Treatment of hypertonicity in muscles of lip retraction.

An EMG biofeedback program was developed for a 56-year-old Parkinsonism patient who exhibited pathological lip hypertonia and retraction. The program was designed to achieve the following goals: (1) to demonstrate a reduction in postural lip hypertonicity and (2) to demonstrate a reduction in lip hypertonicity during a series of increasingly complex speech activities. To achieve the first goal, contrastive tasks of full contraction and relaxation were utilized. Each posture was sustained while voltage measurements were made at specific intervals. Procedures to modify lip retraction during speech included five tasks in which the patient was to monitor the audio feedback signal. The tasks involved: prolongation of a neutral vowel, consonant-vowel combinations, monosyllabic words, sentences, and a paragraph-reading task. Data collected over six biofeedback sessions are presented. Trend analyses showed consistent muscular reduction within each task. The following explanations for the decrease in the patient's hypertonicity were discussed: (1) reduction of anisometric contraction, (2) reduction of isometric contraction, (3) relearning of agonistic-antagonistic muscle balance.     

Localization of neonatal secretory proteins in different cell types of the rat submandibular gland from embryogenesis to adulthood

In the neonatal rat submandibular gland, Type III cells contain a group of related proteins that we call the B1-immunoreactive proteins (B1-IP; 23.5, 26, and 27.5 kDa). Type I cells lack these, but synthesize a different protein, Protein C (89 kDa). With maturation of the gland, these neonatal cell types are no longer seen in the seromucous acini, which are no longer reactive for the B1-IP. Here, we report the ultrastructural immunocytochemical localization of the B1-IP and Protein C over the course of development. From their first appearance in the embryo, the B1-IP and Protein C are present in different cells which become morphologically typical Type I and III cells prior to birth. At all stages, Type I cells have strong Protein C labeling and no B1 labeling. By 3 days postpartum, ultrastructurally atypical Type III cells are seen (Type IIIP); these label for the B1-IP, but also show labeling with antibody to Protein C. In the next week, as mucous cells appear in the acini, these show both B1-IP and C labeling; the B1 marker is lost by 30 days postpartum, but adult mucous acinar cells continue to show Protein C reactivity. In view of the appearance of Protein C reactivity in neonatal Type IIIP and then in mucous cells, and the presence of B1 reactivity in early but not mature mucous cells, we suggest that Type III cells differentiate into mucous cells and that Type IIIP cells are intermediates in this transformation. We see no evidence for the differentiation of either Type III or mucous cells from Type I cells, although our data cannot rule out this possibility. In adult glands, cells with B1 labeling are seen in intercalated ducts. Cells that appear to be Type I cells are also present in these ducts and label for Protein C. Double labeling for B1-IP and Protein C demonstrated that the two markers were exclusively present in different cells within intercalated ducts. This is of considerable interest, as intercalated ducts have been reported to be the stem cell population for normal and trauma-induced cellular replacement.     

Role of phospholipase D-derived diradylglycerol in the activation of the human neutrophil respiratory burst oxidase. Inhibition by phosphatidic acid phosphohydrolase inhibitors.

An agonist-activated phospholipase D/phosphatidic acid phosphohydrolase (PAH) pathway was recently demonstrated in human neutrophils, and evidence suggests that phosphatidic acid (PA) and/or diradylglycerol (DG) generated from this pathway participates in activation of the O2(-)-generating respiratory burst. We have used a series of cationic amphiphilic compounds (sphingosine, propranolol, chlorpromazine, and desipramine) and antibiotics (clindamycin, trimethoprim, and roxithromycin) all of which inhibit the respiratory burst, to investigate the role of the phospholipase D/PAH pathway in neutrophil activation. The phosphatidylcholine (PC) pool in intact cells was first labeled using [3H]-1-O-alkyl-lysoPC; released [3H]-PA and [3H]-DG were then quantified after the addition of either chemo-attractant or PMA. Using either agonist, all compounds showed a dose-dependent inhibition of [3H]-DG generation which correlated with inhibition of O2- generation, but compounds failed to inhibit directly the NADPH oxidase in a cell-free system. For either activator, a plot of the ID50 values for O2- generation vs those for DG generation was linear over four orders of magnitude. In many cases, inhibition of [3H]-DG generation corresponded to an increase in [3H]-PA, implicating PAH as the locus of inhibition. Superoxide generation was inhibited under conditions where PA was either elevated or minimally affected. Neither O2- release nor DG generation showed any selectivity for stereoisomers of propranolol, suggesting that this inhibition does not act via a specific binding site on PAH. No evidence was obtained for an effect of the inhibitors on PA mobility as monitored by electron spin resonance studies of spin-labeled PA in a model membrane system. Data are consistent with an effect of the inhibitors at the level of the interaction of PAH with the membrane and/or its substrate. These data imply that DG produced via the phospholipase D/PAH pathway functions in the activation or maintenance of the respiratory burst.     

Investigation of thermotolerance in mouse testis

The effect of a two-fraction heat treatment on mouse testis has been assessed by measuring testis weight loss at 1 week after treatment. The rate of repair of 'sublethal' heat damage following the first treatment was dependent on the severity of the treatment. Using a primary treatment of 41.5 degrees C for 30 min, the weight loss following a test treatment of 41.5 degrees C for 30 min returned to that of the test treatment alone within an interval of 16-24 h. Using a milder primary treatment of 40.0 degrees C for 30 min, repair of sublethal heat damage appeared to be complete by 1-2 h. When a single test treatment was used, there was no evidence of heat-induced thermal resistance (thermotolerance) following primary treatments of 40.0 or 41.5 degrees C for 30 min, for periods up to 24 h between treatments. A small degree of thermotolerance could, however, be demonstrated following the most severe primary treatment used if full dose: effect curves were obtained. Thermotolerance, manifest as a decrease in slope, was maximal at approximately 4 h after the primary treatment. The results are discussed with reference to other normal tissue data.     

Physical and chemical characteristics of ephemeral pond habitats in the Maracaibo basin and Llanos region of Venezuela

Physical and chemical variables of ephemeral rainwaterpond habitats in the Maracaibo basin and Llanos regionof Venezuela were investigated to assess environmentalfeatures important for future studies of thephysiological ecology and bioenergetics of annualkillifish. Dissolved oxygen, temperature, pH, Eh, andconductivity measurements were made in the field ateach collection site. Water and filter samples werecollected and analyzed for trace metals, cations,anions, and osmolality. Physical and chemicalcharacteristics of rainwater ponds are highly variableboth temporally and spatially. Large diurnalfluctuations occur in temperature and dissolvedoxygen. Dissolved oxygen content, temperature, pH andconductivity values exhibit a high degree of interpoolvariation. All pools sampled have a high amount ofsuspended solids consistent with high turbidity. Poolsediments appear to be anoxic as indicated bymeasurement of Eh. Llanos region pools are dominatedby calcium as the major cation, while Maracaibo basinpools are dominated by sodium as the major cation. Maracaibo pools can be further separated into twodistinct regions, inland savanna and coastal desert,based on ionic composition. Annual killifishinhabiting ephemeral ponds may be exposed to extremesin dissolved oxygen concentration, temperature and pHvalues during adult, juvenile, and embryonic stages. This revised version was published online in July 2006 with corrections to the Cover Date.     

Overload-induced androgen receptor expression in the aged rat hindlimb receiving nandrolone decanoate.

This study's purpose was to examine whether functional overload with nandrolone decanoate (ND) administration increased muscle mass and steroid receptor concentration in aged rat soleus (Sol) and plantaris (Plan) muscle. ND (6 mg/kg body wt) was administered once a week for 4 wk, whereas control rats received sesame seed oil injections. Functional overload of the hindlimb Sol and Plan was induced by synergistic gastrocnemius muscle ablation at the beginning of the fourth week. Adult (5 mo of age) and aged rats (25 mo of age) were randomly assigned to four groups: control, overload, control-ND, and overload-ND. Seven days of functional overload increased adult Sol muscle mass 27%, whereas the aged Sol muscle mass did not change. The aged overloaded Sol muscle receiving ND significantly increased muscle weight by 35% and total muscle protein by 24%. Aged Plan muscle did not increase muscle weight with overload or ND treatment. Androgen receptor protein was induced by ND treatment and functional Ov, and combining the two treatments induced Sol androgen receptor protein concentration above either alone. Sol glucocorticoid receptor protein concentration increased in overload groups of both ages. ND administration can increase aged Sol muscle mass and protein content after 7 days of functional overload, and the cooperative induction of androgen receptor may be important for this response.     

Reactivities of an anti-CEA peptide monoclonal antibody.

Synthetic peptides representing different areas of the CEA molecule were used as immunogens for the development of anti-CEA antibodies. Both polyclonal and monoclonal antibodies were generated using peptides composed of CEA amino acid positions 99-128 and 585-613, respectively. One MAb, designated CP4, generated using the CEA peptide 99-128, was chosen for a more detailed analysis of reactivity. MAb CP4 reacts in solid phase RIAs with CEA peptide 99-128 immunogen and purified native CEA. CP4 did not react with purified non-specific cross reacting antigen (NCA), even though there were two single amino acid differences between NCA and CEA in the 29 amino acid peptide. The affinity constants of CP4 for the CEA peptide 99-128 and native CEA are 4.07 x 10(9) M-1 and 5.75 x 10(8) M-1, respectively. When CP4 was reacted with purified CEA in Western blotting experiments, the Mr 180,000 glycoprotein characteristic of CEA was detected, but CP4 reacted to various size entities in tumor cell extracts. The results of liquid competition RIAs showed that the epitope that MAb CP4 recognized on native CEA is not available for binding when CEA is in solution. Physical (adsorption to a solid matrix) or chemical (deglycosylation or formalin-fixation) alteration of CEA is required for binding of CP4 to CEA. MAb CP4 reacted approximately 1,000-fold greater to deglycosylated CEA than native CEA. Immunohistochemical studies using formalin-fixed paraffin-embedded tissue sections demonstrated that, among carcinomas, CP4 reacts selectively with colorectal carcinomas, while normal colon is negative. Although stomach carcinoma is negative, dysplastic lesions and areas of intestinal metaplasia are reactive. Two of 7 normal stomach tissues showed focal cytoplasmic reactivity of the surface epithelium. CP4, therefore, appears to react with an epitope with highly restricted expression in colorectal carcinoma. These studies demonstrate the complexities in dealing with an anti-peptide MAb with reactivity to an epitope which is accessible only under certain conditions.