Biomedical subjects
Publications and source records attributed to T S Li.
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DATA FAVORING IMMUNE RECONSTITUTION: Multiple drug therapies for HIV infection have enabled a major reduction in the viral load, higher CD4 counts, and a lower incidence of opportunistic infections and tumor formations, and subsequently lower hospitalization rates and mortality. TWO STAGES OF CD4 RECONSTITUTION: In HIV-positive patients with advanced stage disease treated with a protease inhibitor associated with 2 nucleoside analog reverse transcriptase inhibitors and followed prospectively, it has been observed that CD4 counts rise considerably, with a rapid increase during the first 2 months followed by a slower but still positive slope over a period of 18 months. Discordant results have however also been observed suggesting an ineffective anti-viral effect or a retarded immune reconstitution. SEVERAL MECHANISMS: The lymphocyte amplification observed during the early phase corresponds to re-circulation of CD4 and CD8 lymphocytes which had been sequestered in lymphoid organs; most of these CD4 lymphocytes are memory cells. A second phase corresponds to a more moderate and progressive rise in naive CD4 cells which originate from an unknown source. This biphasic reconstitution of CD4 lymphocytes is associated with a correction of the chronic lymphocyte overactivation. PARTIAL IMMUNE RECONSTITUTION: With treatment, the capacity to respond to known antigens reappears. This restored capacity is secondary to the amplification of CD4 memory cells and appears prior to the expansion phase of naive cells. The response remains moderate and is only observed against antigens from microorganisms highly prevalent during advanced stage infection.
Clinical benefits of highly active anti-retroviral treatments (HAART) are increasingly evidenced by resolving opportunistic infections and malignancies, as well as declining hospitalization and mortality rates [1]. This suggests that potent and sustained suppression of viral replication, at least to some extent, is associated with reconstitution of the immune system even in adult patients treated at advanced stages of the disease. Increased susceptibility to opportunistic infections and tumors mainly results from the loss of memory CD4+ T cell reactivity against recall antigens which is an early event in HIV disease progression. Primary responses of naive CD4+ T cells against new pathogens are suppressed even earlier in the course of HIV disease, and the progressive depletion in naive CD4+ T cells reflects profound alterations in T cell regeneration capacities. Previous studies revealed that monotherapy with ritonavir, a protease inhibitor, resulted in a slight improvement in memory CD4+ T cell responses to recall Ags only when detectable prior to onset of therapy, suggesting that the loss of CD4+ T cell reactivity might be irreversible at advanced stages of the disease [2]. In contrast our group demonstrated more recently that restoration in CD4+ T cell reactivity to specific antigens was feasible when HAART was administered in progressors [3]. Here we address some of the questions raised by immune restoration with HAART when administered at advanced stages of the disease.
Isolated lung perfusion has been performed for the treatment of unresectable lung tumours; however, the pharmacokinetics of this procedure remain unclear. This study was conducted to investigate the changes in antitumour drug concentrations in tumour and lung tissues after isolated lung perfusion, using different perfusion times and perfusate drug concentrations. Isolated left lungs were perfused for 20, 40 or 60 min with 25, 50 or 100 micrograms/ml of cisplatin after solitary lung tumour nodules were established in rats, and the total platinum concentrations in the perfused lung and tumour tissues were determined by flameless atomic absorption spectroscopy. The oedema in the perfused lung tissues was evaluated by histological examination and by the wet to dry weight ratios of the lungs. The total platinum concentration increased significantly with perfusion time and increasing perfusate cisplatin concentrations in the lung tissue, but it did not change in the tumour tissue. The wet to dry weight ratios of the lung tissues did not differ significantly among the perfusion groups. Oedema of the perfused lung tissue did not change significantly with the perfusion time or perfusate cisplatin concentration. The results of this study indicate the possibility that different pharmacokinetics exist between tumour and lung tissues following isolated lung perfusion with cisplatin, which could be used as a clinical guide for the selection of appropriate perfusion times and perfusate drug concentrations.
Sea buckthorn (Hippophae rhamnoides) is a unique plant currently being domesticated. The fruit is the main component of value, although the leaves are occasionally made into sea buckthorn tea. The two main sources of valuable products are derived from the berries, juice from the fleshy tissue and seed as a single seed from each berry. The juice provides a nutritious beverage, high in suspended solids and very high in vitamin C and carotenes. The juice may contain an oil phase trapped within the suspended solids, or the oil may be removed as pulp oil and provided separately. The pulp remaining after juice removal provides for extraction of "sea buckthorn yellow", a pigment that has potential use as a food coloring material. The seed is a source of seed oil, which is very unsaturated and shows promise, because of its light absorption and emollient properties, as an ingredient in cosmetics, phytopharmaceuticals, or UV skin protectant preparations. It may be prepared by conventional extraction techniques or by supercritical carbon dioxide extraction. The manufacture of the main products derived from sea buckthorn is described, including several examples from the patent literature. The available compositional data for the main products are tabulated to form a comprehensive source of information on the manufacture and composition of sea buckthorn products.
The course of the HIV infection has been dramatically modified since the introduction of highly active antiretroviral therapy (HAART) combining inhibitors of the HIV-1 reverse transcriptase and protease. Despite some controversies about the extent to which the immune system can normalize, it is generally admitted nowadays that a numerical and functional CD4 cell profile more akin to asymptomatic HIV-infected individuals can be restored in AIDS patients and can confer host protection against opportunistic events. The best hallmark of such immune restoration is the massive decline in the mortality and morbidity related to AIDS that have been registered in all industrialized countries. These changes involve a recirculation of mature peripheral T cells, a regeneration of naive T cells from thymic origin and a restoration of memory CD4 T cell réactivities. Although these recent advances warrant increased optimism, HAART by reducing the virus burden is unable to restore immunity against HIV itself, except when introduced at the very early stage after virus inoculation. The single condition required for immune reconstitution is an efficient and durable inhibition of virus replication. These positive effects can be obtained at late stages of the disease even when the patients have been heavily pre-treated. They also demonstrate that HIV does not definitively alter the lymphoid tissues nor the immune defenses, even aller years of infection and severe immune suppression, except for HIV-specific CD4 T helper cells.
Diploid strains homozygous for both MAT allele and STA genes (a/a, STA1/STA1 or STA2/STA2 or STA3/STA3) and diploid strains homozygous for MAT allele but intercombinative for STA genes (a/a, STA1/STA2 or STA2/STA3 or STA1/STA3) were constructed by means of the protoplast fusion or the colchicine treatment. According to glucoamylase activity in YPS medium, we studied the gene-dosage effect and their interrelation of these three polymeric genes coding for glucoamylase. The results of the glucoamylase activity determination showed that the gene-dosage effect of glucoamylase is obvious in diploid and triploid strains homozygous for both MAT allele and STA gene, such as the glucoamylase activity of a diploid strain SFY56-6 and a triploid strain SFY56-104 homozygous for both MAT allele and STA genes were respectively 2.35 and 3.18-fold as compared with that of the their parental strain IATA-Y56 that is a haploid Saccharomyces diastaticus. Moreover, the glucoamylase activity of diploid strains homozygous for MAT allele but intercombinative for STA genes also showed the combinative gene-dosage effect to a certain extent.
BACKGROUND: Highly active antiretroviral therapy (HAART) decreases viral load and increases CD4 T-cell counts in patients with advanced HIV-1 infection. Whether HAART can improve CD4 T-cell function, and the biological characteristics affecting immune reconstitution, remain unclear. We undertook an open prospective pilot study to address these issues. Both treatment-naïve and previously treated patients were included. METHODS: 20 patients (seven naïve, 13 previously treated) were treated with one protease inhibitor and two reverse-transcriptase inhibitors and followed up for 12 months. We measured CD4-cell proliferation in response to cytomegalovirus and tuberculin antigens and counted subsets of CD4 cells at baseline and months 1, 3, 6, 9, and 12. Patients who had no antigen-specific reactivity at baseline but developed it while receiving HAART were classified as immunological responders. FINDINGS: Four patients had antigen-specific reactivity at baseline compared with 14 at month 12 (p <0.001). Between month 3 and month 12 viral load fell by a median of 1.5 log copies/mL from baseline (4.6 log copies/mL) and CD4-cell count increased by a median of 63/microL (from 93/microL). Ten patients (six of seven naïve, four of 13 previously treated) were immunological responders. They differed significantly from the ten non-responders in that their viral-load reduction was sustained for 12 months, the increase in CD4 count was greater, and they showed an early increase in memory CD4 T cells with an increase of naïve T cells. INTERPRETATION: HAART can induce sustained recovery of CD4 T-cell reactivity against opportunistic pathogens in severely immunosuppressed patients. This recovery depends not on baseline values but on the amplitude and duration of viral-load reduction and the increase of memory CD4 T cells.
Oxidation of cholesterol (1a) or pregnenolone (1b) with pyridinium dichromate (PDC) in dimethylformamide (DMF) or in dichloromethane (DCM) and pyridinium chlorochromate (PCC) in DCM provided cholest-4-en-3,6-dione (2a) or pregn-4-en-3,6,20-trione (2b). TLC monitoration of the reactions implied that cholest-5-en-3-one (3a) or pregn-5-en-3,20-dione (3b) and cholest-4-en-3-one (4a) or pregn-4-en-3,20-dione (4b) might be intermediates. Individual oxidation of 3a or 3b with PDC and PCC could give 2a or 2b, but 4a or 4b remained unchanged. Further investigation indicated that 4a or 4b was an isomerization product of 3a or 3b on silica gel TLC plate rather than really existence in the reaction mixture. These results shown steroidal 5-en-3-ones were intermediates of the transformation of steroidal 5-en-3 beta-ols to steroidal 4-en-3,6-diones oxidized by PDC and PCC.
OBJECTIVE: To describe the epidemiological characteristics of toxoplasmic encephalitis in HIV-infected patients with a more than 12-year follow-up. METHODS: From a data base of 1,628 AIDS subjects hospitalized from 1983 to 1994, we studied the epidemiological characteristics of 399 patients with toxoplasmic encephalitis. Diagnosis of toxoplasmic encephalitis was based on the association of central neurological disorders, typical lesions on CT scan or MRI, and favorable outcome under appropriate toxoplasmosis therapy. RESULTS: Four hundred sixty-four cases of toxoplasmic encephalitis were reported in 399 patients (24.5% of the patients with AIDS). The overall incidence was 20.5 per 100 patients-year. Toxoplasmic encephalitis was the first AIDS defining event in 51% of the cases and revealed HIV infection in 13% of the cases. In the remaining 49%, the mean delay from AIDS diagnosis to toxoplasmic encephalitis was 13 months (range: 1-71 months). At the time of diagnosis, mean CD4 count was 44/mm3 (range: 0-408/mm3). Antibodies to Toxoplasma gondii were found in 97% of the cases. Before the first episode of toxoplasmic encephalitis, 58% of the patients were given antiretroviral therapy (mean: 17.8 months; range: 1-64 months). Of the 399 patients with toxoplasmic encephalitis, 366 (92%) did not receive any primary toxoplasmosis prophylaxis. Among them, 205 (56%) did not receive any drug prophylaxis, and 161 (44%) had Pneumocystis carinii pneumonia prophylaxis alone (aerosolized pentamidine). Thirty-three failures were observed (8%) with cotrimoxazole: 14 cases (3%) were considered to have irregular compliance. Sixty-five relapses were observed in 52 patients. At the end of the study 334 patients had died (84%). The median survival was 11.4 months (95% confidence interval, range: 10.4-12.4 months). CONCLUSIONS: Toxoplasmic encephalitis incidence has decreased since the introduction of appropriate drug prophylaxis.
In the presence of montmorillonite K 10, 5(6)-unsaturated sterols (1) were heated under ultrasound at 45 degrees C in dichloromethane for 2-5.5 h to provide 3 beta,3'beta-5(6)/5'(6')-unsaturated disteryl ethers (2) in 35-79% yield. Meanwhile, 3 alpha,3'alpha-diandrost-5-en-17-one-3-yl ether (3a) and 3 alpha,3'alpha-dipregn-5-en-20-one-3-yl ether (3b) were also obtained as by-products from 3 beta-hydroxyl-androst-5-en-17-one (1a) and 3 beta-hydroxyl-pregnan-5-en-20-one (1b) respectively.
Highly active antiretroviral therapy (HAART) increases CD4(+) cell numbers, but its ability to correct the human immunodeficiency virus (HIV)-induced immune deficiency remains unknown. A three-phase T cell reconstitution was demonstrated after HAART, with: (i) an early rise of memory CD4(+) cells, (ii) a reduction in T cell activation correlated to the decreasing retroviral activity together with an improved CD4(+) T cell reactivity to recall antigens, and (iii) a late rise of "naïve" CD4(+) lymphocytes while CD8(+) T cells declined, however, without complete normalization of these parameters. Thus, decreasing the HIV load can reverse HIV-driven activation and CD4(+) T cell defects in advanced HIV-infected patients.
In a study of 50 family caregivers of elderly Chinese patients with dementia in Singapore, 28 (56%) scored five points or more on the 28-item General Health Questionnaire (GHQ). The GHQ scores correlated significantly with duration of care; presence of delusion, hallucination, depression, insomnia, incontinence and agitation; and the total score of the Behavioural Pathology in Alzheimer's Disease Rating Scale. On multiple regression analysis the only variables to achieve a significant relationship with the GHQ scores were duration of care, depression and the total behavioural score.
Six cases of hepatic sarcoma are reported: leiomyosarcoma in two, malignant fibrous histiocytoma in two malignant hemagiopericytoma in one and fibrosarcoma in one. In addition to the routine paraffin section and HE stain, immuno-histochemical studies with antibodies against vimentin, EMA, CK, S100, ACT, AAT, desmin, AFP, lysozyme and factor VIII and Masson trichrome staining and argyrophilia staining were done. AFP was negative in all 6 patients and the primary sarcoma was characterized by the absence of accompanying liver cirrhosis. The diagnosis, histogenesis and prognosis of primary liver sarcoma are discussed.
Granulocyte colony stimulating factor (G-CSF) level in the serum rises within minutes after people infected by bacteria. It can reach almost 1,000 fold above normal level. We established an ELISA test for measuring G-CSF using McAb. After injected with endotoxin into mice, this method was used to observe the peak serum G-CSF in mouse. Again 200 normal people were tested on G-CSF, but all showed negative results. In 100 bacteria-infected patients, 82 (82%) showed positive results. In 100 non-bacteria-infected patients with fever, only 7(7%) was positive. It is indicated that testing body fluids and serum can determine whether the patient is infected with bacteria or not.
4,5-Secocholestane (1a) and 4-methyl-4,5-secocholestane (1b) were synthesized from cholesterol (2) in five and seven steps, respectively. The key intermediate, 5-oxo-4,5-secocholestan-4-al (7) was reduced by the Clemmensen method to afford 1a. Meanwhile, 7 underwent selective Wittig reaction, Clemmensen reduction, and hydrogenation to give another target molecule, 1b. The structure of an unknown biomarker was shown to be different from the proposed 1a by gas chromatographic and mass spectrometric comparison.
13,17-Secodiacholestanes (6) were synthesized from cholesterol (1) in six steps. The key intermediates, (20R)- and (20S)-diacholest-13(17)-enes (3a and 3b), underwent ozonization and reduction to provide (20R)- and (20S)-13,17-secodiacholesta-13,17-dione (5a and 5b), respectively. On Clemmensen reduction, the diones (5a and 5b) yielded the target molecule 6. The structure of an unknown biomarker was shown to be different from the proposed 6 by gas chromatographic/mass spectrometric comparison.
The gene encoding the beta-subunit of rod photoreceptor cGMP phosphodiesterase (gene symbol PDEB, homolog of the mouse rd gene) is mapped to human chromosome 4 using somatic cell hybrids and further localized to the chromosome band 4p16 using in situ hybridization. A mutation in the mouse gene underlies the recessive trait of retinal degeneration in the rd mouse. Thus, the human homolog is a candidate for lesions causing retinal degeneration.