Autoradiographic analysis of second messenger and neurotransmitter system receptors in the gerbil hippocampus following transient forebrain ischemia.

Changes in second messenger and neurotransmitter system receptor ligand binding induced by transient forebrain ischemia were studied in the gerbil hippocampus. The animals were allowed variable periods of recovery ranging from 2 h to 7 days after 5-min bilateral carotid artery occlusion. The binding of second messenger systems ([3H]inositol 1,4,5-trisphosphate ([3H]IP3)to inositol 1,4,5-triphosphate, [3H]forskolin to adenylate cyclase and [3H]phorbol 12,13-dibutylate to protein kinase C) and neurotransmitter receptor systems ([3H]PN200-110 to L-type calcium channels. [3H]N6-cyclohexyl-adenosine to adenosine A1 and [3H]quinuclidinyl benzilate to muscarinic cholinergic receptor) were assayed using quantitative autoradiography. In the CA1 subfield, 2 h after ischemia, [3H]IP3, [3H]forskolin, and [3H]quinuclidinyl benzilate binding activities significantly decreased by 25, 17 and 13%, respectively, though no morphological abnormalities were obvious. Six hours after ischemia, the [3H]phorbol 12,13-dibutylate binding activity in the stratum oriens of the CA1 subfield increased by 15%. One day after ischemia, [3H]PN200-110 binding activity in this subfield decreased by 26%, and 7 days after ischemia, [3H]phorbol 12,13-dibutylate and [3H]N6-cyclohexyl-adenosine receptor binding activities decreased in this subfield. In particular, at 7 days after ischemia, [3H]IP3 binding activity in the CA1 subfield showed a complete decline. In the CA3 subfield, [3H]PN200-110 binding activity decreased 2 days after ischemia, and [3H]IP3 and [3H]N6-cyclohexyl-adenosine binding activities decreased 7 days after ischemia. In the dentate gyrus, the structure of which remained histologically intact after ischemic insult, [3H]IP3 and [3H]forskolin binding activities decreased 7 days after ischemia. In contrast, the [3H]phorbol 12,13-dibutylate binding activity increased in the molecular layer of the dentate gyrus 7 days after ischemia. These results indicate that marked alteration of intracellular signal transduction precedes neuronal damage in the hippocampal CA1 subfield and that the histologically intact CA3 and dentate gyrus also shows modulated neuronal transmission after ischemia.     

Age- and sex-related differences in the nerve growth factor distribution in the rat brain.

Levels of the nerve growth factor (NGF) have been measured in various brain regions of young and aged male and female rats of Wistar strain by means of a highly sensitive two-site enzyme immunoassay system for beta-NGF. Among the ten regions examined, the amount of NGF per wet weight of tissue was found to be highest in the hippocampus, irrespective of the sex and age. The NGF concentration in the hippocampus of female rats at 3 months of age was comparable to that of same aged males. Further, there was no significant difference in the NGF levels of the hippocampus between young and age males. However, the NGF level was significantly lower in aged females as compared to that in 3- or 4-month-old females, and hence the marked male-female difference was found in the NGF levels in aged Wistar rats.     

Qualitative abnormalities of choline acetyltransferase in Alzheimer type dementia

The maximum activity of choline acetyltransferase (ChAT), the affinity for choline or acetyl-CoA and the isozyme pattern in the cerebral cortex of 5 cases of Alzheimer type dementia (ATD) and 6 age-matched control subjects were examined post-mortem. Maximum activities of ChAT were estimated in 5 cerebral cortical areas of Brodmann: 4, 7, 10, 17 and 22. A significant reduction in maximum activities of ChAT was found in all cortical areas for the cases of ATD. The affinity for choline or acetyl-CoA was measured in the frontal cortex (Brodmann's areas 4 and 6) and in the temporal cortex (Brodmann's areas 21 and 22). The affinity was significantly decreased in both cortices of demented patients. A significant correlation was observed between maximum activity of ChAT and the affinity for choline or acetyl-CoA. The isozyme pattern obtained by column chromatography on Sephadex G-200 was similar to that obtained by centrifugation on a sucrose density gradient. The isozyme pattern of ATD was different from that of the control subjects. These results suggest qualitative as well as quantitative abnormalities in the ChAT in autopsied brains of ATD.     

Cancer of remnant stomach following gastric surgery for benign conditions

Eighteen patients received gastrectomy for primary cancer of the gastric remnant were studied clinico-histopathologically. Gastric ulcer had been the most common condition requiring previous gastric surgery, and Billroth II resection had been the most often employed procedure. The cancer of the gastric remnant was in an advanced stage in all patients. Tumors were detected in the sutured or anastomosed region (especially the latter) of the remnant stomach in a great majority of the patients studied. In spite of combined resection of the adjacent organs, such as spleen, pancreas and colon in most patients, curative resection could be done in only a half of them and the prognosis was poor in general. These observations seem to stress the importance of following up gastrectomized patients periodically and precautiously by endoscopic examination with multiple biopsy, because early detection of cancer of remnant stomach may lead to improvements in therapeutic results.     

Protective effects of serotonin reuptake inhibitors, citalopram and clomipramine, against hippocampal CA1 neuronal damage following transient ischemia in the gerbil

To clarify the role of serotonin in cerebral ischemia, we examined the effects of selective serotonin reuptake inhibitors, citalopram and clomipramine, on ischemic neuronal damage in the gerbil. Pretreatment with citalopram (40 mg/kg i.p.) and clomipramine (20 mg/kg i.p.) protected against neuronal destruction of hippocampal CA1 pyramidal cells following 5 min of forebrain ischemia. Furthermore, microdialysis assays showed that a striking increase in extracellular excitatory amino acid levels during ischemia was significantly inhibited by pretreatment with citalopram and clomipramine. However, citalopram (40 mg/kg i.p.) did not alter the extracellular amino acid concentrations in normal gerbils. Thus, serotonin reuptake inhibitors have a protective effect against ischemic neuronal damage. Furthermore, the present result suggests that the protective effect is mediated through prevention of the accumulation of extracellular excitatory amino acids during and after ischemia.     

Prospective study of serum cholesterol and site-specific cancers.

From 1965 to 1968, 7716 Japanese-American men were examined and tested for serum cholesterol. After 22 years, 1380 incident cancer cases were identified. Of the site-specific cancers, only colon cancer cases had a significantly lower mean serum cholesterol value than that of noncases (213.0 mg/dl vs 219.0 mg/dl). When the study subjects were separated into either a low, middle or high group, based on their serum cholesterol values, there was a significant inverse trend for cases of oral/pharyngeal/esophageal cancer combined. The association was present for cases diagnosed within 10 years of examination (p = 0.012), but not for cases diagnosed after 10 years. This suggests that the inverse association is due to the metabolic effects of undiagnosed oral/pharyngeal/esophageal cancer upon serum cholesterol levels. These results are discussed in relation to other studies on serum cholesterol.     

The difference between response of nasal mucosa to specific antigen and non-specific stimulation

To examine the difference between response of nasal mucosa to specific antigen and that to non-specific stimulus in the same patient, specific nasal provocation was performed using the house dust antigen disk while nasal respiratory resistance was continuously measured by Rhinograph. On the other hand, non-specific nasal provocation was performed with inhalation of methacholine while nasal respiratory resistance was continuously measured with Astograph. Thereafter the resulting response curves were analyzed. Subjects were 12 males and 9 females, who had nasal obstruction, watery rhinorrhoea and sneeze, and were proved to have allergic rhinitis by house dust. To analyze specific response curve, primary nasal respiratory resistance (Rrs.N), reacting time (Ta) and slope signifying increase of nasal respiratory resistance (delta Rrs.N) were used as parameters. To analyze non-specific response curve, primary nasal respiratory resistance (Rrs.N.cont), minimum dose of methacholine that caused an increase of nasal respiratory resistance (Dmin.N) and slope signifying increase of nasal respiratory resistance (Sd.N) were used as parameters. Ta and Dmin.N reflect sensitivity of nasal mucosa. Their values become smaller, it means sensitivity of nasal mucosa becomes higher. Delta Rrs.N and Sd.N reflect reactivity of nasal mucosa. Their values become larger, it means reactivity of nasal mucosa becomes larger.(ABSTRACT TRUNCATED AT 250 WORDS)     

Growth after bone marrow transplantation in children.

Growth of the patients with hematological malignancies, aplastic anemia, Fanconi's anemia, and Wiscott-Aldrich syndrome who had been treated with bone marrow transplantation (BMT) was studied. Fourteen out of 21 patients showed suppression of linear growth after BMT. Recovery of the growth velocity after 1-2 years tended to occur if BMT was performed at younger age. Six of eight patients with chronic graft-versus-host-disease (CGVHD) had impaired growth after BMT, whereas eight of 13 (61%) without CGVHD did. Provocative tests for growth hormone (GH) performed 5-72 months after BMT revealed three boys who showed poor response to more than two different stimuli. Two of these three boys had prolonged suppression of growth. Neither the age at BMT, difference in disease, nor presence of posttransplant growth retardation gave significant difference in the response of GH to provocative tests. It was concluded that approximately two-thirds of marrow-grafted children experienced transient decrease in growth velocity after BMT.     

Clinical statistics on inpatients admitted to the Department of Urology, Hyogo Prefectural Hospital Nishinomiya during 20 years from 1972 to 1991]

A statistic analysis was carried out on the 4,956 inpatients admitted to our Department of Urology from April 1972 to December 1991. The patients included 3,399 males and 1,557 females. A total of 4,105 operations including 255 renal allotransplantations were performed on 3,590 patients. Open surgery for upper urinary tract stones has been replaced by extracorporeal shock-wave lithotripsy (ESWL) in the last three years.