-five (17.6%) of the 142 patients screened, had proteinuria/abnormal urinary sediment however none of the patient had proteinuria in nephrotic range. Fourteen of these 25 patients were asymptomatic while others had AIDS. Renal biopsy was studied by light microscopy in all and by electron microscopy in 11 cases. On histology mesangioproliferative GN was encountered in eight, focal segmental glomerulosclerosis in four and collapsing GN in one patient. In two cases cryptococcal infiltration and in one lymphomatous deposits were seen in glomerulus and interstitium. In one patient interstitium showed granulomas and in other three mononuclear cell infiltration. Histology was normal in 8 (32%) patients. On EM visceral cell hyperplasia and vacuolisation was seen in all, two had collapse of glomerular basement membrane and in three cases tubuloreticular structures were seen. There was no co-relation of renal histology with duration or severity of the disease (p > 0.05). No deterioration of renal function was seen over a short follow up period of 4.2 months (1-20 months). CONCLUSION: This study highlights that HIV patients exhibiting abnormal urinary sediment usually have underlying renal lesion and at times unexpected opportunistic infections may be present.

CORRELATIONSHIP OF CATHEPSIN D AND TOPOISOMERASE II ALPHA WITH NUCLEAR GRADING IN BREAST CANCERS.

56 cases of infiltrating duct carcinoma of the breast were studied for the expression of cathepsin D and topoisomerase II alpha. The results were correlated with the morphological differentiation, as determined by the Nottingham's modification of the Bloom-Richardson system. Cathepsin D posltivity in tumour cells and stromal cells was seen in 44.6% and 55.4% cases respectively, whereas topoisomerase II alpha positivity was seen in 33.9% cases. In grade II tumours cathepsin D in tumour cells and stromal cells was 44.4% and 47.2% respectively, as compared to 27.8% posltivity for topoisomerase II alpha. The corresponding figures for grade III tumours were 50.0%, 79.6% and 64.3 % respectively. As grade I comprised only 3 cases no statistical correlation could be observed. It is evident that with increase in tumour grade there is a statistical increase in expression of cathepsin D, a lysosomal acidle protease-implicated in the process of tumour invasion and metastasis, and of topoisomerase II alpha, a marker of rapid cell proliferation and aneuploidy.

AGAROSE GEL ELECTROPHORESIS AS SCREENING TEST FOR MULTIPLE MYELOMA CASES.

OBJECTIVE: To study effectiveness of agarose gel electrophoresis as a screening tool for early detection of multiple myeloma. DESIGN: A prospective study in OPD setting. PATIENTS: Two hundred and nineteen patients (126 females and 93 males) in the age group of 28-82 year referred to Department of Physical Medicine and Rehabilitation from various departments for treatment of unexplained pains and aches (with or without osteoporosis). They had been investigated and were adjudged organic disease free. INTERVENTION: Agarose gel electrophoresis was carried out on sera of these patients. Bone marrow aspiration was done for all those patients whose serum showed a monoclonal protein peak. Characterisation of M peak was also carried out by Immunoelectrophoresis. MAIN RESULT: Out of the 219 patients, sera of 29 patients showed a monoclonal protein peak. Immunoelectrophoresis and bone marrow aspiration confirmed the diagnosis of multiple myeloma in these patients. 17 were male and 12 were female patients. All of them were over 50 years of age. CONCLUSION: Agarose gel electrophoresis was found to be very sensitive test for early detection of multiple myeloma cases. Hence it was strongly recommended to be used as a screening test for all elderly people who present with unexplained aches and pains with or without osteoporosis.

CAN IMMUNOHISTOCHEMISTRY DISTINGUISH BETWEEN PRIMARY AND METASTATIC HEPATIC CARCINOMA?

OBJECTIVE: To determine if immunohistochemistry is useful to distinguish between primary and metastatic hepatic carcinoma. STUDY DESIGN: Cases of hepatocellular and adenocarcinoma of liver from surgical and autopsy pathology files as diagnosed on routine histopathology with the help of haematoxylin-eosin stain. PATIENTS: Thirty four patients with hepatic space - occupying lesions (a single lesion in 6 patients, multiple lesions in 5 patients and unspecified in remaining 23 patients). The histopathology diagnosis included 14 hepatocellular carcinoma (HC), 10 cholangiocarcinoma (CC), 7 metastatic carcinoma (MC) (colonic: n=4, pancreatic: n=2, mammary: n=l) and three cases were unclassified. INTERVENTION: The paraffin embedded blocks of biopsy and autopsy cases were taken out and sections of 4 µm thickness were cut. The immunohistochemistry staining was carried out by using a panel of 7 monoclonal antibodies. The monoclonal antibodies which were used were as follows - a fetoprotein (AFP), α 1 antitrypsin (AAT), monoclonal carcinoembryonic antigen (MCEA), myelomonocytic antigen (Leu-Ml), tumour associated glycoprotein (B72-3), A-subunit coagulation Factor XIII (Factor XIIIa) and blood group substance (Lex). MAIN OUTCOME MEASURES: Sections were defined as immunohistochemically 'positive' if definitive crisp labelling was seen in atleast 10% of tumour cells by two observers. The positive staining was classified as either predominantly cytoplasmic or membranous or both. The presence or absence of nuclear staining was also noted. MAIN RESULTS: The typical immunoreactivity of HCs included positivity for AAT, AFP and factor XIIIa and no staining for B 72-3 and Leu-Ml. Of 14 patients who were originally diagnosed as having HC, AAT was expressed in 86% and AFP was expressed in cytoplasm in half of the patients. Factor XIIIa displayed cytoplasmic reactivity in 71% cases of HC. Lex was present focally in 3 cases of HC, as was monoclonal CEA. These 3 cases showed features of hepatocholangiocarcinoma. In all 10 cases of CC there was staining for both Leu-Ml and Lex. The pattern of reactivity was cytoplasmic for Leu-Ml and it was both cytoplasmic and membranous for Lex. In 6 cases there was expression of B72-3 and monoclonal CEA in cytoplasm. None of the cases of CC showed staining for AFP and AAT only one case showed staining for AAT and factor XIIIa. As far as MC is concerned, there was expression of both Leu-M, and Lex in a cytoplasmic distribution in all the seven cases. The membranous accentuation of Lex seen in all cases of CC was not present in the cases of MC. Four of the 7 cases of MC showed reactivity for B72-3 as well and the staining pattern of Leu-M, and B72-3 was predominantly both cytoplasmic and membranous. In 3 of the 7 cases of MC, there was expression of monoclonal CEA, in 1 case there was expression of AAT and in 2 cases there was expression of factor XIIIa. CONCLUSIONS: Histologic differentiation of HC from CC and MC can be greatly aided by immunohistochemical studies. Using a panel of 7 antibodies, cases of HC displayed cytoplasmic reactivity for AAT, AFP and factor XIIIa. Cases of CC showed membranous and cytoplasmic reactivity for Lex but only cytoplasmic reactivity for Leu-M, and B72-3. On the other hand cases of MC showed only cytoplasmic staining but not membranous accentuation for Lex but Leu-M, and B72-3 showed membranous as well as cytoplasmic staining. The antibody MCEA showed variable results and hence was considered not useful. Therefore the results strongly suggest that a panel of 6 monoclonal antibodies (except MCEA) will greatly help in differentiating between primary and metastatic carcinoma.

AN OVERVIEW OF PROGNOSTIC MARKERS IN BREAST CANCER.

For many years axillary lymph nodes metastasis was the most important prognostic factor to predict the overall and disease free survival and guided the oncologists for institution of chemotherapy in breast cancer cases. However this factor alone or in combination with other parameters like, age of the patient, tumour size, histological type and tumour grade failed to predict the prognosis accurately in number of these cases. In pursuit to achieve the perfection, many new parameters which are biological or molecular in nature have been discovered. It is claimed that these factors not only have the capability to predict the prognosis but are also able to identify 'high risk' group of patients. However analysing all these parameters in a given case is not only cost prohibitive but also not essential. In order to solve this problem few important biological parameters have been reviewed, which are considered to cover all the important facets of the breast cancer. The parameters reviewed are ER, PR, S phase fraction, DNA ploidy, MIB-1 antibody, p53, C-erb-2, nm23, Cathepsin, Topoisomerase II alpha.

SPECTRUM OF NEPHROPATHIES WITH SPECIAL REFERENCE TO PRIMARY GLOMERULOPATHIES.

A retrospective study was carried out where histopathology records of Department of Pathology, Armed Forces Medical College, Pune were scrutinised covering a period of 10 years. We came across 325 cases of nephropathies. The sample comprised of 92.6% adults and 7.4% children. 79.7% were males and 20.3% were females. The patient population comprised of 35.1% serving soldiers, 37.8% their family members and 27.1% not related to Armed Forces. The study is based on only light microscopy findings. It was observed that primary glomerular disease was the commonest entity and comprised of 61.5% of all the nephropathies. Acute diffuse proliferative glomerulonephritis was not only the commonest primary glomerulopathy (23.5%) but the commonest nephropathy as well. The other primary glomerulopathies in descending order of frequency were, membranoproliferative glomerulonephritis (22.5%), mesangioproliferative glomerulonephritis (21.5%), chronic glomerulonephritis (9%), minimal change disease (7.5%), membranous glomerulopathy (7%), focal segmental glomerulosclerosis (5%) and crescentic glomerulonephritis (4%). We had only 14 cases (4.3% of all nephropathies) of secondary glomerulopathies, amongst which amyloidosis was the commonest cause. We came across 2 cases (0.6% of all nephropathies) of Alport's syndrome. In the other nephropathies, 22.2% were tubulointerstitial diseases and 5.5% were malignant kidney tumors. In 5.8% renal biopsies, no significant pathology was seen on light microscopy.

CORRELATIONSHIP OF HORMONE RECEPTOR STATUS, p53 MUTATION AND c-erb B-2 OVEREXPRESSION WITH NUCLEAR GRADING IN BREAST CANCERS.

Thirty cases of infiltrating duct carcinoma of the breast were studied for the expression of estrogen receptor (ER) and progesterone receptor (PR) status; p 53 protein mutation and c-erb B2 overexpression. The results were correlated with the morphological differentiation, as determined by the Nottingham's modification of the Bloom-Richardson system. Hormone receptor positivity was seen in 46.67% cases, whereas p 53 mutation and c-erb B2 overexpression were seen in 50.00% and 60.00% cases respectively. In grade II tumours receptor positivity, p53 mutation and c-erb B-2 overexpression were 57.15%, 42.85% and 52.38% respectively. The corresponding figures for grade III tumours were 33.33%, 83.33% and 66.67% respectively. As grade 1 comprised only 3 cases no statistical correlation could be observed. Thus we conclude that receptor positivity declined, whereas p 53 mutation and c-erb B-2 overexpression increased, with increase in tumour grade.

IMPROVED ACCURACY RATES OF FNAC INTERPRETATION IN BENIGN BREAST LESIONS.

We carried out a retrospective study of 194 biopsy proved benign breast lesions comparing the fine needle aspiration cytology (FNAC) diagnosis offered earlier. We reviewed the cytology smears based on recently advocated criteria and offered our fresh diagnosis. It was observed that we still overdiagnosed five cases of fibroadenomas and underdiagnosed four cases of fibrocystic change. However the quantum of such discrepancies decreased considerably than seen earlier. We could correctly diagnose two tubular adenomas and two intraductal papillomas. We also reduced the number of nonspecific diagnosis of benign breast disease from 24 to 08. Hence we could register an overall improvement of accuracy rate to 84.5% as compared to 58.8% achieved earlier.