Approach to non-compressive myeloneuropathy through a rendezvous of 11 cases from an Indian backdrop.

Introduction: Myeloneuropathy is a diagnosis ascribed to disorders that concomitantly affect the spinal cord and peripheral nerves. Recognizing this syndrome may sometimes be arduous, even for the most consummate clinicians, because symptomatology can mimic either spinal cord or peripheral nerve disease. Besides, examination findings suggest a predominantly myelopathic or neuropathic picture. This article reports a rendezvous of rare cases of clinically diagnosed myeloneuropathy with different etiological backgrounds and therapeutic responses. Methods: Eleven cases of non-compressive myeloneuropathy were admitted to the Department of General Medicine of Burdwan Medical College and Hospital, Burdwan, West Bengal, India, between May 2018 and May 2022. Results: We report the cases of 11 patients (6 men and 5 women) who presented with myeloneuropathy of different etiologies (vitamin B12, copper, and vitamin E deficiencies, organophosphate poisoning, chronic alcohol abuse, illicit substances abuse, anti-thyroid peroxidase/anti-thyroglobulin antibody-related neurologic disorder responsive to steroids, Sjögren syndrome, chikungunya infection, paraneoplastic, and hereditary). Conclusion: Meticulous historical analysis, careful clinical examination, and apposite utilization and interpretation of biochemical, electrophysiological, and neuroimaging findings are sine-qua-non for an accurate and consistent approach to evaluating a suspected case of myeloneuropathy, facilitating early treatment and recovery. Differential identification of these disorders needs an in-depth perception of the mode of onset of symptoms, the course of progression of the disease, the pattern of myelopathic/neuropathic findings, and recognition of other neurological or systemic manifestations. For untroubled understanding, etiologies of myeloneuropathies should be subdivided into a few broad categories, e.g., metabolic (nutritional), toxic (toxin-induced), infectious, inflammatory (immune-mediated), paraneoplastic, and hereditary disorders.

Introducción: La mieloneuropatía es un síndrome que afecta concomitantemente la médula espinal y los nervios periféricos. Reconocerlo a veces puede ser arduo, incluso para los médicos más experimentados, porque la sintomatología puede simular una enfermedad de la médula espinal o de los nervios periféricos. Además, los hallazgos del examen sugieren un cuadro predominantemente mielopático o neuropático. Este artículo describe una serie de casos raros de mieloneuropatía de distintas causas y con respuestas terapéuticas distintas. Métodos: Once casos de mieloneuropatía no compresiva fueron ingresados en el Departamento de Medicina General del Burdwan Medical College, and Hospital, Burdwan, Bengala Occidental, India, entre mayo de 2018 y mayo de 2022. Resultados: Presentamos 11 pacientes (seis hombres y cinco mujeres) con mieloneuropatía de diferentes etiologías (deficiencias de vitamina B12, cobre y vitamina E, intoxicación por organofosforados, abuso crónico de alcohol, abuso de sustancias ilícitas, trastorno neurológico relacionado con anticuerpos anti-tiroglobulina / antiperoxidasa tiroidea que responde a esteroides, síndrome de Sjögren, infección por chikungunya, paraneoplásico y hereditario). Conclusión: El análisis meticuloso de la historia y del examen clínico, así como la utilización e interpretación adecuadas de los hallazgos bioquímicos, electrofisiológicos y de neuroimagen son condiciones sine qua non para un enfoque preciso y consistente para evaluar un caso sospechoso de mieloneuropatía, lo que facilita el tratamiento temprano y su recuperación. El diagnóstico diferencial de esta patología requiere un conocimiento del modo de inicio de los síntomas, su progresión, el patrón de hallazgos mielopáticos/neuropáticos y el reconocimiento de otras manifestaciones neurológicas o sistémicas. Las etiologías de las mieloneuropatías deben subdividirse en trastornos metabólicos (nutricionales), tóxicos (inducidos por toxinas), infecciosos, inflamatorios (mediados por mecanismos inmunitarios), paraneoplásicos y hereditarias.

T-Box Genes in Human Development and Disease.

T-box genes are important development regulators in vertebrates with specific patterns of expression and precise roles during embryogenesis. They encode transcription factors that regulate gene transcription, often in the early stages of development. The hallmark of this family of proteins is the presence of a conserved DNA binding motif, the "T-domain." Mutations in T-box genes can cause developmental disorders in humans, mostly due to functional deficiency of the relevant proteins. Recent studies have also highlighted the role of some T-box genes in cancer and in cardiomyopathy, extending their role in human disease. In this review, we focus on ten T-box genes with a special emphasis on their roles in human disease.

Silk fibroin hydrogel as physical barrier for prevention of post hernia adhesion.

BACKGROUND: Adhesion formation remains a major complication following hernia repair surgery. Physical barriers though effective for adhesion prevention in clinical settings are associated with major disadvantages, therefore, needs further investigation. This study evaluates silk fibroin hydrogel as a physical barrier on polypropylene mesh for the prevention of adhesion following ventral hernia repair. STUDY DESIGN: Peritoneal explants were cultured on silk fibroin scaffold to evaluate its support for mesothelial cell growth. Full thickness uniform sized defects were created on the ventral abdominal wall of rabbits, and the defects were covered either with silk hydrogel coated polypropylene mesh or with plain polypropylene mesh as a control. The animals were killed after 1 month, and the adhesion formation was graded; healing response of peritoneum was evaluated by immunohistochemistry with calretinin, collagen staining of peritoneal sections, and expression of PCNA, collagen-I, TNFα, IL6 by real time PCR; and its adverse effect if any was determined. RESULTS: Silk fibroin scaffold showed excellent support for peritoneal cell growth in vitro and the cells expressed calretinin. A remarkable prevention of adhesion formation was observed in the animals implanted with silk hydrogel coated mesh compared to the control group; in these animals peritoneal healing was complete and predominantly by mesothelial cells with minimum fibrotic changes. Expression of inflammatory cytokines decreased compared to control animals, histology of abdominal organs, haematological and blood biochemical parameters remained normal. CONCLUSION: Therefore, silk hydrogel coating of polypropylene mesh can improve peritoneal healing, minimize adhesion formation, is safe and can augment the outcome of hernia surgery.

The levels of zinc and molybdenum in hair and food grain in areas of high and low incidence of esophageal cancer: a comparative study.

The outcome of different studies on the role of Zn & Mo in esophageal cancer (EC) is conflicting. Here, the levels of those elements in hair as well as food grain of two different ethnic populations across two continents have been studied to explore their role in EC. Two different ethnic populations are taken from (i) Eastern Cape, South Africa (RSA), an area of very high incidence of EC and (ii) West Bengal, India, an area of low incidence of that disease. Each ethnic population is divided into two groups: case and control (n=30 for all groups). Hair samples from all groups and food grain from RSA and India are analyzed for Zn & Mo content. This study shows a strong correlation between reduced levels of those elements in hair and the development of EC in RSA (both Zn &Mo: p < 0.0001), though it is only suggestive in Indian context (both Zn & Mo p ? 0.05). Interestingly, control group of RSA shows significantly reduced level of those elements in hair even with respect to Indian case group (Zn: p<0.001 & Mo: p< 0.00001). Food grain from RSA has significantly reduced level of those elements with respect to India (both Zn & Mo: p <0.0001). This deficiency of Zn & Mo in food grains can be correlated to the deficiency of those elements in hair of RSA population. The deficiency of Zn & Mo can be correlated to the development of EC.

A new unstable hemoglobin variant Hb Acharnes or [ß53(D4) Ala - Thr]: a case report.

Hb Acharnes or [ß53(D4) Ala - Thr] is a newly discovered unstable hemoglobin variant. It has been reported in very few literatures across the world and no cases have been reported from India till date. Hb Acharnes is known to interact with ß°-thalassemia to produce thalassemia intermedia and heterozygotes may present with borderline HbA2 levels. Here we report a rare case discovered during routine screening of thalassemia and hemoglobinopathies in a 19 year old pregnant lady. To emphasize the diagnostic difficulties and importance of detection of a rare hemoglobin variant Hb Acharnes [ß53(D4) Ala - Thr] in an asymptomatic patient in West Bengal, India. The 19 year old asymptomatic pregnant lady P1+0, LMP - 21.01.2011 reported in antenatal OPD of Burdwan Medical College & Hospital, Burdwan, West Bengal, India for routine follow up. After proper antenatal check up her blood was collected as a routine screening for Thalassemia, EDTA blood was taken on 5th April 2011 and was subjected to Hemoglobin estimation by Cyanmethemoglobin method, Cell parameters in automated cell counter (SYSMEX KX21) and Hemoglobin analysis by HPLC in BIORAD VARIANT system. The patient was normal with respect to clinical examination and urinalysis. Routine blood counts revealed mild microcytic hypochromic anemia and on HPLC an unknown band (retention time 2.2 minutes, 21.2%, appearing as a shoulder of HbA0 band) of hemoglobin variant was discovered with normal level of HbF and HbA2. Hemoglobin analysis of her mother showed similar pattern while her father and her husband had normal Hb-HPLC pattern. The unknown hemoglobin variant was identified as Hemoglobin Acharnes or [ß53 (D4) Ala - Thr] by the Biorad laboratories upon consulting the standard chromatogram patterns for this particular hemoglobin variant. Only Haemoglobin Electrophoresis by conventional gel technique may miss the case and the HPLC pattern may be used as a standard control for identification.

Factors influencing synonymous codon and amino acid usage biases in Mimivirus.

Synonymous codon and amino acid usage biases have been investigated in 903 Mimivirus protein-coding genes in order to understand the architecture and evolution of Mimivirus genome. As expected for an AT-rich genome, third codon positions of the synonymous codons of Mimivirus carry mostly A or T bases. It was found that codon usage bias in Mimivirus genes is dictated both by mutational pressure and translational selection. Evidences show that four factors such as mean molecular weight (MMW), hydropathy, aromaticity and cysteine content are mostly responsible for the variation of amino acid usage in Mimivirus proteins. Based on our observation, we suggest that genes involved in translation, DNA repair, protein folding, etc., have been laterally transferred to Mimivirus a long ago from living organism and with time these genes acquire the codon usage pattern of other Mimivirus genes under selection pressure.

Factors influencing the synonymous codon and amino acid usage bias in AT-rich Pseudomonas aeruginosa phage PhiKZ.

To reveal how the AT-rich genome of bacteriophage PhiKZ has been shaped in order to carry out its growth in the GC-rich host Pseudomonas aeruginosa, synonymous codon and amino acid usage bias of PhiKZ was investigated and the data were compared with that of P. aeruginosa. It was found that synonymous codon and amino acid usage of PhiKZ was distinct from that of P. aeruginosa. In contrast to P. aeruginosa, the third codon position of the synonymous codons of PhiKZ carries mostly A or T base; codon usage bias in PhiKZ is dictated mainly by mutational bias and, to a lesser extent, by translational selection. A cluster analysis of the relative synonymous codon usage values of 16 myoviruses including PhiKZ shows that PhiKZ is evolutionary much closer to Escherichia coli phage T4. Further analysis reveals that the three factors of mean molecular weight, aromaticity and cysteine content are mostly responsible for the variation of amino acid usage in PhiKZ proteins, whereas amino acid usage of P. aeruginosa proteins is mainly governed by grand average of hydropathicity, aromaticity and cysteine content. Based on these observations, we suggest that codons of the phage-like PhiKZ have evolved to preferentially incorporate the smaller amino acid residues into their proteins during translation, thereby economizing the cost of its development in GC-rich P. aeruginosa.

Experience with telepathology at a tertiary cancer centre and a rural cancer hospital.

BACKGROUND: Telepathology allows quick and timely access to an expert opinion, no matter where the patient is located. We analysed the experience with the use of telepathology between a tertiary cancer centre and a rural cancer hospital. METHODS: Ninety-three cases were analysed in which static telepathology was used to obtain a consultation between Tata Memorial Centre and Nargis Dutt Memorial Cancer Hospital at Barshi, a rural area. RESULTS: Successful teleconsultation was achieved in all cases. A diagnosis was offered in 92 cases (98.9%) and was deferred in 1 case (1.1%). Complete concordance, clinically unimportant minor discrepancy and hedged diagnosis were obtained in 83 cases (90.2%). Major discrepancies were encountered in 9 cases (9.7%). The number of images per case ranged from 3 to 27 (average: 7 images). Images were of diagnosable quality in 89.2% of cases. Most of the cases (77.4%) were reported within 3 days; 32.2% were reported within 8 hours (a single working day) and 45.1% within 1-3 days. CONCLUSION: Telemedicine can be effectively used to bridge the gap between medically underprivileged, geographically distant rural areas and advanced centres using the static store and forward methodology.

Synonymous codon usage in Lactococcus lactis: mutational bias versus translational selection.

In this study codon usage bias of all experimentally known genes of Lactococcus lactis has been analyzed. Since Lactococcus lactis is an AT rich organism, it is expected to occur A and/or T at the third position of codons and detailed analysis of overall codon usage data indicates that A and/or T ending codons are predominant in this organism. However, multivariate statistical analyses based both on codon count and on relative synonymous codon usage (RSCU) detect a large number of genes, which are supposed to be highly expressed are clustered at one end of the first major axis, while majority of the putatively lowly expressed genes are clustered at the other end of the first major axis. It was observed that in the highly expressed genes C and T ending codons are significantly higher than the lowly expressed genes and also it was observed that C ending codons are predominant in the duets of highly expressed genes, whereas the T endings codons are abundant in the quartets. Abundance of C and T ending codons in the highly expressed genes suggest that, besides, compositional biases, translational selection are also operating in shaping the codon usage variation among the genes in this organism as observed in other compositionally skewed organisms. The second major axis generated by correspondence analysis on simple codon counts differentiates the genes into two distinct groups according to their hydrophobicity values, but the same analysis computed with relative synonymous codon usage values could not discriminate the genes according to the hydropathy values. This suggests that amino acid composition exerts constraints on codon usage in this organism. On the other hand the second major axis produced by correspondence analysis on RSCU values differentiates the genes into two groups according to the synonymous codon usage for cysteine residues (rarest amino acids in this organism), which is nothing but a artifactual effect induced by the RSCU values. Other factors such as length of the genes and the positions of the genes in the leading and lagging strand of replication have practically no influence in the codon usage variation among the genes in this organism.

The catalytic, glycosyl transferase and acyl transferase modules of the cell wall peptidoglycan-polymerizing penicillin-binding protein 1b of Escherichia coli.

The penicillin-binding protein (PBP) 1b of Escherichia coli catalyses the assembly of lipid-transported N-acetyl glucosaminyl-beta-1, 4-N-acetylmuramoyl-L-alanyl-gamma-D-glutamyl-(L)-meso-diaminopimelyl+ ++- (L)-D-alanyl-D-alanine disaccharide pentapeptide units into polymeric peptidoglycan. These units are phosphodiester linked, at C1 of muramic acid, to a C55 undecaprenyl carrier. PBP1b has been purified in the form of His tag (M46-N844) PBP1bgamma. This derivative provides the host cell in which it is produced with a functional wall peptidoglycan. His tag (M46-N844) PBP1bgamma possesses an amino-terminal hydrophobic segment, which serves as transmembrane spanner of the native PBP. This segment is linked, via an congruent with 100-amino-acid insert, to a D198-G435 glycosyl transferase module that possesses the five motifs characteristic of the PBPs of class A. In in vitro assays, the glycosyl transferase of the PBP catalyses the synthesis of linear glycan chains from the lipid carrier with an efficiency of congruent with 39 000 M-1 s-1. Glu-233, of motif 1, is central to the catalysed reaction. It is proposed that the Glu-233 gamma-COOH donates its proton to the oxygen atom of the scissile phosphoester bond of the lipid carrier, leading to the formation of an oxocarbonium cation, which then undergoes attack by the 4-OH group of a nucleophile N-acetylglucosamine. Asp-234 of motif 1 or Glu-290 of motif 3 could be involved in the stabilization of the oxocarbonium cation and the activation of the 4-OH group of the N-acetylglucosamine. In turn, Tyr-310 of motif 4 is an important component of the amino acid sequence-folding information. The glycosyl transferase module of PBP1b, the lysozymes and the lytic transglycosylase Slt70 have much the same catalytic machinery. They might be members of the same superfamily. The glycosyl transferase module is linked, via a short junction site, to the amino end of a Q447-N844 acyl transferase module, which possesses the catalytic centre-defining motifs of the penicilloyl serine transferases superfamily. In in vitro assays with the lipid precursor and in the presence of penicillin at concentrations sufficient to derivatize the active-site serine 510 of the acyl transferase, the rate of glycan chain synthesis is unmodified, showing that the functioning of the glycosyl transferase is acyl transferase independent. In the absence of penicillin, the products of the Ser-510-assisted double-proton shuttle are glycan strands substituted by cross-linked tetrapeptide-pentapeptide and tetrapeptide-tetrapeptide dimers and uncross-linked pentapeptide and tetrapeptide monomers. The acyl transferase of the PBP also catalyses aminolysis and hydrolysis of properly structured thiolesters, but it lacks activity on D-alanyl-D-alanine-terminated peptides. This substrate specificity suggests that carbonyl donor activity requires the attachment of the pentapeptides to the glycan chains made by the glycosyl transferase, and it implies that one and the same PBP molecule catalyses transglycosylation and peptide cross-linking in a sequential manner. Attempts to produce truncated forms of the PBP lead to the conclusion that the multimodular polypeptide chain behaves as an integrated folding entity during PBP1b biogenesis.

Cold stress facilitates calcium mobilization from bone in an ovariectomized rat model of osteoporosis.

In an ovariectomized rat model of osteoporosis, the effects of cold stress on intestinal Ca2+ transference and rate of bone turnover were evaluated. In the ovariectomized rats, a significant reduction in intestinal transference of Ca2+ was associated with decreased activities of intestinal mucosal enzymes, alkaline phosphatase (AP), and calcium ATPase (Ca2+-ATPase) in all the different segments of small intestine in a descending gradient. The development of a high rate of bone turnover and osteoporosis in these animals was confirmed by significant alteration in plasma AP activity and calcium (Ca) level, urinary excretion of Ca and phosphate, and Ca : creatinine ratio. Cold stress in this model, apart from its unique influence in elevating plasma corticosterone and thyroid hormone level, enhanced all the above referred parameters studied in connection with intestinal transference of Ca2+, bone turnover rate, and osteoporosis. The results of this study emphasize that cold stress may have a positive influence on bone loss for an early development of hypogonadal osteoporosis in rats.

Argyrophilic nucleolar organiser regions (AgNORs) in breast lesions.

Nucleolar organiser regions (NORs) demonstrated by argyrophilia of NOR-proteins are indicator of cellular proliferative activity. The NORs can be identified in the nuclei as brown or black dots with silver colloidal staining technique in formalin fixed paraffin sections and in cytology smears. Seventy-five cases including 45 tissue sections and 30 fine needle aspiration cytology (FNAC) smears of benign and malignant lesions of breast have been studied to evaluate the significance and practical application of AgNOR count per nucleus. Out of 45 tissue sections 15 belonged to fibrocystic disease, 10 fibro-adenomas and 20 carcinomas and of the 30 FNAC smears, 10 were fibrocystic disease, 8 fibro-adenomas and 12 carcinomas. In fibrocystic disease the mean AgNOR count was 1.60 (FNAC group-0.75, tissue section-1.61). In fibro-adenomas it was 1.61 (FNAC-1.63, tissue section-1.59). The mean count in carcinoma was 12.10 (FNAC-12.08, tissue section-12.10). The difference in AgNOR count in fibrocystic disease and fibro-adenoma was not significant, but that between benign breast lesion and carcinoma was significant. No difference was observed between FNAC and tissue section groups in benign or malignant lesions. The simple staining technique can be used as an additional criterion to differentiate the benign and malignant lesions of breast.

PIP: Nucleolar organizer regions (NORs) are loops of DNA encoding ribosomal RNA genes located in the short arms of 5 acrocentric human chromosomes. NORs demonstrated by the argyrophilia of NOR-proteins are indicative of cellular proliferative activity. The NORs can be identified in nuclei as brown or black dots with silver colloidal staining technique in formalin fixed paraffin sections and in cytology smears. 75 cases, including 45 tissue sections and 30 fine needle aspiration cytology (FNAC) smears of benign and malignant breast lesions, were studied to evaluate the significance and practical application of AgNOR count per nucleus. 15 of the 45 tissue sections were of fibrocystic disease, 10 were fibroadenomas, and 20 were carcinomas. Of the 30 FNAC smears, 10 were fibrocystic disease, 8 were fibroadenomas, and 12 were carcinomas. The mean AgNOR count in fibrocystic disease was 1.60; 1.61 in fibroadenomas and 12.10 in carcinomas. Although the difference in AgNOR count between fibrocystic disease and fibroadenomas was insignificant, that between benign breast lesion and carcinoma was significant. No significant difference was observed between FNAC and tissue section groups in benign or malignant lesions. This simple staining technique can be used as an additional criterion to differentiate the benign and malignant lesions of breast.

Activation of water-responsive laryngeal afferents: role of epithelial ion transport.

The role of epithelial ion transport in the activation of water-responsive laryngeal afferent was investigated in anesthetized, spontaneously breathing cats. Single-fiber recordings from the peripheral cut-end of the superior laryngeal nerve were carried out to identify water-responsive laryngeal afferent. Substitution of chloride ions (Cl-) of the Krebs solution with gluconate activated the water-responsive endings when the gluconate concentration was > or = 50 mM. Amiloride (10(-4), 10(-3) and 10(-2) M), an inhibitor of epithelial sodium channels, reduced the water-responsiveness of these afferents, whereas EIPA (5 x 10(-5) M), an amiloride analogue which inhibits Na+/H+ exchange, had no effect. Both ouabain (10(-4) M), an inhibitor of Na+/K+ ATPase, and bumetanide (10(-4) M), an inhibitor of Na(+)-K(+)-2Cl- cotransport, reduced the water response, but no significant reduction in the response was observed with DIDS and DPC, two chloride channel inhibitors. These findings suggest that the epithelium modulates the water-responsiveness of laryngeal afferent but is not the primary determinant of the response.

Extraperitoneal hypogastric artery ligation in control of intractable haemorrhage from advanced carcinoma of cervix and choriocarcinoma.

Seven cases of extraperitoneal ligation of the hypogastric arteries to control bleeding from advanced cervical cancer and choriocarcinoma is presented. This method was able to arrest haemorrhage and there was no further transfusion. The surgical technique and advantages are described.

Metal ion interaction with penicillins--Part VII: Mixed-ligand complex formation of cobalt(II), nickel(II), copper(II), and Zinc(II) with ampicillin and nucleic bases.

Equilibrium study on the mixed-ligand complex formation of M2+ ions (M = Co, Ni, Cu, and Zn) with alpha-d-(-)aminobenzyl penicillin popularly known as ampicillin, (hereafter, ampH +/-), and nucleic bases, viz. adenine, guanine, thymine, uracil, and cytosine (B), in aqueous solution at 37 degrees C at a fixed ionic strength, I = 0.1 M (NaNO3) indicates the formation of complexes of the types: M(amp), M(B), M(amp)(B), M(H-1 amp)(B), and M(H-1 amp)(B)(OH). Stability constants of the ternary complexes are in the order: Co2+ < Ni2+ < Cu2+ > Zn2+ with regard to the mental ions and guanine > adenine > uracil > thymine > cytosine with regard to the nucleic bases. Complex formation equilibria have been worked out on the basis of species distribution curves.