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Biomedical subjects

M Jacob

Publications and source records attributed to M Jacob.

At least 37 records · Page 2Linked to original sources

The 5' splice site: phylogenetic evolution and variable geometry of association with U1RNA.

The 5' splice site sequences of 3294 introns from various organisms (1-672) were analyzed in order to determine the rules governing evolution of this sequence, which may shed light on the mechanism of cleavage at the exon-intron junction. The data indicate that, currently, in all organisms, a common sequence 1GUAAG6U and its derivatives are used as well as an additional sequence and its derivatives, which differ in metazoa (G/1GUgAG6U), lower eucaryotes (1GUAxG6U) and higher plants (AG/1GU3A). They all partly resemble the prototype sequence AG/1GUAAG6U whose 8 contigous nucleotides are complementary to the nucleotides 4-11 of U1RNA, which are perfectly conserved in the course of phylogenetic evolution. Detailed examination of the data shows that U1RNA can recognize different parts of 5' splice sites. As a rule, either prototype nucleotides at position -2 and -1 or at positions 4, 5 or 6 or at positions 3-4 are dispensable provided that the stability of the U1RNA-5' splice site hybrid is conserved. On the basis of frequency of sequences, the optimal size of the hybridizable region is 5-7 nucleotides. Thus, the cleavage at the exon-intron junction seems to imply, first, that the 5' splice site is recognized by U1RNA according to a "variable geometry" program; second, that the precise cleavage site is determined by the conserved sequence of U1RNA since it occurs exactly opposite to the junction between nucleotides C9 and C10 of U1RNA. The variable geometry of the U1RNA-5' splice site association provides flexibility to the system and allows diversification in the course of phylogenetic evolution.

Animals

Atypical cilia in the choroid plexus of guineapig.

Ultrastructural study of choroid plexus of normal and kaolin induced hydrocephalic guineapigs showed clusters of cilia arising from the apical part of some of the epithelial cells. Some of these cells had typical 9 + 2 cilia, while most of the control and the hydrocephalic groups showed 9 + 0 type of cilia. These atypical (9 + 0 type) cilia of choroidal epithelium differ from the primary cilia of other mammalian tissues in that, clusters of long cilia arise from a single cell and have no associated centrioles within the cytoplasm. They may be motile and sensory (osmoregulator or pressure sensor or both) in nature.

Animals

[Adsorbed plant extracts, use of extracts of dried seeds of Orthosiphon stamineus benth].

The work presented is related to the elaboration and the control of spray dried vegetable extracts of Orthosiphon Stamineus Benth. From these studies, it feasibility of the spray dried extracts. The best result concerning a pulverulent structure and the stability under moisture conditions is obtained using Aerosil 200. Pharmacological studies on rats have shown a diuretic activity under our experimental conditions with alcoholic and water extracts.

Diuretics

Epidemiology & clinical profile of genital herpes.

During 1983-86, genital herpes (GH) was diagnosed in 225 (19%) of 1194 patients attending the STD clinic, attached to a Medical College in south India. The patients included 169 men and 56 women; 50 had primary GH and 175 had recurrent GH. The prevalence of GH in men and women did not differ significantly but the proportion of primary GH was significantly higher in women. There was no seasonal variation. The clinical epidemiology of these patients is compared with those in other countries. Virological confirmation of GH was obtained in 38 per cent of patients through culture and in a further 12 percent through serological tests. Papanicolaou smears were positive in 30 per cent men regardless of the type of GH, and in 38.5 and 7.1 per cent women with primary and recurrent GH, respectively. Cultures were positive for herpes simplex virus (HSV) in 38.7 per cent of patients with primary and 38.2 per cent with recurrent GH. Among the 52 viral isolates typed, nine of the 10 isolates from primary GH and all 42 from recurrent GH, were HSV-2. The geometric mean titres of antibody against HSV were higher in patients than in controls.

Adult

Alternative use of a polyadenylation signal and of a downstream 3' splice site. Effect of 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole.

A minor pathway for the processing of transcripts from the early region 3 transcription unit of adenovirus 2 is described. It results from the selection of a promoter-proximal polyadenylation site P1 instead of the major promotor-distal sites P2 and P4. 5,6-Dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) considerably reduces the use of the major pathways and enhances the minor one. The characterization of three novel nuclear RNAs whose amount increases in DRB-treated cells leads us to propose the following steps for the selection of P1. The nascent transcript is first cleaved in the branch point-3' splice site region of the first E3 IVS (intervening sequence), generating a promoter-proximal RNA with a heterogeneous 3' end (F-RNA) and a promoter-distal RNA with a heterogeneous 5' end (G-RNA). This cleavage prevents the formation of the premessenger RNAs ending at P2 and P4. The 3' end of F-RNA is about 130 nucleotides downstream from P1 and F-RNA contains the signals required for cleavage-polyadenylation. It may thus generate CP1, which is the transcript ending at P1. The cleavage of the nascent transcript in a region crucial for spliceosome assembly suggests that defective assembly may render RNA sequences at the 3' end of IVS accessible to intracellular nucleases and trigger the use of an upstream polyadenylation site. Such a mechanism may explain the alternative use of neighbouring, mutually exclusive, splice and polyadenylation sites.

Adenoviridae

The distribution of two hnRNP-associated proteins defined by a monoclonal antibody is altered in heat-shocked HeLa cells.

A monoclonal antibody obtained after mice were immunized with hnRNP purified from HeLa cells recognizes two polypeptides of Mr 35,000 and 37,000. By immunocytofluorescence, these antigens can be visualized only in cells previously heat shocked at 45 degrees C for 5 or 10 min, although they are present at the same level in unstressed and stressed cells. The signal, which is mostly concentrated in the interchromatin space, where hnRNP fibrils are located, does not accumulate with time and disappears 4 to 5 h after heat shock. Discrimination between the two types of hnRNP substructures, the 30-50 S monoparticles and the nuclear matrix fibrils, based on differential sensitivity to salt or ribonuclease treatment, showed that in unstressed cells the antigens behave as monoparticle proteins. In contrast, in heat-shocked cells, most 35-37K antigens behave as nuclear matrix proteins. Thus, heat shock seems to induce a rapid and reversible switch of these two antigens from hnRNP monoparticles to the nuclear matrix. The data demonstrate that heat shock, which was previously shown not to alter the overall RNA: protein packaging ratio of hnRNP, induces subtle modifications of their substructure. Such modifications might be of importance since heat shock is known for instance to affect pre-mRNA processing.

Antibodies, Monoclonal

First case of subcutaneous zygomycosis caused by Saksenaea vasiformis in India.

The first case of subcutaneous zygomycotic infection caused by Saksenaea vasiformis in a rice mill worker from India is described. The infection, confined to the man's left foot, showed multiple draining sinuses, inflammation, and intermittent low-grade fever following a crushing injury when a log fell on his foot. Histopathologic examination of two biopsy specimens, taken at 3-wk intervals, revealed the presence of broad, sparsely septate, branched, hyaline hyphae characteristic of a zygomycete. When they were grown on a nutritionally deficient medium, two cultures isolated from the biopsied tissues formed numerous, vase-shaped sporangia typical of S. vasiformis. Necrosis of the affected area led to amputation of the fore part of the foot. A split thickness graft was well accepted, and treatment with potassium iodide, following the graft, cured the infection.

Adult

Infrared and visible thermoluminescence signals of Tm-doped CaF2 measured by a semiconductor photodiode.

A silicon semiconductor photodiode was used to measure the TL-signal of TLD-300 (CaF2:Tm) detectors irradiated with 60Co gamma rays and 226Ra alpha particles. The applied dose values varied from 0.12 to 14.3 Gy for gamma rays and from about 50 to 300 Gy for alpha particles. Because of the infrared sensitivity of the photodiode the infrared emission of the planchet and the TLD-detector produced a high output signal above about 200 degrees C. In addition to this background signal an infrared emission from the TLD-300 detectors could be detected. This infrared TL-signal exhibited the same dose dependences as the visible signal, but the amplitude was higher than that of the visible TL-signal. For the applied photodiode the ratio of the infrared TL-signal to the visible TL-signal was about 24 for the 100 degrees C peak, about 15 for the 150 degrees C peak and 6 for the 240 degrees C peak.

Alpha Particles

Aluminum metabolism in rats: effects of vitamin D, dihydrotachysterol, 1,25-dihydroxyvitamin D and phosphate binders.

In order to study the effects of vitamin D on aluminium balance when different forms of vitamin D and phosphate binders are used simultaneously for therapeutic purposes, 30 Sprague-Dawley weanling rats, weighing 44-66 g, were randomly assigned to 5 groups: (A) control, (B) aluminum hydroxide, (C) dihydrotachysterol at 16 micrograms/kg/day, (D) 1,25-dihydroxyvitamin D at 16 ng/kg/day and (E) vitamin D at 2,000 IU/kg/day. Aluminum hydroxide (60 mg/kg/day) in the feed was provided to all except the control group. The vitamin D or metabolites were fed by stomach tube daily for a period of 10 days. At the end of the study, the mean (+/- SEM) serum aluminum concentration, as determined by flameless atomic absorption spectrophotometry, was 5.0 +/- 2.4 micrograms/l; there were no significant differences in these results between groups. During the last three days of the study, 24-hour urine and stool collections were made with the usual precautions against trace mineral contamination. The means (+/- SEM) of aluminum balances for groups A, B, C, D and E were -388 +/- 261, 1,121 +/- 331; 2,316 +/- 304; 2,387 +/- 245, and 1,968 +/- 337 micrograms/day, respectively. We conclude that at therapeutic doses of aluminum hydroxide and vitamin D or its metabolites, hyperaluminemia was not observed. However, the positive aluminum balances imply retention, and the use of vitamin D, especially its potent metabolites dihydrotachysterol and 1,25-dihydroxyvitamin D, intensified this risk.

Aluminum

Diagnostic efficacy of cutaneous nerve biopsy in primary neuritic leprosy.

The role of nerve biopsy in the diagnosis of primary neuritic leprosy was evaluated in a study of 77 patients who had symptoms of peripheral neuropathy without hypopigmented patches, positive skin smears, or a skin biopsy consistent with leprosy. A biopsy of a representative cutaneous nerve near the site of the neurological deficit was taken for histopathological examination and acid-fast staining. Nearly half of the patients had leprosy confirmed by nerve biopsy, and the entire spectrum of leprosy was represented. No significant relationship was seen by age or sex or type of neuropathy. The duration of symptoms did not correlate with the severity of nerve damage as seen histologically. The probability of false-positive or false-negative results is discussed in light of clinical management. Being a relatively simple office procedure, a cutaneous nerve biopsy is strongly recommended as an important diagnostic tool, particularly for primary neuritic leprosy.

Adolescent

In-vivo degradation pathway of an excised intervening sequence.

A study of the distribution in heterogeneous nuclear RNP (hnRNP) of the different forms of the first intervening sequence (IVSI) from the E3 transcription unit of adenovirus serotype 2 suggests a three-step pathway for IVS excision and degradation. First, the lariat IVS is formed in a large RNP of the size of premessenger RNP where it is resistant to nuclease attack. Second, the lariat IVS is released from this large structure as a small RNP where it is very susceptible to enzymic degradation. Third, the lariat IVS is linearized after the release of the small RNP. Our studies suggest that only the intact lariat and linear IVS are involved in the excision-degradation pathway in vivo, whereas the lariat nicked in its circular part and the IVS trimmed at its 3' end are not pre-existing but generated during isolation of hnRNA or hnRNP.

Adenoviruses, Human

Salmonella ealing infections associated with consumption of infant dried milk.

In an outbreak of Salmonella ealing infections in November and December, 1985, the proportion of infants infected was in excess of the normal distribution pattern and the cases were geographically widespread. All the infected infants had been fed with a dried-milk product from one manufacturer. Despite intensive efforts to isolate S ealing from packets of the product, it was found only in low numbers in 4 of 267 sealed packets. The source of infection was traced to the factory spray-drier, which had a hole in its inner lining, allowing escape of powder and its return from contaminated insulation material. The plant was closed and the equipment scrapped and later replaced. It is recommended that raw milk and whey, which frequently contain salmonellae, should not be allowed onto the site of milk-drying plants.

Adult

Nuclear non-polyadenylated RNAs containing the first intervening sequence of the major late premessenger RNA from adenovirus-2: characterization and distribution in ribonucleoproteins.

The nuclear non-polyadenylated RNA from HeLa cells infected with adenovirus-2 was examined for the presence of molecules containing the first intervening sequence (IVS1) of the major late premessenger RNA. Four molecules with the approximate size of free IVS1 in sucrose gradients (1021 nucleotides) were separated by polyacrylamide gel electrophoresis and characterized by complementary methods: S1 nuclease mapping, susceptibility to debranching enzyme, RNAase-H-directed cleavage. The results indicate that the most abundant RNA form is the excised lariat IVS1. We also find linear IVS1 and a randomly nicked lariat, the latter probably being made during RNA isolation. The fourth RNA is a leader 1-IVS1 molecule. No truncated IVS1 which might indicate that IVS1 is excised by several cycle of cleavage-ligation was detected. A study of the distribution of the four RNAs in hnRNP shows that they are part of RNPs of about 70 S. However, each RNP has distinct sedimentation characteristics and sensitivity to salt dissociation. Together, the results suggest that the excised lariat IVS1 is released from the large late premRNP under the form of a 70 S RNP, where it is linearized.

Adenoviruses, Human

Structure, self-regulating sequences, and institutional third parties in therapy: the Veterans Administration as a model.

This article examines the structural organization and sequences of interaction among therapists, institutions, and patients and their families that contribute to the problem of institutional dependence. Our contention is that when patients have become dependent on an institution for the livelihood and/or for the stability it represents, they are only one part of a systemic relationship characterized structurally by enmeshed boundaries, and sequentially by self-regulating feedback loops. We use this premise to outline the nature of the enmeshed transactions in patient-therapist, patient-institution, and therapist-institution relationships. Family interfaces with this triad are also addressed. Sequentially, we outline the interactions among patient, family, therapist, and institution that lead to hierarchical incongruities. These sequences tend to produce self-regulating feedback loops that perpetuate and maintain the structure of the system and its patterns of interaction. The final part of this article demonstrates how we strategically use a therapy team to manipulate the hierarchical incongruities and, hence, the recursive complementarity, that characterize the interactions between and among the members of this suprasystem. Besides manipulating the role of the therapist through team intervention, we also present several paradoxical and structural interventions that have been helpful when institutions have become third parties to therapy.

Adult

Pregnancy-related affective episodes among women with recurrent depression.

The authors examined 52 women with recurrent depression to determine the differences between women with and without histories of pregnancy-related affective episodes. The women with histories of such episodes (N = 24) had been significantly younger at illness onset, were more severely depressed at baseline, and tended to show less emotional stability. The EEG-recorded sleep of the women with pregnancy-related affective episodes was distinguished by longer REM sleep time and more REM activity, differences accounted for almost entirely by the women with histories of only postpartum episodes.

Adult

A psychoeducational workshop for depressed patients, family, and friends: description and evaluation.

Since 1982 depressed patients enrolled in a treatment study at the Western Psychiatric Institute and Clinic and their family and friends have participated in a day-long psychoeducational workshop conducted by the clinic's staff. The workshop is designed to help family and friends become useful, long-term resources for patients with recurrent depression and to enlist their assistance in the treatment study. During the morning session, the group discusses the symptomatology, theory, etiology, and treatment of depression, and staff describe the treatment study. In the afternoon, patients and their families and friends meet separately, the patients to discuss methods of coping with depression and interacting with significant others, and the families to discuss the impact of the patient's depression on their lives and to share common problems. More than 83 percent of family and friends who evaluated the workshop considered it moderately or extremely helpful. The results of the evaluation are summarized.

Consumer Behavior