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Biomedical subjects

J Langer

Publications and source records attributed to J Langer.

At least 19 recordsLinked to original sources

Impaired acetylcholine release in the inflamed rat intestine is T cell independent.

We investigated mechanisms underlying the suppression of [3H]acetylcholine ([3H]ACh) release from myenteric plexus-longitudinal muscle preparations of rats infected 6 days previously with Trichinella spiralis. There was a 73% suppression of KCl-evoked release of [3H]ACh in the jejunum, and a 76% suppression was observed in the worm-free ileum, indicating that the local presence of the parasite in the lumen is not prerequisite for the suppression of ACh release from the myenteric plexus. Treatment of rats with betamethasone (3 mg.kg-1.day-1 ip) during the infection prevented the acute inflammatory response and attenuated the suppression of [3H]-ACh release (from 73 to 22%) in the jejunum of infected rats. This finding is consistent with the hypothesis that the suppression of ACh release occurs as a result of the inflammatory process. Marked suppression of [3H]ACh release was also seen in T. spiralis-infected nude athymic rats, which were shown to lack functioning T lymphocytes. Thus changes in ACh release are not dependent on T lymphocytes. Taken in conjunction with our previously published study showing that altered muscle function in this model is T cell dependent, the results of the present study indicate that different components of the inflammatory response mediate changes in smooth muscle and myenteric nerves in the T.spiralis infected rat.

Acetylcholine

[Endoscopic cytodiagnosis of the pancreas and bile ducts].

During the last twelve years we made in 3868 cases cytological investigations of the pancreatic and bile duct systems. The techniques for endoscopic cell collection and microscopic observation are demonstrated. Cellular material consists of epithelia, inflammatory cells and tumor cells. Their cytological details are described. Of primary importance are the differentiations of the epithelial cells in cases of chronic cholangitis and pancreatitis from tumor cells. We found 211 cases with proven malignant tumors of the papilla, the pancreas or the bile ducts. In 81.5% of these cases a significant cellular material could be collected with 59.3% tumor cell diagnoses. No false-positive tumor cell diagnosis was found (n = 3657). A comparison with preoperative bioptic histology was possible only in the papilla region. Here, the sensitivity of histology was 60% compared to 86% sensitivity of cytology. We conclude that the cytodiagnosis of the papilla, the pancreas and the bile duct by means of endoscopic techniques can be done routinely in order to obtain a preoperative diagnosis of inflammatory as well as malignant cellular findings in these organs.

Aged

The ontogeny of feline temporal lobe epilepsy: kindling a spontaneous seizure disorder in kittens.

We describe the ontogeny of feline temporal lobe epilepsy after amygdala kindling in 24 cats, aged 2.5 months to over 1 year. In so doing, we report the first experimental model of spontaneous epilepsy in immature animals. Preadolescent kittens (n = 12 less than or equal to 6.5 months) are far more likely to develop epilepsy, indexed by spontaneous seizures, than are adult cats (n = 12 greater than 1 year). Moreover, youth accelerated the development of epilepsy. The younger the kitten at the beginning of kindling, the more probable and rapid the onset of spontaneous seizures. Failed postictal depression was the most reliable precursor of spontaneous seizures in immature cats. However, spontaneous epilepsy continued after postictal refractory periods stabilized and was still present when kittens matured to adulthood. Collectively, the results suggest that failed inhibition contributes to the onset of spontaneous epilepsy in immature animals but that other morphologic, physiological and/or chemical changes might sustain epilepsy afterwards.

Aging

Altered smooth muscle function in worm-free gut regions of Trichinella-infected rats.

We have extended a recent study demonstrating increased contractility of jejunal smooth muscle of rats infected with the nematode parasite Trichinella spiralis, the primary habitat of which is the jejunum. In this study, muscle from the worm-free ileum of infected rats showed decreased contractility compared with control, illustrating regional differences in muscle responses to the infection. However, in jejunal muscle from worm-free segments that had been excluded from the rest of the gut before the infection, we observed increased tension generation, suggesting a systemic mechanism. To evaluate whether the changes in jejunal muscle were due to the host's inflammatory reaction, the effect of beta-methasone was examined. In a dose of 3.0 mg/kg sc daily, the steroid abolished the increase in myeloperoxidase activity associated with the infection and attenuated the increased tension generation in jejunal muscle from Trichinella-infected rats. These results support the hypothesis that alterations in intestinal smooth muscle function in this model do not require the presence of the parasite in the lumen and are mediated by the host's inflammatory reaction.

Animals

Radiation therapy of esophageal carcinoma: correlation of clinical and radiographic findings.

Seventeen patients with esophageal carcinoma treated by radiation therapy (RT) at our hospital between 1981 and 1984 had initial diagnostic esophagrams and 1 or more repeat esophagrams after completing RT. Total regression of the tumor was observed radiographically in 10 patients (59%) with a normal esophagus (24%) or benign-appearing residual stricture (35%) at the site of the previous lesion. Partial regression was observed in 4 patients, and progression of the tumor in 3. No correlation was found between the size, stage, or morphology of the lesion and its response to therapy. Although local recurrences were relatively uncommon, patient survival was often limited by the development of distant metastases. Fourteen of 15 patients with clinical follow-up initially had significant relief from dysphagia as the tumor regressed. However, 9 of those patients had recurrent or increased dysphagia over a subsequent 3-9-month period. Exacerbation of symptoms did not necessarily indicate recurrent carcinoma; it also resulted from benign radiation strictures, opportunistic esophagitis, or other complications of RT detected on esophagography.

Aged

[Incidence and significance of the gastric mucosal constellation in pernicious anemia].

1977 cases with gastric complains but without localized findings like ulcer or cancer were investigated by gastroscopy with biopsies of corpus and antrum ventriculi. We found in 5.5% an isolated mucosal atrophy of the gastric corpus (mean age 67.2 years compared to 59.4 years in cases with normal mucosa). 0.7% showed an atrophic gastritis of the antral mucosa, 0.9% an atrophic gastritis of the body and the antrum. Most of the cases with an isolated atrophy of the gastric body gave findings of hematologic disturbances. In all cases with isolated atrophy of the gastric body, including localized findings in the stomach, we found in 10.8% neoplastic processes, in another 3.9% hyperplasiogenic polyps. It seems to us of clinical importance to evaluate the gastric histology of the antral and body mucosa routinely because of the high incidence of pernicious anemia-like gastric atrophy and its relation to gastric neoplasias.

Adult

Regulation of insulin secretion by energy metabolism in pancreatic B-cell mitochondria. Studies with a non-metabolizable leucine analogue.

In mouse pancreatic islets the kinetics of insulin secretion and O2 uptake in response to the non-metabolizable leucine analogue (+/-)-BCH (2-endo- aminonorbornane -2-carboxylic acid) were compared. In addition, the fuel-mobilizing effect of (+/-)-BCH was studied with a mitochondrial fraction from islets. (1) Within 2 min 20 mM-(+/-)-BCH markedly enhanced insulin release or O2 consumption by islets respiring in the absence of exogenous fuels. During prolonged exposure to 20 mM-(+/-)-BCH secretion declined more rapidly than O2 uptake. (2) L-Glutamine (10 mM) prevented the decrease of both insulin release and O2 uptake of islets exposed to 20mM-(+/-)-BCH. During the second phase of insulin release in response to 20 mM-(+/-)-BCH + 10 mM-L-glutamine, kinetics of secretion and respiration correlated closely. (3) Initial peaks were consistently seen in the (+/-)-BCH-induced secretory profiles, but never in the respiratory profiles. (4) In contrast with L-glycerol 3-phosphate, L-malate or pyruvate, L-glutamine or L-glutamate maintained low rates of oxidative phosphorylation in B-cell mitochondria. The effects of L-glutamine or L-glutamate were potentiated severalfold by (+/-)-BCH. (5) The effects of other branched-chain amino acids on oxidative phosphorylation resembled their effects on insulin release, redox state of nicotinamide nucleotides and glutamate dehydrogenase activity. (6) The results support the view that (+/-)-BCH stimulates insulin secretion via a primary enhancement of hydrogen supply to the respiratory chain of B-cell mitochondria.

Adenosine Triphosphate

Effects of alpha-adrenoceptor antagonists on clonidine-induced inhibition of insulin secretion by isolated pancreatic islets.

The effects of clonidine, yohimbine, corynanthine and prazosin on glucose-induced insulin secretion by incubated or perifused mouse pancreatic islets were investigated. Clonidine (0.1 microM) inhibited glucose-induced insulin secretion alone and in the presence of yohimbine (0.1 microM), corynanthine (10 microM) or prazosin (1 microM). In higher concentrations, yohimbine (1-10 microM) antagonized the inhibitory effect of clonidine (0.1 microM) upon glucose-induced insulin secretion by incubated islets and by perifused islets. The results support the view that adrenergic inhibition of insulin secretion is mediated by alpha 2-adrenoceptors on pancreatic beta-cells.

Adrenergic alpha-Antagonists

The effect of radiofrequency hyperthermia and chemotherapy upon human neoplasms when used with adjuvant metronidazole.

It appears that metronidazole causes an increase in tumor core temperature above that achieved with RFHT alone, by an as yet undetermined mechanism. Furthermore, radiofrequency hyperthermia, in combination with chemotherapy, can produce objective evidence of tumor repression in 30 to 50 per cent of the patients with metastatic cancer. These results justify proceeding to a randomized prospective trial of RFHT and chemotherapy in specific human neoplasms. Such a study is currently being undertaken at this center.

Adult

Mechanism of 3-phenylpyruvate-induced insulin release from isolated pancreatic islets.

3-Phenylpyruvate evoked a monophasic insulin release from perifused mouse islets. L-Phenylalanine was not an insulin secretagogue and was oxidized by islets at a very low rate, suggesting that 3-phenylpyruvate does not trigger insulin release by enhancing production of reducing equivalents. Moreover, allosteric activation of glutamate dehydrogenase does not play a role in 3-phenylpyruvate-induced insulin secretion.

Amino Acids

Eccrine sweat glands are not innervated in hereditary sensory neuropathy type IV. An electron-microscopic study.

The ultrastructural study of a skin biopsy in a patient afflicted with hereditary sensory neuropathy type IV (congenital insensitivity to pain with anhidrosis) did not reveal any unmyelinated axons or axonal terminals around eccrine sweat glands but only processes, partially covered by a basement membrane and therefore resembling Schwann cell processes. The absence of such unmyelinated axons in close proximity to eccrine sweat glands where they normally occur appears to be the morphological equivalent to the anhidrosis and also corresponds to the deficiency of unmyelinated axons in the sural nerve of the same patient, as previously reported.

Basement Membrane

Effect of haloperidol on reflex activation of rat alpha-motoneurones. A possible explanation for akinesia and catalepsy?

Effects of haloperidol on rat flexor and extensor alpha-motoneurones were studied in ventral roots of laminectomized rats under halothane anesthesia. The alpha-motoneurones were activated by tetanic stimulation of low-threshold afferents (group I and II), either of the ipsilateral peroneal nerve ("flexor alpha-motoneurones") or gastrocnemius-soleus nerve ("extensor alpha-motoneurones"). Haloperidol, given in the doses of 0.075, 0.15 and 0.30 mg/kg i.p. inhibited the reflex activation of flexor alpha-motoneurones; higher doses seemed to be more effective than lower ones. Apomorphine (2 mg/kg s.c.) partially antagonized the inhibitory action of haloperidol with some latency. Higher doses of haloperidol (0.15-0.60 mg/kg i.p.) also inhibited the reflex activation of extensor alpha-motoneurones; this inhibitory effect was, at least for a short time, antagonized by apomorphine (2 mg/kg s.c.). The threshold for reflex activation both of flexor and extensor alpha-motoneurones was raised by haloperidol and lowered by a subsequent administration of apomorphine. Our results suggest that akinesia and catalepsy, induced in rats by haloperidol might be, at least in part, due to a decrease in sensitivity of alpha-motoneurones to proprioceptive stimuli.

Animals