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M Jacob

Publications and source records attributed to M Jacob.

At least 55 records · Page 3Linked to original sources
PubMed1999

Early development of the müllerian duct in avian embryos with reference to the human. An ultrastructural and immunohistochemical study.

In vertebrates, the female reproductive system arises from the Müllerian (paramesonephric) duct which develops in both sexes under the influence of the Wolffian (mesonephric) duct. For a better understanding of the interactions between the Müllerian duct and its adjacent tissues, we present a systematic scanning and transmission electron microscopic investigation of early stages of avian Müllerian duct development. This starts within the cranial part of the Müllerian ridge from a placode-like thickening and deepening of the coelomic epithelium containing nephrostomes as remnants of the last pronephric and first mesonephric tubules. Groups of cells detach from this placode and rapidly expand caudally as a solid cord. This becomes canalized, but the tip region remains mesenchymal and is found enclosed within the basal lamina of the Wolffian duct. Immunostaining reveals that the Müllerian duct migrates within a matrix rich in laminin and entactin. When the canalized duct has opened into the coelomic cavity, one or more secondary ducts are found immediately caudal of the main funnel, for a short period only, possibly to supply material to the expanding duct. BrdU-anti-BrdU reaction reveals a high proliferation of the duct epithelium. The thickened epithelium of the Müllerian ridge dissolves to form the mesenchymal layers of the duct. Immunostaining with vimentin argues against a cellular contribution of Wolffian duct cells to the Müllerian duct. Comparing the data from avian embryos with those of human indicates that the modalities of early Müllerian duct development are similar in both species.

Animals↗
PubMed1999

Role of S-100 staining in differentiating leprosy from other granulomatous diseases of the skin.

Since Mycobacterium leprae are rarely demonstrable in the tuberculoid spectrum of leprosy, a confirmatory diagnosis of leprosy can be made on the basis of finding active destruction of cutaneous nerves by granulomatous inflammation in a skin biopsy. Immunoperoxidase staining for S-100 protein, which is a marker for Schwann cells, was used to delineate nerves in lesional skin biopsies of 25 patients with tuberculoid and borderline tuberculoid leprosy as well as 15 controls with nonleprous granulomatous inflammation. Four different patterns of nerve damage were observed: infiltrated, fragmented, absent, and intact. All of the nonleprous granulomatous dermatoses showed only intact nerves, either inside or outside the granuloma, and so S-100 staining can be used to rule out leprosy.

Diagnosis, Differential↗
PubMed1998

Polymorphism of the 1-palmitoyl-2-arachidonoyl-phosphatidyl-ethanolamine/dimyristoyl-phos phatidylmethanol mixture, a phospholipase A2 substrate.

The polymorphism of the equimolar mixture of 1-palmitoyl-2-arachidonoyl-phosphatidylethanolamine (PAPE) and dimyristoyl-phosphatidylmethanol (DMPM) was examined by infrared and 31P nuclear magnetic resonance spectroscopy to determine the suitability of this widely used but yet uncharacterized lipid mixture as a phospholipase A2 substrate. The results show that the mixture undergoes a gel-to-liquid crystalline phase transition between 12 and 35 degrees C. The transitions of the individual lipids were also examined. We report that the temperature of the gel-to-liquid crystalline phase transition of DMPM is 40 degrees C. At 2 degrees C, PAPE exists in the fluid lamellar form. This lipid undergoes a lamellar-to-inverted hexagonal phase transition at 31 degrees C. In conclusion, the equimolar PAPE/DMPM mixture forms fluid lamellar phase at the physiological temperature. However, the upper end of the gel-to-liquid crystalline phase transition of the mixture is really close to the physiological temperature and this situation is a serious source of potential artefacts.

Glycerophospholipids↗
PubMed1998

Phospholipases A2 of rod outer segment-free bovine retinae are different from well-known phospholipases A2.

We have recently demonstrated the presence of phospholipase A2 (PLA2) activity in a rod outer segment-free retinal fraction which we called P200 and which contains neuronal cells, Müller cells and rod inner segments. We report here our results on the characterization of this P200-PLA2 activity. We show that P200 probably contains more than one type of PLA2, as indicated by the results obtained with different chromatographically eluted PLA2-active fractions which were treated with either Ca2+, EGTA, dithiothreitol (DTT) or p-bromophenacyl bromide (pBPB), or heated. Moreover, the results from PLA2 assays using different substrates, as well as those obtained after treatment of the homogenate with H2SO4, guanosine 5'-O-(3-thio)triphosphate (GTPgammaS) and ATP, suggest that P200-PLA2 are different from well-known secretory PLA2, cytosolic PLA2 and Ca2+-independent PLA2. Control experiments using our 'back-and-forth'-thin layer chromatography (bf-TLC) technique allowed us to confirm that, in our assay conditions, the release of fatty acids was due to PLA2 enzymes. These results, which constitute the first characterization of PLA2 of the neural retina, thus suggest that it contains novel types of PLA2 enzyme, in contrast to well-known PLA2.

Adenosine Triphosphate↗
PubMed1998

Merkel cell carcinoma of the eyelid: histological and immunohistochemical features with special respect to differential diagnosis.

BACKGROUND: Merkel cell carcinomas (MCC) not infrequently involve the periorbital region and the eyelids. Clinically, they are relatively characteristic but often unsuspected. Histologically, MCC are often misdiagnosed as lymphoma, melanoma, or metastatic small cell carcinoma of the lung (SCCL). METHODS: We present clinical, histological, and immunohistochemical data on six eyelid cases (all females; age 63-102 years; one with concomitant CLL) from our files of 77 MCC with special respect to differential diagnosis. For comparison, 22 SCCL were analyzed. Immunohistochemistry was done with antibodies against pan-cytokeratin (pan-CK), cytokeratin-20 (CK-20), neurofilament protein (NF), neuron-specific enolase (NSE), chromogranin (CHR), and S100 protein (S100). RESULTS: Morphologically, five of six MCC were prototypic, one was of the small cell variant. Immunohistochemically, dot-like positivities for pan-CK and CK-20 were seen in all six MCC, and for NF in five tumors. None of the 22 SCCL stained positively for CK-20 or NF but 21/22 cases were positive for pan-CK. Only 1/21 SCCL showed dot-like patterns for pan-CK; 20/21 reacted diffusely. All MCC and 13/22 SCCL displayed CHR-positive cells. All MCC and all SCCL were positive for NSE and negative for S100. CONCLUSIONS: Dot-like positivities for CK-20 or NF are important to prove MCC and to exclude SCCL in clinically and morphologically doubtful cases. Dot-like positivities for pan-CK favor MCC, but do not always exclude SCCL. NSE and CHR are of no value for the differential diagnosis of MCC and SCCL. Melanoma and lymphoma are ruled out by negativity for S100 and pan-CK, respectively.

Aged↗
PubMed1998

Cutis laxa.

Two sisters with inherited generalized cutis laxa and a young man with possible acquired cutis laxa are presented.

Adolescent↗
PubMed1998

Comparison of indomethacin and nimesulide, a selective cyclooxygenase-2 inhibitor, on key pathophysiologic steps in the pathogenesis of nonsteroidal anti-inflammatory drug enteropathy in the rat.

BACKGROUND: The predicted gastrointestinal tolerability of specific cyclooxygenase-2 inhibitors could be due to either a lack of 'topical' irritation and/or lack of effect on cyclooxygenase-1. METHODS: Key pathophysiologic steps (in vitro and in vivo uncoupling, intestinal prostanoid levels (prostaglandin E, thromboxane B2, and 6-keto-prostaglandin F1alpha), intestinal permeability (51Cr-ethylenediaminetetraacetic acid), inflammation (faecal excretion of a granulocyte marker protein), and ulcer counts) in enteropathy induced by nonsteroidal anti-inflammatory drugs were assessed after administration of indomethacin, 10 mg/kg, and 15 (roughly equipotent), 30, and 60 mg/kg of the preferential cyclooxygenase-2 inhibitor nimesulide. RESULTS: Indomethacin uncoupled oxidative phosphorylation at lower concentrations than nimesulide in vitro. Indomethacin was associated with electron microscopy changes suggestive of uncoupling in 60%-70% of enterocytes examined, whereas nimesulide affected 10%-30% of enterocytes, depending on the dose. Indomethacin increased intestinal permeability and caused inflammation and ulcers with 71%-96% reductions in prostanoid levels. Nimesulide at 15 mg/kg caused no damage, whereas 30 and 60 mg/kg nimesulide were associated with significant decreases in mucosal prostanoids (46%-75%), but only the 60-mg/kg dose caused a transient increase in intestinal permeability. However, at none of the doses did nimesulide cause intestinal inflammation or ulcers. CONCLUSIONS: These results endorse the idea that selective cyclooxygenase-2 inhibitors may be associated with some gastrointestinal tolerance due to their selectivity for cyclooxygenase-2, inhibiting cyclooxygenase-1 at only very high doses, and reduced topical irritation.

Animals↗
PubMed1998

Enantiomers of flurbiprofen can distinguish key pathophysiological steps of NSAID enteropathy in the rat.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) cause gastrointestinal damage by a non-prostaglandin (PG) dependent "topical" action and by inhibiting cyclooxygenase. AIMS: To discriminate between these two effects by studying some key pathophysiological steps in NSAID enteropathy following administration of (R)- and (S)-flurbiprofen, the racemic mixture, and an uncoupler, dinitrophenol. METHODS: The effects of dinitrophenol, racemic, (R)-, and (S)-flurbiprofen on mitochondria were assessed in vitro and on key pathophysiological features of small intestinal damage in vivo (ultrastructure by electron microscopy, mucosal prostanoid concentrations, intestinal permeability, inflammation, and ulcer count) in rats. RESULTS: All the drugs uncoupled mitochondrial oxidative phosphorylation in vitro, caused mitochondrial damage in vivo, and increased intestinal permeability. Dinitrophenol and (R)-flurbiprofen caused no significant decreases in mucosal prostanoid concentrations (apart from a decrease in thromboxane (TX) B2 concentrations following (R)-flurbiprofen) while racemic and (S)- flurbiprofen reduced mucosal prostanoids significantly (PGE, TXB2, and 6-keto-PGF1alpha concentrations by 73-95%). Intestinal inflammation was significantly greater following administration of (S)-flurbiprofen and racemate than with dinitrophenol and (R)-flurbiprofen. No small intestinal ulcers were found following dinitrophenol or (R)-flurbiprofen while both racemic and (S)-flurbiprofen caused numerous ulcers. CONCLUSIONS: Dinitrophenol and (R)-flurbiprofen show similarities in their actions to uncouple mitochondrial oxidative phosphorylation in vitro, alter mitochondrial morphology in vivo, increase intestinal permeability, and cause mild inflammation without ulcers. Concurrent severe decreases in mucosal prostanoids seem to be the driving force for the development of severe inflammation and ulcers.

Animals↗
PubMed1998

Counterregulatory hormones oscillate during steady-state hypoglycemia.

During hypoglycemia, the magnitude of the counterregulatory response depends on the extent of plasma glucose reduction. However, our clinical observations during steady-state hypoglycemia indicate that symptom severity can change independently of plasma glucose concentrations, i.e., symptoms appeared to fluctuate despite stable glucose levels. This study was therefore designed to test the hypothesis that hormonal and symptomatic responses to hypoglycemia are pulsatile. Seven healthy subjects had serial blood sampling at 3-min intervals during 90 min of insulin-induced hypoglycemia. Mean +/- SE plasma glucose levels plateaued at 62 +/- 3 mg/dl. Counterregulatory hormones were significantly elevated (P < 0.05-0. 01, except norepinephrine) and strikingly pulsatile. Cluster analysis revealed pulses of large magnitude in plasma glucagon, epinephrine, and norepinephrine concentrations. Amplitudes were, respectively, 72 +/- 4, 64 +/- 8, and 48 +/- 3% of the mean. Interpeak intervals were 27 +/- 7, 19 +/- 4, and 25 +/- 5 min, respectively. Symptom score and cardiovascular responses were also pulsatile; their peaks were found to coincide with epinephrine peaks. We conclude that hormonal and symptomatic counterregulation in hypoglycemia, while critically driven by plasma glucose levels, is also influenced by an endogenous pulsatility that exists despite steady-state glucose concentrations.

Activity Cycles↗
PubMed1998

Cutaneous leishmaniasis in Nepal.

We report an imported case of cutaneous leishmaniasis in a 30 year old adult male from Nepal caused by Leishmania tropica. This case from Dharan is the first such report of imported cutaneous leishmaniasis in Nepal.

Adult↗