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Biomedical subjects

M Jacob

Publications and source records attributed to M Jacob.

At least 109 records · Page 6Linked to original sources
PubMed1995

The secondary structure of the adenovirus-2 L4 polyadenylation domain: evidence for a hairpin structure exposing the AAUAAA signal in its loop.

The secondary structure of the adenovirus-2 L4 polyadenylation domain was established using enzymatic attacks and chemical modifications. This domain is characterized by the co-existence of several variants including stem-loop structures of low stability such that its secondary structure is clearly distinct from that of the upstream sequence which harbors large stable hairpin structures. The L4 polyadenylation site is located in a free single-stranded region and the AAUAAA signal is exposed in the 14 nucleotide loop of a hairpin structure with a six-base-pair stem. The 5' arm of this stem includes six nucleotides of a previously identified upstream efficiency element (USEa), whose deletion or substitution reduces cleavage-polyadenylation efficiency by 50%. Several evidences suggest that a signal hairpin structure may be important for polyadenylation. First, the AAUAAA signal is well exposed to enzymes and reagents in its two co-existing variants, suggesting that it is also accessible to cleavage-polyadenylation factors. Second, the disruption of the stem induces a 50% decrease of cleavage efficiency in vitro. Third, the reduction of the size of the loop to five nucleotides reduces cleavage efficiency by 90%. Fourth, polyadenylation domains of other origins can be folded into hairpin structures harboring the AAUAAA signal in their loop. We propose that one of the functions of an upstream efficiency element could be to participate in the presentation of the signal to trans-acting factors.

Adenovirus E3 Proteins↗
PubMed1995

Very-low-energy diets alter the counterregulatory response to falling plasma glucose concentrations.

A consequence of short-term very-low-energy diets (VLEDs) in lean subjects is reactive hypoglycemia. We therefore tested the responses of overweight women on prolonged (14 d) VLEDs. Subjects lost 4.8 +/- 0.2 kg (mean +/- SEM, n = 13, P < 0.001). Group A (n = 6) was challenged with an oral-glucose-tolerance test (OGTT) and group B (n = 7) with an oral-sucrose-tolerance test (OSTT) on days 1 and 14. In group A, mean nadir plasma glucose after the OGTT was lower on day 14, 3.75 +/- 0.16 vs 4.7 +/- 0.19 mmol/L (P < 0.01), because of an accelerated rate of glucose decline (RGD, 26.7 +/- 3.3 vs 17.2 +/- 3.9 mumol.l-1.min-1, P < 0.05) late in the OGTT. Plasma insulin was also lower (P < 0.03) and the VLED suppressed two growth hormone (GH) peaks on day 14 (P < 0.05 for each). In group B on day 14, a greater RGD was also observed late in the OSTT, 16.9 +/- 4.1 vs 6.5 +/- 2.0 mumol.L.min-1 (P < 0.03). GH peaks were also significantly suppressed. We conclude that a VLED results in altered glucose regulation late after carbohydrate loading, characterized by an accelerated decline in plasma glucose and GH suppression. Patients on a VLED may be at risk for abnormally low plasma glucose concentrations when ingesting high carbohydrate loads.

Adolescent↗
PubMed1995

Diagnostic evaluation of the lupus band test in discoid and systemic lupus erythematosus.

BACKGROUND: The usefulness of the lupus band test (LBT) in the diagnosis of cutaneous lupus erythematosus remains controversial. The study was done to determine the sensitivity, specificity, and predictive value of the LBT in discoid lupus erythematosus (DLE) and systemic lupus erythematosus (SLE). METHODS: During the study period, 32 patients with SLE and 28 patients with DLE were included. The final classification of cases was based on the American Rheumatism Association Criteria (ARA) for SLE, histopathology, and consensus of the clinical staff. Thirty controls, 15 each for DLE and SLE, were chosen from a group of patients, who had lesions clinically simulating DLE and SLE, but could be excluded by histopathology, laboratory tests, and follow-up. Histopathologic examinations and direct immunofluorescence (DIF) tests were done on lesional skin. RESULTS: In DLE, the sensitivity of the LE band test was 58% and the specificity 87%. The positive predictive value was 95% and negative predictive value was 32%. In SLE the sensitivity was 93% and specificity 87%. The positive predictive value was 64% and negative predictive value 98%. CONCLUSIONS: The high negative predictive value of LBT in SLE suggests that it is valuable in excluding diseases clinically similar to SLE.

Adolescent↗
PubMed1995

Light & electron microscopic structure of choroid plexus in hydrocephalic guinea pig.

With a view to study the morphological changes, if any, in the choroid plexus in association with hydrocephalus, obstructive hydrocephalus was created in 15 young guinea pigs. The choroid plexus of the control group (n = 16) showed high cuboidal or columnar epithelium. The mitochondria of the choroid plexus ependyma converged towards the apex. Varying concentrations of Golgi complex and rough surfaced endoplasmic reticulum (RER) were noticed in the apical part of the epithelium. Subsurface cistern-like structures and occasional formation of vesicles from the adjacent cells of the epithelium were observed. Basolateral infoldings were numerous and compactly arranged. Most capillaries had their fenestrated part facing the base of the epithelium. Choroid plexus of hydrocephalic guinea pigs showed flattened epithelial cells with less extensive Golgi complex and RER. Mitochondria were found lying parallel to the flattened nucleus. Intercellular spaces were dilated with loosely packed basolateral infoldings. Most of the features observed in the hydrocephalic guinea pig are indicative of reduced activity of the choroid plexus epithelium.

Animals↗
PubMed1995

[Reduction of thyroid volume following radioiodine therapy for functional autonomy].

In a retrospective study we evaluated the data of 112 patients who underwent radioiodine treatment for functional autonomy of the thyroid at Essen University Hospital from 1988 to 1993. Therapeutic activities of radioiodine were administered after individual determination of activity for intended radiation doses (150-300 Gy) taking into consideration autonomously functioning volume, maximum uptake, and effective half-life. The achieved dose was calculated by means of measurement of the radioiodine kinetics during therapy. Depending on the type of autonomous function of the thyroid (solitary autonomously functioning nodule, multiple autonomously functioning nodules, autonomously functioning thyroid tissue) volume reductions between 39 and 46% were found approximately 6 months after treatment.

Aged↗
PubMed1995

Increasing prevalence of human immunodeficiency virus infection among patients attending a clinic for sexually transmitted diseases.

Of 5883 patients screened during 1986 to 1993 in the sexually transmitted diseases (STD) clinic at a hospital in Vellore, south India, 105 (1.79%) were positive for human immunodeficiency virus (HIV) antibody. The prevalence of HIV infection increased from 0.26 per cent in 1986 to 2.64 per cent in 1993. In 1992 the prevalence was even higher, namely 3.94 per cent. The overall prevalence in these 8 yr was 1.98 per cent among men (n = 4392) and 1.21 per cent among women (n = 1491), the difference being statistically significant (P < 0.05). The prevalence in men rose from 0.36 per cent in 1986 to 4.24 per cent in 1992, and in women from 0 to 3.04 per cent during the same period. The major source of infection in men was female commercial sex workers, but among women it was mostly their husbands. The increase in prevalence of HIV infection is alarming, and indicates that the massive educational campaigns and other preventive measures have not resulted in decreased transmission.

Ambulatory Care Facilities↗
PubMed1995

Clinical profile of AIDS in India: a review of 61 cases.

Among 61 patients with AIDS seen in our hospital from February 1986 to June 1992, 38 (62%) had significant weight loss, 34 (56%) had fever of more than a month and 19 (31%) had chronic diarrhoea; 43 (70%) patients had at least one of the above symptoms. Tuberculosis diagnosed in 32 (52%) patients was the commonest secondary infection: 10 had only pulmonary, 15 had pulmonary and extrapulmonary and 7 only extrapulmonary tuberculosis. Secondary infections commonly found in the general population, predominantly with pathogenic bacteria were found in 27 (44%) patients, 45 (74%) patients had opportunistic infections such as oropharyngeal candidiasis 25 (41%) cryptococcal meningitis 4 (7%), recurrent zoster 1 (1.6%). Two (3.3%) patients had interstitial pneumonitis of unknown aetiology. One (1.6%) patient each had oral hairy leukoplakia or immunoblastic lymphoma. Kaposi's sarcoma was not seen in any patient. At the time of writing this, 33 (54%) patients have died; the mean duration from diagnosis of AIDS to death was 4.5 months.

AIDS-Related Opportunistic Infections↗
PubMed1994

Structural study of the 5' end of a synthetic premessenger RNA from adenovirus. Evidence for a long-range exon-intron interaction.

In order to establish the structural features of the cis-elements involved in splicing and in its regulation, we have analyzed a synthetic premessenger RNA, derived from the E3 transcription unit of adenovirus-2 and previously shown to be a good substrate for in vitro splicing. The transcript was probed by enzymatic and chemical methods and we present the structure in solution of the upstream exon and of the 5' part of the intron. This 417 nucleotide long fragment, which overlaps the exon-intron junction harbors the natural 5' splice site D1 and an intronic cryptic site, Dcr1, used when D1 is suppressed. The 5' exon is folded in three stem-loop structures and D1 is located in a free single-stranded region close to the foot of the most stable of these structures (ex1-HP1). The 5' part of the intron also contains a stable hairpin structure (IVS1-hp1), which sequesters Dcr1. The different structural context of the two 5' splice sites may partly explain the selection of D1 and the silencing of Dcr1. We also found a long-range, 20 base-pair, exon-intron interaction, which agrees with the enzymatic and chemical probings and was further demonstrated by the study of the colinear messenger RNA, lacking the intron and of 5' deletion transcripts, lacking the 5' part of the exon. This folding creates a three-branched structure, including IVS1-hp1 and divides the 5' part of the transcript into two domains. Finally, only a few sequences are not involved in folded structures. Free single-stranded fragments are found between the exonic hairpins and at the beginning of the intron and are mostly U-rich. All the structural features of the adenovirus-2 transcript are conserved in adenovirus-5, in spite of 37 nucleotide substitutions.

Adenoviridae↗
PubMed1994

Upstream and downstream cis-acting elements for cleavage at the L4 polyadenylation site of adenovirus-2.

A study of the cis-acting elements involved in the 3' end formation of the RNAs from the major late L4 family of adenovirus-2 was undertaken. Series of 5' or 3' end deletion mutants and mutants harboring either internal deletions or substitutions were prepared and assayed for in vitro cleavage. This first allowed the demonstration of a sequence, located at -6 to -29, relative to AAUAAA, whose deletion or substitution reduces cleavage efficiency at the L4 polyadenylation site two to three fold. This upstream efficiency element 5' AUCUUUGUUGUC/AUCUCUGUGCUG 3' is constituted of a partially repeated 12 nucleotide long, UCG rich sequence. The activities of the 2 sequence elements in cleavage are additive. We also searched for regulatory sequences downstream of the L4 polyadenylation site. We found that the deletion or substitution of a 30 nucleotide long UCG rich sequence, between nucleotides +7 and +35 relative to the cleavage site and harboring a UCCUGU repeat reduces cleavage efficiency at least ten fold. A GUUUUU sequence, starting at +35 had no influence. Thus, the usage of the L4 polyadenylation site requires down-stream sequences different from the canonical GU or U boxes and is regulated by upstream sequence elements.

Adenoviruses, Human↗
PubMed1994

Principles of ontogenesis of leg and foot in man.

Human leg and foot anlagen of different developmental stages were studied by means of light and scanning electron microscopy. The findings were compared with principles of human arm and hand development and results obtained experimentally from chicken limbs. The limbs studied have in common the shaping, cell differentiation, and spatial arrangement of different cells as basic processes of development. On the other hand, upper and lower limbs are very different in human and avian embryos with regard to their position, form, and function. We found that the different positions in relation to the dorsal and ventral surfaces and maintenance of the apical ectodermal ridge (AER) are important factors leading to the different orientations and forms of limbs. The unequal length of the fingers and toes might also be explained in this way. Differences in the position of the most distal muscles in the hand and foot could be a consequence of the cranio-caudal sequence of development. The factors controlling the developmental differences between arm and leg are discussed.

Animals↗
PubMed1994

Cutaneous lymphatic sporotrichosis.

The first case of cutaneous lymphatic sporotrichosis from Nagaland and a case of cutaneous sporotrichosis from Kerala who had acquired infection from Assam are reported. The diagnosis in both cases were established by isolating Sporothrix schenckii from multiple cutaneous lesions. The dimorphic nature of fungus was established in vitro by demonstrating the mycelial phase at 25-30 degrees C and yeast phase at 37 degrees C and pathogenicity to white mice. Both the patients were successfully treated with oral administration of potassium iodide for 3 months.

Adult↗
PubMed1993

Regional diastolic dysfunction in postischaemic myocardium in calf: effect of nisoldipine.

OBJECTIVE: The aim was to assess the effect of nisoldipine on left ventricular systolic and diastolic function during prolonged myocardial ischaemia. METHODS: The left circumflex coronary artery was ligated for 2 h and reperfused for 4 h in 12 calves. The animals were randomised to a control group (n = 6) or to treatment with 1.25 mg.h-1 intravenous nisoldipine (n = 6) during 2 h of ischaemia. Circulatory support by a ventricular assist device was performed throughout the experiment except for the time of haemodynamic measurements. Regional wall thickening of a normal and an ischaemic left ventricular region was determined using pairs of ultrasonic crystals. Left ventricular pressure was measured by micromanometry. Left ventricular wall thickness and regional wall stiffness at a common preload of 10 mm Hg were calculated using an elastic model with shifting asymptote. RESULTS: Ten animals survived after 6 h. No difference was observed in systolic function between controls and nisoldipine treated animals. Systolic thickening of the ischaemic wall remained depressed 4 h after reperfusion and showed some recovery after dopamine infusion. Ischaemic wall stiffness at a common preload was lower after nisoldipine during ischaemia and reperfusion than in controls. Control wall stiffness remained unchanged during the whole experiment with and without nisoldipine. Diastolic thinning of the ischaemic wall was prevented by nisoldipine during ischaemia and after reperfusion. CONCLUSIONS: Prolonged myocardial ischaemia is associated with increased myocardial stiffness of the ischaemic wall. Mechanical unloading can help to bridge the acute phase but cannot prevent postischaemic diastolic dysfunction of the ischaemic wall. Nisoldipine has a beneficial effect on regional diastolic function during ischaemia and reperfusion by decreasing regional wall stiffness and preventing diastolic thinning of the ischaemic wall.

Animals↗
PubMed1993

The epidemiology of AIDS in the Vellore region, southern India.

OBJECTIVE: To describe the epidemiology of patients with AIDS in Vellore region, Southern India. DESIGN AND METHODS: Sixty-one patients with AIDS were diagnosed and treated between July 1987 and June 1992. Information on their demographic characteristics and probable modes of acquiring HIV infection was collected at interviews with them and their spouses. RESULTS: There was a progressive increase in the number of patients seen over the 5 years. The mean ages of the 51 men and the 10 women were 33 and 29 years, respectively. Of the 44 patients from our district (population, 5 million), 28 were from Vellore town and 10 from rural areas. Forty-seven (92%) men had frequently used prostitutes. Of the women, four were prostitutes, one had had multiple sex partners and five had not had extramarital sexual contact. One man and one woman had no other risk factor except blood transfusion. Thirty-one (51%) patients had died by August 1992. CONCLUSION: The AIDS epidemic in this region is in its early ascending phase, with a doubling time of approximately 1 year. Most men with AIDS were infected by heterosexual contact with prostitutes, while some women were prostitutes themselves. Together with the male-to-female ratio of 5:1, these results suggest that the male population at risk has sex with a much smaller population of female prostitutes, constituting the major chain of transmission. HIV infection is occurring in both urban and rural populations.

Acquired Immunodeficiency Syndrome↗