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Biomedical subjects

K Rao

Publications and source records attributed to K Rao.

At least 19 recordsLinked to original sources

Temperature-sensitive mutations in the III-IV cytoplasmic loop region of the skeletal muscle sodium channel gene in paramyotonia congenita.

Paramyotonia congenita (PMC), a dominant disorder featuring cold-induced myotonia (muscle stiffness), has recently been genetically linked to a candidate gene, the skeletal muscle sodium channel gene SCN4A. We have now established that SCN4A is the disease gene in PMC by identifying two different single-base coding sequence alterations in PMC families. Both mutations affect highly conserved residues in the III-IV cytoplasmic loop, a portion of the sodium channel thought to pivot in response to membrane depolarization, thereby blocking and inactivating the channel. Abnormal function of this cytoplasmic loop therefore appears to produce the Na+ current abnormality and the unique temperature-sensitive clinical phenotype in this disorder.

Amino Acid Sequence

Child sexual abuse of Asians compared with other populations.

This retrospective chart review study of a child sexual abuse clinic compared a consecutive sample of substantiated sexual abuse cases of Asian victims with random samples of black, white, and Hispanic victims. The findings suggest that there are clinically relevant differences between Asians and the other three populations. Asian victims showed a distinct demographic profile, suffered less physically invasive forms of abuse, were more likely to express suicidality, less likely to display anger and sexual acting out, and had less supportive primary caretakers than non-Asians. Awareness of such ethnic differences will help clinicians better evaluate and treat minority victims.

Adolescent

Pulmonary and systemic vascular smooth muscle mechanical characteristics in newborn sheep.

To investigate the hypothesis that the higher pulmonary vascular resistance in newborn sheep is the result of developmental differences in the vascular muscle mechanical properties, we evaluated pulmonary arteries from newborn and adult sheep and compared them with their respective systemic counterparts (common carotid arteries). The newborn pulmonary artery mechanical stress (13.0 +/- 1.4 mN/mm2) and shortening capacity (11.4 +/- 1.1% of optimal length) were lower (P less than 0.01) than in the adult (20.4 +/- 2.5 and 15.6 +/- 1.3, respectively). The adult carotid artery muscle developed a greater stress (97.6 +/- 18.5 mN/mm2) than the newborn (40.7 +/- 5.0; P less than 0.01), whereas no age differences in shortening capacity were observed (newborn = 19.4 +/- 1.7; adult = 18.4 +/- 1.5% of optimal length). The contraction half-time was similar for the pulmonary and carotid arteries and was not affected by age, whereas the relaxation half-times of the newborn pulmonary (30.7 +/- 2.9 s) and carotid artery (23.3 +/- 1.5) were greater than in the adult (24.9 +/- 2.9 and 14.6 +/- 1.4, respectively; P less than 0.01). The myosin contents of the pulmonary and carotid arteries, as an indicator of the tissue muscle mass, were similar and did not change with age. In conclusion, while the lower stress and shortening capacity of the newborn pulmonary arteries limit their maximum capacity to vasoconstrict, the significantly greater relaxation time of their vascular muscle, a new observation, may account for the higher resistance to blood flow after birth.

Aging

Bronchial smooth muscle mechanics of a canine model of allergic airway hyperresponsiveness.

Although we have reported that tracheal smooth muscle from sensitized dogs shows altered mechanical properties, we did not know, because of technical difficulties with the preparation, whether similar changes occur in the properties of sensitized central bronchial smooth muscle (BSM), the site at which the acute asthmatic response is believed to develop. We have now succeeded in developing a cartilage-free BSM preparation that retains optimal mechanical properties. Such strips were obtained from mongrel dogs that had been sensitized to ragweed pollen. Controls were littermates injected with adjuvant alone. Length-tension relationships were obtained for both control and sensitized BSM strips (CBSM and SBSM, respectively). The maximal active stresses were the same (P greater than 0.05) when normalized to muscle fraction in total tissue cross-sectional area [6.2 +/- 0.6 x 10(4) and 5.9 +/- 0.6 x 10(4) (SE) for SBSM and CBSM, respectively]. This suggests that optimal tension is an insensitive indicator of bronchial hyperresponsiveness and that isotonic studies might be more revealing. The maximal shortening velocity (Vo) for SBSM at 2 s [0.35 +/- 0.017 (SE) lo/s, where lo signifies optimal muscle length], in the course of a 10-s contraction, was significantly greater (P less than 0.05) than Vo measured for CBSM (0.27 +/- 0.015 lo/s). However, Vo did not differ at the 8-s point of contraction. The sensitized group demonstrated a statistically significantly greater maximal shortening capacity (0.67 +/- 0.04 lo) than the control group (0.51 +/- 0.04 lo). At 2 s of contraction, 80% of maximal SBSM shortening had been completed and was significantly greater than for CBSM.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Ragweed sensitization-induced increase of myosin light chain kinase content in canine airway smooth muscle.

Previous studies have identified changes of mechanical properties of airway smooth muscle (ASM) from a canine model of atopic airway hyperreactivity. These changes, including increased maximum shortening capacity (delta Lmax) and early shortening velocity (Vo), may be responsible for the airway hyperresponsiveness in asthma. We have suggested that these changes may be due to increased actomyosin ATPase activity, controlled via phosphorylation of the 20 kD myosin light chain (MLC20) by MLC kinase (MLCK). Therefore, ATPase activity, MLC20 phosphorylation, and MLCK content and activity were assessed in tracheal and bronchial smooth muscles (TSM and BSM) of ragweed pollen-sensitized dogs (S) and their littermate controls (C). Specific ATPase activities from STSM and SBSM were significantly higher than their control counterparts (CTSM, CBSM). Phosphorylation of MLC20 in STSM was greater both at rest and during electrical stimulation due to the increased amount of MLCK in STSM and SBSM by 30 and 25%, respectively. MLCK activity was also increased significantly in STSM and SBSM (from 46.99 +/- 8.33 and 42.85 +/- 5.92 to 91.9 +/- 6.43 and 64.12 +/- 7.88 32P mmol/mg fresh tissue weight/min respectively [mean +/- SEM]). When normalized to the amount of MLCK in the tissue, however, specific MLCK activity in STSM and SBSM was similar to that in controls. It is unlikely that myosin phosphatase plays any role in the changes of MLC20 phosphorylation in sensitized animals. Peptide mapping showed no visible change in primary structure of MLCK in STSM and SBSM compared with those of controls. We report that ASM actomyosin ATPase activity is increased in STSM and SBSM. The increased ATPase activity is the result of increased MLC20 phosphorylation, the latter likely resulting from the increased MLCK content, which may account for the hyperresponsiveness found in ASM from these animals.

Allergens

Radiotherapy and verrucous carcinoma of the oral cavity. A study of 107 cases.

One hundred and seven cases of oral verrucous carcinoma treated primarily with radiotherapy at Kasturba Hospital, Manipal, India between 1977 and 1987 were analysed concerning location within the oral cavity, clinical extent, and effectiveness of radiotherapy. The most common site was the buccal mucosa followed by the buccogingival sulcus. Only 13.2% of the patients presented with T1 or T2 tumours and 32.7% had clinically negative nodes. Biopsy had to be repeated more than once in 22 patients to get confirmation of invasive carcinoma. The 5-year survival rate was 35% for stage III and 26% for stage IV. The treatment results with radiotherapy were comparable with those for ordinary squamous cell carcinoma of the oral cavity. It is felt that the treatment policy for verrucous carcinoma can be the same as for ordinary squamous cell carcinoma. In order to prevent delay in diagnosis and treatment, proper cooperation between the treating oncologist and the pathologist is essential.

Adult

Enhancement of macrophage tumouricidal activity by the alkaloid derivative Ukrain. In vitro and in vivo studies.

Ukrain is a semisynthetic drug with immunomodulatory properties, derived from Chelidonium majus L. alkaloids and thiophosphoric acid. The effect of this compound on the growth of Balb/c syngenic mammary adenocarcinoma was assessed. Intravenous, but not subcutaneous or intraperitoneal, administration of this drug was found to be effective in delaying tumour growth in an actual therapeutic protocol initiated five days after tumour implantation. No untoward side-effects were observed using these in vivo treatment modalities. The role of macrophages in the observed retardation of tumour development was investigated using peritoneal exudate macrophages (PEM) in cytotoxicity assays. In previous studies, the authors have found that PEM of mammary tumour bearing mice lose their capacity to kill a variety of tumour target cells including the in vitro cultured homologous tumour cells (DA-3). Pretreatment of PEM from normal mice with 2.5 microM Ukrain for 24 h followed by stimulation with either IFN-gamma or with LPS+IFN-gamma enhanced their cytotoxic activity. Treatment of PEM from tumour bearing mice with 2.5 microM Ukrain and LPS results in a reversal of their defective cytotoxic response against the DA-3 target cells. Furthermore, Ukrain alone, in the absence of a secondary signal, induced the activation of tumouricidal function of PEM from tumour bearing but not from normal mice. These data indicate that Ukrain's in vivo effects against the development of mammary tumours may be due, at least in part, to its ability to restore macrophage cytolytic function.

Adenocarcinoma

Bacterial flora of the endometrium in infertile women from Manipal.

Endometrial curettage specimen culture of 140 infertile women showed 64 (45%) organisms. Mycobacterium tuberculosis 8 (5.7%) and Anonymous mycobacteria 14 (10%) were the commonest organisms isolated. Among the anonymous mycobacteria, following species were isolated M. scrofulaceum 10, M. kansasii 2, M. fortuitum 2. Gram positive and gram negative organisms were isolated from 42 (30%) specimens of the endometrium; 76 (54%) of the endometrium specimens were sterile.

Bacteria

Bypass of carrier-induced epitope-specific suppression using a T-helper epitope.

A gonadotropin-releasing hormone (GnRH)-based vaccine is being developed as a method for non-surgical immunotherapy as immunization with this vaccine results in atrophy of the prostate. This vaccine, a conjugate of GnRH and diphtheria toxoid (DT), provides a unique hapten-carrier system for investigating the influence of carrier presensitization on antibody responses to self haptens. In a recent communication we showed that preimmunization with carriers diphtheria toxoid and tetanus toxoid results in a strain-dependent inhibition of anti-GnRH responses in mice and that T cells from carrier-presensitized mice are responsible for anti-haptenic suppression. In the present report we describe a strategy for bypassing DT-induced epitopic suppression using a T-helper epitope from DT.

Animals

Clinical and bacteriological study of normal and inflamed neonatal conjunctivae.

Maternal vaginal and neonatal conjunctival flora were prospectively studied in a 117 mother baby pairs. The commonest isolates from both vaginal and conjunctival flora were E. coli, Staphylococcus aureus and Klebsiella species. In 85% of mother-baby dyads, isolates from vagina and conjunctiva were similar. The commonest bacterial isolates in neonates with conjunctivitis were Staphylococcus aureus (37.4%), E. coli (27.9%) and Klebsiella species (19.3%). Maternal coitus, infections, rupture of membranes and baby's birth weight and sex did not influence the occurrence of conjunctivitis.

Bacteria

Normalization of force generated by canine airway smooth muscles.

A variety of normalizations have been employed to compare maximal isometric force (Po) produced by smooth muscles at different locations and stages of maturation. Because these procedures have not always been based on rigorous principles, confusion has resulted. To obtain a less ambiguous index of force production, we measured in vitro Po from mongrel canine tracheal (TSM) and bronchial (BSM) smooth muscle with an electromagnetic lever and normalized it to force per unit cross-sectional area of whole tissue (tissue stress), to force per unit cross-sectional area of muscle in the cross section of total tissue (muscle stress), and to force per fractional unit of myosin in the tissue cross section (myosin stress). Proportion of myosin in cross-sectional area of tissue was deduced from data obtained by sodium dodecyl sulfate gel electrophoresis of crude muscle extracts. For TSM, tissue stress was 1.499 X 10(5) N/m2 +/- 0.1 (SE), whereas it was only 0.351 X 10(5) N/m2 +/- 0.05 (SE) for BSM, representing a 4.27-fold difference (P less than 0.01). There was a 1.60-fold difference (P less than 0.05) in muscle stress, which was correlated to the morphometric finding that 79 +/- 1.4% (SE) of the tracheal strip cross section was muscle, whereas only 30 +/- 1.0% (SE) of bronchial tissue was occupied by muscle. Average myosin content was the same in smooth muscle cells of TSM and BSM, indicating that total amount of myosin in tissue cross sections was essentially a function of proportional area of muscle cells in total tissue cross sections.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Pulmonary vascular smooth muscle: biochemical and mechanical developmental changes.

To evaluate the developmental changes in pulmonary vascular smooth muscle contractile protein content, mechanical properties, and their contribution to the high resistance characteristic of the fetal and immediate neonatal period, we studied pulmonary vessels of fetal, newborn, and adult sheep, as well as newborn and adult pigs. Strips of the second- through fifth-generation vessels were dissected, and their content of tissue total smooth muscle cell protein, myosin, and actin-to-myosin ratio were measured; the mechanical properties of the second-generation vascular strips were also studied. For all ages the smooth muscle protein and myosin content of the second-generation vessels were significantly greater than for the lower pulmonary vascular orders (P less than 0.05). The myosin content in fetal sheep (0.77 +/- 0.03 micrograms/mg wet tissue) was similar to that of the newborn (0.79 +/- 0.04) and adult (0.86 +/- 0.05). However, the smooth muscle protein content (7.94 +/- 0.21 micrograms/mg wet tissue) and the actin-to-myosin ratio of the pulmonary vascular tissue of the fetus (1.00 +/- 0.04) were lower (P less than 0.01) in the fetal than in the newborn (9.16 +/- 0.26 and 1.60 +/- 0.12) and adult (9.38 +/- 0.3 and 1.60 +/- 0.11, respectively). No differences were observed for these parameters between the newborn and adult pig. Stress (16.5 +/- 1.7 mN/mm2) and the maximum shortening capacity (13.0 +/- 1.5% of optimal length) in the newborn pulmonary vascular strips were significantly greater than for the fetus (6.8 +/- 1.4 and 5.9 +/- 1.0, respectively) but similar to those of the adult sheep.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins

Primary amenorrhoea (analysis of 40 cases).

Forty cases of primary amenorrhoea attending gynaecological department of Kasturba Medical College Hospital, Manipal, in the year 1987-88, were analysed. Majority (50%) of cases were of muellerian dysgenesis. One case was a true hermaphrodite with bilateral ovotestis and one case of genital tuberculosis. Attempt has been made to establish value of laparoscopy in primary amenorrhoea. It is seen that laparoscopy gives much better information and obviates the need for costly tests like radio-immuno-assays in some cases of primary amenorrhoea.

Adolescent

Differential expression of class I and class II major histocompatibility complex antigen in early postnatal rats.

Cells expressing major histocompatibility complex (MHC) antigens are rarely found in normal mature brains, but cells resembling microglia can be induced to express these antigens following the onset of neural degeneration. In young rats, these cells show spontaneous expression of class I MHC antigens, which is further enhanced in the superior colliculus by the degeneration resulting from eye removal. By contrast, class II MHC antigen expression does not occur spontaneously and can only be induced by eye removal when the lesion is performed after the first postnatal week, when the optic tract begins to myelinate. We suggest that different signals are responsible for induction of class I and of class II MHC antigen expression.

Animals