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Biomedical subjects

J Mitra

Publications and source records attributed to J Mitra.

At least 73 records · Page 4Linked to original sources
PubMed1984

Nasal and laryngeal reflex responses to negative upper airway pressure.

The effects of negative pressure applied to just the upper airway on nasal and laryngeal muscle activity were studied in 14 spontaneously breathing anesthetized dogs. Moving average electromyograms were recorded from the alae nasi (AN) and posterior cricoarytenoid (PCA) muscles and compared with those of the genioglossus (GG) and diaphragm. The duration of inspiration and the length of inspiratory activity of all upper airway muscles was increased in a graded manner proportional to the amount of negative pressure applied. Phasic activation of upper airway muscles preceded inspiratory activity of the diaphragm under control conditions; upper airway negative pressure increased this amount of preactivation. Peak diaphragm activity was unchanged with negative pressure, although the rate of rise of muscle activity decreased. The average increases in peak upper airway muscle activity in response to all levels of negative pressure were 18 +/- 4% for the AN, 27 +/- 7% for the PCA, and 122 +/- 31% for the GG (P less than 0.001). Rates of rise of AN and PCA electrical activity increased at higher levels of negative pressure. Nasal negative pressure affected the AN more than the PCA, while laryngeal negative pressure had the opposite effect. The effects of nasal negative pressure could be abolished by topical anesthesia of the nasal passages, while the effects of laryngeal negative pressure could be abolished by either topical anesthesia of the larynx or section of the superior laryngeal nerve. Electrical stimulation of the superior laryngeal nerve caused depression of AN and PCA activity, and hence does not reproduce the effects of negative pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intranasal↗
PubMed1984

Respiratory function of hyoid muscles and hyoid arch.

The position of the hyoid arch suggests that it supports soft tissue surrounding the upper airway (UA) and can act to maintain UA patency. We also suspected that muscles inserting on the hyoid arch might show respiratory patterns of activity that could be affected by respiratory stimuli. To test these possibilities, we moved the hyoid arch ventrally in six anesthetized dogs either by traction on it or by stimulation of hyoid muscles. UA resistance was decreased 73 +/- (SE) 6% and 72 +/- 6% by traction and stimulation during expiration and 57 +/- 15% and 52 +/- 8% during inspiration. Moving averages of the geniohyoid (GH) and thyrohyoid (TH) obtained in six other dogs breathing 100% O2 showed phasic respiratory activity while the sternohyoid (SH) showed phasic respiratory activity in only two of these animals and no activity in four. With progressive hypercapnia, GH and TH increased as did SH when activity was already present. Airway occlusion at end expiration augmented and prolonged inspiratory activity in the hyoid muscles but did not elicit SH activity if not already present. Occlusion at end inspiration suppressed phasic activity in hyoid muscles for as long as in the diaphragm. After vagotomy activity increased and became almost exclusively inspiratory. Activity appeared in SH when not previously present. Duration and amplitude of hyoid muscle activity were increased with negative UA pressure and augmented breaths. We conclude that the hyoid arch and muscles can strongly affect UA flow resistance. Hyoid muscles show responses to chemical, vagal, and negative pressure stimuli similar to other UA muscles.

Airway Resistance↗
PubMed1983

Activity of upper airway muscles during augmented breaths.

The effect of augmented breaths on the electrical activity of upper airway (UAW) muscles was studied in fourteen spontaneously breathing anesthetized dogs. Moving average traces of the electrical activity recorded from the genioglossus (GG), the posterior cricoarytenoid (PCA), and the alar portion of the nasalis muscle (AN) were compared to tracings of diaphragm electrical activity. During augmented breaths the electrical activity of the diaphragm showed the characteristic biphasic pattern previously described: an initial phase following the contour of a normal breath (phase I) and an augmented phase arising near the crest of the initial phase (phase II). During all augmented breaths, the GG, PCA and AN showed the same biphasic pattern as the diaphragm. The normally rounded shape of UAW muscle EMG activity during control breaths changed to a more sharply peaked form during the second phase of the augmented breath. Onset of activity of all UAW muscles studied preceded that of the diaphragm; during control breaths, the average interval was 0.29 sec for the PCA, 0.25 sec for the GG and 0.14 sec for the AN (P less than 0.05). The amount of pre-activation was decreased to less than 0.10 sec during the second phase of the augmented breath. The slopes and amplitudes of phase I were similar to that of control breaths. The peak EMG activity of the augmented breath was 214% of the control breaths for the diaphragm, 247% for the GG, 168% for the AN and 161% for the PCA (P less than 0.005 for GG, P less than 0.001 for the others). During hyperoxic hypercapnia the slopes and amplitudes of phase II remained nearly constant for all four muscles, whereas the slopes and amplitudes of phase I changed with the chemical drive just as in control breaths. UAW resistance, recorded in five additional spontaneously breathing anesthetized dogs, was 32% less during inspiration than expiration during control breaths, and 31% less during phase I of augmented breaths; there was a further 18% decrease during phase II of augmented breaths (P less than 0.001). The results suggest that mechanisms responsible for augmented breaths act similarly on upper airway muscles and the diaphragm.

Airway Resistance↗
PubMed1983

The effects of hypercapnia and hypoxia on single hypoglossal nerve fiber activity.

The respiratory related modulation of hypoglossal nerve activity has been studied at the single fiber level in cats under hyperoxic hypercapnia and hypoxic conditions and their conduction velocities determined. Changes in fiber activity were compared to simultaneous changes occurring in phrenic activity. Three different kinds of discharge patterns were observed: (a) inspiratory, (b) phasic activity during both inspiration and expiration, and (c) continuous random activity with no respiratory modulation. These fibers could be grouped into three categories according to their pattern of discharge during CO2 breathing. Type I fibers, mean conduction velocity of 30.0 m/sec, exhibited only an inspiratory phasic discharge during 100% O2 breathing. Their discharge frequency increased rapidly with higher levels of CO2 and hypoxia. Type II fibers, mean conduction velocity of 36.7 m/sec, had three different kinds of inspiratory-expiratory discharge patterns during 100% O2 breathing. With increasing hypercapnia or hypoxia fibers of this group discharged phasically during inspiration and discharge at low frequency during expiration. Type III fibers had a non phasic discharge pattern at 100% O2 breathing and at all levels of CO2 tested (up to 10%). Discharge frequency rose during CO2 rebreathing and hypoxia, but the rate of increase was much less than Type I and Type II fibers. Their mean conduction velocity was 41.3 m/sec. The inspiratory activity of Type I and II fibers increased their activity more than the phrenic during hypercapnia and hypoxia. Type II and Type III fibers are responsible at least in part for the tonic activity of the nerve.

Animals↗
PubMed1983

Sister chromatid exchanges and chromosome aberrations induced by radiosensitizing agents in bone marrow cells of treated tumor-bearing mice.

The frequency of sister chromatid exchanges (SCE) in vivo and chromosome aberrations and/or alterations were analyzed from the bone marrow cells of the treated dbrB tumor-bearing DBA/1J inbred mouse host. The results were compared with analogous data obtained from the bone marrow cells of untreated tumor-bearing mice for evaluation of the "indirect," i.e., somatic stress, effect on the normal host cells following triple-agent therapy intended for a mammary adenocarcinoma. Misonidazole (MIS), which is a known radiosensitizing drug, microwave hyperthermia (delta), and X-radiation (X) were used as therapeutic agents. Significant (P less than 0.05) numbers of SCE were induced in the bone marrow cells of the mice whose tumors received these triple-agent treatments (MIS + delta + X) simultaneously as compared with values of SCE per cell noted in bone marrow cells of untreated tumor-bearing control mice. The highest number of chromosome aberrations and alterations, including an increase in heteroploidy, was also noticed in the bone marrow cells of the mice whose tumors were treated simultaneously with MIS + delta + X. The triple-agent therapy on dbrB tumor also resulted in an unusually high polyploid metaphase plate in the bone marrow cell consisting of 320 chromosomes, indicating that this mode of therapy may act directly on the genetic material of the tumor-bearing host cells, inducing cytogenetic abnormalities as a side effect.

Animals↗
PubMed1983

Combined effects of misonidazole, microwave hyperthermia, and X-rays on the in vivo sister chromatid exchanges and chromosomal abnormalities of the dbrB tumor and on the survival of its host.

A rapidly proliferating mammary adenocarcinoma designated dbrB growing s.c. in isogeneic female DBA/1J mice in their 278th passage of transfer constituted the experimental host tumor system. A 5-bromodeoxyuridine pellet (2.5 mg/g body weight) was used for sister chromatid exchange analysis of the 0.5-cu cm dbrB tumor. Experiments were performed on Group I, untreated tumor-bearing mice, and Group II, tumor-bearing mice treated with triple agents: misonidazole (1 mg/g body weight); 42.5 degrees microwave hyperthermia for 10 min; and X-rays administered singly or in combination at about 4 hr following the implantation of a 5-bromodeoxyuridine pellet. The X-ray treatments consisted of 400, 1000, 1500, and 2000 rads, respectively. X-rays and hyperthermia were delivered to the tumors directly, while the rest of the mouse body was lead shielded. Survival of the untreated tumor-bearing control mice in Group I was 12 +/- 3 (S.D.) days, whereas the mice in Group II whose tumors were treated with misonidazole, hyperthermia, and 2000 rads of X-rays survived 27 +/- 3 days. 5-bromodeoxyuridine per se had no effect on the survival of the experimental mice. Only a dose of 400 rads administered to the dbrB tumors permitted detailed evaluation of chromosomal analyses, whereas the larger doses of radiation caused cellular destruction. Simultaneous treatment with triple agents resulted in sister chromatid exchanges of 33.78 +/- 0.39/cell as compared with sister chromatid exchanges of 14.74 +/- 0.39/cell of untreated control tumors. This mode of treatment also induced various types of chromosomal abnormalities in the tumor cells.

Adenocarcinoma↗
PubMed1982

Thiamine responsive anaemia: a study of two further cases.

A brother and sister of Pakistani origin suffered from sensorineural deafness, diabetes mellitus and a macrocytic anaemia. Their bone marrows showed megaloblastic erythropoiesis and contained many ringed sideroblasts. Electron microscope studies of the bone marrow revealed (1) iron-laden mitochondria in many erythroblasts, (2) non-specific abnormalities indicative of dyserythropoiesis in some erythroblasts, and (3) evidence of ineffective erythropoiesis. The deoxyuridine suppression test indicated that the megaloblastic changes were not caused by an impairment of the methylation of deoxyuridylate. Studies of nucleic acid synthesis in the bone marrow cells showed that the rate of incorporation of [3H]thymidine into DNA was increased and that the rates of incorporation of [14C]glycine and [14C]adenine into both DNA and RNA were essentially within the normal range. The anaemia did not respond to therapy with hydroxocobalamin, folic acid or pyridoxine but responded to 25 mg thiamine, daily, by mouth. In one of the cases a post-thiamine marrow aspirate showed a considerable improvement in both the megaloblastic and sideroblastic changes.

Anemia, Macrocytic↗
PubMed1982

Effect of chemical stimuli on nerves supplying upper airway muscles.

Studies of upper airway resistance suggest that the activity of cranial nerves supplying upper airway muscles changes with chemical drive and that imbalances in the activation of these nerves as compared to the phrenic play a role in causing upper airway obstruction. We assessed the effect of hypoxia and hypercapnia on the activity of the hypoglossal nerve, the recurrent laryngeal nerve, and phrenic nerve in paralyzed anesthetized artificially ventilated dogs. Comparison of hypoglossal and phrenic nerves were also repeated after vagotomy. Both hypoglossal and recurrent laryngeal nerves exhibited increased activity with inspiration. Hypoxia and hypercapnia increased phrenic nerve activity as well as the activity of the two cranial nerves. While linear increases occurred in phrenic and recurrent laryngeal nerve activity with both chemical stimuli, the relationship between hypoglossal and phrenic nerve activity was curvilinear. At lower levels of chemical drive, changes in hypoglossal nerve were less than in the phrenic, and the reverse was true at higher levels of chemical stimulation. There were also differences in the response of both cranial nerves and the phrenic to changing vagal stimulation. The dissimilarities observed in the cranial response of the nerves (versus the phrenic) could potentially affect the forces developed during inspiration and lead to obstruction in the upper airway.

Airway Resistance↗
PubMed1982

Central and peripheral chemoreceptor inputs to phrenic and hypoglossal motoneurons.

We tested the hypothesis that phrenic and hypoglossal responses to progressive hypercapnia differ qualitatively because the CO2-related drive inputs to their respective motoneuron pools are different. The relative contributions of carotid sinus and central chemoreceptor inputs to hypoglossal and phrenic responses during hyperoxic hypercapnia were determined by comparing the two nerve activities during rebreathing runs done either before and after bilateral carotid sinus nerve (CSN) section, or without and with cooling of the intermediate, I(s), area on the ventral surface of the medulla. The studies were performed on chloralose-anesthetized, vagotomized, paralyzed cats. Cooling of the I(s) area impaired phrenic responsiveness to hypercapnia more than hypoglossal responsiveness, whereas CSN section had the opposite effect. Thus phrenic nerve response was more dependent on central chemoreceptor input than was the hypoglossal response, but hypoglossal response was more dependent on carotid sinus chemoreceptor input. We conclude that the phrenic and hypoglossal motoneuron pools each receive a different functional input from both the medullary and the carotid sinus chemoreceptors.

Action Potentials↗
PubMed1981

The effects of methadone on cortical and subcortical EEG in the rat.

(1) Administration of methadone in rats elicited high voltage, slow activity in the cerebral cortex and low voltage irregular waves in the hippocampus. Intravenous administration of methadone (0.2-0.5 mg/kg) markedly increased the threshold for cortical desynchronization by stimulation of the MRF. This increase by methadone was dose dependent. (2) Cortical desynchronization following mechanical stimulation of the tail or foot was blocked by methadone at a dose level of 0.5 mg/kg. At this dose level, the cortical desynchronizing threshold for MRF stimulation increased more than 8-fold whereas the threshold for MT and DH stimulations showed only small but measurable increases. A minimum dose of 0.5 mg/kg was needed to raise the threshold of these structures significantly (3) The increased threshold following injection of methadone was completely blocked by prior injection of the antagonist naloxone, indicating this response to be specific. Naloxone alone had no effect on electrical activity at any site. (4) The incidence of dissociation of the cortical response from the limbic system response after stimulation of the dorsal hypothalamus was approximately 4 times greater in methadone-treated than in untreated animals.

Animals↗
PubMed1981

Studies on hydrogen bonds. Part IV. Proposed working criteria for assessing qualitative strength of hydrogen bonds.

The data obtained in the earlier parts of this series for the donor and acceptor end parameters of N-H...O and O-H...O hydrogen bonds have been utilised to obtain a qualitative working criterion to classify the hydrogen bonds into three categories: "very good" (VG), "moderately good" (MG) and weak (W). The general distribution curves for all the four parameters are found to be nearly of the Gaussian type. Assuming that the VG hydrogen bonds lie between O and +/- 1 sigma, MG hydrogen bonds between +/- 1 sigma and +/- 2 sigma, W hydrogen bonds beyond +/- 2 sigma (where sigma is the standard deviation), suitable cut-off limits for classifying the hydrogen bonds in the three categories have been derived. These limits are used to get VG and MG ranges for the four parameters 1 and theta (at the donor end) and zeta and xi (at the acceptor end). The qualitative strength of a hydrogen bond is decided by the cumulative application of the criteria to all the four parameters. The criterion has been further applied to some practical examples in conformation studies such as alpha-helix and can be used for obtaining suitable location of hydrogen atoms to form good hydrogen bonds. An empirical approach to the energy of hydrogen bonds in the three categories has also been presented.

Chemical Phenomena↗
PubMed1981

Respiratory responses in reversible diaphragm paralysis.

The effects of diaphragm paralysis on respiratory activity were assessed in 13 anesthetized, spontaneously breathing dogs studied in the supine position. Transient diaphragmatic paralysis was induced by bilateral phrenic nerve cooling. Respiratory activity was assessed from measurements of ventilation and from the moving time averages of electrical activity recorded from the intercostal muscles and the central end of the fifth cervical root of the phrenic nerve. The degree of diaphragm paralysis was evaluated from changes in transdiaphragmatic pressure and reflected in rib cage and abdominal displacements. Animals were studied both before and after vagotomy breathing O2, 3.5% CO2 in O2, or 7% CO2 in O2. In dogs with intact vagi, both peak and rate of rise of phrenic and inspiratory intercostal electrical activity increased progressively as transdiaphragmatic pressure fell. Tidal volume decreased and breathing frequency increased as a result of a shortening in expiratory time. Inspiratory time and ventilation were unchanged by diaphragm paralysis. These findings were the same whether O2 or CO2 in O2 was breathed. After vagotomy, no significant change in phrenic or inspiratory intercostal activity occurred with diaphragm paralysis in spite of increased arterial CO2 partial pressure. Ventilation and tidal volume decreased significantly, and respiratory timing was unchanged. These results suggest that mechanisms mediated by the vagus nerves account for the compensatory increase in respiratory electrical activity during transient diaphragm paralysis. That inspiratory time is unchanged by diaphragm paralysis whereas the rate or rise of phrenic nerve activity increases suggest that reflexes other than the Hering-Breuer reflex contribute to the increased respiratory response.

Animals↗