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Biomedical subjects

J F Morris

Publications and source records attributed to J F Morris.

At least 145 records · Page 8Linked to original sources

Hyperprolactinemia induced by pituitary isografts suppresses the priming effect of LH-releasing hormone in normal and hypogonadal mice.

We have investigated the effects of hyperprolactinemia, produced by pituitary isografts under the kidney capsule (16-20 days), on the LH releasing action and priming effect of LH-releasing hormone (LHRH) in normal and hypogonadal (hpg) female mice. The pituitary grafts increased the plasma prolactin concentrations about 3-fold in normal intact mice and 4-fold in hpg mice. The extent of the graft-induced hyperprolactinemia was reduced by ovariectomy in normal mice, but was the same in grafted hpg compared with intact normal mice despite the absence in the hpg mice of functioning ovaries. The priming effect of LHRH could be elicited in both types of mice by giving two injections of LHRH separated by an interval of 60 min. Hyperprolactinemia did not reduce the amount of LH released in response to a first injection of LHRH, but did reduce significantly the amount of LH released (primed) in response to a second injection of LHRH. Ovariectomy significantly increased the magnitude of the releasing action of LHRH in normal mice and prevented the graft-induced reduction of LHRH priming. These results show that hyperprolactinemia in normal and hpg mice suppresses the magnitude of the priming effect of LHRH. This may be an important mechanism by which prolactin reduces gonadotropin secretion.

Animals↗

Comparison of lung volume measurements by single breath helium and multiple breath nitrogen equilibration methods in normal subjects and COPD patients.

The validity of the single breath helium dilution method for accurate measurement of the total lung capacity (TLC) was investigated. Comparison was made with the multiple breath nitrogen equilibration technique in 22 normal subjects and 37 patients with chronic obstructive pulmonary disease (COPD). The single breath method underestimated the TLC in all the normal individuals and 33 of 37 patients with COPD. Possible explanations for the falsely low lung volumes include uneven distribution of inspired air due to closing volumes and induced bronchoconstriction.

Adult↗

Effects of common therapeutic concentrations of oxygen on lung clearance of 99mTc DTPA and bronchoalveolar lavage albumin concentration.

We studied the effects of oxygen concentrations (21 to 50%) considered clinically "safe" on clearance of inhaled technetium-labeled diethylene triamine pentaacetate (99mTc DTPA) and the concentration of albumin in bronchoalveolar lavage (BAL) fluid of normal subjects. We also measured several markers of cell injury and inflammation in the BAL fluid including total and differential cell counts, lactate dehydrogenase, alkaline phosphatase, extracellular potassium, and several eicosanoids. Subjects inhaled oxygen (50, 40, 30, or 21%) for a mean of 45 h; there were no symptoms or bronchoscopic signs of oxygen toxicity. The concentration of albumin in BAL fluid was increased compared with baseline measurements in a dose-dependent manner in subjects exposed to 30% oxygen and above. Clearance of 99mTc DTPA was increased only in subjects who inhaled 50% oxygen. There were no significant changes in BAL fluid volume or total and differential cell counts after oxygen exposure. A trend towards an increased percentage of polymorphonuclear leukocytes was noted in the 50% oxygen group. We found no evidence of cell injury or inflammation in the BAL fluid. Supplemental humidity did not appear to influence the findings in the 50% oxygen group. Thus, oxygen in concentrations considered clinically "safe" increases clearance of 99mTc DTPA and BAL albumin concentration in normal subjects after a relatively short time of exposure.

Adult↗

Changes in the granule population of gonadotrophs of hypogonadal (hpg) and normal female mice associated with the priming effect of LH-releasing hormone in vitro.

Changes in the size and position of secretory granules in pituitary gonadotrophs have been studied in relationship to LH release and self-priming induced by LH-releasing hormone (LHRH) in pituitary glands from normal and hypogonadal (hpg) female mice. Hemipituitary glands were preincubated and then incubated for either 1 or 2 h in the absence or presence of LHRH (8.5 nmol/l). The glands were either processed for ultrastructural morphometry or homogenized for the determination of pituitary LH content. Morphometry was carried out on gonadotrophs identified by immunocytochemistry for LH beta using the thin/semi-thin section method. Pituitary LH content and the amount of LH released were determined by radioimmunoassay. The amount of LH released in response to the first and second hours of incubation with LHRH were similar in hpg and normal mice with a clear priming effect (three- to fourfold increase in pituitary responsiveness to LHRH) occurring in both strains. Despite a substantially reduced total number of granules (and amount of LH) in unstimulated hpg gonadotrophs, the number of granules in the outer 500 nm marginal zone of the cells was similar to that in normal mice. This could explain the similar amount of LH released from normal and hpg glands by the first LHRH challenge. The initial exposure to LHRH was also associated with a marked translocation of secretory granules from the central to the outer marginal region of cytoplasm subjacent to the gonadotroph plasmalemma, such that in 'primed' glands 60% of granules were found in this marginal zone compared with 40% (hpg) or 33% (normal) in unstimulated glands. The mean diameter of granules in the marginal zone was significantly less than that of granules in the central zone of the gonadotrophs of unstimulated glands from both normal and hpg animals. Exposure to LHRH for 1 h was associated with an increase in the number of small granules in the marginal zone and a significant decrease in the mean diameter of the gonadotroph granule population as a whole. After the primed release of LH, increased proportions of granules were still located in the marginal zone of gonadotrophs, indicating that granule migration continued during the second hour of exposure to LHRH in which primed release occurred. The primed release was associated with a detectable reduction in both the LH and granule content of gonadotrophs in normal, but not hpg glands.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Multiple injections of LH-releasing hormone into hypogonadal (hpg) mice induce the appearance of two morphologically distinct populations of gonadotrophs.

We have investigated the effects of multiple 2-hourly injections of LH-releasing hormone (LHRH) on the number and size of the gonadotrophs and gonadotroph secretory granules, and the lipid content of gonadotrophs in the pituitary glands of intact and gonadectomized male and female hypogonadal (hpg) mice. Gonadotrophs were identified by immunocytochemistry for LH beta, and the size and secretory status of the gonadotrophs were assessed by quantitative ultrastructural analysis of immunoidentified gonadotrophs. The administration of 60 ng LHRH by subcutaneous injection every 2 h for 15 days resulted in an increase in the number, size and granule content of LH beta-immunoidentified gonadotrophs of hpg mice to values found in normal adult mice. Large lipid droplets accumulated in 30-40% of the gonadotrophs in both male and female LHRH-treated hpg mice. Although lipid-containing gonadotrophs were larger than lipid-free cells in all LHRH-treated groups irrespective of the presence or absence of gonads, a marked difference in the number, position within the cell, and size of the secretory granules between the lipid-containing and lipid-free cells was found only in the pituitary glands of intact LHRH-treated hpg females. These results demonstrate: (a) that the effects of multiple injections of LHRH on the morphology of the gonadotrophs of hpg mice is not dependent on the presence of functioning gonads, although ovarian factors are required for the full development of morphological, and hence possibly functional, heterogeneity in the gonadotroph population in female animals, and (b) that, although multiple injections of LHRH in hpg mice are more effective than single daily injections of LHRH in stimulating pituitary-gonadal function, there is no obvious difference in the morphologically recognizable effects that these two modes of administration have on the pituitary gonadotrophs.

Animals↗

Effect of oral penicillin on pneumococcal carriage in elderly men with chronic bronchitis.

A double-blind, randomized, placebo-controlled trial was undertaken to evaluate the effect of penicillin on the pneumococcal carrier state of 32 men with chronic bronchitis. Treatment consisted of 250-mg phenoxymethyl penicillin or placebo tablets taken by mouth twice daily for periods of one to three years. Penicillin eradicated Streptococcus pneumoniae from the respiratory tracts of all carriers and prevented colonization with pneumococci for the duration of treatment, whereas placebo had no discernible effect on the carrier state (P = 0.0015). The conclusion is that daily penicillin orally in low doses eliminates pneumococci from the oropharynx of elderly patients with clinically stable chronic bronchitis.

Administration, Oral↗

Effects of water deprivation and deamino [8-D-arginine] vasopressin on [14C]2-deoxyglucose uptake by the hypothalamo-hypophysial system in mice with hereditary nephrogenic diabetes insipidus.

The effects of water deprivation and the injection of deamino [8-D-arginine] vasopressin (dDAVP) on the metabolic activity of the hypothalamo-neurohypophysial neurones of mice with inherited nephrogenic diabetes insipidus (DI +/+ Severe) have been investigated by quantitative autoradiography using the [14C]2-deoxyglucose (2-DG) technique. The relative metabolic activities (rma) of the paraventricular nuclei (PVN) and pars nervosa (PN) in severely diabetic mice were not significantly different from the rma of the PVN and PN in Non-severe or Normal mice, but the rma of the pars distalis (PD) was greater in the Severe mice than in the other two strains. Water deprivation (4-5 h) significantly increased the rma of the PVN and PN in Severe mice compared with those in Non-severe mice that had been similarly deprived of water. The increased rma of the PVN and PN produced by water deprivation in Severe mice was not reduced to normal by injection of dDAVP. The injection of dDAVP alone had no effect on the rma of the PVN or PN, but dDAVP injection alone, water deprivation alone, or both treatments combined decreased the rma of the PD in Severe mice. Neither the supraoptic nuclei (SON) nor any of the other 19 brain areas studied were affected, in terms of rma, by either water deprivation, injection of dDAVP, or both.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Granule populations in oxytocin and abnormal perikarya of the supraoptic nucleus of homozygous Brattleboro rats: effects of colchicine administration.

Magnocellular neurones in the supraoptic nucleus of the homozygous Brattleboro rat, which are unable to produce vasopressin, were investigated by immunocytochemistry to identify both the oxytocin cells and the abnormal neurones, which in normal animals would produce vasopressin. The abnormal cell profiles were significantly more rounded than those of the oxytocin cells. Both cell types showed evidence of hyperactivity, but the Golgi apparatus was more extensive in the oxytocin cells, probably as a result of the failure of the abnormal cells to produce vasopressin and its neurophysin and the resultant reduction in hormone packaging. Neurosecretory granules (NSG) 160 nm in diameter were found in the oxytocin perikarya but were absent from the abnormal cell bodies. In addition, a population of small dense granules (SDG) 100 nm in diameter was observed in both types of neurone, in numbers equal to the NSG in oxytocin cells. Injection of a low, non-lethal dose of the axonal transport inhibitor colchicine resulted in a rapid and equal accumulation of both NSG and SDG in oxytocin perikarya and of SDG in the abnormal perikarya after one day. The effects of colchicine were reversed 2-3 days after administration. The SDG, which may contain a co-transmitter or co-hormone substance, are thus produced at a similar rate to NSG, and appear to be transported from the perikarya for subsequent release at the nerve endings.

Animals↗

Spirometric "lung age" estimation for motivating smoking cessation.

Motivation for smoking cessation benefits from physician counseling. To further improve this educational process, spirometry can demonstrate ventilatory impairment to the smoker. In addition to comparing a person's spirometric results with predicted reference values for normal subjects, estimation of "lung age" can be used to demonstrate the effects of cigarette smoking. Equations were developed from reference linear regression equations permitting lung age estimation in terms of ventilatory function. This age can then be compared with the individual's chronological lung age. Normal and abnormal groups determined by a respiratory health questionnaire and pulmonary function testing were used to compare the value of single and combination spirometric tests. The forced expiratory volume at 1 sec proved superior to any other single test or combination for best separation of the two groups and had the lowest standard error for estimated lung age. Both spirometry and estimated lung age calculation may be useful for motivating cessation of cigarette smoking.

Adult↗

Enteroglucagon cell hyperfunction in rat small intestine after gut resection.

The ultrastructural characteristics of immunoreactive enteroglucagon cells from three groups of experimental rat models (i.e., massive small bowel resection alone, massive small bowel resection with bombesin infusion, and transection with bombesin infusion) have been investigated. The results show that the cells did not undergo significant change in size or in the area of cytoplasm. All three groups displayed highly significant decreases of between 200% and 400% in the area of cytoplasm occupied by the secretory granules (expressed as volume density) and highly significant increases between 150% and 200% in the area occupied by the rough endoplasmic reticulum. Significant decreases (7%-10%) in secretory granule diameter were found in the two bombesin-treated groups, whereas resection alone was without significant effect on granule size. These results indicate that the enteroglucagon cells in these three groups are in a hyperfunctional state.

Animals↗

Lack of intramembranous particle clusters in collecting ducts of mice with nephrogenic diabetes insipidus.

We suggested previously, on the basis of indirect evidence, that in two strains of mice with nephrogenic defects of urinary concentration the deficiency arose from an inadequate rise in water permeability of the collecting duct system. In this study we tested the question further by assuming that the frequency of intramembranous particle (IMP) clusters seen by freeze-fracture can be used as a morphological marker of vasopressin-induced water permeability. Three genotypes of mice were studied: 1) DI +/+ Severe, with florid, vasopressin-resistant diabetes insipidus; 2) DI +/+ Nonsevere, with an intermediate deficiency of urinary concentration; and 3) normal, VII +/+ mice. In addition, we examined a group of DI +/+ Severe mice that had been injected with exogenous 1-desamino-8-D-arginine vasopressin (DDAVP) subcutaneously for 3 days. Since the results in this group did not differ from those in untreated DI +/+ Severe mice, all data for this genotype were combined. IMP clusters within luminal membranes of inner medullary collecting duct principal cells were quantified by freeze-fracture electron microscopy. Urinary osmolality and percentage of cells showing clusters were, respectively: 203 +/- 43 mosmol/kg H2O and 0% in DI +/+ Severe mice; 1,133 +/- 86 and 33 +/- 4 in DI +/+ Nonsevere mice; and 2,234 +/- 190 and 52 +/- 5 in VII +/+ animals. With the exception of one animal, there was no overlap of the data, which were significantly different from one another for each variable. We conclude that in DI +/+ Severe mice, both endogenous and exogenous vasopressin are unable to increase the water permeability of medullary collecting ducts.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The role of microfilaments in the priming effect of LH-releasing hormone: an ultrastructural study using cytochalasin B.

We have investigated the possibility that microfilaments are involved in the priming effect of LH-releasing hormone (LHRH) by ultrastructural morphometry of hemipituitary glands from adult female mice. Glands incubated for 2 consecutive hours with 8.5 nmol LHRH/l responded with a marked increase in the amount of LH released into the medium during the second hour compared with the first hour of incubation. This priming effect of LHRH on LH secretion was accompanied by a significant margination of secretory granules and a drop in the total granule content of the gonadotrophs. Although the number of microfilaments remained the same, there was an increase in their length and a change in orientation so that the angle between the microfilaments and the plasmalemma was significantly reduced after both the first and second hour of exposure of LHRH. The addition of 14.3 mumol cytochalasin B/1 to the incubation medium significantly increased the amount of LH released in the first hour of incubation when compared with the amount of LH released by LHRH alone, but completely abolished the priming effect of LHRH. Cytochalasin B also prevented the LHRH-induced increase in the length and the change in orientation of the microfilaments. These results indicate that LHRH priming involves an increase in length of microfilaments and a change in their orientation relative to the plasmalemma.

Animals↗

Methods and prognostic value of bone marrow examination in small cell carcinoma of the lung.

The technique and predictive value for survival of initial and restaging bone marrow examinations in small cell carcinoma (SCC) of the lung were evaluated by 76 examinations of 72 patients. In 76 examinations, only 2 (2.6%) of the bilateral iliac crest bone marrow examinations revealed tumor cells unilaterally and these two were restaging examinations. If SCC was found in the marrow, bone marrow biopsy was always positive. In no instance was an aspirate positive with a negative bone marrow biopsy. Thus a unilateral bone marrow biopsy is an adequate technique for the initial staging of the bone marrow in SCC of the lung. Survival of patients with or without positive initial bone marrow examinations was not significantly different.

Biopsy, Needle↗

Method for quantitating the molecular content of a subcellular organelle: hormone and neurophysin content of newly formed and aged neurosecretory granules.

A method is described for the quantitative determination of the content of subcellular organelles such as secretory granules. Purified subcellular fractions of the organelle are prepared and aliquots are assayed for hormones, for example. To determine the number of organelles per fraction, known numbers of latex particles of a size similar to the organelle are added to other aliquots of the subcellular fractions. Latex particles and organelles are then pelleted together by centrifugation. The ratio between latex particles and organelles can be determined by morphometric analysis of ultrathin sections taken through the full thickness of the pellet. The number of organelles and hence their content of the substance assayed can then be calculated. We have applied this technique to posterior pituitary neurosecretory granules, the content of which has already been estimated by a different method. Newly formed neurosecretory granules from oxen and rats were found to have a content of approximately equal to 85,000 molecules of hormone and neurophysin. Aged neurosecretory granules from the same neural lobes appeared to contain less hormone and neurophysin, but this was shown to be the result of loss of material from the granules during isolation in media of 360 mosM. Such loss could be prevented by isolation in hypertonic (660 mosM) media.

Animals↗

Hemophilus influenzae biotypes and chronic bronchitis.

Hemophilus influenzae can be differentiated into 6 biotypes on the basis of 3 biochemical reactions. This study was undertaken to determine the biotypes of respiratory isolates from an adult population with chronic bronchitis and to compare the biotypes of upper and lower respiratory tract isolates of individual patients. For rapid biotyping of serologically nontypable H. influenzae, we used 2 commercially prepared kits (Minitek and IDS RapID Systems). Twenty-three of 29 isolates (79%) had biochemical characteristics of biotype II with the Minitek system. Eighteen of the same 29 isolates were retested with the IDS RapID System and reacted as biotype II organisms. Seven of 9 and 4 of 4 paired transtracheal/oropharyngeal samples had identical biotypes when tested with the Minitek and IDS RapID System, respectively. These findings suggest that H. influenzae organisms are exchanged between the oropharynx and tracheobronchial tree of elderly male patients with chronic bronchitis.

Bronchitis↗