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Biomedical subjects

H K Hsu

Publications and source records attributed to H K Hsu.

At least 19 recordsLinked to original sources

[Kinetic studies of protein kinase A in rat liver during late sepsis].

The covalent modification of receptor proteins via phosphorylation and dephosphorylation is one of the principal mechanisms controlling carbohydrate metabolism and is known to be regulated by various protein kinases. Recent studies indicated that many hormones may exert their effects on cellular metabolism by regulating intracellular c-AMP levels and by activating a c-AMP dependent protein kinase, i.e., protein kinase A. The metabolic disturbances during sepsis are characterized by an initial hyperglycemia followed by a progressive hypoglycemia and a depletion of hepatic glycogen content. The latter is coupled with a slowdown in glycogenesis, an accelerated glycogenolysis, and a depression in gluconeogenesis in the liver. Since the liver is the major organ that regulates the homeostatic level of blood glucose, it is conceivable that the sepsis-induced glucose dyshomeostasis might be mediated by changes in protein kinase activity and the kinetic characteristics of enzymes. The present experiment was designed to study the correlation between protein kinase A and the pathophysiology of hepatic glucose dyshomeostasis during sepsis. Sepsis was induced in rats by cecal ligation and puncture (CLP). Late sepsis occurred 18 hours after CLP. Protein kinase A was extracted from the rat livers by acid precipitation and ammonium sulfate fractionation, and then partially purified by DEAE-cellulose. The results show that in the late sepsis, type-I protein kinase A (eluted at low ionic strength) activity was significantly decreased by 34-52% (P < 0.01). The kinetic parameters such as Vmax's for ATP, histone, and c-AMP were also significantly decreased from the control values of 6.1 +/- 0.9, 5.4 +/- 0.8, and 5.1 +/- 1.9 nmoles/mg.min. to 3.6 +/- 0.5, 2.8 +/- 0.3, and 2.5 +/- 0.5 nmoles/mg.min., respectively. Analysis using Hill's equation indicates that the S0.5 and n (Hill coefficient) values of the various substrates and activators for type-I protein kinase A remained unchanged. In the case of type-II protein kinase A (eluted at high ionic strength), the Vmax, S0.5, and n values for ATP, histone, and c-AMP were unchanged during late sepsis. The results of the present study indicate that the activities and kinetic characteristics of type I protein kinase A in rat liver are modified during late sepsis. Since protein kinase A is known to regulate glucose metabolism through adrenergic receptor mediation, these findings may have a pathophysiological significance in the understanding of hepatic glucose dyshomeostasis during sepsis.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Improvement of sexual behavior in aged rats by p-chlorophenylalanine and methysergide.

The effects of methysergide, a serotonin antagonist, and p-chlorophenylalanine (PCPA), a serotonin synthesis blocker on the sexual behavior of intact old male rats at 19-23 months of age and female rats at 17-18 months of age were studied. Female rats with prolonged vaginal cornification and a lordosis quotient (LQ) of less than 50%, and male rats displaying no ejaculation were selected as experimental animals. The receptivity of aged female rats, but not the approach behavior to males nor proceptivity was improved by PCPA or methysergide. The LQ of intact aged female rats in non-exit tests was improved by the i.p. administration of 50 mg/kg B.W. of PCPA 2 to 4 hours prior to the sexual behavior test or 3 mg/kg B.W. of methysergide 4 hours prior to the test. Total mount frequency and mount latency of intact aged male rats were improved by the administration of methysergide (3 mg/kg B.W.), while total mount frequency and intromission latency were improved by the administration of PCPA (20 mg/kg B.W. for 4 days). The present results together with the finding from our previous study suggest that the increase of serotonin (5-HT) activity per se plays an important role in the decline of receptivity of aged female rats and the copulatory activity of aged male rats.

Aging

[The effect of monosodium L-glutamate (MSG) treatment during neonatal period on the pineal function in young female rats].

The purpose of this study is to examine whether monosodium L-glutamate (MSG) influences the function of pinealocytes in female rats. MSG was administered at a does of 4 mg/g body weight to rat pups on days 1 and 3 postnatally. As the rats matured, sexual receptivity as well as proceptivity were observed by testing the lordosis quotient (LQ), rejection quotient (RQ) and solicitation. Pineal function was estimated by measuring the serum level of melatonin and the activity of protein kinase A (PKA) in the pineal gland. Blood samples were withdrawn at light and dark phases for four consecutive days, respectively. The serum concentration of melatonin was determined by radioimmunoassay and the data of each phase were pooled together. The results showed that both the receptivity and proceptivity of MSG-treated female rats were significantly lower than that of the control ones. Melatonin levels during the dark phase were significantly higher than those during the light phase in both control and MSG-treated groups, but whenever in the light or dark phase, the levels of melatonin were the same in both groups. There was no significant difference in PKA activity in the pineal gland between the control and MSG-treated group. These results indicate that MSG used as a neurotoxin to induce hypogonadal status affected neither the PKA activity of pineal gland nor the serum level of melatonin in young female rats. Thus, the decrease in receptivity and proceptivity of MSG-treated female rats was not caused by the alteration of pineal function.

Animals

[The mechanism of the pineal gland in inhibiting sexual receptivity of female rats: (II) Does it concern progesterone?].

The present study was designed to find the role of progesterone in modulating the effect of pineal gland upon reproductive behavior in the female rat. Monosodium L-glutamate (MSG) was used as a neurotoxin to induce hypogonadal function. In the first part of the experiment, rats were divided into four groups: (1) normal, (2) pinealectomized (Px), (3) MSG-treated (MSG), and (4) pinealectomized MSG-treated (Px-MSG), as immature rats became mature, the IEC (Incidence of Estrous Cycle) in each group was determined by vaginal smear for three weeks. Serum samples for estimating the levels of progesterone were collected at estrous. Then, ovariectomy was performed. Two weeks later, estradiol was primed for three days following progesterone administration and sexual receptivity as well as solicitation were observed. The results showed that, the serum progesterone levels and IEC of Px-MSG rats were significantly higher than that of the MSG group. In addition, Px and Px-MSG rats showed a higher sexual receptivity than normal and MSG rats, respectively. In the second part of the experiment, rats were divided into two groups: (1) normal and (2) Px. All rats were ovariectomized at 2.5 months of age and implanted with a 2-mm 20% estradiol benzoate-filled silastic capsule. Then, sexual receptivity to various doses of progesterone (0, 0.02, 0.1, 0.5 mg/rat) were observed. The results showed that receptivity of Px rats was significantly higher than that of the normal ones in a dose-dependent manner. It is concluded that pineal gland plays an important role in the regulation of ovary function as well as sexual receptivity in female rats. Also, progesterone may be one of the factors modulating the effect of pineal gland on sexual receptivity.

Animals

Sex-specific impairment in sexual and ingestive behaviors of monosodium glutamate-treated rats.

L-monosodium glutamate (MSG) (4 mg/g b.wt.) was injected subcutaneously to pups on days 1 and 3. At age 3.5 months, sexual and ingestive behaviors were observed. Neonatal MSG treatment resulted in severe and widespread neuron destruction in the basomedial hypothalamus of both sexes, but only super-chiasmatic nucleus in male rats. A decline in sexual behavior was also observed. Serum levels of testosterone and dihydrotestosterone in male rats as well as serum level of progesterone in female rats were decreased. Ovariectomized MSG-treated female rats injected with estradiol benzoate followed by progesterone showed a dramatic improvement in sexual behavior, whereas castrated MSG-treated male rats injected with testosterone propionate did not meliorate the decline of sexual behavior. Neonatal MSG treatment also induced reductions of body weight in male rats, higher diurnal percentages of food and water intake in male rats than in female rats, and a decline of water-to-food ratio. These observations suggest that neonatal male rats show higher susceptibility to glutamate-induced dysfunction of sexual and ingestive behaviors than females. Our findings also suggest a sex difference in the mechanism of dysfunction of sexual behavior, i.e., decreased copulatory activity in male rats is mainly due to CNS damage, in contrast to decreased blood progesterone level in female rats.

Animals

Usefulness of bronchoalveolar cell profile in early detection of canine lung allograft rejection.

To evaluate the value of a bronchoalveolar cell profile in the early detection of canine lung allograft rejection, bronchoalveolar lavages were done serially in mongrel dogs before and after single lung transplantation. The dogs were divided into 3 groups. In group 1, neither donor nor recipient dogs were treated with cyclosporine. In group 2, only donors were treated with cyclosporine, orally at a single dose of 20 mg/kg/day for 3 days prior to single lung transplantation. In group 3, only recipients were treated with cyclosporine (20 mg/kg/day) for 9 days after single lung transplantation. A marked increase in the number of bronchoalveolar cells and their cell differentials, and of major histocompatibility complex (MHC) class II-positive cells obtained from the grafted lungs after lung transplantation, was seen in groups 1 and 2. The changes in bronchoalveolar cell profile obtained from the rejecting grafted lungs were significantly different from those obtained from the normal and native lungs (P less than 0.05). In group 3, the bronchoalveolar cell profile obtained from the grafted lungs did not significantly differ from those present in normal and native lungs during the period of cyclosporine treatment after lung transplantation. On various days after withdrawal of cyclosporine treatment, bronchoalveolar cell profiles obtained from the grafted lungs showed similar changes to those observed in groups 1 and 2. Abnormal changes in bronchoalveolar cell profiles obtained from the grafted lungs heralded the appearance of abnormalities detected by chest X-ray films. Our results indicate that serial measurements of bronchoalveolar cell profile may serve as a useful means for early detection of canine lung allograft rejection.

Animals

Significance of biochemical markers in early detection of canine lung allograft rejection.

To evaluate the significance of bronchoalveolar lavage fluid, levels of tumor necrosis factor-alpha (TNF), gamma-interferon, interleukin 2, and soluble IL-2 receptor in early detection of canine lung allograft rejection, bronchoalveolar lavages were performed serially in mongrel dogs before and after single lung transplantation. The dogs were divided into three groups. Group 1 (control group) consisted of one in which neither donor nor recipient dogs were treated with cyclosporine. In group 2 (CsA-pretreated group) only donors were treated with CsA orally at a single dose of 20 mg/kg/day for 3 days prior to single lung transplantation. In group 3 only recipients were treated with CsA orally at a single dose of 20 mg/kg/day for a short period of 9 days after single-lung transplantation. Marked elevation was found of TNF, IFN-gamma, IL-2, and IL-2R in BALF obtained from the grafted lungs in group 1 and group 2 dogs. The levels of these markers were significantly higher than those obtained from the normal, native lungs (P less than 0.05). Two of three recipients in group 2 had pneumonia in the native lungs on day 10 after single-lung transplantation. All markers except IFN-gamma in BALF obtained from the infected native lungs were also increased, but the titers were less than those obtained from the grafted lungs at the same time. There were significantly higher levels of TNF, IL-2, and IL-2R present in the BALF of grafted lungs of dogs in group 1 than group 2 (P less than 0.05). In group 3, BALF levels of these markers from the grafted lungs were not significantly different from those of the normal and native lungs during the period of CsA treatment after single-lung transplantation. On various days after discontinuation of CsA treatment, BALF levels of all markers began to rise. Abnormal levels of BALF markers obtained from the grafted lungs heralded the appearance of abnormalities detected by chest x-ray films. Our study suggests that serially measuring BALF levels of TNF, IFN-gamma, IL-2, and IL-2R may serve as a useful means in monitoring the immunologic status of canine lung allografts and in the early detection of lung allograft rejection. The role of BALF IFN-gamma in distinguishing lung allograft rejection from pulmonary infection needs further studies.

Animals

[The action mechanism of the pineal gland in inhibiting sexual receptivity of female rats: (I). Is it concerned with the extrahypothalamic inhibitory pathway?].

Monosodium L-glutamate (MSG), as a neurotoxin, was administered subcutaneously at a dose of 4 mg/g body weight to rat pups on days 1 and 3 postnatally. The sexual receptivity expressed as lordosis quotient (LQ) in MSG-treated female rats (2.5 months old) was significantly lower than that of the normal female ones, and this poor sexual receptivity of MSG-treated females could be improved by pinealectomy at the age of six weeks. In order to investigate the relationship between the inhibitory role of the pineal gland and the extrahypothalamic inhibitory pathway, normal control and MSG-treated rats were ovariectomized and implanted subcutaneously with estradiol capsule (20% estradiol benzoate, in 2mm silastic tube) at the age of 2.5 months. Three days after implantation, sexual receptivity was observed. Then, the anterior roof deafferentation (ARD) was preformed one week later and the sexual receptivity in both groups was compared again. The results showed that there was no significant difference of the lordosis response between the MSG-treated and the control groups before ARD, and the level of restoration by ARD in LQ of MSG-treated rats was similar to that of the control group. It seems that the extrahypothalamic inhibitory pathway of sexual receptivity may not be influenced by neonatal MSG-treatment. Our previous results indicated that the behavioral sensitivity to estradiol was altered by ARD. However, in the present study, the lordosis responses of MSG-treated and pinealectomized female rats were not significantly different from that of the control group after ovariectomy and exogenous estradiol implantation. This means that the behavioral sensitivities to estradiol were not changed by MSG-treatment or pinealectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Increased expression of MHC class II antigens in rejecting canine lung allografts.

Expression of major histocompatibility complex class II antigens was investigated in the normal lungs and in lung allografts of mongrel dogs after single-lung transplantation. Cryostat sections were stained with an indirect immunoperoxidase technique that used B1F6 and 7.5.10.1 as anti-MHC class II monoclonal antibodies. In the normal lungs and native lungs of the recipient dogs after single-lung transplantation, only some cells of lymphoid tissue and macrophages/dendritic cells were MHC class II-positive. During acute rejection, increased infiltration with MHC class II-positive cells in perivascular, peribronchial, and interstitial areas and intraalveolar spaces was found in lung allografts. In addition, expression of MHC class II antigens was induced on the bronchial epithelium and vascular endothelium. Induced expression of MHC class II antigens on the bronchial epithelium and vascular endothelium in rejecting lung allografts was found as early as two days after single-lung transplantation. The intensity of MHC class II antigen expression on bronchial epithelium and vascular endothelium in graft lungs increased with the progression of rejection response and directly correlated with the bronchoalveolar lavage fluid (BALF) levels of biochemical markers, as tumor necrosis factor alpha, gamma-interferon (IFN-gamma), interleukin 2 (IL-2) and soluble interleukin 2 receptor (SIL-2R). Abnormal expression of MHC class II antigens on bronchial epithelium and vascular endothelium and abnormal elevation of BALF levels of the cytokines in lung allografts could be prevented by cyclosporine (CsA) treatment. Our results suggested that MHC class II antigen expression could be induced on the bronchial epithelium and vascular endothelium of canine lung allografts during acute rejection. This abnormal expression of MHC class II antigens on bronchial epithelium and vascular endothelium of graft lungs may serve as a specific index for diagnosis of lung allograft rejection when infection as an inducing factor can be excluded. Furthermore, bronchial epithelium and vascular endothelium of lung allografts have become MHC class II-positive, and are likely to be the targets for low-grade rejection, resulting in the development of bronchiolitis obliterans and occlusive vascular disease in lung allografts.

Animals

Influence of pinealectomy on sexual behavior of normal and monosodium L-glutamate-treated rats.

Subcutaneous injections of monosodium L-glutamate (MSG) were administered, as a neurotoxin, at a dose of 4 mg/g body weight to rat pups on days 1 and 3 postnatally. Pinealectomy was performed at 6 weeks of age, and animals were allowed to mature. The intact MSG-treated rats showed a decrease of lordosis quotient in females and a reduction of ejaculation frequency and an increase in mount frequency in males. Pinealectomy caused no significant improvement on sexual behavior of the saline-treated normal rats, but it caused a marked improvement of the sexual receptivity in MSG-treated female rats and reinstated ejaculation in MSG-treated males. The circulatory sex steroid levels, estrogen in females and androgen in males, were not significantly different between the intact and pinealectomized MSG-treated groups in the respective sexes, whereas the progesterone level in females was significantly elevated in the pinealectomized MSG-treated group compared with the intact MSG-treated group. These findings suggest that the pineal gland plays an inhibitory role on the sexual behavior of MSG-treated rats and the improvement of sexual behavior following pinealectomy may be dependent on certain mechanisms other than the actions of circulatory androgens or estrogens.

Analysis of Variance

Reconstruction of the esophagus with the left colon.

This report reviews our experience with 96 patients with benign or malignant stricture of the esophagus who underwent interposition of the left colon with or without esophageal resection from July 1982 to June 1987. There were 67 male and 29 female patients ranging in age from 8 to 80 years. Thirty-seven patients had fibrotic stricture secondary to corrosive injury of the esophagus, 42 had cancer of the esophagus, and 17 had cancer of the gastric cardia. The incidence of postoperative complications and surgical mortality, respectively, was 16.2% and 2.7% for patients with corrosive stricture of the esophagus, 35.7% and 11.9% for patients with cancer of the esophagus, and 35.2% and 5.8% for patients with cancer of the gastric cardia. Reconstruction resulted in good function in 75.6% of the patients with corrosive stricture of the esophagus, 66.6% of the patients with cancer of the esophagus, and 70.5% of patients with cancer of the gastric cardia. The morbidity and mortality were higher in the group with malignant esophageal strictures because of advanced age, poor general condition of the patient, and extent of the surgical procedure needed. Cervical anastomotic leakage was the most frequently encountered complication (13.5%), and all the poor-function results were caused by this complication. In our experience, reconstruction of the esophagus with left colon is a satisfactory method that can be accomplished with acceptable morbidity and mortality. The left colon is a durable and functional substitute.

Adolescent

Double lung transplant in primate.

Experimental en-bloc double lung transplantation was first reported by Dark et al. to broaden the indications for heart-lung and single lung transplantations. They used puppies as an acute model: however primates are optimal in expecting improving survival. In this study we used Taiwan cynomolgus monkeys for 20 enbloc double lung transplants. The animals weighing 2.4-8.0 kgs. were divided into two groups: one with surface cooling and profound hypothermia and the other one with bypass using heart lung machine. For surface cooling group the average ischemic time was 58.5 minutes, and the result was disappointing: The best survivor sustained only 8 hours after transplant, and 5 died on table. In the group with bypass, the perioperative course was rather smooth. The animals could restore their respiratory function after transplant. Postoperative bleeding was the major course of complication. All the animals died within one day. During operation, evidence of tuberculosis and filariasis were observed. While some problems have to be solved before a clinical trial starts, clinical en-bloc double lung transplant is technically feasible.

Animals

Adhesions as a cause of persistent spontaneous pneumothorax.

The authors present a case of a patient with a persistent spontaneous pneumothorax (after seven days of chest tube drainage) in whom a tear in an upper lobe bleb was held open by adhesions between the bleb and the chest wall. Radiographic findings which might indicate such a condition are presented, thus altering one to the need for early surgical intervention. Current theories regarding the pathophysiology of pneumothorax in the young and elderly patient are reviewed.

Humans

Primary mediastinal seminoma.

Primary mediastinal seminoma is a rare neoplastic disease. Only 133 cases have been reported in the literature. Five patients with primary mediastinal seminoma had been treated at VGH from 1974 to 1986. All of them received exploratory thoracotomy but only two of them were resectable. Postoperative radiation therapy was given regardless of resection. One had additional chemotherapy due to nodal involvement. All five patients showed complete resolution and were alive and free of disease for an average follow-up period of 42.6 months (range, 5-82 months). So we conclude that mediastinal seminoma is a rare neoplastic disease and can be treated primarily by surgery. Irradiation can also induce complete remission and long term survival in those with unresectable tumors.

Adult

Contained thoracic empyema presenting as an anterior chest wall abscess: empyema necessitatis revisited.

Protean manifestation of pulmonary and pleural space infections can be expected in drug addicts. Because of the need to establish strict environmental protection for staff and patients, even simple drainage procedures should be performed in the operating room. Without testing, these patients should be considered as potential carriers of the AIDS virus. If a subcutaneous abscess is found to extend into the pleural space, drainage and full lung expansion are attempted through a limited rib resection. If this is unsuccessful, a full thoracotomy should be done to meet these surgical objectives.

Adult