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Biomedical subjects

K M Lin

Publications and source records attributed to K M Lin.

At least 73 records · Page 4Linked to original sources

Prolongation of serum half-life of interleukin 2 and augmentation of lymphokine-activated killer cell activity by pepstatin in mice.

We reported previously using a murine model that the kidney is the organ involved in catabolism of exogenous human recombinant interleukin 2 (IL-2) and that cathepsin D, a major renal acid protease, is responsible for the degradation of IL-2. In the present report also using BALB/c mice we have investigated the effect of in vivo pepstatin, an acid protease inhibitor, treatment on serum half-life of IL-2, and generation of lymphokine-activated killer (LAK) cell activity. The in vivo pepstatin treatment by i.p. injection resulted in a significant reduction in the accumulation of 125I-IL-2 by the kidney in a reverse dose-response manner. Pepstatin treatment prolonged the serum half-life of 125I-IL-2, and the increase in serum half-life of 125I-IL-2 was pepstatin dose dependent. A significant reduction in renal cathepsin D activity, as monitored by the degradation of 125I-IL-2, was detected. In vivo pepstatin (0.6 mg/kg) treatment along with IL-2 (300,000 IU/mouse) daily for 3 or 6 days resulted in an augmentation of natural killer activity exhibited by freshly prepared and uncultured splenocytes against YAC-1 cells. An additional culturing of the splenocytes with IL-2 (3,000 IU/ml) in vitro for 1 day significantly enhanced the effect of in vivo pepstatin treatment; i.e., LAK cell activity generated from the splenocytes of animals treated with IL-2 plus pepstatin was greatly augmented in comparison with that treated with IL-2 alone. Phenotypic assessment by cell surface markers (Thy-1.2, Lyt-2, L3T4, and asialo-GM1) on the fresh splenocytes prepared from animals treated in vivo with pepstatin plus IL-2 revealed a decrease in the percentage of cells expressing Thy-1.2 and Lyt-2 and an increase in those carrying asialo-GM1. These results demonstrated that, as a result of in vivo pepstatin treatment, renal cathepsin D activity was greatly inhibited, which in turn reduced the degradation of circulating IL-2, then prolonged serum half-life of IL-2, and subsequently augmented natural killer and LAK cell activity. The in vivo pepstatin and IL-2 treatment decreased the T-cells and increased the natural killer-like LAK precursor cells, possibly also with an increase in its activity, which were further induced by in vitro IL-2 culture to generate an augmented LAK cell activity. This study also suggests the clinical potential of pepstatin in IL-2-related immunotherapy.

Animals↗

A longitudinal assessment of haloperidol doses and serum concentrations in Asian and Caucasian schizophrenic patients.

Over 3 months, 13 Caucasian and 16 Asian schizophrenic patients were sequentially treated with weight-adjusted fixed doses and clinically determined, variable doses of haloperidol. During the fixed-dose phase, Asians had a slightly higher mean serum haloperidol concentration and a significantly higher rating for extrapyramidal symptoms. During the variable-dose phase, the Asian patients' mean required dose was significantly lower, resulting in lower serum haloperidol concentrations at the first emergence of extrapyramidal symptoms and for optimal clinical response. These results indicate pharmacodynamic differences in therapeutic response but no significant difference in steady-state serum concentration between the two groups.

Adult↗

The significance of new abnormal isoenzymes of 5'-nucleotide phosphodiesterase in the diagnosis of human liver cancer.

In 1986, we reported that abnormal 5'-nucleotide phosphodiesterase (5'-NP) (oligonucleate: 5'-nucleotidohydrolase, EC 3.1.4.1) isoenzymes (5'-NP I and 5'-NP V + VI) were observed in the serum of patients with liver cancer. The results of the present study show that the 5'-NP I positivity rate is 99.2% (234/236), specificity 74.9%; and the 5'-NP V + VI positivity rate is 77.5% (183/236), specificity 95.3% in liver cancer. 5'-NP I positivity rate is 86.7% (13/15) and 5'-NP V + VI positivity rate is 46.7% (7/15) in metastatic liver cancer. These 3 abnormal isoenzyme bands were all present in the serum of 6 patients with liver cancer before radical resection and disappeared after successful resection, but they were all present in the serum of 6 other liver cancer patients before and after palliative operation. In 2 cases of small liver cancer (diameter less than 4cm), 5'-NP I and 5'-NP V + VI were strongly positive. It may be considered that the new 5'-NP abnormal isoenzyme bands are specific markers and will be useful for diagnosis of human liver cancer.

Clinical Enzyme Tests↗

Comparison of alprazolam plasma levels in normal Asian and Caucasian male volunteers.

Single-dose pharmacokinetics of alprazolam was studied in 42 normal male volunteers (14 Caucasians, 14 American-born Asians, and 14 foreign-born Asians), after both oral and parenteral (IV) administration of a small dose (0.5 mg) of the test drug. Asians manifested significantly higher Cmax, larger AUC, slower CL and longer t1/2 under both testing situations. When body surface area was used as a covariate, these cross-ethnic differences remained statistically significant (except Cmax) after oral but not IV drug administration. There were no differences between the two Asian groups in any of these parameters examined in this study. These results confirmed previous observations of ethnic differences in the pharmacokinetic response between Asians and Caucasians and suggested that smaller doses of alprazolam may be required for Asians for similar clinical effects as compared to their Caucasian counterparts.

Administration, Oral↗

Psychopathology and clinical course of schizophrenia: a cross-cultural perspective.

The authors critically review the existing literature on the outcome of schizophrenia in non-Western countries. Compared to studies conducted in Europe and North America, the majority of these non-Western longitudinal followup studies indicated significantly better outcome. Such cross-national variations in the outcome of schizophrenia have been substantiated by two large-scale multicentered studies sponsored by the World Health Organization. Along with this literature review, the authors also discuss potential methodological problems of these studies and examine in detail several key hypotheses concerning mediating factors that could differentially influence the fate of schizophrenic patients in divergent cultural settings. Finally, specific suggestions are made for future research directions.

Cross-Cultural Comparison↗

Haloperidol and prolactin concentrations in Asians and Caucasians.

Serum haloperidol and prolactin concentrations were measured in 34 normal male volunteers (12 Caucasians, 11 American-born Asians, and 11 foreign-born Asians) over a 7-hour period after haloperidol administration (0.5 mg given intramuscularly or 1.0 mg given orally). The results were similar between the two Asian groups but significantly different between Caucasians and Asians. After controlling for body surface area, Caucasians still had lower serum haloperidol concentrations and less prominent prolactin responses than did Asians. Furthermore, the ethnic difference in prolactin responses could not be fully accounted for by the differences in serum haloperidol concentrations between the two ethnic groups. These results indicate that both pharmacokinetic factors, including absorption and hepatic first-pass metabolism, and pharmacodynamic factors (dopamine receptor-mediated responses) contribute to the difference in responses between Caucasians and Asians.

Adult↗

New abnormal isoenzyme of 5'-nucleotide phosphodiesterase in the serum of human hepatoma.

5'-nucleotide phosphodiesterase (5'-NP) isoenzymes were separated from the serum of human primary liver cancer (PLC) patients by 4-20% tubular polyacrylamide gel gradient electrophoresis. Electrophoresis showed 11 isoenzymes in which bands I, V and VI (from anode to cathode) were all absent in 125 normal control sera; bands V and VI were detectable in 31(73.8%) of 42 patients with PLC, but absent in 70 cases of other diseases. Bands V and VI may represent specific isoenzyme bands of PLC, comprising a new addition to the markers used in the diagnosis of this disease. By the same method, it was also found that the abnormal serum isoenzyme bands of PLC correspond to those found in the cord blood sera of the newborn and fetus. These abnormal isoenzymes diminish gradually after birth and all disappear when children reach the age of 10.

Carcinoma, Hepatocellular↗

Ethnicity and psychopharmacology.

In clinical studies and cross-national surveys, cultural or ethnic factors have been found to be significant determinants in patients' responses to psychotropic medication. Dosage requirements and the potential for toxic reactions might differ amongst racial and ethnic groups. In this paper, the authors review the relevant literature and examine pharmacodynamic, pharmacokinetic and cultural-psychological factors, all of which could be responsible for such ethnic variations.

Anti-Anxiety Agents↗

Propranolol in psychiatry. Therapeutic uses and side effects.

There are speculations that beta-adrenergic blocking agents are useful in the treatment of psychiatric disorders. Clinically, propranolol, an agent of this group, has been investigated in the treatment of various clinical disorders including schizophrenia, other psychoses, anxiety disorders, and stress reactions. This paper critically evaluates its efficacy in these disorders and provides a useful clinical perspective. In addition, propranolol produces a number of psychiatric side effects which are due to its central action or due to the peripheral receptor blockade. In addition, idiosyncratic reactions as well as withdrawal effects have also been reported to produce psychiatric side effects. It is important that the physician who wishes to use this drug know the existing knowledge of its usefulness in the treatment of psychiatric disorders as well as its psychiatric side effects.

Adolescent↗

Self-inflicted enucleation of an eye: two case reports.

There are a number of reports of self-inflicted enucleation of the eye which indicate that this act probably protects the patients from guilt. It appears that religious delusions play a dominant role irrespective of primary diagnosis. Hence, enucleation of an eye may occur in various psychotic syndromes with religious delusions. In this report the history of two patients are presented to suggest that self-enucleation of the eye served as a protection from suicide. The management of these patients includes rapid neuroleptization and a close follow-up with both drug and psychological therapies.

Adult↗

Hwa-Byung: a Korean culture-bound syndrome?

The author reports three cases of Hwa-Byung, a Korean folk illness ordinarily understood by patients and families to be a physical affliction despite the fact that its manifestations include both physiological and psychological symptoms. In addition, the patient often recognizes interpersonal conflicts and anger as precipitating factors. In the three cases reported, the patients also identified an epigastric mass that was not present on physical examination. Symptoms were accompanied by a fear of impending death that was not easily dispelled by medical reassurance. The author discusses the role of depression in the symptom formation of Hwa-Byung as well as the treatment implications.

Adult↗

Sociocultural determinants of the help-seeking behavior of patients with mental illness.

This descriptive study employed semistructured interviewing and questionnaire administration to delineate the sociocultural determinants of the help-seeking process in 48 psychiatric patients. The help-seeking process is considered in two stages. The first stage starts from the recognition of initial symptoms and ends in the first contact with a mental health professional. The second stage is defined as that time between the first contact and actual participation in a planned treatment program. In both stages, patients typically go through phases of lay consultation, nonpsychiatric professional consultation, and referral. The multiple steps which are usually involved in help seeking often result in significant delay of both mental health contact and treatment. The help-seeking process was found to correlate strongly with ethnicity. Both Asians and Blacks showed more extended family involvement, and the involvement of key family members tended to be persistent and intensive in Asians. Ethnicity was also associated with the length of delay, with Asians showing the longest delay and Caucasians the least. These ethnic differences were also reflected in help-seeking pathway assignment using Lin's criteria. Although modernity and parochialism, as measured by the level of modernization and the cohesiveness of the social network system of the subjects, were also found to be correlated with delay, they appeared to exert an influence independent from that of ethnicity.

Adult↗